Long-Term Care Updates

Transcription

1 Long-Term Care Updates January 2016 By Yunuo (Enora) Wu, PharmD Chronic kidney disease (CKD) is defined as kidney damage (including structural or functional abnormalities) or glomerular filtration rate (GFR) <60 ml/min/1.73m 2 (with or without kidney damage) for 3 months. 1 CKD can progress and worsen over time, increasing the risk of adverse outcomes. Currently, 10% of the global population is diagnosed with CKD. 2 Lack of access to affordable treatment leads to millions of deaths each year, raising CKD to the 18 th cause of death worldwide in In the geriatric population specifically, it is estimated that one in five men and one in four women between the ages of 65 and 74 years have CKD. 2 CKD can often progress to kidney failure due to other comorbidities such as diabetes and hypertension. In addition, CKD can affect drug absorption, distribution, metabolism, and excretion. In the presence of kidney disease, certain medications may accumulate and lead to an increased therapeutic effect or adverse drug effects. Addressing CKD early and adjusting medication therapy where necessary can help to prevent progression of the disease and ultimately improve patient outcomes. The article that follows will summarize and synthesize clinical practice guidance on the pharmacologic management of CKD from the National Kidney Foundation (NKF). While these documents provide significant evidence-based guidance on the management of CKD, patient-specific factors and the clinician s judgement should ultimately dictate an appropriate care plan. Clinical practice guidelines from the NKF are available for evaluating, classifying, and slowing the progression of CKD. These include the Kidney Disease Outcomes Quality Initiative (KDOQI) published in 2002 and the Kidney Disease: Improving Global Outcomes (KDIGO) international guidelines published in 2013 as an update and clarification of the 2002 guidelines.

2 Current guidelines recommend that CKD be classified based on cause, GFR category, and albuminuria category. CKD is mainly detected and monitored by the calculated GFR and the urine albumin-to-creatinine ratio (UACR). GFR reflects the rate of total filtration by all of the functioning nephrons in the kidney. As kidney damage progresses, GFR declines as the nephrons are damaged or destroyed. UACR (mg albumin/gram creatinine) indicates albuminuria at a ratio 30 mg/gram and is an early indication of kidney damage. Important laboratory tests to monitor include serum creatinine (SCr) and albumin, in order to estimate and calculate GFR and UACR in the presence of kidney disease. Guidelines recommend assessing GFR and albuminuria at least annually in those with stable CKD, and more frequently in those at higher risk of progressing CKD. KDIGO also suggests additional laboratory tests such as cystatin C or its clearance in order to confirm CKD in instances where GFR based on SCr is not as reliable. 4 Although neither KDOQI nor KDIGO focus their recommendations on the long-term care setting specifically, the goals of managing CKD are similar in all patient populations. It is important to identify CKD early to avoid progression to kidney failure. Tables 1 and 2 provide a summary of GFR and albuminuria categories used in the classification of CKD. 4 Whereas KDOQI guidelines recommended classification of CKD based on GFR alone, KDIGO updated this classification to include both GFR and albuminuria measurements. Table 1. CKD Categories Based on GFR 4 Stage Description GFR (ml/min ) G1 Normal or high 90 G2 Mildly decreased (relative to young adult level) G3a Mildly to moderately decreased G3b Moderately to severely decreased G4 Severely decreased G5 Kidney failure <15, or dialysis Category Table 2. CKD Categories Based on Albuminuria 4 Description AER (mg/24hr) ACR (mg/mmol) Abbreviations: AER = albumin excretion rate; ACR = albumin-to-creatinine ratio * Includes nephrotic syndrome (albumin excretion >2200mg/24hr or ACR >220mg/mmol or ACR >2200mg/g ACR (mg/g) A1 Normal to mildly increased <30 <3 <30 A2 Moderately increased (relative to young adult level) A3 Severely increased* >300 >30 >300

