Nephrology. Times. It is estimated that 11.3 million. Approximately 8% of pregnancies are complicated by hypertension, a

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1 Nephrology Practical News, Trends, and Analysis Times May/June 2017 VOLUME 9, NUMBER 4 Dietary Intervention to Reduce Vasopressin Secretion in ADPKD Patients A pilot randomized controlled trial to examine the effect of a low-osmolar, low-protein diet and adjusted water intake on vasopressin secretion in ADPKD. 10 CMS Reimbursement Reform and Hospitalizations and Readmissions among Hemodialysis Patients In 2004, CMS changed physician reimbursement for patients receiving hemodialysis, targeting a specific care process: the frequency of face-to-face provider visits. 11 Fluid Overload in AKI Patients Receiving Continuous Renal Replacement Therapy A retrospective study evaluating the association between fluid overload and mortality in critically ill patients. 12 PLUS... From the Field New Medicare Patient ID System 22 Undocumented Immigrants with No Access to Scheduled Hemodialysis It is estimated that 11.3 million undocumented immigrants live and work in the United States, representing a low-income population excluded from public benefits such as federally funded Medicaid and insurance provisions of the Affordable Care Act. Healthcare for individuals in that population is largely limited to safety-net provisions designed to protect the uninsured, including community health centers, public clinics, and treatment in hospital emergency departments (EDs) mandated by the 1986 Emergency Medical Treatment and Active Labor Act (EMTALA). When an undocumented immigrant is diagnosed with end-stage renal disease (ESRD), arranging care is complex, requiring access to hemodialysis. There are approximately 6480 undocumented immigrants with ESRD in the United States. Access to hemodialysis for those individuals depends on state policy and local safety net investments. California and New York, for example, use state emergency Medicaid programs to finance scheduled hemodialysis for those patients; other states offer only nonstandard emergent-only hemodialysis, accessed through the ED under EMTALA and reimbursed by emergency Medicaid programs. Lila Cervantes, MD, and colleagues recently conducted a qualitative, continued on page 7 Using a Dynamic Model to Predict Progression of CKD to Kidney Failure The worldwide incidence and prevalence of chronic kidney disease (CKD) is increasing; recent estimates indicate that 24 million Americans have CKD and are at risk for comorbidities and complications such as cardiovascular disease, anemia, bone mineral metabolism abnormalities, and progression to kidney failure. Patients with end-stage renal disease require treatment with dialysis or kidney transplantation. Shared Risk Factors of Preeclampsia and End-Stage Renal Disease continued on page 6 Approximately 8% of pregnancies are complicated by hypertension, a complication that can lead to significant maternal morbidity and mortality. Previous studies have documented some long-term effects on maternal health of hypertensive pregnancies, especially the risk for cardiovascular disease. Several large registry-based studies have also shown associations between pregnancy hypertension and the development of kidney disease, including end-stage renal disease (ESRD). According to Andrea G. Kattah, MD, those studies had some limitations, including use of International Classification of Disease codes in lieu of an actual review of medical records, and the inability to determine the frequencies of potential confounders such as kidney disease and obesity prior to pregnancy. Dr. Kattah and colleagues conducted a population-based nested case-control study designed to examine the magnitude of the association between preeclampsia and ESRD. Preeclampsia was identified using complete medical records of cases and controls, and ESRD was identified using the US Renal Data System (USRDS) database. The researchers also sought to examine how pre-pregnancy comorbid conditions such as decreased kidney function, obesity, hypertension, and diabetes mellitus may confound the association between preeclampsia and ESRD. Study results were reported in the American Journal of Kidney Diseases [2017;69(4): ]. The medical records search revealed 34,581 women with live or stillbirths from continued on page 8

2 Introducing Parsabiv The first and only IV calcimimetic You control delivery. Parsabiv lowers 3 key shpt lab values. A new era in the delivery of calcimimetic treatment has begun. Lower PTH, phosphate, and corrected calcium with the only calcimimetic you administer at the end of hemodialysis. With Parsabiv, control of calcimimetic delivery is now in your hands. Not an actual Parsabiv vial. The displayed vial is for illustrative purposes only. Indication Parsabiv (etelcalcetide) is indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis. Limitations of Use: Parsabiv has not been studied in adult patients with parathyroid carcinoma, primary hyperparathyroidism, or with CKD who are not on hemodialysis and is not recommended for use in these populations. Important Safety Information Contraindication: Parsabiv is contraindicated in patients with known hypersensitivity to etelcalcetide or any of its excipients. Hypersensitivity reactions, including pruritic rash, urticaria, and face edema, have occurred. Hypocalcemia: Parsabiv lowers serum calcium and can lead to hypocalcemia, sometimes severe. Significant lowering of serum calcium can cause QT interval prolongation and ventricular arrhythmia. Patients with conditions that predispose to QT interval prolongation and ventricular arrhythmia may be at increased risk for QT interval prolongation and ventricular arrhythmias if they develop hypocalcemia due to Parsabiv. Closely monitor corrected serum calcium and QT interval in patients at risk on Parsabiv. Significant reductions in corrected serum calcium may lower the threshold for seizures. Patients with a history of seizure disorder may be at increased risk for seizures if they develop hypocalcemia due to Parsabiv. Monitor corrected serum calcium in patients with seizure disorders on Parsabiv. Concurrent administration of Parsabiv with another oral calcimimetic could result in severe, life-threatening hypocalcemia. Patients switching from cinacalcet to Parsabiv should discontinue cinacalcet for at least 7 days prior to initiating Parsabiv. Closely monitor corrected serum calcium in patients receiving Parsabiv and concomitant therapies known to lower serum calcium. Measure corrected serum calcium prior to initiation of Parsabiv. Do not initiate in patients if the corrected serum calcium is less than the lower limit of normal. Monitor corrected serum calcium within 1 week after initiation or dose adjustment and every 4 weeks during treatment with Parsabiv. Measure PTH 4 weeks after initiation or dose adjustment of Parsabiv. Once the maintenance dose has been established, measure PTH per clinical practice. Worsening Heart Failure: In Parsabiv clinical studies, cases of hypotension, congestive heart failure, and decreased myocardial performance have been reported. Closely monitor patients treated with Parsabiv for worsening signs and symptoms of heart failure. Upper Gastrointestinal Bleeding: In clinical studies, 2 patients treated with Parsabiv in 1253 patient years of exposure had upper gastrointestinal (GI) bleeding at the time of death. The exact cause of GI bleeding in these patients is unknown and there were too few cases to determine whether these cases were related to Parsabiv. Patients with risk factors for upper GI bleeding, such as known gastritis, esophagitis, ulcers or severe vomiting, may be at increased risk for GI bleeding with Parsabiv. Monitor patients for worsening of common Parsabiv GI adverse reactions and for signs and symptoms of GI bleeding and ulcerations during Parsabiv therapy. Adynamic Bone: Adynamic bone may develop if PTH levels are chronically suppressed. Adverse Reactions: In clinical trials of patients with secondary HPT comparing Parsabiv to placebo, the most common adverse reactions were blood calcium decreased (64% vs. 10%), muscle spasms (12% vs. 7%), diarrhea (11% vs. 9%), nausea (11% vs. 6%), vomiting (9% vs. 5%), headache (8% vs. 6%), hypocalcemia (7% vs. 0.2%), and paresthesia (6% vs. 1%). Please see Brief Summary of full Prescribing Information on adjacent page. IV = intravenous; shpt = secondary hyperparathyroidism; PTH = parathyroid hormone. Parsabiv (etelcalcetide) prescribing information, Amgen Amgen Inc. All rights reserved. Not for Reproduction. USA Visit ParsabivHCP.com for more information.

3 BRIEF SUMMARY OF PRESCRIBING INFORMATION Please see package insert for full Prescribing Information. INDICATIONS AND USAGE PARSABIV is indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis. Limitations of Use: PARSABIV has not been studied in adult patients with parathyroid carcinoma, primary hyperparathyroidism, or with chronic kidney disease who are not on hemodialysis and is not recommended for use in these populations. CONTRAINDICATIONS Hypersensitivity PARSABIV is contraindicated in patients with known hypersensitivity to etelcalcetide or any of its excipients. Hypersensitivity reactions, including pruritic rash, urticaria, and face edema, have occurred with PARSABIV [see Adverse Reactions (6.1) in PARSABIV full prescribing information]. WARNINGS AND PRECAUTIONS Hypocalcemia PARSABIV lowers serum calcium [see Adverse Reactions (6.1) in PARSABIV full prescribing information] and can lead to hypocalcemia, sometimes severe. Significant lowering of serum calcium can cause paresthesias, myalgias, muscle spasms, seizures, QT interval prolongation, and ventricular arrhythmia. QT Interval Prolongation and Ventricular Arrhythmia In the combined placebo-controlled studies, more patients treated with PARSABIV experienced a maximum increase from baseline of greater than 60 msec in the QTcF interval (0% placebo versus 1.2% PARSABIV). In these studies, the incidence of a maximum post-baseline predialysis QTcF > 500 msec in the placebo and PARSABIV groups was 1.9% and 4.8%, respectively [see Adverse Reactions (6.1) in PARSABIV full prescribing information]. Patients with congenital long QT syndrome, history of QT interval prolongation, family history of long QT syndrome or sudden cardiac death, and other conditions that predispose to QT interval prolongation and ventricular arrhythmia may be at increased risk for QT interval prolongation and ventricular arrhythmias if they develop hypocalcemia due to PARSABIV. Closely monitor corrected serum calcium and QT interval in patients at risk receiving PARSABIV. Seizures Significant reductions in corrected serum calcium may lower the threshold for seizures. Patients with a history of seizure disorder may be at increased risk for seizures if they develop hypocalcemia due to PARSABIV. Monitor corrected serum calcium in patients with seizure disorders receiving PARSABIV. Concurrent administration of PARSABIV with another oral calcium-sensing receptor agonist could result in severe, life-threatening hypocalcemia. Patients switching from cinacalcet to PARSABIV should discontinue cinacalcet for at least 7 days prior to initiating PARSABIV [see Dosage and Administration (2.4) in PARSABIV full prescribing information]. Closely monitor corrected serum calcium in patients receiving PARSABIV and concomitant therapies known to lower serum calcium. Measure corrected serum calcium prior to initiation of PARSABIV. Do not initiate in patients if the corrected serum calcium is less than the lower limit of normal. Monitor corrected serum calcium within 1 week after initiation or dose adjustment and every 4 weeks during treatment with PARSABIV [see Dosage and Administration (2.2) in PARSABIV full prescribing information]. Educate patients on the symptoms of hypocalcemia, and advise them to contact a healthcare provider if they occur. If corrected serum calcium falls below the lower limit of normal or symptoms of hypocalcemia develop, start or increase calcium supplementation (including calcium, calcium-containing phosphate binders, and/or vitamin D sterols or increases in dialysate calcium concentration). PARSABIV dose reduction or discontinuation of PARSABIV may be necessary [see Dosage and Administration (2.2) in PARSABIV full prescribing information]. Worsening Heart Failure In clinical studies with PARSABIV, cases of hypotension, congestive heart failure, and decreased myocardial performance have been reported. In clinical studies, heart failure requiring hospitalization occurred in 2% of PARSABIV-treated patients and 1% of placebo-treated patients. Reductions in corrected serum calcium may be associated with congestive heart failure, however, a causal relationship to PARSABIV could not be completely excluded. Closely monitor patients treated with PARSABIV for worsening signs and symptoms of heart failure. Upper Gastrointestinal Bleeding In clinical studies, two patients treated with PARSABIV in 1253 patient-years of exposure had upper gastrointestinal (GI) bleeding noted at the time of death while no patient in the control groups in 384 patient-years of exposure had upper GI bleeding noted at the time of death. The exact cause of GI bleeding in these patients is unknown, and there were too few cases to determine whether these cases were related to PARSABIV. Patients with risk factors for upper GI bleeding (such as known gastritis, esophagitis, ulcers, or severe vomiting) may be at increased risk for GI bleeding while receiving PARSABIV treatment. Monitor patients for worsening of common GI adverse reactions of nausea and vomiting associated with PARSABIV [see Adverse Reactions (6.1) in PARSABIV full prescribing information] and for signs and symptoms of GI bleeding and ulcerations during PARSABIV therapy. Promptly evaluate and treat any suspected GI bleeding. Adynamic Bone Adynamic bone may develop if PTH levels are chronically suppressed. If PTH levels decrease below the recommended target range, the dose of vitamin D sterols and/or PARSABIV should be reduced or therapy discontinued. After discontinuation, resume therapy at a lower dose to maintain PTH levels in the target range [see Dosage and Administration (2.1) in PARSABIV full prescribing information]. ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Hypocalcemia [see Warnings and Precautions (5.1) in PARSABIV full prescribing information] Worsening Heart Failure [see Warnings and Precautions (5.2) in PARSABIV full prescribing information] Upper Gastrointestinal Bleeding [see Warnings and Precautions (5.3) in PARSABIV full prescribing information] Adynamic Bone [see Warnings and Precautions (5.4) in PARSABIV full prescribing information] Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The data in Table 2 are derived from two placebo-controlled clinical studies in patients with chronic kidney disease and secondary hyperparathyroidism on hemodialysis. The data reflect exposure of 503 patients to PARSABIV with a mean duration of exposure to PARSABIV of 23.6 weeks. The mean age of patients was approximately 58 years, and 60% of the patients were male. Of the total patients, 67% were Caucasian, 28% were Black or African American, 2.6% were Asian, 1.2% were Native Hawaiian or Other Pacific Islander, and 1.6% were categorized as Other. Table 2 shows common adverse reactions associated with the use of PARSABIV in the pool of placebo-controlled studies. These adverse reactions occurred more commonly on PARSABIV than on placebo and were reported in at least 5% of patients treated with PARSABIV. Table 2: Adverse Reactions Reported in 5% of PARSABIV-Treated Patients Adverse Reaction* Placebo (N = 513) PARSABIV (N = 503) Blood calcium decreased a 10% 64% Muscle spasms 7% 12% Diarrhea 9% 11% Nausea 6% 11% Vomiting 5% 9% Headache 6% 8% Hypocalcemia b 0.2% 7% Paresthesia c 1% 6% * Included adverse reactions reported with at least 1% greater incidence in the PARSABIV group compared to the placebo group a Asymptomatic reductions in calcium below 7.5 mg/dl or clinically significant asymptomatic reductions in corrected serum calcium between 7.5 and < 8.3 mg/dl (that required medical management) b Symptomatic reductions in corrected serum calcium < 8.3 mg/dl c Paresthesia includes preferred terms of paresthesia and hypoesthesia

4 Other adverse reactions associated with the use of PARSABIV but reported in < 5% of patients in the PARSABIV group in the two placebo-controlled clinical studies were: Hyperkalemia: 3% and 4% for placebo and PARSABIV, respectively. Hospitalization for Heart Failure: 1% and 2% for placebo and PARSABIV, respectively. Myalgia: 0.2% and 2% for placebo and PARSABIV, respectively. Hypophosphatemia: 0.2% and 1% for placebo and PARSABIV, respectively. Description of Selected Adverse Reactions Hypocalcemia In the combined placebo-controlled studies, a higher proportion of patients on PARSABIV developed at least one corrected serum calcium value below 7.0 mg/dl (7.6% PARSABIV, 3.1% placebo), below 7.5 mg/dl (27% PARSABIV, 5.5% placebo), and below 8.3 mg/dl (79% PARSABIV, 19% placebo). In the combined placebocontrolled studies, 1% of patients in the PARSABIV group and 0% of patients in the placebo group discontinued treatment due to an adverse reaction attributed to a low corrected serum calcium. Hypophosphatemia In the combined placebo-controlled studies, 18% of patients treated with PARSABIV and 8.2% of patients treated with placebo had at least one measured phosphorus level below the lower normal limit (i.e., 2.2 mg/dl). QTc Interval Prolongation Secondary to Hypocalcemia In the combined placebo-controlled studies, more patients treated with PARSABIV experienced a maximum increase from baseline of greater than 60 msec in the QTcF interval (0% placebo versus 1.2% PARSABIV). The patient incidence of maximum post-baseline predialysis QTcF > 500 msec in the placebo and PARSABIV groups was 1.9% and 4.8%, respectively. Hypersensitivity In the combined placebo-controlled studies, the subject incidence of adverse reactions potentially related to hypersensitivity was 4.4% in the PARSABIV group and 3.7% in the placebo group. Hypersensitivity reactions in the PARSABIV group were pruritic rash, urticaria, and face edema. Immunogenicity As with all peptide therapeutics, there is potential for immunogenicity. The detection of anti-drug binding antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to etelcalcetide with the incidence of antibodies to other products may be misleading. In clinical studies, 7.1% (71 out of 995) of patients with secondary hyperparathyroidism treated with PARSABIV for up to 6 months tested positive for binding anti-etelcalcetide antibodies. Fifty-seven out of 71 had pre-existing anti-etelcalcetide antibodies. No evidence of altered pharmacokinetic profile, clinical response, or safety profile was associated with pre-existing or developing anti-etelcalcetide antibodies. If formation of anti-etelcalcetide binding antibodies with a clinically significant effect is suspected, contact Amgen at AMGEN ( ) to discuss antibody testing. USE IN SPECIFIC POPULATIONS Pregnancy Risk Summary There are no available data on the use of PARSABIV in pregnant women. In animal reproduction studies, effects were seen at doses associated with maternal toxicity that included hypocalcemia. In a pre- and post-natal study in rats administered etelcalcetide during organogenesis through delivery and weaning, there was a slight increase in perinatal pup mortality, delay in parturition, and transient effects on pup growth at exposures 1.8 times the human exposure for the clinical dose of 15 mg three times per week. There was no effect on sexual maturation, neurobehavioral, or reproductive function in the rat offspring. In embryo-fetal studies, when rats and rabbits were administered etelcalcetide during organogenesis, reduced fetal growth was observed at exposures 2.7 and 7 times exposures for the clinical dose, respectively. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data There were no effects on embryo-fetal development in Sprague-Dawley rats when etelcalcetide was dosed at 0.75, 1.5, and 3 mg/kg/day by the intravenous route during organogenesis (pre-mating to gestation day 17) at exposures up to 1.8 times human exposures at the clinical dose of 15 mg three times per week based on AUC. No effects on embryo-fetal development were observed in New Zealand White rabbits at doses of etelcalcetide of 0.375, 0.75, and 1.5 mg/kg by the intravenous route (gestation day 7 to 19), representing up to 4.3 times human exposures based on AUC. In separate studies at higher doses of 4.5 mg/kg in rats (gestation days 6 to 17) and 2.25 mg/kg in rabbits (gestation days 7 to 20), representing 2.7 and 7 fold clinical exposures, respectively, there was reduced fetal growth associated with maternal toxicities of hypocalcemia, tremoring, and reductions in body weight and food consumption. In a pre- and post-natal development study in Sprague-Dawley rats administered etelcalcetide at 0.75, 1.5, and 3 mg/kg/day by the intravenous route (gestation day 7 to lactation day 20), there was a slight increase in perinatal pup mortality, delay in parturition, and transient reductions in post-natal growth at 3 mg/kg/day (representing 1.8-fold human exposures at the clinical dose of 15 mg three times per week based on AUC), associated with maternal toxicities of hypocalcemia, tremoring, and reductions in body weight and food consumption. There were no effects on sexual maturation, neurobehavioral, or reproductive function at up to 3 mg/kg/day, representing exposures up to 1.8-fold human exposure based on AUC. Lactation Risk Summary There are no data regarding the presence of PARSABIV in human milk or effects on the breastfed infant or on milk production. Studies in rats showed [ 14 C]-etelcalcetide was present in the milk at concentrations similar to plasma. Because of the potential for PARSABIV to cause adverse effects in breastfed infants including hypocalcemia, advise women that use of PARSABIV is not recommended while breastfeeding. Data Presence in milk was assessed following a single intravenous dose of [ 14 C]- etelcalcetide in lactating rats at maternal exposures similar to the exposure at the human clinical dose of 15 mg three times per week. [ 14 C]-etelcalcetide-derived radioactivity was present in milk at levels similar to plasma. Pediatric Use The safety and efficacy of PARSABIV have not been established in pediatric patients. Geriatric Use Of the 503 patients in placebo-controlled studies who received PARSABIV, 177 patients (35.2%) were 65 years old and 72 patients (14%) were 75 years old. No clinically significant differences in safety or efficacy were observed between patients 65 years and younger patients ( 18 and < 65 years old). No differences in plasma concentrations of etelcalcetide were observed between patients 65 years and younger patients ( 18 and < 65 years old). OVERDOSAGE There is no clinical experience with PARSABIV overdosage. Overdosage of PARSABIV may lead to hypocalcemia with or without clinical symptoms and may require treatment. Although PARSABIV is cleared by dialysis, hemodialysis has not been studied as a treatment for PARSABIV overdosage. In the event of overdosage, corrected serum calcium should be checked and patients should be monitored for symptoms of hypocalcemia, and appropriate measures should be taken [see Warnings and Precautions (5.1) in PARSABIV full prescribing information]. PARSABIV (etelcalcetide) Manufactured for: KAI Pharmaceuticals, Inc., a wholly owned subsidiary of Amgen, Inc. One Amgen Center Drive Thousand Oaks, California Patent: Amgen, Inc. All rights reserved. USA

5 From the Board Profit Is Not a Four Letter Word Kenneth A. Liss, DO Hypertension and Nephrology Associates EATONTOWN, NEW JERSEY If you want to prescribe sacubitril/valsartan, check off the first eight boxes and your patient might get it. I try, perfunctorily, to keep up with journal reading. Some of the publications are fond of placing self-help advice for doctors. Articles about efficiency, making better use of the HER, and how to avoid unnecessary litigation are commonplace. Frankly, some of the advice is timely and helpful, but I often find myself annoyed by the fact that these articles sit side-by-side with information about how to manage anemia in CKD, latest updates on vaccinations in immunocompromised hosts, and new data about initiating RRT in AKI. It s as if we ve come to accept the fact that being the best physician is as much about documentation, billing codes, and staff performance evaluations as it is about patient care. Of course this all speaks to a much larger problem. The reason that self-help has such a large audience is that physicians have been subject to an environment in which regulations trump the patient-physician relationship. As healthcare dollars become more scarce, those in charge of doling them out have decided that healthcare is a basic human right. As a result, consumers of healthcare are no longer subject to capital markets. We have created a system where consumption has no boundaries, but profit is obsolete. Better stated, profit and healthcare delivery are dichotomous. The hospitals and insurance companies have got the jump on this and have created accountable care organizations where they will control the flow of both services and costs. Unlike the previous experiment with HMOs, this will have real teeth because, by attrition, patients will give up their right to choose how their healthcare dollars are spent. To further add insult to injury, the government is adding so many onerous regulations that I hear my colleagues tell me that they are ready for a single-payer system. The truth is that I currently fork over about $30,000 in annual healthcare premiums to the insurance company so that my family has the right to access the type of care we want. The government would have me give that same $30,000 to them so that they can then dictate the type of care we are entitled to receive. Unless we need it, they are likely to take that money and use it to pay other patients costs. This is known more commonly now as Obamacare except that the insurance companies are still part of the equation. With a single-payer system there will be protocols that will determine what and when we receive care. If you want to prescribe sacubitril/valsartan, check off the first eight boxes and your patient might get it. If you want to use ferric citrate as a phosphate binder, you must call profits first. Supposedly, these protocols will be based on best practices. I am not so sure. I am proud of the job I do for my patients and feel that I am entitled to be fairly compensated for my services, much the same way the person who built my house or sells me my water is. These are both necessities, but are subject to market forces. If we remove profit from healthcare, we likely will see a precipitous drop in innovation. We are close to self-contained dialysis systems and functional xenografts. Amgen has developed a parenteral product that has a chance to revolutionize the treatment of mineral bone disease. These treatments might never get to make a real impact in a notfor-profit system. The list is endless. If we want to see the clock set back 50 years, we just need to keep reading the articles about how to make our EMRs more efficient. EDITORIAL BOARD CHAIR Ajay K. Singh, MBBS, MBA Senior Nephrologist Brigham and Women s Hospital Associate Professor of Medicine Harvard Medical School BOSTON, MASSACHUSETTS BOARD Mohamed G. Atta, MD, MPH Associate Professor of Medicine Johns Hopkins School of Medicine Division of Nephrology BALTIMORE, MARYLAND Vinod K. Bansal MD, FACP, FASN Professor of Medicine Division of Nephrology and Hypertension Loyola University Medical Center MAYWOOD, ILLINOIS Timothy E. Bunchman, MD Professor & Director Pediatric Nephrology Children s Hospital of Richmond VCU School of Medicine RICHMOND, VIRGINIA Suphamai Bunnapradist, MD, MS Professor of Medicine David Geffen School of Medicine at UCLA Research Director Kidney Transplant Program, UCLA LOS ANGELES, CALIFORNIA Fernando C. Fervenza, MD, PhD Professor of Medicine Division of Nephrology & Hypertension Mayo Clinic ROCHESTER, MINNESOTA Kenneth A. Liss, DO Hypertension and Nephrology Associates EATONTOWN, NEW JERSEY Sayeed K Malek, MD, FACS Clinical Director of Transplant Surgery Brigham and Women s Hospital Instructor in Surgery Harvard Medical School BOSTON, MASSACHUSETTS Alan Salama, MBBS, PhD Reader in Nephrology University College London LONDON, UNITED KINGDOM Lynda A. Szczech, MD, MSCE Associate Professor of Medicine Division of Nephrology Duke University Medical Center DURHAM, NORTH CAROLINA Nephrology Times May/June

