Chronic Renal Failure(CRF) Shanghai Ruijin Hospital affiliated to Shanghai Second Medical University, