2017 KDIGO Guidelines Update

Transcription

1 2017 KDIGO Guidelines Update Clinic for Hemodialysis Clinical Center University of Sarajevo 13 th Congress of the Balkan cities Association of Nephrology, Dialysis, and Artificial Organs Transplantation Sarajevo, October 2017.

2 What is on the agenda? 1. The KDIGO guidelines 1. Development process 2. Overview 3. Background 4. Contents and Grading 2. Serum phosphate and calcium targets and treatment 3. Abnormal PTH levels in CKD-MBD and treatment 4. Conclusions

3 KDIGO Kidney Disease: Improving Global Outcomes (KDIGO) is a global organization that aims to improve care and outcomes of kidney disease patients worldwide through the development and implementation of nephrology clinical practice guidelines (CPGs). KDIGO has produced 9 comprehensive guidelines since 2008 that cover major areas of kidney disease care.

4 Modern therapy guidelines are needed for quality scientific and therapeutic progress KDIGO Guideline for Chronic Kidney Disease -Mineral and Bone Disorder (CKD- MBD) Kidney Int 2009 KDIGO Guideline for Chronic Kidney Disease -Mineral and Bone Disorder (CKD- MBD) Update Kidney Int Suppl CKD-MBD Chronic Kidney Disease-Mineral and Bone Disorder KDIGO Clinical Practice Guideline for CKD-MBDKidney International Supplements (2017) 7, 1 59

5 Guideline development process Consensus conference was in September 2005 in Spain Authors: International work group with 19 experts from North- and South America, Europe, Australia, and Asia Evidence review team: Epidemiologists from Tufts University, Boston, grading the quality of originally studies Public review in July/August 2008 with 180 experts participating First Publication was in August 2009

6 KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of CKD MBD based on best information available as of July Cited from the guidelines: It is designed to provide information and assist decision-making. It is not intended to define a standard of care, and should not be construed as one, nor should it be interpreted as prescribing an exclusive course of management. KDIGO Clinical Practice Guideline for CKD-MBDKidney International Supplements (2017) 7, 1 59

7 Overview of KDIGO 2017 Guidelines Update This KDIGO update represents selective update of the prior CKD- MBD Guideline published in Emphasis has been on the rationale for the changes made to the original guideline document. This update, along with the 2009 publication, is intended to assist the practitioner caring for adults and children with chronic kidney disease (CKD), those on chronic dialysis therapy, or individuals with a kidney transplant. 1 1 Markus Ketteler, Executive summary of the 2017 KDIGO Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD) Guideline Update: what s changed and why it matters, Kidney International (4/2017)

8 Background of KDIGO 2017 Guidelines Update Over the years after first Guidelines in 2009 multiple randomized controlled trials (RCTs) and prospective cohort studies emerged, which promted KDIGO to reexamine the currency of its guidelines. 1 Therefore, Workgroup issued a selective update of the 2009 KDIGO CKD- MBD Guideline. 1 A total of 12 recommendations were identified for revision, based on new data. 1 Large gaps of knowledge still remained, despite the availability of results from several new key clinical trials. The structured approach was modeled after the GRADE system, which describes grades to the quality of the overall evidence and strength for each recommendation. Where appropriate, the Work Group issued not graded recommendations, based on general advice, that were not part of a systematic evidence review. 1 1 Markus Ketteler, Executive summary of the 2017 KDIGO Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD) Guideline Update: what s changed and why it matters, Kidney International (4/2017)

9 KDIGO -Guidelines: Grading Grade A B Quality of evidence High Moderate Meaning We are confident that the true effect lies close to that of the estimate of the effect The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different C Low The true effect may be substantially different from the estimate of the effect D Very low The estimate of effect is very uncertain, and often will be far from the truth Grade Strength Wording Level 1 Level 2 Strong Weak We recommend should Most patients should receive the recommended course of action We suggest might Different choices will be appropriate for different patients. KDIGO Clinical Practice Guideline for CKD-MBDKidney International Supplements (2017) 7,