6 News TAKEAWAY POINTS Using a static model to predict progression of kidney disease may be limited; researchers developed and evaluated a dynamic prediction model based on latest-available measurements to predict risk of disease progression. In a comparison of the static model with the dynamic model, estimated glomerular filtration rate was more strongly associated with kidney failure with the latestavialable-measurement model. In the dynamic model, male sex, and levels of phosphorus, albumin, and bicarbonate were no longer significantly associated with the outcome of progression to kidney failure. Using a Dynamic Model continued from page 1 Due to the varied complications of CKD and the heterogeneous CKD population, it is difficult to predict progression to kidney failure in CKD patients. Predicting CKD progression is important in decision-making concerning renal replacement therapy (RRT) options and planning for the possibility of RRT, including fistula insertion for hemodialysis and/or preemptive kidney transplantation. Traditional predictive models take a patient s data from a single snapshot in time and try to predict outcomes going forward. In clinical practice, physicians often integrate data from multiple visits to try and estimate risk of disease progression. Our dynamic approach suggests that integrating multiple data points in a predictive model is feasible, and produces an improvement in accuracy over a traditional static modeling approach. Navdeep Tangri, MD, PhD, FRCPC Navdeep Tangri, MD, PhD, FRCPC, and colleagues previously developed the Kidney Failure Risk Equations (KFREs), an accurate static prediction model that used singletimepoint measurements of demographic and laboratory variables. However, according to Dr. Tangi et al., because the KFREs are static and treat laboratory data derived from each provider encounter in isolation with no consideration of prior values, they are of limited value. More recently, the researchers evaluated whether a dynamic predictive model for progression of CKD to kidney failure incorporating changes in kidney function and other laboratory variables as time-dependent predictors would improve predictive performance compared with the static model. They reported results of their study in the American Journal of Kidney Diseases [2017;69(4): ]. The study population included 3004 patients with CKD stages 3 to 5 who were seen from April 2, 2001, through December 31, 2009, at the outpatient CKD clinic of Sunnybrook Hospital, a tertiary referral facility serving the North York region of Toronto, Ontario, Canada. A majority of the study cohort was >65 years of age, and 42% were women. Those with more advanced stages of CKD had higher levels of urine albumin-creatinine ratio (ACR), phosphorus, and potassium, and lower levels of serum albumin, calcium, and bicarbonate. Median duration of follow-up was 1.7 years. At time of referral, more than twothirds of the patients had CKD stage 3; only 3% of those patients progressed to kidney failure by the end of follow-up. Six percent of patients had CKD stage 5 at referral; of those, 60% progressed to kidney failure by the end of follow-up. The median number of visits per patient was six; the average span between clinic visits was 4 months. In the static model, mean time to event from the baseline visit creatinine level to the outcome was 893 days; in the dynamic model (using the latest-available measurement), the mean time from the most recent serum creatinine level to the outcome was 182 days. At visit one, median estimated glomerular filtration (egfr) rate was 36 ml/min/1.73 m 2, decreasing to 31 ml/min/1.73 m 2 by visit six. At the first visit, there were 3004 patients available for analysis; the number decreased to 1512 by visit six. The two groups (fewer than six visits and six or more visits) were similar in age, sex, egfr, and ACR. At the baseline visit in the static model, lower egfr, younger age, and male sex were associated with higher risk for progression to kidney failure, as were higher urine ACR, lower levels of serum calcium, albumin, or bicarbonate, and higher levels of phosphorus. In the dynamic model, using latest-available measurements, egfr was a more potent predictor of progression to kidney failure than in the static model: for each 5-mL/min/1.73 m 2 greater egfr, the hazard ratio (HR) for kidney failure was 0.44 (95% confidence interval [CI], ) versus 0.65 (95% CI, ). The HR for urine ACR was attenuated significantly: for each 1-log greater urine ACR, values were 1.30 (95% CI, ) and 1.45 (95% CI, ), respectively. In the dynamic model, the HRs for age and serum calcium level were relatively unchanged; male sex and levels of serum phosphorus, albumin, and bicarbonate were no longer associated independently with the outcome of progression to kidney failure. In comparisons of the two models, the latest-available-measurement model had modestly better discrimination compared with the baseline visit static model, as evidenced by the C statistic (0.91; 95% CI, versus 0.90; 95% CI, ) and integrated discrimination improvement statistic (IDI) (absolute IDI, 1.39%; 95% CI, 1.23%-1.56%). Calibration was adequate for both models; however, the latest-available-measurement model showed greater dispersion between risk deciles and better agreement between the observed and predicted probabilities. Goodness of fit was also significantly improved in the dynamic model. Limitations to the analysis cited by the researchers included deriving the data from a nephrology clinic at a single center; the inability to include time-dependent changes in albuminuria in the model because of a lack of longitudinal data; inconsistent times between laboratory measurements (particularly egfr); an inability to evaluate timedependent covariates in a predictive model using competing-risk analyses; the possibility that a small bias exists in the multiple imputation model; and the possible inability to generalize the findings of the analysis to settings in which the frequency of laboratory value measurements differ from those in this study. We present a dynamic predictive model for progression to kidney failure that modestly improves risk prediction over a static model for progression of kidney disease. Our model using electronically obtained covariates can lead to automatic risk calculation and reporting in the context of an electronic medical record and may enhance risk prediction of short-term events. Further studies comparing dynamic with static predictive models for kidney failure and competing outcomes of mortality and cardiovascular disease are needed, the researchers said. 3 Ways to read Nephrology Times: Print ipad Online Check out online exclusives at Nephtimes.com! 6 Nephrology Times May/June 2017

7 News Undocumented Immigrants continued from page 1 semistructured, interview study to examine the illness experience of undocumented immigrants (undocumented patients) with ESRD and no access to scheduled hemodialysis. Results were reported in JAMA Internal Medicine [doi: / jamainternmed ]. Twenty patients were approached to participate; all 20 agreed to be interviewed. Mean age of the participants was 51.4 years, 10% were female, all were Latino, 10 were employed, and mean Charlson Comorbidity Index score was 6.5. All had resided in the United States for a minimum of 5 years before their diagnosis of ESRD. Interviews ranged from 43 to 72 minutes in length. Four main themes were used to describe participants illness experience: (1) distressing burden of symptoms and the unpredictability of access to emergent-only hemodialysis; (2) anxiety about mortality associated with weekly life-threatening illness; (3) family and social consequences of accommodating emergent-only hemodialysis; and (4) perceptions of the healthcare system. Responses from participants indicated that they felt well for 2 days following hemodialysis and then gradually became impaired by accumulation of symptoms. The most burdensome symptom reported was shortness of breath. Fluid built up in the chest caused dyspnea, even with restrictions on beverage consumption. When patients were admitted with a planned second hemodialysis session, they were often discharged without receiving the second session due to a lack of hemodialysis chairs. In addition, when a hemodialysis unit was at capacity, patients were denied admission if laboratory values, particularly potassium levels, did not meet the threshold for critical illness, even when the patients met other criteria. Some patients reported waiting until their symptoms were life threatening to seek treatment rather than presenting earlier with the risk of being turned away. Possible consequences of waiting for a high serum potassium level, including the Some reported consuming food or beverages high in potassium outside the hospital entrance to ensure levels high enough for admission. need for cardiopulmonary resuscitation or severe arrhythmia requiring admission to the intensive care unit, were reported by many survey respondents. Some reported consuming food or beverages high in potassium outside the hospital entrance to ensure levels high enough for admission. They also knew that laboratory values too low for admission on a day when the hemodialysis unit was at capacity would enable admission on days with low hemodialysis unit utilization. Survey respondents reported recurrent fear of dying that occurred each week as symptoms accumulated and they waited for admission for emergent-only hemodialysis. They often described near-death and resuscitation experiences in a matter-of-fact way. Patients often formed comforting relationships with each other as they underwent hemodialysis and during their 2- to 3-day hospital stays. In addition to support from other patients, survey respondents said their families were crucial in helping them persevere with emergent-only hemodialysis. Family members took them to the hospital, called while they were inpatients, and were there to take them home on discharge. When asked about organ transplant, participants were aware that while they were eligible to donate organs, they could not receive transplantation because they were unable to afford lifelong antirejection medications. However, many reported they were identified as organ donors on their driver s license. The study is, to the authors knowledge, the first to describe the experience of emergent-only hemodialysis among undocumented immigrants first-hand. Possible limitations include respondents being from a single safety-net hospital in Colorado, all participants being Latino, possibly limiting generalizability of the patients experiences. Undocumented patients with ESRD and no access to scheduled hemodialysis describe significant physical and psychological distress that affects their families and their own ability to work. This distress, coupled with higher costs for emergent dialysis, indicate that we should reconsider our professional and societal approach to ESRD care for undocumented patients. Comparing the experiences of different states and localities may aid in identifying more humane and higher-value solutions, the researchers said. TAKEAWAY POINTS In some states, physicians are required to manage undocumented immigrants with end-stage renal disease (ESRD) with emergentonly hemodialysis, a treatment that is expensive and burdensome for patients. Researchers in Colorado conducted a qualitative, semistructured, interview study with 20 undocumented immigrants diagnosed with ESRD; all participants had been in this country for a minimum of 5 years. The study participants reported debilitating, often life-threatening symptoms of ESRD as well as psychological distress resulting from the inability to receive treatment with scheduled hemodialysis. National Kidney Foundation Etelcalcetide Safe and Efficacious over 18 Months Orlando Researchers led by Sunfa Cheng, MD, recently conducted an analysis of data from a 52-week open label extension trial and an open label extension trial of up to 2.5 years of etelcalcetide, an intravenous calcimimetic that reduced secondary hyperparathyroidism in hemodialysis patients. The efficacy of etelcalcetide in reducing parathyroid hormone was demonstrated in three phase 3 trials. The researchers reported results of the analysis during a poster session at the NKF 2017 Spring Clinical Meetings. The poster was titled Analysis of a Single-Arm Extension Study Evaluating Etelcalcetide Starting Dose for Treatment of Secondary Hyperparathyroidism in Patients on Hemodialysis. In the open label extension 2.5- year trial, patients enrolling from the etelcalcetide versus cinacalcet phase 3 trial had a washout period of 4 weeks, followed by treatment with etelcalcetide at 5.0 mg (original protocol) or 2.5 mg (protocol amendment). Etelcalcetide dose was titrated to achieve parathyroid hormone 2 times to 9 times the upper limit of normal (ULN). The current analysis aimed to evaluate the relationship between the etelcalcetide starting dose on adverse events, the ability to maintain parathyroid hormone targets, and phosphate level ULN at months 6, 12, and 18. At the start of the open label extension 2.5-year trial, mean parathyroid hormone was pg/ml for participants with starting etelcalcetide dose of 2.5 mg and pg/ml for those with starting dose of 5.0 mg. Decrease in asymptomatic calcium (with serum corrected calcium less than lower limit of normal) in the 2.5-mg dose group was 27%; in the 5.0-mg dose group, the decrease was 40%. In the 2.5-mg group, 1% had symptomatic hypocalcemia; no one in the 5.0-mg group had symptomatic hypocalcemia (also with serum corrected calcium less than lower limit of normal). At month 6, parathyroid hormone 2 times and 9 times the ULN occurred in 134 of 216 patients (62%) in the 2.5-mg starting dose group and in 87/137 (64%) of patients in the 5.0- mg starting dose group. Results at month 12 were 118 of 184 (64%) in the 2.5-mg starting dose group and 87 of 124 (70%) in the 5.0-mg starting dose group; at 18 months, results were 28 of 39 (72%) in the 2.5-mg starting group and 52 of 77 (68%) in the 5.0-mg starting dose group. At month 6, 82 of 204 participants (40%) in the 2.5-mg starting dose group had phosphate level ULN, as did 44 of 132 (33%) in the 5.0- mg starting dose group. Results at month 12 were 65 of 167 (39%) in the 2.5-mg starting dose group and 37 of 111 (33%) in the 5.0-mg starting dose group. At month 18, results were 14 of 37 (38%) in the 2.5-mg starting dose group and 23 of 72 (32%) in the 5.0-mg starting dose group. In summary, the researchers said, Etelcalcetide prescribed at a starting dose of either 5 mg or 2.5 mg demonstrated similar safety and efficacy over 18 months. Source: Cheng S, Block G, Dehmel B, Deng H, Chertow G. Analysis of a singlearm extension study evaluating etelcalcetide starting dose for treatment of secondary hyperparathyroidism in patients on hemodialysis. Abstract of a poster presented at the National Kidney Foundation 2017 Spring Clinical Meetings, April 19-22, 2017, Orlando, Florida. This study was supported by Amgen Inc. Nephrology Times May/June

8 News Shared Risk Factors of Preeclampsia continued from page to 2010 in Olmsted County, Minnesota. Following linkage to the USRDS database, there were 48 cases, of which five were excluded due to ESRD prior to or during the pregnancy. One other woman underwent kidney transplantation following the linkage, resulting in a final cohort of 44 confirmed cases. Median time from the last pregnancy to the onset of ESRD was 17.7 years. Median evaluate hypertension pregnancy disorders among the 132 women (44 cases and 88 controls). There was a median of 11 blood pressure measurements and nine urine dipstick measurements from prenatal visits. Using the diagnostic algorithm for hypertensive pregnancy disorders, 18% of cases and 5% of controls had at least one preeclamptic pregnancy. The frequency of ever having a pregnancy complicated by chronic hypertension was more common in cases (7%) than in controls (0%). The frequency of women with PUBLISHER Gene Conselyea NEPHROLOGY TIMES STAFF In an analysis of agreement with diagnostic codes, the sensitivity of using diagnostic codes for any type of hypertensive pregnancy disorder was only 61.5% (95% CI, 40.7%-79.1%); the specificity was 98.1% (95% CI, 95.4%-99.3%). EDITORIAL MANAGING EDITOR Victoria Socha EDITOR AT LARGE Eric Raible DIGITAL PROJECTS MANAGER Chris Gedikli ART DIRECTOR Ari Mihos ASSISTANT ART DIRECTOR John Salesi ADVERTISING ACCOUNT MANAGERS Jane Liss jliss@nephtimes.com TAKEAWAY POINTS Researchers conducted a population-based study to examine the magnitude of the association between preeclampsia and end-stage renal disease (ESRD). They also sought to determine the role of shared risk factors for ESRD and preeclampsia. The study included 44 women with ESRD from a cohort of 34,581 women who gave birth in 1976 to 2010 in Minnesota. The 44 cases were matched with 88 controls. Per chart review, eight of 44 cases versus four of 88 controls had preeclamptic pregnancies. Following independent adjustment for race, education, diabetes, and hypertension, results were similar. The association was attenuated and no longer significant when adjusted for obesity. age at ESRD diagnosis was 45.5 years. The 44 cases were matched with 88 controls; by design, age at first birth (either live or stillbirth) and parity were comparable. Among the cases, 64% of the pregnancies were full-term; in controls, 80% delivered at term. Cases were significantly more likely to be nonwhite, less educated, obese, and to have diabetes mellitus and hypertension. Using definitions of reduced estimated glomerular filtration rate (egfr) and/or proteinuria, pre-existing kidney disease was identified in nine cases and one control; however, only five of those women had diagnostic codes for kidney disease in the Rochester Epidemiology Project database prior to their first pregnancy. The nine cases of kidney disease were attributed to autosomal dominant polycystic kidney disease (n=4), glomerulonephritis (n=3), and diabetic nephropathy (n=3); the one case in the control group was attributed to autosomal recessive polycystic kidney disease. Baseline serum creatinine level prior to the first pregnancy was available for 20 cases and 32 controls. Median range of serum creatinine levels was 0.65 mg/dl in cases and 0.72 mg/dl in controls. One woman in the case group had egfr <60 ml/min/1.73 m 2 ; 92% of cases and controls had egfrs >90 ml/min/1.73 m 2. Thirty women in the cases group and 64 in the controls group had available baseline urine protein measurements: 23 of the 30 cases had normal urine dipstick findings, six had protein excretions 1+ on urine dipstick, and two had 24-hour urine collections with protein excretion >1000 mg/24 hours. In the control group, 60 had normal urine dipstick findings, three had normal protein-osmolality rations, and one had an elevated protein-osmolality ratio. There were 292 total pregnancies that lasted >20 weeks and had sufficient data to at least one pregnancy affected by gestational hypertension was similar in cases (5%) and controls (7%). Two women in the case group and one in the control group had 2 pregnancies that were complicated by a hypertensive pregnancy disorder. In the cases group, 71% of the women had exclusively normotensive pregnancies; in the control group, 90% did so. In comparison with controls, a history of preeclamptic pregnancy occurred more frequently in the cases group (odds ratio [OR], 4.0; 95% confidence interval [CI], ). The OR remained significant following independent adjustments for race (OR, 4.85; 95% CI, ), higher education, defined as some college or greater versus high school graduate or less (OR, 5.29; 95% CI, ), diabetes mellitus (OR, 7.00; 95% CI, ), and hypertension (OR, 3.68; 95% CI, ). Following adjustment for obesity, the association was attenuated and no longer significant. Finally, in an analysis of agreement with diagnostic codes, the sensitivity of using diagnostic codes for any type of hypertensive pregnancy disorder was only 61.5% (95% CI, 40.7%-79.1%); the specificity was 98.1% (95% CI, 95.4%-99.3%). Using codes specifically for preeclampsia, sensitivity was reduced further to 42.9% (95% CI, 18.8%- 70.4%) and specificity increased to 99.3% (95% CI, 97.2%-99.9%). Study limitations cited by the authors included the small number of cases due to the limited number of ESRD cases, and the missing data for prepregnancy kidney function. In conclusion, the researchers said, Our findings confirm that there is a sizable association between preeclampsia and ESRD; however, obesity is a previously unexplored confounder. Pre-existing kidney disease was common, but not consistently coded or diagnosed. Jen Callow jcallow@nephtimes.com Recruitment advertising orders can be sent to: DIRECTOR, RECRUITMENT CLASSIFIEDS Lauren Morgan lmorgan@americanmedicalcomm.com 630 Madison Avenue Manalapan, NJ Nephrology Times (ISSN ) is published monthly by American Medical Communications, at Madison Avenue, Manalapan, NJ Printed in the U.S.A. Copyright 2017 by American Medical Communications. Subscription information and orders: Physicians who are listed with AMA/AOA as having a primary or secondary specialty related to nephrology within the US are eligible for a free subscription. If you are not currently receiving the publication, send an with your name, address, and specialty to Tori Socha at: tsocha@ americanmedicalcomm.com. For customer service on your free subscription, please call Annual subscription rates: US: $99 individual, $200 institution. Postmaster: Send address change to: Nephrology Times, 630 Madison Avenue, 2nd Floor, Manalapan, NJ No part of this publication may be reproduced without the written permission of the publisher. The appearance of advertising in Nephrology Times does not constitute on the part of American Medical Communications a guarantee of endorsement of the quality or value of the advertised product or services or of the claims made for them by their advertisers. 8 Nephrology Times May/June 2017