3 According to both the KDOQI and KDIGO guidelines, factors associated with CKD progression and prognosis may include GFR, level of albuminuria, elevated blood pressure, hyperglycemia, dyslipidemia, smoking, obesity, history of cardiovascular disease (CVD), and exposure to nephrotoxic medications. It is important to note that small fluctuations in GFR do not always indicate CKD progression. KDIGO describes CKD progression as a decline in GFR category, a drop in GFR 25% from baseline, a sustained decline in GFR >5 ml/min/1.73m 2 per year, and increased SCr measurements. 4 Age, sex, race/ethnicity, and socioeconomic development are associated with CKD progression. The prevalence of CKD is quickly growing among the poorest parts of the world. A strong association has been observed between availability of renal replacement therapy and economic development. In addition, the risk of CKD increases with age and is most prominent in the African American, Asian, Hispanic, and Native American populations. 3 High blood pressure has been identified as both a cause and complication of CKD. Uncontrolled blood pressure can lead to a faster decline in kidney function and development of CVD. KDOQI and KDIGO recommend that all adults with CKD and urine albumin excretion <30 mg/24hr should have a blood pressure target of 140/90 mmhg. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) should be used as first line treatment in both diabetic and non-diabetic patients for blood pressure control. 5 In the case that a patient cannot tolerate ACE inhibitor or ARB therapy due to worsening renal function, other alternatives such as diuretics, beta-blockers, or calcium-channel blockers that do not require renal dosage adjustment can be considered. 5 Glycemic control is also important in the CKD population with a recommended target hemoglobin A1C (HbA1C) of <7% to prevent progression of microvascular complications, such as diabetic kidney disease. 6 HbA1C goals should be individualized to the specific patient, with a higher HbA1C goal for those at risk of hypoglycemia, other comorbidities, and/or limited life expectancy. While the guidelines do not list specific preferred agents for diabetic patients with CKD, hypoglycemic therapy should also be individualized to each individual patient depending on response and glycemic control. Certain diabetes medications may require dosage adjustments in patients with CKD as inappropriate dosing can lead to toxic or suboptimal treatment. 4,6 Another therapeutic goal in slowing the progression of CKD is preventing acute kidney injury (AKI). KDIGO defines AKI as: an increase in SCr by 0.3 mg/dl within 48 hours; an increase in SCr to 1.5 times the baseline value within the past 7 days of monitoring time; or urine volume <0.5 ml/kg/h for 6 hours. Guidelines recommend that patients be monitored for increased AKI risk via SCr and urine output. 7 Patients who develop AKI should be evaluated 3 months after the event for resolution of AKI, new AKI onset, or progression of pre-existing CKD. In order to avoid development of AKI, guidelines suggest discontinuing potentially nephrotoxic agents that are renally eliminated when GFR <60 ml/min/1.73m 2, controlling plasma glucose between mg/dl, monitoring SCr and urine output, and considering alternatives to radiocontrast procedures. 7 Table 3 provides a list of commonly prescribed nephrotoxic medications that should be discontinued in the presence of CKD. Patients taking potentially nephrotoxic agents should be regularly monitored to assess GFR, electrolytes, and drug levels. 4 Table 4 provides a summary of recommended interventions for achieving therapeutic goals in slowing CKD progression.

4 Table 3. Nephrotoxic Medications Analgesics Acetaminophen Aspirin NSAIDs Benzodiazepines Alprazolam Clonazepam Diazepam Antidepressants / Mood Stabilizers Amitriptyline Doxepin Fluoxetine Lithium Cardiovascular Agents ACE inhibitors ARBs Clopidogrel Statins Diuretics Antihistamines Diphenhydramine Doxylamine Proton Pump Inhibitors Lansoprazole Omeprazole Pantoprazole Antimicrobials Acyclovir Aminoglycosides Amphotericin B Beta-Lactams Quinolones Rifampin Sulfonamides Vancomycin Others Allopurinol Haloperidol Phenytoin Quinine Ranitidine Zoledronic acid Abbreviations: ACE = angiotensin converting enzyme; ARB = angiotensin receptor blocker; NSAID = non-steroidal anti-inflammatory drug