10 Contents of KDIGO guidelines Diagnosis of CKD MBD: biochemical abnormalities Parameters (P, Ca, PTH, ALP, calcidiol (25 OHD), individual values of serum calcium and phosphate, evaluated together, rather than the mathematical construct of calcium-phosphate product (Ca x P). Diagnosis of CKD MBD: bone Recommended and not recommended routine measurements, causes for bone biopsies Treatment of CKD MBD targeted at lowering high serum phosphorus and maintaining serum calcium Treatment of abnormal PTH levels in CKD MBD Diagnosis of CKD MBD: vascular calcification Method, classification as highest cardiovascular risk Treatment of bone with bisphosphonates, other osteoporosis medications, and growth hormone Evaluation and treatment of kidney transplant bone disease

11 What is on the agenda? 1. The KDIGO guidelines 1. Development process 2. Overview 3. Background 4. Contents and Grading 2. Serum phosphate and calcium targets and treatment 3. Abnormal PTH levels in CKD-MBD and treatment 4. Conclusions

12 Serum phosphorus levels greater than 5.5 mg/dl (1.8 mmol/l) Are independently associated with a 20 % to 40% increase in mortality risk in ESRD pts. In addition, hyperphosphatemia appeared to be involved in the development of atherosclerotic heart disease, secondary hyperparathyroidism,and bone disease among CKD pts. Sullivan, JAMA 2009

13 Lower, challenging serum phosphorus target Normal range: mg/dl ( mmol/l) KDIGO Clinical Practice Guideline for CKD-MBDKidney International Supplements (2017) 7, 1 59

14 High P serum levels are strongly and independently associated with a more rapid decline of renal function in patients with advanced CKD Caravaka F, Revista Nefrologia,2011

15 Choice of phosphate binder: No specific recommendation, aluminium is not recommended KDIGO Clinical Practice Guideline for CKD-MBDKidney International Supplements (2017) 7, 1 59

16 Weekly Phosphate Balance in HD patients B e f o r e A f t e r Diet 1000 mg/day 7 x 1000 (per week) = 7000 mg Absorption 60% Diet 1000 mg/day 7000 x 60% = 4200 mg 7 x 1000 (per week) = 7000 mg Dialysis 800 mg Absorption 60% 3 x 800 (per week) = 2400 mg 7000 x 60% = 4200 mg Balance = 1800 mg Dialysis 800 mg 3 x 800 (per week) = 2400 mg Balance = 1800 mg Red wine mg Cola Beverages mg Beer mg Red wine + Beer mg Red wine +Cola Beverages mg + - Faeces elimination ~ 15 % - 20 % Polyphosphates in foods 1000 mg /day

17 Effect of Food Additives on Hyperphosphatemia in ESRD Polyphosphates, etc. ortho-phosphoric acid,etc Meats,cheeses,baked goods,beverages (to preserve moisture or color,to emulsify ingredients, to enhance flavor,to stabilize foods) Sullivan C. et Al., JAMA, 2009

18 Phosphate elimination by hemodialysis treatmentpossibilities Prolonged treatment time P removal (mean, per week) 3 x 4 3 x 5 h/wk + 13 % 1 Long-term sp reduction 3 x 4 6 x 3 h/wk - 22 % 2 3 x 4 6 x 8 h/wk % 3 Procedure High-flux HD Online-HDF (post-dilution) Treatment details: 6 Dialysate flow ml/min + 19 % 4-24 % 5 P clearance (ml/min) % Blood flow ml/min % Dialyzer surface m² % 1 Vaithilingam AJKD 43:85, 2004; 2 Achinger, KI 67 Suppl 95:S28, 2005; 3 Mucsi KI 53:1399, Lornoy, J Ren Nutr 16: ; 5 Minutolo, JASN13:1046, 2002; 6 Mandolfo IJAO 26:113, 2002

19 Management of Hyperphosphatemia *Dietary restriction (of protein) *Dialysis *Phosphate binders : - aluminum salts - calcium salts - iron containing compounds - magnesium salts - sevelamer - lanthanum carbonate *Vitamin D analogs paricalcitol *Calcimimetics cinacalcet KDIGO Clinical Practice Guideline for CKD-MBDKidney International Supplements (2017) 7, 1 59

20 Hemodial Int Apr;18(2): doi: /hdi Epub 2014 Jan 20.

21 Maintaining serum calcium Normal range: mg/dl ( mmol/l) KDIGO Clinical Practice Guideline for CKD-MBDKidney International Supplements (2017) 7, 1 59