9 The Only Iron Replacement Therapy That Maintains Hemoglobin Triferic is an innovative iron therapy that effectively treats the iron loss and anemia that hemodialysis patients suffer from. Gives Iron When and Where Patients Need it Triferic enters the blood via dialysate and donates its iron immediately to transferrin, making red blood cells and maintaining hemoglobin. Increases Healthy Red Blood Cells Hemoglobin enables red blood cells to carry oxygen to all parts of the body, providing energy. Proven Safety Profile No iron trapped in the liver and no increase in ferritin, inflammation, toxicity or infections. No anaphylaxis. Decrease in blood transfusions. 1 The Only FDA Approved Drug Indicated to Replace Iron and Maintain Hemoglobin in Adult CKD-HD Patients To schedule a web-enabled presentation on the benefits that Triferic can provide to your patients us at trifericpres@rockwellmed.com or call Triferic Rockwell Medical IMPORTANT SAFETY INFORMATION Warnings and Precautions Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been lifethreatening and fatal, have been reported in patients receiving parenteral iron products. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. Monitor patients for signs and symptoms of hypersensitivity during and after hemodialysis until clinically stable. Personnel and therapies should be immediately available for the treatment of serious hypersensitivity reactions. Hypersensitivity reactions have been reported in 1 (0.3%) of 292 patients receiving Triferic in two randomized clinical trials. Iron status should be determined on pre-dialysis blood samples. Post dialysis serum iron parameters may overestimate serum iron and transferrin saturation. Adverse Reactions The most common adverse reactions (>3% and at least 1% greater than placebo) in controlled clinical studies include: headache, peripheral edema, asthenia, AV fistula thrombosis, urinary tract infection, AV fistula site hemorrhage, pyrexia, fatigue, procedural hypotension, muscle spasms, pain in extremity, back pain, and dyspnea. For full Safety and Prescribing Information please visit 1 In Clinical Trials vs. Placebo. Triferic [Package Insert]. Rockwell Medical, Wixom, MI, September Triferic is a registered trademark of Rockwell Medical Inc.

10 News Dietary Intervention to Reduce Vasopressin Secretion in ADPKD Patients TAKEAWAY POINTS At present, there are no treatments that prevent the development of end-stage renal disease in patients with autosomal dominant polycystic kidney disease (ADPKD). Researchers recently conducted a pilot randomized controlled trial to examine the effect of combining a low-osmolar, lowprotein diet and adjusted water intake on vasopressin secretion in patients with ADPKD. The stepwise dietary intervention significantly reduced vasopressin secretion in patients with ADPKD; the intervention also led to a reduction in water needed for vasopressin reduction. An estimated eight to ten percent of patients in the United States and Europe with end-stage renal disease (ESRD) are also affected by autosomal dominant polycystic kidney disease (AD- PKD). At present, there are no treatments to prevent the development of ESRD in patients with ADPKD. Compared with healthy controls, ADPKD patients have impaired urine-concentrating ability and higher levels of arginine vasopressin (AVP; as reflected by plasma copeptin levels); this concentrating defect occurs despite overexpression of the vasopressin V2 receptor. In animal and human models, the inhibition of AVP V2 receptor controls disease progression, as does elimination of vasopressin in the polycystic kidney (PCK) rat. Researchers, led by Osama W. Amro, MD, MS, recently conducted a randomized controlled trial with equal (1:1) allocation to assess the effect of a low-osmolar diet and adjusted water intake on AVP secretion (measured by change in copeptin levels and decreased urine osmolality). In addition, according to the researchers, plasma vasopressin and copeptin levels solidly correlate across a span of osmolalities and circulating copeptin levels, reflecting the antidiuretic effect of vasopressin at the level of the target organ. The stated long-term goal of this study is to develop a safe, easily tolerated, and affordable intervention that can be adopted early in the ADPKD process to slow cyst progression. Results of the pilot study were reported in the American Journal of Kidney Diseases [2016;68(6): ]. Study participants were assigned in a 1:1 ratio to receive either a low-osmolar (low-sodium [1500 mg/d], low-protein [0.8 g/kg body weight]) diet and adjusted water prescription or no intervention. Permuted block randomization was performed within strata of age (18-39 and years) and sex. The primary outcome of interest was change in copeptin levels and urine osmolality between the intervention and control groups from baseline to 2 weeks. Participants were recruited from May 2014 through April 2015 using the Tufts Polycystic Kidney Disease Registry. Of 356 patients screened, a total of 272 did not meet inclusion criteria (age, n=61; low estimated glomerular filtration rate, n=176; use of an opioid or a selective serotonin reuptake inhibitor, n=20; or other reasons, n=15). Eighty-four patients were approached; of those, 40 declined to participate and 10 could not be reached, resulting in a final cohort of 34 patients (28 women) who were randomly assigned to a lowosmolar diet followed by adjusted water intake (n=17) or to no dietary intervention (n=17). Thirty-three of the patients completed the protocol; one in the intervention group withdrew due to a job conflict. The two groups were similar at baseline with the exception of the mean 24-hour urine volume, which was statistically significantly higher in the control group (2726 vs 1903 in the intervention group). In the intervention group, plasma copeptin levels declined significantly from 6.2 pmol/l at baseline to 5.3 pmol/l at visit 3 (week 2), P=.02; the change in the control group was not significant (from 4.7 to 5.07 pmol/l), P=.2. The change in mean plasma copeptin levels between baseline and visit 3 (week 2) was statistically significant between the two groups ( 0.86 pmol/l in the intervention group vs pmol/l in the control group; P=.009). There was a similar effect with urine osmolality. There was not a significant difference between the intervention and control groups at baseline (426 and 329 mosm/ kg water, respectively). At visit 3 (week 2), those in the intervention group had a significant decline from baseline in urine In the intervention group, plasma copeptin levels declined significantly from 6.2 pmol/l at baseline to 5.3 pmol/l at visit 3 (week 2), P=.02; the change in the control group was not significant (from 4.7 to 5.07 pmol/l), P=.2. osmolality from 426 to 258 mosm/kg water (P=.01); the change in the control group was nonsignificant (from 329 to 349 mosm/ kg water (P=.3). The change in mean urine osmolality level between baseline and visit 3 was statistically significant between the two groups: 167 mosm/kg water in the intervention group versus +20 mosm/kg water in the control group; P=.007. In the low-osmolar diet group of the intervention group, urinary solute (measured in a 24-hour urine collection) decreased from 722 to 602 mosm/d; P=.02 compared with 856 to 884 mosm/d (P=.7) in the control group. The study s small sample size and short follow-up period were cited by the researchers as the main study limitations. The small sample size may have allowed baseline imbalances that are difficult to account for. Although the study duration was sufficient to reflect a true change in vasopressin secretion, the researchers said that future studies are needed to examine the longterm adoption and maintenance of diet and water prescriptions in clinical practice. The researchers said in conclusion, We developed a dietary intervention that led to significant reduction in vasopressin secretion as measured by reduction in plasma copeptin levels and 24-hour urine osmolality in patients with early ADPKD. Furthermore, this dietary intervention significantly reduced the water required for vasopressin reduction. Long-term studies are needed to evaluate diet and adjusted water intake adherence and determine whether lowering vasopressin slows ADPKD progression. 10 Nephrology Times May/June 2017

11 News CMS Reimbursement Reform and Hospitalizations and Readmissions among Hemodialysis Patients Many healthcare reforms rely on payfor-performance (P4P) initiatives. In P4P models, quality of care affects the reimbursement received by the provider. Quality of care is determined by either deliver-of-care processes deemed important or achieving specific health outcomes. Recent P4P initiatives that target care processes include Centers for Medicare & Medicaid (CMS) programs that pay for transitional care management and longterm care coordination. The End-Stage Renal Disease Quality Incentive Program, a P4P initiative focused on kidney care, is an example of a program that targets care processes and health outcomes. In 2004, CMS changed physician reimbursement for patients receiving hemodialysis, targeting a specific care process: the frequency of face-to-face provider visits. Before the 2004 change, nephrologist reimbursement was capitated: nephrologists received the same monthly payment without regard to the frequency with which they saw their patients. The 2004 model changes to a tiered fee-for-service model that pays more for each additional face-to-face. It is unknown whether encouraging more frequent provider visits through the revised reimbursement policy resulted in improved outcomes such as fewer hospitalizations and rehospitalizations. Kevin F. Erickson, MD, MS, and colleagues conducted a retrospective cohort interrupted time-series study design to assess whether the 2004 reform led to a reduction in hospitalizations and 30-day hospital readmissions in patients with ESRD. The researchers also utilized published data to estimate a range of annual economic costs associated with more frequent visits. Study results were reported in the American Journal of Kidney Diseases [2017;69(2): ]. The CMS physician reimbursement reform for dialysis care became effective January 1, The researchers identified prevalent patients who received dialysis in the United States from January 1, 2002, through December 31, 2005, (2 years prior to and 2 years following the reform), using the US Renal Data System database. They divided the 4-yer study into 24 2-month intervals. The primary study outcomes of interest were the odds of hospitalization during each 2-month interval of the 4-year study period, and the odds of readmission within 30 days of hospital discharge; also of interest were hospitalizations and readmissions for fluid overload. The analysis of all-cause hospitalizations included 343,844 patients. Of those, 229,728 patients were in the prereform period and 248,278 patients were in the postreform period. Many of the overall cohort were followed up in both periods. Characteristics were similar across groups in the pre- and postreform periods, with the exception that patients in the postreform period on average had been on dialysis therapy for more days. The analysis of all-cause rehospitalizations included 259,818 patients. Of those, 157,262 were in the prereform period and 168,654 were in the postreform period. The odds of all-cause hospitalization during any 2-month period declined by ~0.4%; however, there was no significant change in the odds of hospitalization immediately following reimbursement reform and no significant change in the downward trend of reduced hospitalizations over time in the period following reform. There was a small nonsignificant increase in the likelihood of all-cause 30-day readmission over time prior to the policy reform. Immediately following implementation of the reform, there was no change in the likelihood of 30-day readmission. There was a small nonsignificant relative decline in the odds of readmission over time following implementation of the reimbursement reform policy. On average, patients had a 2.4% probability of hospitalization for fluid overload in a 2-month period and a 3.4% probability of being readmitted for fluid overload within 30 days of discharge. The likelihoods of both hospitalization and rehospitalization for fluid overload increased slightly over time in the period prior to reimbursement reform; there was no significant change immediately following reform. Trends toward increasing hospitalizations and readmission over time stopped or reversed in the 2 years after reform implementation. Depending on who patients saw during faceto-face visits (physicians or advanced practitioners) and how much additional time was spent, the estimated economic costs incurred with additional visits after reimbursement reform ranged from $13 to $87 million per year. The researchers cited a few limitations to the analysis, including focusing on the policy as a whole, without examining the various mechanisms by which reimbursement reform may have changed practices, and estimating how much additional time was spent with patients and what percentage of increased face-to-face visits were performed by advanced practitioners. The researchers summarized their findings by saying, We find that a national Medicare reimbursement reform designed to encourage increased face-to-face visits by physicians (nephrologists) and advanced practitioners to patients receiving hemodialysis was not associated with significant improvements in overall hospitalizations or 30-day overload readmissions, but led to reductions in fluid overload hospitalizations. Combined with previous studies that have failed to identify a benefit from this policy, these analyses suggest that the 2004 CMS reimbursement reform resulted in unnecessary use of some healthcare resources without materially improving health outcomes for most patients. They also suggest that efforts to encourage the care of patients most likely to benefit from additional visits, such as those at risk for fluid overload complications, could be cost-effective. Finally, our analysis highlights the importance of evaluating downstream health consequences of national reimbursement reform. TAKEAWAY POINTS Researchers conducted a retrospective cohort interrupted time-series study to examine whether the 2004 CMS physician reimbursement reform policy, a tiered fee-for-service system that encourages increased face-to-face visits, has resulted in improved patient outcomes. The outcomes of interest were the odds of hospitalization for all causes and for fluid overload and 30- day readmissions for all-causes and fluid overload in the 2 years prior to and 2 years following implementation of the reimbursement policy reform. There was an association between the implementation of the policy and fewer hospitalizations and readmissions for fluid overload, but no association between policy implementation and all-cause hospitalizations and 30-day readmissions. Nephrology Times May/June