5 Table 4. Goals and Recommendations for Slowing CKD Progression 4-7 Therapeutic Goal Target Intervention Improve Lifestyle Slow CKD progression 1. Reduce sodium intake (<2 grams/day) 2. Reduce excessive protein intake 3. Smoking cessation 4. Weight management (BMI <30 kg/m 2 ) Control Blood Pressure Control Diabetes <140/90mmHg HbA1c <7%; Meet target blood glucose range; Goals should be individualized 1. ACE inhibitor or ARB (first line) 2. Diuretics Thiazides preferred 3. Beta-blockers Carvedilol, propranolol, or metoprolol preferred for CKD patients with heart failure 4. Calcium channel blockers Avoid nicardipine in elderly patients with CKD 5. Monitor serum potassium ACE inhibitors and ARBs may increase levels Dietary potassium restriction if needed 1. Dose adjust diabetes medications as needed 2. Consider less stringent HbA1c and blood glucose goals for: Elderly patients Patients with multiple comorbidities Patients with a history of hypoglycemia 3. Annual eye and feet screenings 4. Biannual dental exams 5. Quarterly HbA1c if uncontrolled; biannual HbA1c if controlled Prevent AKI Lower risk of AKI 1. Avoid nephrotoxic medications (see Table 3) 2. Control blood glucose between mg/dl 3. Monitor SCr and urine output 3. Avoid other nephrotoxic agents Iodinated contrast media Abbreviations: ACE=angiotensin converting enzyme; AKI=acute kidney injury; ARB=angiotensin receptor blocker; BMI=body mass index; HbA1C=hemoglobin A1C; SCr=serum creatinine

6 Current guidelines also make recommendations for managing complications related to CKD. Dyslipidemia or uncontrolled cholesterol is a common presentation in CKD patients due to decreased GFR and the presence of comorbidities such as hypertension and diabetes. Although there is limited data showing improved renal outcomes with the treatment of dyslipidemia, the guidelines still make recommendations for treatment in order to prevent possible complications such as atherosclerosis or CVD. KDIGO recommends an initial lipid profile evaluation upon diagnosis of CKD, including total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride levels. Statin therapy has been shown to reduce mortality associated with CVD in the CKD population; thus, the guidelines focus recommendations on the use of statins in the CKD population at higher risk of future cardiovascular events. KDIGO recommends that adults 50 years of age with GFR <60 ml/min/1.73m 2 (stage G3a-G5) should be treated with a statin or statin with ezetimibe combination therapy. In adults 50 years of age with GFR 60 ml/min/1.73m 2 (stage G1-G2), statin monotherapy should be recommended. Lifestyle modifications are recommended for patients with hypertriglyceridemia or triglycerides >500 mg/dl. 9 Anemia is diagnosed as hemoglobin (Hgb) <13 grams/dl in males and Hgb <12 grams/dl in females. KDIGO recommends that all CKD patients should be monitored for anemia at least annually in those with CKD stage G3, at least twice per year in those with CKD stage G4- G5, and at least every 3 months in patients with CKD stage G5. The presence of anemia should be evaluated based on a complete blood count, including Hgb concentration, red blood cell (RBC) count, white blood cell count, and platelet count. Anemia should also be assessed via absolute reticulocyte count, serum ferritin levels, serum transferrin saturation, and serum vitamin B12 and folate levels. 10 Bone mineral metabolism, as well as calcium and phosphate homeostasis, change as CKD progresses. KDIGO recommends measuring serum levels of calcium, phosphate, parathyroid hormone, and alkaline phosphatase activity at baseline in adults with GFR <45 ml/min/1.73m 2 (stage G3b-G5) in order to evaluate the values and determine progression of the disease. 11 Guidelines do not recommend routinely supplementing with vitamin D analogs if there is no suspected deficiency as there are a lack of robust data to support the treatment of vitamin D deficiency in non-dialysis patients. 11 Other complications that may occur with CKD include hyperkalemia (due to concomitant medication therapy) and malnutrition. 4 Table 5 summarizes complications as a result of decreased GFR and albuminuria over time, treatment targets, and recommended interventions. KDIGO guidelines recommend referring CKD patients to a nephrology specialist when there is an acute or chronic reduction in renal function, treatment-resistant hypertension, severe electrolyte disturbances, urinary tract structure abnormalities, or other systemic diseases with renal involvement. Patients should also be referred for education on progressive diseases and psychological implications that could be associated with CKD. Box 1 summarizes the specific situations in which patients should be referred to specialist nephrology services. 4

