Management of Chronic Kidney Disease: Diagnosis, Treatment, and Prevention

1. Management of chronic kidney disease Dr. Péter Studinger Semmelweis University, First Department of Medicine 27/11/2015

2. Chronic kidney disease (CKD) - definition • Abnormalities of kidney structure or function • present for > 3 months • with implications for health • Glomerular filtration rate < 60ml/min/1.73 m2 • Markers of kidney damage • albuminuria (AER > 30 mg/24 h / UACR > 3 mg/mmol) • urine sediment abnormalities • electrolyte and other abnormalities due to tubular disorders • abnormal histological finding • imaging abnormalities (small kidneys, polycystic kidneys) • history of kidney transplantation

3. Chronic kidney disease (CKD) - staging

4. Chronic kidney disease (CKD) – who should be referred to a nephrologist ? eGFR • <15 ml/min/1.73m2 urgently (except pre mortem condition) • 15-29 ml/min/1.73m2 always, urgently if unstable • 30-60 ml/min/1.73m2 if age < 70 years if eGFR falls rapidly (> 4 ml/min/1.73m2 / year) if Hgb < 110 g/l or abnormal K, Ca, P, HCO3 • 60-90 ml/min/1.73m2 if other condition necessitates referral

5. Chronic kidney disease (CKD) – who should be referred to a nephrologist? proteinuria / hematuria • nephrotic syndrome: urgently • UPCR > 350 mg/mmol: always, diabetes included • UPCR >100 mg/mmol: always, except in diabetes • UPCR > 45 mg/mmol: if associated with microhematuria or suspicion if systemic immunologic disorder (SLE, vasculitis) • microalbuminuria: only if other cause necessitates referral • macrohematuria: urgently, if associated with proteinuria and rising Screat • micro/macrohematuria: without proteinuria, after exclusion of urologic causes

6. Progression of chronic kidney disease Complications Kidney failure  GFR normal death injury risk Prevention of progression Treatment of complications Preparation to dialysis Screening for risk factors Screening for kidney injury Risk reduction Diagnosis and treatment Prevention of progression Dialysis Transplantation

7. Risk factors in chronic kidney disease • Impressionable • high blood pressure • impaired glycemic control • dyslipidemia • lifestyle • smoking • obesity • high protein diet • anemia • proteinuria • disorders of Ca-PO4 homeostasis • „acute-on-chronic” kidney injury • Unimpressionable • age • male gender • genetic abnormalities • race

8. Blood pressure goals in chronic kidney disease Blood pressure goal : < 140/90 mmHg • „significant proteinuria”: < 130/90 mmHg • RAS-inhibitor (ACEI /ARB) • dual RAS-inhibition contraindicated • eGFR < 30 – spironolacton • contraindicated ESH/ESC Recommendations,2013 Ravera M et al. JASN 2006

9. Blood pressure goals in chronic kidney disease CKD 4 -5: tiazide/indapamide alone insufficient furosemide should be added CKD 5D : ??? home blood pressure vs. pre-dialysis/post-dialysis blood pressure * * * * * * pre-dialyis Zager P et al. Kidney Int.1998

10. Management of diabetes in chronic kidney disease • Goals: • HbA1c ~ 7% • fasting glucose: < 6 mmol/l, postprandial glucose: < 7.5 mmol/l CDA Clinical Practice Guidelines 2013

11. Management of dyslipidemia in chronic kidney disease • Large CV risk, independent of CKD stage and lipid levels • Chol < 4.5 mmol/l • LDL < 2.5 mmol/l • TG < 1.7 mmol/l • HDL > 1.0 (men) > 1.3 (women) mmol/l • statin: atorvastatin / fluvastatin / ezetimibe safe • rosuvastatin: CKD 3 – 20 mg, CKD 4-5 – 10 mg max. • fibrate: CKD 4-5 – only gemfibrozil • statin + fibrate: contraindicated in CKD 3-5D • CKD 5D – statin /ezetimibe treatment should not be initiated • – statin treatment should not be stopped if applied already

12. Lifestyle modification in chronic kidney disease • Cessation of smoking • Regular physical activity (min. 30 minutes, 5x/week) • Decrease salt intake (< 5g NaCl = 2g Na+ = 90 mmol Na+ /day) • Decrease protein intake : CKD 1-3: < 1.3 g/kg/day • CKD 4-5: < 0.8 g/kg/day ± • keto acid supplementation • Dietary recommendations CKD 5D - obesity is favorable! Kalantar-Zadeh et al., 2004

13. Anemia associated with chronic kidney disease • Anemia: Hb < 130 g/l (men), < 120 g/l (women) • ScreeningFollow-up • CKD 3: yearly CKD 3-5PD: every 3 months • CKD 4-5: every 6 months CKD 5HD: monthly • CKD 5D: every 3 months • Iron supplementation: CKD 3-5: per os /iv. CKD 5D: optimally iv. • if TSAT < 30% (20%), ferritin < 500 (200) ug/l • control at least every 3 months (TSAT, ferritin) • iv. iron (iron dextran) should be administered cautiously • active infection – do not supplement iron!

14. Anemia associated with chronic kidney disease • Erythropoietin (EPO) treatment: • Initial Hb: 90-100 g/l (above 100 g/l individualized decision) • goal Hb: 100 -115 g/l, always < 130 g/l • avoidance of EPO considered /: previous stroke, tumor • EPO-resistance: • iron deficiency , Vitamin B12/folate deficiency, malnutrition, infection, uremia (underdialized condition) , hyperparathyroidism, hypothyroidism, bleeding, hemolysis, • malignancies, hematologic disorders

15. Proteinuria in chronic kidney disease 24 halbumin (mg) 24 hprotein (mg) Dipstick ACR mg/mmol TPCR (mg/mmol) Healthy < 3 < 15 < 30 < 150 – Micro-albuminuria – /trace 3 - 30 15 - 45 30 - 300 150-450 False positive results: fever, strenuous exercise, urinary infection, menstruation, uncontrolled hypertension / diabetes Screening: morning urine sample TPCR – proteinuria morning urine sample ACR - microalbuminuria Proteinuria + > 30 > 45 > 300 > 450

16. Proteinuria in chronic kidney disease screening Screening proteinuria / albuminuria morning urine sample screening confirmation morning urine ACR morning urine TPCR follow-up Significant PU Nephrotic PU referral to nephrologist if other cause if + hematuria if + non-diab. always treatment ACEI if diab. ACEI if non-diab. + statin + anticoag. Mátyus et al., 2012

17. Ca-PO4 homeostasis in chronic kidney disease

18. Ca-PO4 homeostasis in chronic kidney disease Floege J. (ed): Comprehensive Clinical Nephrology , 2010 Diagnosis: bone biopsy (seldom performed) ODM – CKD 3B-5D: no sense / therapeutic consequence measurement of collagen synthesis /degradation markers: no sense

19. Ca-PO4 homeostasis in chronic kidney disease PO4 control: - PO4 intake < 800-1000 mg/day - application of phosphate binders CKD 3-5: CaCO3, Ca-acetate CKD 5D: above ± sevelamer, lanthanum Goal: normal range Native vitamin D: CKD 3-5D: measure 25OH vitamin D level correct vitamin D deficiency Active Vitamin D: CKD 3-5D: calcitriol, alpha-calcidol CKD 5D: paricalcitol PTH:CKD 5D: calcimimetic – cinacalcet Goal: CKD 3-5: ??? (probably normal range) CKD 5D: 2-9 x upper normal level