12 News Fluid Overload in AKI Patients Receiving Continuous Renal Replacement Therapy TAKEAWAY POINTS In critically ill patients with acute kidney injury (AKI), fluid overload (FO) is associated with increased morality; researchers in Korea conducted a retrospective study to determine if the adverse effects of FO on survival can be applied to all patients with AKI who received continuous renal replacement therapy (CRRT). The study included 341 patients with AKI who received CRRT in intensive care units in Korea; the presence of FO was defined as a minimum 10% in body weight from baseline. Survival rate among patients with total FO from 3 days prior to initiation of CRRT to discharge from the ICU was significantly lower after admission to the ICU compared with patients with no FO (P<.001). Critically ill patients often experience acute kidney injury (AKI), which despite advances in intensive care medicine, has poor prognosis. Patients with AKI are at significant risk for morbidity and mortality. Among patients with AKI, approximately 4% require renal replacement therapy and may receive continuous renal replacement therapy (CRRT) to achieve hemodynamic stability. A mainstay of management of critically ill patients with AKI is maintaining an appropriate fluid balance. However, according to Il Young Kim, MD, and colleagues in Korea, there are few data on the optimal fluid management. Traditionally, patients are treated with aggressive fluid resuscitation designed to maintain renal perfusion and prevent further ischemic injury during ongoing renal dysfunction. Recent studies have shown an association between fluid overload (FO) and mortality in critically ill children and adults with AKI, calling for stricter and more timely fluid management to avoid fluid overload. Dr. Kim et al. conducted a retrospective study aimed at the evaluation of the association between fluid overload and mortality in critically ill patients with AKI being treated with CRRT. The study was designed to test the hypotheses that (1) FO may be associated with mortality in AKI patients on CRRT; (2) proper fluid removal by CRRT may reduce mortality in that patient population; and (3) the adverse effect of FO on survival may be more evident in some subgroups of patients with AKI, such as those with sepsis or greater severity of illness. Results of the study were reported online in PLoSOne [doi: journal.pone ]. The study included 341 patients with AKI who received CRRT in intensive care units (ICUs) at Pusan National University hospitals in the Republic of Korea. Of those 341 patients, 182 died within 30 days following admission to the ICU. There were no significant demographic differences between patients who survived and patients who did not survive in age, sex, and baseline body weight. Survivors had a higher prevalence of chronic obstructive pulmonary disease (COPD), liver cirrhosis, and congestive failure than nonsurvivors. At the time of admission to the ICU, nonsurvivors had lower levels of mean arterial pressure and platelet count, and were more likely to have a higher incidence of oliguria and elevated levels of serum creatinine and prothrombin time, compared with survivors. Nonsurvivors experienced more severe illness, as shown by higher sequential organ failure assessment (SOFA) scores; a greater number of vasopressors; and increased frequency of mechanical ventilation. There was no significant difference in prevalence of sepsis between the group of survivors and the group of nonsurvivors. Nonsurvivors had a higher incidence of total FO (% FO total 10%). More days elapsed between diagnosis of AKI and initiation of CRRT in nonsurvivors compared with survivors. Patients with % FO total 10% demonstrated a significant decrease in survival over the 30 days following admission to the ICU compared with patients with % FO total <10% (30-day mortality: 66.9% vs 45.6%; P<.001). When patients with % FO total 10% were stratified according to the percentage of FO, 30-day mortality was highest in patients with % FO total 40% (81.8%, n=70). In univariate analyses, significant predictors of 30-day mortality were COPD (P=.006), liver cirrhosis (P=.003), congestive heart failure (P=.001), mean arterial pressure (P<.001), oliguria (P<.001), serum creatinine (P=.003), platelet count (P=.001), prothrombin time (P=.005), SOFA score (P<.001), number of vasopressors (P<.001), use of ventilator (P<.001), % FO total 10% (P<.001), and time elapsed between diagnosis of AKI and initiation of CRRT (P<.001). Following adjustment for sepsis status and variables that were significant in the univariate analysis, there was a significant association between the presence of total FO (% FO total 10%) and increased 30-day mortality (hazard ratio, 1.13; 95% confidence interval, ). There was also an association between increased 30-day mortality and ventilator dependency, oliguria, SOFA score at ICU admission, days elapsed between diagnosis of AKI and initiation of CRRT, mean arterial pressure, congestive heart failure, and COPD. There were no associations between sepsis, serum creatinine, platelet count, liver cirrhosis, prothrombin time (international normalized ratio), and number of vasopressors and 30-day mortality. Among patients with sepsis or with high SOFA scores, there was a significant difference in survival of patients with and without FO. In patients without sepsis or with low SOFA score, there was no significant difference in patient survival regardless of FO. There were limitations to the study, including the retrospective design that limits the ability to discern whether FO is a marker of more servere disease or a causal contributor to mortality in the study population, only including data on fluid balance gathered from 3 days prior to initiation of CRRT to ICU discharge, and the specific nature of the study population of critically ill patients with AKI who received CRRT. The researchers concluded by saying, Our study demonstrated that fluid overload was independently associated with mortality, and that fluid removal by CRRT appears to reduce mortality in critically ill patients with AKI. This study also showed that the adverse effect of fluid overload on survival was more evident in patients with sepsis or more severe illness, suggesting that a more rigorous effort to reduce fluid overload is necessary in those patients, which might not apply to patients without sepsis or with less severe sepsis. 12 Nephrology Times May/June 2017

13 Help your new-to-dialysis patients succeed with Velphoro Start with high potency. Stay with long-term control. *1 Long-term efficacy with a low pill burden 1,2 Long-term tolerability as demonstrated in the 52-week study 1,2 Access and affordability for most patients VISIT VELPHORO.COM/HCP TO DOWNLOAD $0 CO-PAY SAVINGS CARDS AND OTHER RESOURCES. * Clinical results of individual patients from long-term trial. INDICATION Velphoro (sucroferric oxyhydroxide) is a phosphate binder indicated for the control of serum phosphorus levels in patients with chronic kidney disease on dialysis. IMPORTANT SAFETY INFORMATION Velphoro must be administered with meals. Velphoro tablets must be chewed and not swallowed whole. To aid with chewing and swallowing, the tablets may be crushed. Patients with peritonitis during peritoneal dialysis, significant gastric or hepatic disorders, following major gastrointestinal (GI) surgery, or with a history of hemochromatosis or other diseases with iron accumulation have not been included in clinical studies with Velphoro. Monitor effect and iron homeostasis in such patients. In a parallel design, fixed-dose study of 6 weeks duration, the most common adverse drug reactions to Velphoro chewable tablets in hemodialysis patients included discolored feces (12%) and diarrhea (6%). Velphoro can be administered concomitantly with oral calcitriol, ciprofloxacin, digoxin, enalapril, furosemide, HMG CoA reductase inhibitors, hydrochlorothiazide, losartan, metoprolol, nifedipine, omeprazole, quinidine and warfarin. Take doxycycline at least 1 hour before Velphoro. Velphoro should not be prescribed with oral levothyroxine. Please see Brief Summary on adjacent page or visit for full Prescribing Information. A 52-week, open-label, active-controlled, phase 3 study evaluated the safety and efficacy of Velphoro in lowering serum phosphorus levels in patients (N=1,054) with chronic kidney disease on hemodialysis or peritoneal dialysis. 1 References: 1. Velphoro [package insert]. Waltham, MA: Fresenius Medical Care North America; Floege J, Covic AC, Ketteler M, et al; on behalf of the Sucroferric Oxyhydroxide Study Group. Long-term effects of the iron-based phosphate binder, sucroferric oxyhydroxide, in dialysis patients. Nephrol Dial Transplant. 2015;30(6): Velphoro is a registered trademark of Vifor Fresenius Medical Care Renal Pharma Ltd. Distributed by: Fresenius Medical Care North America Waltham, MA Fresenius Medical Care, all rights reserved. PN Rev. A 03/2016

14 Brief Summary: Please see Full Prescribing Information for additional information INDICATIONS AND USAGE Velphoro (sucroferric oxyhydroxide) is a phosphate binder indicated for the control of serum phosphorus levels in patients with chronic kidney disease on dialysis. DOSAGE AND ADMINISTRATION Velphoro tablets must be chewed and not swallowed whole. To aid with chewing and swallowing, tablets may be crushed. The recommended starting dose of Velphoro is 3 tablets (1,500 mg) per day, administered as 1 tablet (500 mg) 3 times daily with meals. Adjust by 1 tablet per day as needed until an acceptable serum phosphorus level is reached, with regular monitoring afterwards. Titrate as often as weekly. DOSAGE FORMS AND STRENGTHS Velphoro (sucroferric oxyhydroxide) chewable tablet 500 mg. CONTRAINDICATIONS None. WARNINGS AND PRECAUTIONS Patients with peritonitis during peritoneal dialysis, significant gastric or hepatic disorders, following major gastrointestinal surgery, or with a history of hemochromatosis or other diseases with iron accumulation have not been included in clinical studies with Velphoro. Monitor effect and iron homeostasis in such patients. ADVERSE REACTIONS In a parallel design, fixed-dose study of 6 weeks duration, the most common adverse drug reactions to Velphoro chewable tablets in hemodialysis patients included discolored feces (12%) and diarrhea (6%). To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Medical Care North America at or FDA at FDA-1088 or DRUG INTERACTIONS Velphoro can be administered concomitantly with oral calcitriol, ciprofloxacin, digoxin, enalapril, furosemide, HMG-CoA reductase inhibitors, hydrochlorothiazide, losartan, metoprolol, nifedipine, omeprazole, quinidine and warfarin. Take doxycycline at least 1 hour before Velphoro. Velphoro should not be prescribed with oral levothyroxine. USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category B: Reproduction studies have been performed in rats and rabbits at doses up to 16 and 4 times, respectively, the human maximum recommended clinical dose on a body weight basis, and have not revealed evidence of impaired fertility or harm to the fetus due to Velphoro. However, Velphoro at a dose up to 16 times the maximum clinical dose was associated with an increase in post-implantation loss in pregnant rats. Animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Labor and Delivery No Velphoro treatment-related effects on labor and delivery were seen in animal studies with doses up to 16 times the maximum recommended clinical dose on a body weight basis. The effects of Velphoro on labor and delivery in humans are not known. Nursing Mothers Since the absorption of iron from Velphoro is minimal, excretion of Velphoro in breast milk is unlikely. Pediatric Use The safety and efficacy of Velphoro have not been established in pediatric patients. Geriatric Use Of the total number of subjects in two active-controlled clinical studies of Velphoro (N=835), 29.7% (n=248) were 65 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. OVERDOSAGE There are no reports of overdosage with Velphoro in patients. Since the absorption of iron from Velphoro is low, the risk of systemic iron toxicity is low. Hypophosphatemia should be treated by standard clinical practice. Velphoro has been studied in doses up to 3,000 mg per day. HOW SUPPLIED/STORAGE AND HANDLING Velphoro are chewable tablets supplied as brown, circular, bi-planar tablets, embossed with PA 500 on 1 side. Each tablet of Velphoro contains 500 mg iron as sucroferric oxyhydroxide. Velphoro tablets are packaged as follows: NDC Bottle of 90 chewable tablets Storage Store in the original package and keep the bottle tightly closed in order to protect from moisture. Store at 25 C (77 F) with excursions permitted to 15 to 30 C (59 to 86 F). PATIENT COUNSELING INFORMATION Inform patients that Velphoro tablets must be chewed and not swallowed whole. To aid with chewing and swallowing, the tablets may be crushed [see Dosage and Administration]. Velphoro should be taken with meals. Instruct patients on concomitant medications that should be dosed apart from Velphoro [see Drug Interactions]. Inform patients that Velphoro can cause discolored (black) stool. Distributed by: Fresenius Medical Care North America 920 Winter Street Waltham, MA US Patent Nos and pending, comparable and/or related patents Fresenius Medical Care North America. All rights reserved.

