1. CHRONIC RENAL FAILURE JAKUB ZÁVADA KLINIKA NEFROLOGIE 1.LF UK

2. DEFINITION PROGRESSIVE AND IRREVERSIBLE LOSS OF RENAL FUNCTION K/DOQI CLASSIFICATION: 1. NORMAL/INCREASED GFR BUT SOME EVIDENCE OF RENAL DISEASE (microalbuminuria/proteinuria, hematuria, histological changes) 2. MILD DECREASE OF GFR (60-89 ml/min/1,73m2 = 1-1,49 ml/s/1,73m2) 3. MODERATE DECREASE OF GFR (30-59 ml/min/1,73m2 = 0,5-0,99 ml/s/1,73m2) 4. SEVERE DECREASE OF GFR (15-30 ml/min/1,73m2 = 0,25-0,49 ml/s/1,73m2) 5. KIDNEY FAILURE, RRT TO BE CONSIDERED (GFR < 15 ml/min/1,73m2 = 0,25ml/s/1,73m2)

5. EPIDEMIOLOGY INCIDENCE OF ESRD: 110 (UK)- 315 (USA) PTS/1000000/YEAR (IN 1999) PREVALENCE OF ESRD: 659 (EU) – 1217 (USA) PTS/1000000/YEAR (IN 1999) INCIDENCE OF ESRD IS RISING AT A RATE OF 6-7% PER YEAR MOST COMMON ETIOLOGY: DM, HYPERTENSION, CHRONIC GLOMERULONEPHRITIS ESRD=END STAGE RENAL DISEASE RRT=RENAL REPLACEMENT THERAPY CRF=CHRONIC RENAL FAILURE GFR=GLOMERULAR FILTRATION RATE

7. FACTORS AFFECTING PROGRESSION OF CRF NONMODIFIABLE RISK FACTORS: –UNDERLYING NEPHROPATHY –AGE, GENDER, RACE, GENES MODIFIABLE RISK FACTORS: –PROTEINURIA –HYPERTENSION –GLYCEMIA –LIPIDS –OBESITY –HYPERURICEMIA –SMOKING

11. MECHANISMS OF PROGRESSION OF CRF GLOMERULOSCLEROSIS –ENDOTHELIAL INJURY → MESANGIAL PROLIFERATION → GLOMERULAR SCLEROSIS TUBULOINTERSTICIAL SCARRING –TUBULAR CELL INJURY → RELEASE OF INFLAMMATORY MEDIATORS → STIMULATION OF RENAL FIBROBLASTS → FIBROSIS VASCULAR SCLEROSIS –ARTERIOLAR HYALINOSIS, LOSS OF PERITUBULAR CAPILLARIES → INTERSTITICIAL ISCHEMIA → INTERSTICIAL FIBROSIS

14. CLINICAL PRESENTATION OF CRF CHRONIC KIDNEY DISEASE (K/DOQI STAGES 2-4) ACUTE-ON-CHRONIC RENAL FAILURE LATE REFERRAL OF CRF, UREMIC EMERGENCY

15. COMPLICATIONS AND CONSEQUENCES OF CRF CARDIOVASCULAR DISEASE ANEMIA RENAL BONE DISEASE METABOLIC ACIDOSIS MALNUTRITION HYPERVOLEMIA HYPERKALEMIA BLEEDING DIATHESIS DERMATOLOGIC MANIFESTATIONS NEUROLOGIC MANIFESTATIONS IMMUNOSUPRESSION

16. MANAGEMENT OF CRF DEFINE THE CAUSE LOOK FOR REVERSIBILITY –PRE-RENAL, DRUG TOXICITY, IMMUNE-MEDIATED, INFECTION, OBSTRUCTION, HYPERCALCEMIA, HYPERTENSION MINIMIZE PROGRESSION OF CRF PREVENT AND TREAT COMPLICATIONS OF CRF PREPARE FOR RENAL REPLACEMENT THERAPY DRUGS –ADJUST DOSE: ANTIMICROBIAL DRUGS, DIGOXIN, LITHIUM, CARBAMAZEPINE –AVOID: METFORMIN, NSAID, CYCLOSPORINE, MAGNESIUM

18. DIETARY INTERVENTIONS IN CRF –LOW PROTEIN DIET (?) MDRD STUDY FAILED TO SHOW BENEFIT –LOW-PHOSPHATE DIET (HELPS TO CONTROL HYPERPHOSPHATEMIA AND RENAL OSTEODYSTROPHY) –SUPPLEMENTAION OF FISH OILS (?) PERHAPS HELPFUL IN IGA NEPHROPATHY (CONTROVERSIAL) –SALT RESTRICTION (HELPS TO CONTROL HYPERTENSION AND VOLUME OVERLOAD)

19. PHARMACOLOGICAL INTERVENTIONS IN CRF BLOOD PRESSURE CONTROL –BP GOAL: GENERAL POPULATION 140/90 CKD STAGE 1-4 + PROTEINURIA<1G/DAY 135/85 CKD STAGE 1-4 + PROTEINURIA>1G/DAY 125/75 –ANTIHYPERTENSIVE AGENTS 1) ACEI (ACE INHIBITORS) 2) + DIURETIC + LOW SALT DIET 3) + ATRA (ANGIOTENSIN RECEPTOR ANTAGONISTS) 4) + NDCCB (NONDIHYDROPYRIDINE CALCIUM CHANNEL BLOCKERS) CAVE: ACEI and ATRA are renoprotective via reduction of intraglomerular pressure, which could lead to mild decrease in GFR and mild increase in s-creatinin (not a reason to avoid them!). In older patients and patients with renovascular disease these drugs could lead to severe deterioration of renal function (close monitoring needed, if this happens, avoid them) ACEi and ATRA could cause hyperkalemia (close monitoring needed)

22. SUPPORTIVE CARE AND PREPARATION OF RENAL REPLACEMENT THERAPY SALT, POTASSIUM AND WATER BALANCE –LOW SODIUM, LOW POTTASIUM DIET, DIURETICS SECONDARY HYPERPARATHYROIDISM AND BONE DISEASE –LOW PHOSPHATE DIET, ORAL PHOSPHATE BINDERS –VITAMIN D SUPPLEMENTATION ANEMIA –ERYTHROPOETIN HBV VACCINATION CHOICE OF RRT –HEMODIALYSIS, PERITONEAL DAILYSIS, PRE-EMPTIVE TRANSPLANTATION DIALYSIS ACCESS TIMING OF STARTING DIALYSIS TREATMENT