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

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

Chronic kidney disease (CKD) - staging

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

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

Progression of chronic kidney disease Complications Kidney failure normal  risk injury  GFR death 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

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

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

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

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

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

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

Anemia associated with chronic kidney disease Anemia: Hb < 130 g/l (men), < 120 g/l (women) Screening Follow-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!

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

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

Proteinuria in chronic kidney disease Screening proteinuria / albuminuria screening 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

Ca-PO4 homeostasis in chronic kidney disease

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

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