15 Focus on Transplantation News Interventions Improve Adherence to Tacrolimus after Transplantation Nonadherence to immunosuppression medications among kidney transplantation recipients can cause rejection and transplant loss. There is a high barrier to adherence during the first year post-transplantation due to the need to take multiple medications with various adverse effects as well as frequent dose changes. Younger age and further time from transplant are associated with lower adherence to the immunosuppression medication regimen, driven by nonmodifiable and modifiable factors such as medication beliefs, forgetfulness, confusion about complex regimens, competing priorities, concerns about adverse effects, or costs. All of these factors point to a need to develop and test strategies for adherence improvement. Wireless technology has created opportunities for enhancing adherence improvement strategies such as visual and audible alarms, texts, telephone calls, and s when a dose is due. According to Peter P. Reese, MD, MSCE, and colleagues, there are few data on real-time provider notification of low adherence using wireless pill bottles. The researchers recently conducted a randomized controlled trial to determine whether automated reminders alone or paired with provider notification in patients with low adherence result in improvement tacrolimus adherence versus adherence monitoring alone. Results were reported in the American Journal of Kidney Diseases [2017;69(3): ]. Study participants were new kidney transplant recipients who were provided with wireless pill bottles. The primary outcome of interest was the percentage of correctly taken tacrolimus doses estimated by pillbottle openings. The secondary outcome of interest was assessing the accuracy of pharmacists predictions of each participant s adherence during the trial. Participants were randomly assigned 1:1:1 to adherence monitoring with customized reminders (alarms, texts, telephone calls and/or s), monitoring with customized reminders plus provider notification (every 2 weeks, providers received notification if adherence decreased to <90% during that period), or wireless pill bottle use alone (control). The study recruited kidney transplant recipients or kidney-pancreas recipients at the Hospital of the University of Pennsylvania from February 2012 through March There were 376 transplantations during the study period. Of those patients, In the final 90 days of the trial, mean adherence was 78% in the reminders group, 88% in the reminders plus notification group, and 55% in the control group. 266 were approached about the study and 45% (n=120) enrolled. Mean age of the participants was 50 years, 60% were men, 40% were black, and 12% had received a prior transplant. Across the three arms of the study (reminders; reminders plus notification; control), demographic and clinical characteristics were similar. Three of the continued on page 16 NKF Spring Clinical Meetings Patients with ESRD Not Interested in Transplantation Orlando Kidney transplantation is the optimal long-term treatment for patients with end-stage renal disease (ESRD) on dialysis. Qualifying for transplantation is a process that requires many steps, starting with the patient s statement of interest. Deborah Evans, LCSW, and colleagues conducted a study aimed at characterizing interest in transplantation among patients of a large dialysis organization in the United States. The researchers were also interested in examining the reasons identified by patients for lack of interest in transplantation. Results of the study were reported during a poster session at the NKF 2017 Spring Clinical Meetings in a poster titled Factors Affecting Interest in Transplant among End-Stage Renal Disease Patients Receiving Dialysis. The study derived data on patient transplant status from the electronic health records of the dialysis organization; the information was collected by social workers during the course of routine care. There were eight transplant status categories identified: active, delisted, denied, in work-up, inactive, not interested, on hold, and pending patient followup. Reasons for lack of interest were obtained from the not interested group; characteristics of patients not interested in transplant were compared with those of the patients with active transplant status. The database included 182,906 patients with available transplant status information. Of those, 31.7% (n=58,057) indicated they were not interested in transplant. The most frequent reasons given for not being interested in transplant were advanced age (25.7%), perceived poor health (12.0%), comfortable with current modality (12.0%), and uninterested in further surgeries (11.9%). Compared with patients with active transplant status, those not interested in transplant were older (64.6% <60 years of age vs 21.4%), more likely to be female (47.7% vs 36.6%), more likely to be white (43.9% vs 30.4%), less likely to be Hispanic (14.7% vs 22.2%), more likely to be receiving incenter hemodialysis (92.0% vs 73.7%), and more likely to have Medicare as primary insurance (91.3% vs 77.3%). Transplant education should respect the specific needs and choices of individual patients. Further research is needed to evaluate whether education and referral to a transplant center could provide patients with greater insight into transplant as an alternative to their current modality, the researchers said. Source: Evans D, Dunn D, Mutell R, Broughton P, Benner D. Factors affecting interest in transplant among end-stage renal disease patients receiving dialysis. Abstract of a poster presented at the National Kidney Foundation 2017 Spring Clinical Meetings, April 19-22, 2017, Orlando, Florida. Nephrology Times May/June

16 News Focus on Transplantation continued from page 15 TAKEAWAY POINTS Nonadherence to immunosuppression medication increased the risk for rejection and transplant loss following kidney transplantation. Researchers conducted a pilot trial to assess the effectiveness of an intervention designed to provide patients with reminders to improve adherence. Wireless pill bottles were distributed to store tacrolimus and record bottle openings. Participants were divided into three groups: reminders, reminders plus provider notification, or no intervention (control). Participants in the two intervention groups demonstrated improved tacrolimus adherence compared with those in the control group. Larger, multicenter studies with clinical end points are needed to confirm these findings. 120 participants dropped out during the first week (two prior to receiving the intervention [control group] and one following enrollment [reminders plus notification]). In the final 90 days of the trial, mean adherence was 78% in the reminders group, 88% in the reminders plus notification group, and 55% in the control group. Compared with the control group, adherence in the reminders group and the reminders plus notifications group was significantly higher (by 24%; 95% confidence interval [CI], 10%-38%; and by 33%; 95% CI, 21%- 46%, respectively; P<.001 for comparisons of each intervention to control). During the final 90 days, adherence in the reminders plus notification group was higher than in the reminders group (by 10%; 95% CI, 0%- 19%; P=.05). In analysis of day 14 through the end of the study, adherence in the reminders group was 82%, in the reminders plus notification group 88%, and in the control group, 58%. Compared with the control group, adherence in the reminders group was higher by 23% (95% CI, 11%-36%) and in the reminders plus notifications group by 30% (95% CI, 18%-42%); P<.001. There was no significant difference in adherence between the two intervention arms. There were no significant differences across arms in scheduled tacrolimus levels, tacrolimus coefficients of variation, or percent of tacrolimus measurements that were in range according to program standards. Analyses of all measured tacrolimus levels showed no difference across the three study arms. In the analyses for the secondary outcome, following adjustment for study arm and time (week), poor adherence was predicted by the pharmacist s agreement with a statement of concern about the patient s adherence issues soon after transplantation. Study limitations cited by the researchers included the outcomes being limited to adherence measurement, all of which have shortcomings; not limiting enrollment to patients with high probability of adherence challenges; and focusing only on tacrolimus adherence. In summary, this pilot trial demonstrated the feasibility of implementing wireless pill bottles into the care of kidney transplant recipients. The strategies of adherence monitoring with customized reminders and customized reminders with provider notification led to improved tacrolimus adherence versus control as estimated by the wireless pill bottle, although tacrolimus levels were similar across trial arms. Transplantation pharmacists were able to successfully identify participants at high risk for poor medication adherence. These results should inform the design and conduct of large multicenter trials with clinical end points, the researchers said. Urine Fibrosis Markers and Increased Risk of Allograft Failure Previous biopsy studies of healthy kidney donors have demonstrated that although tubulointerstitial fibrosis is common and increases with age, the degree of fibrosis is not associated with glomerular filtration rate (GFR) when age is taken into account. There is a strong association between the severity of tubulointerstitial fibrosis on biopsy and progressive loss of estimated GFR (egfr) across causes of kidney disease. According to Joachim H. Ix, MD, MAS, and colleagues, no prior study has jointly evaluated the relationship of urine concentrations of a1-microglobulin (A1M), monocyte chemoattractant protein 1 (MCP-1), and procollagen amino-terminal pro-peptides of type I (PINP) and type III (PIIINP) with the risk for allograft failure in kidney transplantation recipients. The researchers sought to test the hypothesis that higher urine concentrations of each marker would be associated with allograft failure, independent of risk factors for chronic kidney disease (CKD), baseline egfr and urine albumin-creatinine ratio, and urinary concentrations of the other three markers. The researchers utilized data from the FAVORIT (Folic Acid for Vascular Outcome Reduction in Transplantation) Trial to randomly select a subset of participants (n=491) as well as all individuals with allograft failure during follow-up (cases; n=257). Results of the case-cohort study were reported in the American Journal of Kidney Diseases [2017;69(3): ]. Mean age in the 491 subset participants was 51 years, 39% were female, 24% were nonwhite, and 31% were recruited at centers outside the United States. At baseline, mean egfr was 46 ml/min/1.73 m 2, median time since transplantation was 3.9 years, and 43% had received a kidney from a living donor. Distributions of all four urine fibrosis markers were right skewed, with median values of 1.60 mg/dl for A1M, 183 pg/ml for MCP-1, 3.63 µg/l for PIINP, and 2.36 µg/l for PINP. Participants were stratified into quartiles of A1M: <0.79 mg/l, n=122; mg/l, n=122; mg/l, n=122; and 3.79 mg/l, n=120. Compared with those in the lowest quartile, those with higher urine A1M concentrations were more often male and 16 Nephrology Times May/June 2017

17 Focus on Transplantation News black, had shorter times since transplantation, were more likely to be smokers, and had a higher prevalence of cardiovascular disease, higher blood pressures, lower egfrs, and higher urine albumin-creatinine ratios (ACRs), but a lower prevalence of diabetes. The strongest correlation of the four urine fibrosis markers indexed to urine creatinine with one another, with egfr, with urine ACR, and with four kidney tubule cell injury biomarkers was between urine A1M and liver-type fatty acid binding protein levels. The researchers evaluated associations of the four urine fibrosis markers with allograft failure. There was a strong and graded relationship between urine A1M levels and allograft failure. There was an association between each doubling of A1M levels and a more than 2-fold risk for allograft failure; a more than 13-fold gradient in risk was seen in comparison of the highest to the lowest quartile following adjustment for demographics and risk factors of kidney disease. After further adjustment for egfr and urine ACR, the association of doubling of A1M levels remained associated with a 70% higher risk. Those in the fourth quartile were at a more than 7-fold risk for allograft failure compared with those in the first quartile. TAKEAWAY POINTS After adjustment for concentrations of other urine fibrosis and several urine injury markers, the association between urine A1M and MCP- 1 levels with allograft failure remained. There was no association between urine PINP and PINP levels and allograft failure. The researchers cited some limitations to the study, including lack of data for kidney biopsies, BK viremia status, and HLA antibody status. It is uncertain whether those factors influence levels of urine fibrosis markers and should be studied. In addition, urine fibrosis markers were measured over time, making the relationship of trajectory of change with allograft function uncertain. Finally, the observational design of the study raises the possibility of residual confounding. In conclusion the researchers said, Among stable kidney transplant recipients, urine A1M and MCP-1 concentrations are strongly associated with risk for kidney allograft failure. These associations are independent of baseline egfr and urine ACR and of urine concentrations of several markers of kidney tubule cell injury. If the findings are conformed, A1M and MCP-1 measurement may Kidney tubulointerstitial fibrosis is a known marker for risk of allograft failure in kidney transplant recipients, yet its presence is poorly captured with clinical markers of kidney function. Researchers conducted an observational study using data from the FAVORIT (Folic Acid for Vascular Outcome Reduction in Transplantation) Trial to examine the relationship of urine concentrations of four proteins with the risk of allograft failure in recipients of kidney transplantation. There were strong associations between urine concentrations of a1-microglobulin and monocyte chemoattractant protein 1 with the risk for allograft failure in this patient population. provide an opportunity to identify kidney transplant recipients at higher risk for allograft failure, for whom closer surveillance may be warranted. RENAL BILLING MADE EASY EXPERIENCE 20 YEARS OF EXCELLENCE Renal billing specialists At Sceptre Management, we re renal billing specialists. But what we really specialize in is improving your cash flow, reducing your receivables, eliminating frustration, and keeping you in compliance. Contact us today. We ll make it easy partnerwithus@sceptremanagement.com SceptreManagement.com SPECIALIZES IN BILLING FOR Nephrology practices ESRD facilities Vascular Access NKF Spring Clinical Meetings Weight Gain and Blood Pressure Control after Transplantation Orlando It is well known that blood pressure can be lowered by weight loss; however, there are few data on the relationship between weight loss and reductions in blood pressure in recipients of kidney transplantation. Ekamol Tantisattamo, MD, FACP, FASN, FNKF, of the Multi-Organ Transplant Center at the Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, recently conducted a review of records of kidney transplant recipients to examine the association between blood pressure and weight loss. Dr. Tantisattamo reported results of the review during a poster session at the NKF 2017 Spring Clinical Meetings in a poster titled Potential Blood Pressure Control from Weight Loss after Kidney Transplantation. The study cohort included 70 kidney transplant recipients; data on systolic blood pressure, diastolic blood pressure, weight, and body mass index (BMI) were reviewed. The patients were followed for 2 years post-transplantation. More than half of the patients (58.6%) were male, mean age was 52.7 years, mean weight was 81.2 kg, and BMI was 27.6 kg/m 2. One third of the patients were obese (BMI 30 kg/m 2 ). Mean pre-transplant systolic blood pressure was mmhg and mean pre-transplant diastolic blood pressure was 79.3 mmhg. In non-obese patients, weight increased immediately after transplant, followed by weight loss in the early post-transplant period (<12 weeks) with subsequent rebound weight gain after 24 weeks. In obese patients, weight loss began 12 weeks after transplant; there was no rebound weight gain. Throughout the 2 years of follow-up, systolic blood pressure, but not diastolic blood pressure, was significantly lower. This pattern of weight change and significant improvement in systolic blood pressure was also seen in non-obese patients. Patients in the obese group gained weight after transplantation, but lost weight through 84 weeks of follow-up with no subsequent weight gain. Patients in both the obese and non-obese groups who lost weight had improved systolic and diastolic blood pressure, but the improvement in diastolic blood pressure was not statistically significant in the non-obese patients. Systolic blood pressure decreased in patients with post-transplant weight gain in both the obese and non-obese groups; however, diastolic blood pressure increased in obese patients after 12 weeks. In conclusion, the researchers said, Non-obesity trends to lower posttransplant blood pressure regardless of weight change and become protective against high blood pressure; whereas blood pressure and weight changes appear to go along the same direction in obesity without rebound weight gain. Pre- and post-transplant weight loss should be one of the strategies to prevent post-transplant hypertension in both non-obese and obese patients. Source: Tantisattamo E. Potential blood pressure control from weight loss after kidney transplantation. Abstract of a poster presented at the National Kidney Foundation 2017 Spring Clinical Meetings, April 19-22, 2017, Orlando, Florida. Nephrology Times May/June