7 Table 5. Treating CKD Complications 4,9-11 Complication Target Intervention Cardiovascular Disease LDL cholesterol <100mg/dL; Refer also to current ACC/AHA lipid guidelines 1. Statin or 2. Statin + ezetimibe combination 3. Lifestyle modifications for high triglycerides Anemia Hgb 13 g/dl (males) Hgb 12 g/dl (females) 1. Oral iron supplements 2. IV iron supplements (if oral treatment is not tolerated) 3. Injectable ESAs: For dialysis patients If not on dialysis: Hgb <10 g/dl AND Hgb decline requiring RBC transfusion AND Increased RBC transfusion-related risk Mineral and Bone Disorders Hypocalcemia Hyperphosphatemia Secondary parathyroidism Vitamin D deficiency Calcium mg/dl Phosphorous mg/dl PTH <65 pg/ml Vitamin D 20 ng/ml 1. Calcium-based phosphate-binding medications 2. Phosphorous binders 3. Restrict dietary phosphorous 4. Vitamin D supplement Ergocalciferol (Vitamin D2) Cholecalciferol (Vitamin D3) Calcitriol (Vitamin D) Hyperkalemia Potassium meq/l 1. Discontinue use of NSAIDs 2. Monitor potassium levels during ACE inhibitor or ARB therapy 3. Add diuretic therapy Malnutrition Hypoalbumineria Albumin >4.0 g/dl (range g/dl) 1. Biannual dental exam 2. Optimize diet Abbreviations: ACE = angiotensin converting enzyme; ARB = angiotensin receptor blocker; ESA = erythropoiesis-stimulating agent; Hgb = hemoglobin; LDL = low-density lipoprotein; NSAID = non-steroidal anti-inflammatory drug; PTH = parathyroid hormone; RBC = red blood cell

8 Box 1. When to Refer Patients to Nephrology Specialists AKI or an abrupt and sustained decline in GFR CKD progression CKD stages G4-G5 (GFR <30 ml/min/1.73m 2 ) CKD with treatment-resistant hypertension while on 4 antihypertensive agents Hematic cylindruria and hematuria not otherwise explainable Hereditary kidney disease Persistent changes in serum potassium Significant albuminuria (defined as UACR >300 mg/g, albuminuria >300 mg/24hr) Abbreviations: AKI=acute kidney injury; UACR=urine albumin-to-creatinine ratio CKD is a worldwide health issue that causes millions of death each year, with the majority of death due to progression of concomitant chronic diseases. Early diagnosis and treatment is important as it can help to slow the progression of kidney disease in the long-term care population. Current guidelines recommend identifying and controlling diseases that can lead to kidney disease and making necessary lifestyle modifications and therapeutic interventions in order to manage the progression of CKD. 1. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. 2002;39(2 Suppl 1):S Chronic Kidney Disease. World Kidney Day Web site. Available at: Accessed December 21, Jha V, Garcia-Garcia G, Iseki K, et al. Chronic kidney disease: Global dimension and perspectives. 2013;382(9888): Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. 2013;3: Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. 2012;2: Standards of medical care in diabetes--2015: Summary of revisions. 2015;38 Suppl:S4. 7. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. 2012;2: Naughton CA. Drug-induced nephrotoxicity. 2008;78(6): Kidney Disease: Improving Global Outcomes (KDIGO) Lipid Work Group. KDIGO clinical practice guideline for lipid management in chronic kidney disease. 2013;3: Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO clinical practice guideline for anemia in chronic kidney disease. 2012;2: Kidney Disease: Improving Global Outcomes (KDIGO) CKD MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease mineral and bone disorder (CKD MBD). 2009;76(Suppl 113):S1 S130.

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