CHRONIC RENAL FAILURE

JAKUB ZÁVADA

KLINIKA NEFROLOGIE 1.LF UK

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)

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 DISEASERRT=RENAL REPLACEMENT THERAPYCRF=CHRONIC RENAL FAILUREGFR=GLOMERULAR FILTRATION RATE

FACTORS AFFECTING PROGRESSION OF CRF

• NONMODIFIABLE RISK FACTORS:– UNDERLYING NEPHROPATHY– AGE, GENDER, RACE, GENES

• MODIFIABLE RISK FACTORS:– PROTEINURIA– HYPERTENSION– GLYCEMIA– LIPIDS– OBESITY– HYPERURICEMIA– SMOKING

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

CLINICAL PRESENTATION OF CRF

• CHRONIC KIDNEY DISEASE (K/DOQI STAGES 2-4)

• ACUTE-ON-CHRONIC RENAL FAILURE

• LATE REFERRAL OF CRF, UREMIC EMERGENCY

COMPLICATIONS AND CONSEQUENCES OF CRF

• CARDIOVASCULAR DISEASE• ANEMIA• RENAL BONE DISEASE• METABOLIC ACIDOSIS• MALNUTRITION• HYPERVOLEMIA• HYPERKALEMIA• BLEEDING DIATHESIS• DERMATOLOGIC MANIFESTATIONS• NEUROLOGIC MANIFESTATIONS• IMMUNOSUPRESSION

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

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)

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 AGENTS1) ACEI (ACE INHIBITORS)

2) + DIURETIC + LOW SALT DIET3) + 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)

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