18 News Briefs Fresenius and Humana Announce Model of Care Coordination Fresenius Medical North American (FMC- NA) is joining forces with Humana Inc. in a program designed to improve care and outcomes for Humana s members with end-stage renal disease. FMCNA, operating through its Fresenius Health Partners mantle, will apply its proprietary model of care coordination aimed at enhancing the ability of patients to obtain the healthcare services needed to address their illness and improve their quality of life. Patients will be supported by a team of local nephrologists and clinicians working in coordination with the Care Navigation Unit (CNU) at Fresenius. The CNU is a group of specialized nurses and service coordinators who are available 24 hours a day 7 days a week for support and care coordination. In a press release from Fresenius, William McKinney, president of FMCNA s integrated care group, said, Through this partnership, we will positively impact the overall medical care of Humana s ESRD members who receive treatment within our dialysis centers, and it s our responsibility to ensure they can access the care they need, when they need it. Ultimately, we believe our coordinated approach to patient care will be a natural extension of Human s existing platform and can boost their patients health outcomes. Mark Steffen, MD, medical director at Humana, said, We strive to help our chronically ill members achieve their optimal health. By working with Fresenius Medical Care to bring this highly specialized program to Humana s medically fragile members who need it most, we can help them experience more coordinated care that meets their needs and improves both health outcomes and quality of life as they move along their healthcare journey. ANNA Releases Third Edition of Contemporary Nephrology Nursing The American Nephrology Nurses Association (ANNA) has released the third edition of Contemporary Nephrology Nursing. In a press release from ANNA, Sandy M. Bodin, MA, RN, CNN, editor, said, Contemporary Nephrology Nursing has always been my favorite nephrology nursing text and it was a pleasure for me to manage this third edition. I am pleased that our strategy produced some fresh and innovative chapters. My hope is that Contemporary Nephrology Nursing will be a principal reference for nephrology nurses and will serve as a tool to improve the health outcomes of patients with kidney disease. The new edition includes more than 75 contact hours of continuing nursing education, 22 completely updated chapters with evidence-based data, 28 new chapters, a new section on managing comorbidities and complications, an advocacy section, and a section on regenerative medicine and innovations in nephrology nursing. For more information and to order Contemporary Nephrology Nursing, visit ly/2psit9o. THEORY Trial Results Presented at Transplant Conference At the 2017 American Transplant Congress in Chicago, Robert Redfield, MD, presented data from the THEORY trial, an open-label phase 1b study evaluating obinutuzumab, a type two CD20-directed cytolytic antibody, in candidates for kidney transplant, according to a press release. The study was designed to measure the safety, pharmacokinetics, and pharmacodynamics of obinutuzumab in hypersensitized patients with end-stage renal disease who were awaiting kidney transplantation. In the study population, obinutuzumab was well tolerated and resulted in substantial peripheral B-cell depletion at both study dose levels. Emerging experience with obinutuzumab indicates acceptable tolerability in patients with ESRD undergoing desensitization, the researchers said. Drug to Treat Lupus Nephritis Shows Promising Results During the National Kidney Foundation 2017 Spring Clinical Meetings, Aurina Pharmaceu- Robotic Surgical Removal of Stage IV Tumor Thrombus Successful A surgical team at Keck Medicine of the University of Southern California (USC) has performed the first robotic, minimally invasive surgical removal of a stage IV tumor thrombus (kidney cancer extending into the heart). In a press release from USC, Inderbir S, Gill, MD, distinguished professor of urology and founding executive director of the USC Institute of Urology and associate dean of clinical innovation at the Keck School of Medicine of USC, said, This exciting feat promises to redefine the boundaries of what is surgically possible through skill, collaboration, and technology. Our hope is that we can now propel the field at large to turn such futuristic robotic surgery into our present standard of care. The surgery included cardiac and urologic surgical teams that worked together to coordinate the complex efforts required for the surgery. This was the driver of our success and exactly the standard we strive for across the institution, Mark Cunningham, MD, associate professor of surgery said. In 2015, Dr. Gill became the first surgeon to use robotic high intensity focused ultrasound surgical ablation to ablate a kidney tumor. Currently, the USC Institute of Urology has one of the world s highest volumes of advanced robotic surgeries annually and is a premier worldwide robotic training center, according to the press release. 18 Nephrology Times May/June 2017

19 News Briefs ticals, Inc. presented previously unreported results from a phase 2 study on the use of voclosporin for the treatment of lupus nephritis. Patients with lupus nephritis are at risk for renal damage that, left untreated, may result in irreversible tissue damage in the kidney, leading to end-stage renal disease. At present, there are no approved therapies for lupus nephritis. Samir Parikh, MD, a clinical investigator for the study and assistant professor of clinical nephrology at Ohio State University, presented 48-week results from the AURA study. According to a press release from Aurina, the trial met the end points of complete and partial remission at 48 weeks. In addition, all secondary end points that have been analyzed to date were also met. Both study doses of voclosporin demonstrated continued improvement compared with the control group at 48 weeks. The voclosporin groups had statistically significantly improved speed and rates of compete and partial remission. Of those in the low-dose voclosporin group who achieved complete remission at 24 weeks, 100% remained in complete remission at 48 weeks. Proteinuria levels and reduction in systemic lupus erythematosus disease activity index scores also continued to significantly separate over time versus the control group. Additional analyses are ongoing. Aurina plans to initiate a phase 3 clinical trial (AURORA) in the second quarter of Early Predictor of Transplant Rejection Detected Researchers at the Perelman School of Medicine at the University of Pennsylvania have discovered a method that appears to provide warning of rejection of organ transplants sooner than standard current methods. The new method requires only a blood test rather than a more invasive needle biopsy. According to a press release from the National Institutes of Health, Prashanth Vallabhajosyula, MD, and Ali Naji, MD, transplanted human islet cells into mice. The researchers confirmed that the transplanted islets released exosomes in the animals bloodstreams. The exosomes had donor-specific markers on their surfaces that could be used for detection. Levels of donor cell-released exosomes dropped sharply in the bloodstream, and their contents changed, before glucose levels changed in response to tissue rejection. The findings suggest that exosomes may be useful in detecting transplant injury sooner than current technologies. Dr. Naji said, I believe that analyses of exosomes released by transplanted organs into the patient s blood will ultimately provide a very powerful and unprecedented ability to understand the conditional state of the organ as a whole. Major Meetings American Society of Nephrology Kidney Week 2017 October 31-November 5, 2017 New Orleans, Louisiana Annual Dialysis Conference March 3-6, 2018 Orlando, Florida American Nephrology Nurses Association 2018 National Symposium April 15-18, 2018 Las Vegas, Nevada National Kidney Foundation Spring Clinical Meetings 2018 April 10-14, 2018 Austin, Texas American Transplant Congress 2018 June 2-6, 2018 Seattle, Washington American Society of Nephrology Kidney Week 2018 October 23-28, 2018 San Diego, California Nephrology Times May/June

20 Abstract Roundup ACUTE KIDNEY INJURY Prepregnancy AKI Associated with Adverse Outcomes in Pregnancy Journal of the American Society of Nephrology. 2017;28(5): There are few data available on the effect of clinically recovered acute kidney injury (AKI) on future pregnancy outcomes. Jessica Sheehan Tangren, MD, and colleagues retrospectively studied all women who delivered infants between 1998 and 2007 at Massachusetts General Hospital. The outcome of interest was whether there was an association of a previous episode of recovered AKI with subsequent adverse maternal and fetal outcomes. The women with recovered AKI had increased rates of preeclampsia compared with the control group (women without kidney disease) (23% vs 4%; P<.001). Infants of women in the recovered AKI group were born earlier than infants of women in the control group (37.6 vs 392 weeks; P<.001), with increased rates of small for gestational age births (15% vs 8%; P=.03). Following adjustment for multiple variables, recovered AKI remained associated with increased risk for preeclampsia and adverse fetal outcomes. The association also remained following matching 1:2 by age, race, body mass index, diastolic blood pressure, parity, and diabetes status. In summary, the researchers said, A past episode of AKI, despite return to normal renal function before pregnancy, associated with adverse outcomes in pregnancy. Dipyrone in the ICU Associated with Adverse Renal Side Effects European Journal of Anaesthesiology. DOI: /EJA Dipyrone (metamizole) is used in perioperative and intensive care unit (ICU) pain therapy, but there are few data on its potential renal side effects, particularly in the critical care environment. Researchers, led by Thomas Stueber, MD, recently conducted a retrospective cohort study to examine the perioperative nephrotoxic potential of dipyrone in patients prone to acute kidney injury (AKI). The single-center study was conducted in a tertiary referral hospital from January 2013 until June 2013, and included 500 consecutive patients 18 years of age who were referred to the anesthesia ICU. Analysis found an association between the use of dipyrone and an increased incidence of AKI in dose-dependent manner with a 1.6-fold increase in the incidence of AKI with each additional gram of intravenous dipyrone per day. In addition, patients who received dipyrone in the ICU presented with a prolonged duration of vasopressor therapy. Increasing dipyrone dosage is a potential independent risk factor for AKI in adult ICU patients and may prolong vasopressor therapy. Clinical evidence for a benefit of dipyrone therapy in the ICU is insufficient and needs further critical evaluation, the researchers said. CHRONIC KIDNEY DISEASE A Review of Anemia Management in Patients with Kidney Disease Current Opinion in Nephrology and Hypertension. Doi: / MNH David Collister, MD, and colleagues provided a review of the state of anemia management with erythropoietin (EPO)-stimulating agents and iron supplementation in patients with chronic kidney disease and in patients with end-stage renal disease on dialysis. The review focused on novel therapies. The review includes data on health-related quality of life as well as the uncertainties concerning the optimal iron utilization in patients with kidney disease. Novel therapies for iron supplementation discussed were iron-based phosphate binders and dialysate iron delivery, as well as alternatives to EPOstimulating agents such as hypoxia-inducible factor prolyl hydroxylase inhibitors. In summary, the researchers said, Individualization of hemoglobin targets using EPO-stimulating agents and iron supplementation may be considered in younger, healthier patients with kidney disease to improve health-related quality of life. Optimal iron utilization in kidney disease patients in unclear, but novel iron base phosphate binders and dialysate iron delivery may play a role in intravenous iron avoidance and its potential complications. Phase 3 randomized controlled trials of hypoxia-inducible factor prolyl hydroxylase inhibitors are ongoing and are promising new alternatives to EPO-stimulating agents and their known adverse effects. CONTINUOUS RENAL REPLACEMENT THERAPY Timing of Initiation of CRRT in the ICU Journal of Critical Care. dx/doi. org/ /j.jcrc Optimal timing for initiation of early continuous renal replacement therapy (CRRT) is uncertain. Seung Don Baek, MD, and colleagues recently conducted an investigation to examine the clinical impacts of three time-interval parameters on morbidity and mortality in a cohort of 177 patients with septic shock-induced acute kidney injury. The intervals studies were: (1) time from vasopressor initiation to CRRT initiation (T vaso-crrt ); (2) time from intensive care unit (ICU) admission to CRRT initiation (T ICU-CRRT ); and (3) time from endotracheal intubation to CRRT initiation (T endo-crrt ). The proportion of patients with T vaso-crrt less than 24 hours was significantly higher compared with those in the non-survival group (84.3% vs 58.5%, P<.001). T vaso-crrt less than 24 hours and Sequential Organ Failure Assessment score were independent factors associated with 28-day mortality and 90-day mortality. Length of stay in the ICU and duration of mechanical ventilation were significantly correlated with T ICU-CRRT and T endo-crrt, but not with mortality (P<.001 for both associations). The researchers said, Considering the possible therapeutic measurement by physicians on the basis of the results in this study, early CRRT could be defined by a T vaso-crrt less than 24 hours. AVF/AVG Access Safe in ICU Patients on CRRT Hemodialysis International. doi: /hdi In critically ill patients with end-stage renal disease (ESRD), insertion of hemodialysis catheters carries the risk of complications; however, the use of arteriovenous fistula of graft (AVF/AVG) is considered contraindicated in this patient population. Anas al Rifai, MD, and colleagues conducted a single-center analysis of 48 consecutive hospitalized patients with ESRD on maintenance hemodialysis who underwent continuous renal replacement therapy (CRRT) using AVF/AVG from 2012 to The primary outcome of interest was complications related to access. Mean age of the cohort was 60 years, 48% were male, and 88% required vasopressor support. Median duration of AVF/AVG use for CRRT was 4 days. Ten of the 48 patients had complications related to the access and five required catheter placement. Sixty-five percent of the overall cohort survived to hospital discharge and 94% (n=29) had functional AVF/AVG access at time of discharge. In their conclusion, the researchers said, In our experience, use of AVF/AVG for CRRT can be performed with a low serious complication rate and low risk of access loss, potentially avoiding catheter-related complications. DIABETES Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes and CKD Journal of Diabetes. Doi: / A recent study was designed to perform a meta-analysis of data from randomized controlled trials on the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes with moderate-tosevere chronic kidney disease (CKD). The meta-analysis, conducted by Man Yang, MD, and colleagues, included 12 studies representing ten trials. Compared 20 Nephrology Times May/June 2017