22 Explanation to recommendation Recommendation was made on the basis of: the RCT by Block et al.(2) in a much larger, similar cohort and 2 additional RCTs (3,4) in hyperphosphatemic CKD patients 3 RTCs represent hard endpoint data when prospectively comparing the calcium-free binders, mostly sevelamer, with calciumcontaining binders in predialysis or dialysis adult patients, respectively New meta- analisys additionally fortified the recommendation (5,6,7,8) Work Group determined that there is new evidence suggesting that: excess exposure to calcium through diet, medications, or dialysate may be harmful across all GFR categories of CKD, regardless of whether other candidate markers of risk such as hypercalcemia, arterial calcification, adynamic bone disease, or low PTH levels are also present 2: Block, 2012; 3,4 DiOrio 2012&2013; 5: Jamal 2013; 6: Palmer 2016; 7. Patel 2016; 8. Sekercioglu 2016.

23 Coronary artery calcification (CAC): Randomized clinical trials comparing Sevelamer HCl and CaPBs Study Design Results Treat-to-Goal- Study (TTG) Chertow GM et al., KI 2002 Renagel in New Dialysis (RIND) Block GA et al., KI 2005 CARE II Qunibi et al, AJKD 2008 BRiC Barreto et al., Nephrol Clin Pract patients, 1 year follow up Patients on sevelamer or any CaPB (CaAc or CaCO 3 ) PB doses to achieve sp and sca target levels 129 incident HD pts, sevelamer or any CaPB for 18 months Management of parameters of bone metabolism at investigators discretion 203 pts (52 weeks) on Ca Ac or Sevelamer, both + atorvastatin 71 pts, on Ca Ac or sevelamer for 12 months Dialysate calcium and vit D regimen changes during study Primary endpoint: No difference in sp and Ca x P Significantly lower increase of CACS in Sevelamer pts Significant decrease in LDL and total cholesterol in sevelamer group Lower increase of CACS in sevelamer group Significant decrease in LDL and total cholesterol in sevelamer group No difference in calcification No difference in LDL levels No difference in calcification No difference in bone turnover No difference in LDL levels

24 What is on the agenda? 1. The KDIGO guidelines 1. Development process 2. Overview 3. Background 4. Contents and Grading 2. Serum phosphate and calcium targets and treatment 3. Abnormal PTH levels in CKD-MBD and treatment 4. Conclusions

25 Abnormal PTH levels and treatment Unfortunately, there is still an absence of RCTs that define an optimal PTH level for patients with CKD G3a to G5. The choice of dialysate calcium concentrations will impact serum PTH levels. Parathyroidectomy remains a valid treatment option, especially when PTH-lowering therapies fail, as advocated in Recommendation from the 2009 KDIGO CKD-MBD Guideline 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). Kidney Int Suppl. 2009; : S1 S130

26 Abnormal PTH levels and treatment KDIGO Clinical Practice Guideline for CKD-MBDKidney International Supplements (2017) 7, 1 59

27 What is on the agenda? 1. The KDIGO guidelines 1. Development process 2. Overview 3. Background 4. Contents and Grading 2. Serum phosphate and calcium targets and treatment 3. Abnormal PTH levels in CKD-MBD and treatment 4. Conclusions

28 Conclusions Hyperphospathemia has been shown to be a PREDICTOR of cardiovascular death in CKD pts and in general community. Control of serum phosphate is considered a goal for CKD pts.

29 Conclusions: Choice of a phosphate binder Consider the patient s serum calcium and PTH levels. Try to lower phoshate to normal range Consider framework that should conciliate: phosphate binder with dialysate calcium concentration, vitamin D regimen and calcimimetic therapy. Restricting the dose of CaPB implies a combination therapy, as is often applied in practice. Dialysis offers possibilities for increasing phosphate removal.

30 Consclusions KDIGO CKD-MBD states that many data for CKD-MBD are not sufficient to give practical clincial advise how to treat. KDIGO gives strong and reassuring quality of evidence. Nevertheless, physician who knows the guidelines but also knows the individual patient has now been important as never before.

31 THANK YOU