21 Abstract Roundup with placebo or no treatment, there was significant improvement in hemoglobin A1c (HbA1c) level at week 12 with DPP-4 inhibitor treatment. The improvement was seen only in patients on dialysis at 24 weeks. Mean change in HbA1c level with DPP-4 inhibitor treatment was equivalent to treatment with sulfonylureas at 52 or 54 weeks. There were no significant differences in severe or any hypoglycemic events between DPP-4 inhibitors and controls at weeks 12, 24, 52, or 54. However, DPP-4 inhibitors were associated with fewer symptomatic hypoglycemic events compared with sulfonylureas at 52 or 54 weeks. DPP-4 inhibitors were effective and comparable with sulfonylureas in type 2 diabetes patients with moderate-to-severe CKD, the researchers said. FABRAY DISEASE Men with Classical Fabray Disease Likely to Experience Renal Events Journal of the American Society of Nephrology. 2017;28(5): Patients with Fabray disease often experience comorbidities with renal, cardiac, and cerebrovascular manifestations. It is known that there are phenotypic differences between classically and nonclassically affected patients, but there are few data on the natural course of classical and nonclassical disease in men and women. Maarten Arends, MD, and colleagues recently conducted a retrospective analysis to examine event-free survival from birth to the first clinical visit, stratified by sex and phenotype. Patients were classified by phenotype on the basis of characteristic symptoms and enzyme activity. Men and women with classical Fabray disease had higher event rate compared with those with nonclassical disease (hazard ratio [HR] for men, 5.63; 95% confidence interval [CI], 3.17 to 10.00; P<.001; HR for women, 2.88; 95% CI, ; P<.001). Men with classical Fabry disease had lower estimated glomerular filtration rate (egfr), higher left ventricular mass, and higher plasma globotriaosylsphingosine concentrations compared with men with nonclassical disease or women with either phenotype (P<.001). In conclusion, the researchers said, Before treatment with enzyme replacement therapy, men with classical Fabray disease had a history of more events than men with nonclassical disease or women with either phenotype; women with classical Fabray disease were more likely to develop complications than women with nonclassical disease. These data may support the development of new guidelines for the monitoring and treatment of Fabray disease and studies on the effects of interventions in subgroups of patients. GERIATRIC NEPHROLOGY Incidence of Gout Associated with egfr Level Clinical Journal of the American Society of Nephrology. 2017;12(4): There are few data on the risk of gout across stages of chronic kidney disease. Researchers, led by Vivian S. Tan, MD, performed a retrospective cohort study using linked healthcare databases from Ontario, Canada, from 2002 to The primary outcome of interest was the 3-year cumulative incidence of gout. The cohort included 282,925 adults 66 years of age. Mean age was 75 years and 57.9% were women. Results were stratified by level of kidney function: egfr 90 ml/ min/1.73 m 2, 60-89, 45-59, 30-44, 15-29, and chronic dialysis. The 3-year cumulative incidence of gout was higher in older adults with lower levels of estimated glomerular filtration rate. In women, the incidence of gout ranged from 0.6% to 3.4%; in men, the incidence ranged from 0.8% to 4.6%, depending on egfr. Among patients on chronic dialysis, the 3-year cumulative incidence of gout was lower than in those with more moderate reductions in kidney function. Following adjustment for clinical characteristics, the association between a greater loss of kidney function and a higher risk of diagnosed gout remained. Patients with a lower level of egfr had a higher 3-year cumulative incidence of gout, with the exception of patients receiving dialysis. Results can be used for risk stratification, the researchers said. Risk of Dementia among Older Kidney Transplant Recipients Journal of the American Society of Nephrology. 2017;28(5): Kidney transplant recipients 55 years of age may develop post-transplant dementia and Alzheimer s disease (AD) associated with their long-standing kidney disease and/ or neurotoxic immunosuppressive agents. Mara A. McAdams-DeMarco, MD, and colleagues studied 40,918 kidney transplant recipients 55 years of age (January 1, 1999, to December 31, 2011) linked to Medicare claims through the US Renal Data System. Older adults had a 10-year dementia risk that ranged from 5.1% for patients 55 to 60 years of age to 17.0% for transplant recipients 75 years of age. The 10-year risk for AD ranged from 1.0% to 6.7%, respectively. Older recipient age and pretransplant diabetes were the strongest predictors for dementia and AD. Among those who developed dementia, the 10-year graft loss risk was 43.1%, compared with 28.8% among those who did not develop dementia. The corresponding mortality risks were 89.9% and 55.7%, respectively. Results were similar for AD. We conclude that older kidney transplant recipients have a high risk of post-kidney transplant dementia and AD, and these sequelae associate with a profound effect on patient and graft survival, the researchers said. Integrated Treatment Approach Helps Older Patients Self-Manage CKD Clinical Journal of the American Society of Nephrology. 2017;12(4): Self-management is an important component of a treatment regimen for patients with chronic kidney disease (CKD). Older patients with CKD may find the self-management component challenging, due to the effect of aging on functional capacity. C. Barrett Bowling, MD, and colleagues conducted an exploratory qualitative study designed to examine the relationship among factors facilitating or impeding CKD management in the older patient population. The researchers held six focus groups at the Veterans Affairs Medical Center in Atlanta, Georgia. The participants were veterans 70 years of age with moderate-to-severe CKD. Mean age was 75.1 years, 60% were black, and 96.7% were men. The main organizing concept that developed was managing complexity. Participants often had other chronic conditions in addition to CKD, and recommendations for self-management of CKD fell within a complex regimen of recommendations for management of other conditions. One effective strategy suggested was prioritization for managing the complexity, such as focusing on blood pressure control. In conclusion, the researchers said, Among older veterans with moderate-to-severe CKD, multimorbidity presents a major challenge for CKD self-management. Because virtually all older adults have multimorbidity, an integrated treatment approach that supports self-management across commonly occurring conditions may be necessary to meet the needs of these patients. Nephrology Times May/June

22 From the Field Rick Collins Sarah Tolson New Medicare Patient ID System Another major change is about to hit healthcare providers in 2018 that has the potential to cause reimbursement delays in Medicare and secondary payer reimbursement. In April 2018, the Centers for Medicare & Medicaid Services (CMS) will begin to replace all current Medicare patient identification numbers with a new numbering system. The current patient identification methodology, the Health Insurance Claim Number (HICN), is based on the patient s social security number. Railroad Medicare beneficiaries are assigned a similar number, known as the Railroad Retirement Number (RRN). The new Medicare identification number, the Medicare Beneficiary Identifier (MBI), will be distinct from the enrollee s social security number and, in theory, all other identification numbers. Since the renal industry s patient population consists mostly of patients with Medicare as their primary payer, this dramatic change will have an especially big impact on renal providers. Thus, it is important for those of us in the renal industry to become informed regarding the implementation of the MBI. Begin preparing now so we can deal with possible reimbursement issues and assist patients who may be confused about the new numbers. What are the time frames associated with MBI implementation? The transition period for the implementation of the MBI will be 21 months, beginning April 1, 2018, and ending December 31, In April 2018, CMS will start mailing to beneficiaries new Medicare cards containing their MBI. Beginning that same month, Medicare will accept either the MBI or the HICN/RRN on all claims through December Additionally, beginning in October 2018, CMS will place the HICN/RRN and the MBI on every remittance advice. Effective with January 1, 2020, dates of service, Medicare will only accept the MBI. What systems need to be updated to accommodate a new policy number format? The current Medicare Health Insurance Claim number follows a format of nine numbers followed by an alpha suffix and sometimes an additional number in the eleventh position. The MBI will have 11 digits, some of which are specified as either alpha or numeric while other positions can be only alpha or numeric. CMS states that the MBI will be non-intelligent and clearly different from the HICN and RRN. For example, 1AE0WT8JR09 is a number that could be generated in the new format and is clearly distinguishable from the current system which always has numbers in the first nine slots. Because the format of the MBI is significantly different from the HICN/ RRN, you should reach out to your EHR vendor to see your software needs updating to accommodate the new Medicare ID number. Also, check with your electronic clearinghouse to ensure they will be able to accept the new number format beginning in April. How will I know if my patients have received a new number if they don t tell me? Providers can determine if a patient has been assigned an MBI number by checking the patient s Medicare eligibility. CMS states the information will be in the message field of the eligibility transaction responses. Of course, you should also inform patients they will be receiving a new Medicare identification card and regularly remind them to bring the card with them to the facility so the their new number can be recorded. What can I do to help my patients through this transition? Not all patients will realize they have received a new number, which they will need to provide to all of their healthcare providers and to their secondary insurance company. If you become aware of a patient s MBI number before a patient informs you, notify the patient of their new number and encourage and/or help them to update their information with other providers and payers. What education should I provide to my staff? Inform all staff regarding the upcoming change and its accompanying timelines and milestones. Because patients could conceivably hand their new Medicare cards to any member of the staff, stress the importance of getting the new ID number to those who can update the patient s insurance information. Staff members responsible for checking patient insurance eligibility should be trained to vigilantly watch for the message from CMS and/or the new ID number whenever they check eligibility. Will my payments from secondary payers be affected? While most large commercial payers will likely be ready to process the new MBI on secondary claims crossed over from Medicare, some smaller payers may not. You will want to have someone on your staff contact smaller payers to ask if they will be prepared to accept the MBI and, if not, how the payer will process secondary claims containing the new number. Whether or not Medicaid systems will be updated in every state is always a mystery when major changes are implemented by Medicare. You will want to regularly check your state s Medicaid website regarding the Social Security Number Removal Initiative (SSNRI) and their acceptance of the new MBI numbers. Medicaid agencies in some states currently include the Medicare HICN on the Medicaid ID card. CMS will be working with these states to either remove the HICN or replace it with the MBI. Sarah Tolson is the director of training and Rick Collins is the chief operating officer for Sceptre Management Solutions, Inc., a company specializing in billing for outpatient ESRD facilities, nephrology practices, and vascular access. Your questions are welcome and they can be reached at , stolson@sceptremanagement. com, rcollins@sceptremanagement.com, or via Sceptre s website, 22 Nephrology Times May/June 2017

23 3 Ways to read Nephrology Times: Nephrology Practical News, Trends, and Analysis Times May/June 2017 VOLUME 9, NUMBER 4 Dietary Intervention to Reduce Vasopressin Secretion in ADPKD Patients A pilot randomized controlled trial to examine the effect of a low-osmolar, low-protein diet and adjusted water intake on vasopressin secretion in ADPKD. 10 CMS Reimbursement Reform and Hospitalizations and Readmissions among Hemodialysis Patients In 2004, CMS changed physician reimbursement for patients receiving hemodialysis, targeting a specific care process: the frequency of face-to-face provider visits. 11 Fluid Overload in AKI Patients Receiving Continuous Renal Replacement Therapy A retrospective study evaluating the association between fluid overload and mortality in critically ill patients. 12 PLUS... From the Field New Medicare Patient ID System 22 Undocumented Immigrants with No Access to Scheduled Hemodialysis t is estimated that 11.3 million undocumented immigrants live and Iwork in the United States, representing a low-income population excluded from public benefits such as federally funded Medicaid and insurance provisions of the Affordable Care Act. Healthcare for individuals in that population is largely limited to safety-net provisions designed to protect the uninsured, including community health centers, public clinics, and treatment in hospital emergency departments (EDs) mandated by the 1986 Emergency Medical Treatment and Active Labor Act (EMATLA). When an undocumented immigrant is diagnosed with end-stage renal disease (ESRD), arranging care is complex, requiring access to hemodialysis. There are approximately 6480 undocumented immigrants with ESRD in the United States. Access to hemodialysis for those individuals depends on state policy and local safety net investments. California and New York, for example, use state emergency Medicaid programs to finance scheduled hemodialysis for those patients; other states offer only nonstandard emergent-only hemodialysis, accessed through the ED under EMTALA and reimbursed by emergency Medicaid programs. Lila Cervantes, MD, and colleagues recently conducted a qualitative, continued on page 7 Using a Dynamic Model to Predict Progression of CKD to Kidney Failure T he worldwide incidence and prevalence of chronic kidney disease (CKD) is increasing; recent estimates indicate that 24 million Americans have CKD and are at risk for comorbidities and complications such as cardiovascular disease, anemia, bone mineral metabolism abnormalities, and progression to kidney failure. Patients with end-stage renal disease require treatment with dialysis or kidney transplantation. Shared Risk Factors of Preeclampsia and End-Stage Renal Disease continued on page 6 pproximately 8% of pregnancies are complicated by hypertension, a complication that can lead to significant maternal morbidity and mortality. Previous studies have documented some long-term effects on maternal A health of hypertensive pregnancies, especially the risk for cardiovascular disease. Several large registry-based studies have also shown associations between pregnancy hypertension and the development of kidney disease, including end-stage renal disease (ESRD). According to Andrea G. Kattah, MD, those studies had some limitations, including use of International Classification of Disease codes in lieu of an actual review of medical records, and the inability to determine the frequencies of potential confounders such as kidney disease and obesity prior to pregnancy. Dr. Kattah and colleagues conducted a population-based nested case-control study designed to examine the magnitude of the association between preeclampsia and ESRD. Preeclampsia was identified using complete medical records of cases and controls, and ESRD was identified using the US Renal Data System (USRDS) database. The researchers also sought to examine how pre-pregnancy comorbid conditions such as decreased kidney function, obesity, hypertension, and diabetes mellitus may confound the association between preeclampsia and ESRD. Study results were reported in the American Journal of Kidney Diseases [2017;69(4): ]. The medical records search revealed 34,581 women with live or stillbirths in continued on page 8 Print or Online at ipad Inside, you will find: Important news, views, and events in the world of nephrology Interviews with key opinion leaders Insights into clinical data and how it impacts your practice Highlights and news from Kidney Week and more

24 When stability is critical, every piece counts. CRRT built for the ICU When you choose Baxter for your CRRT program, you re not only choosing industry-leading CRRT technology, you are also selecting a partner dedicated to ensuring your clinical success in treating AKI patients. Our commitment to you starts with an individualized program customized to your facility s needs and complete support every step of the way: Comprehensive Therapy Implementation Program On-going Clinical Education 24/7 Clinical Support Help-line 24/7 Technical Support With so many pieces to consider in treating critically ill patients, choosing Baxter as your CRRT partner is always the right move. Baxter is a registered trademark of Baxter International Inc. USMP/MG120/ /17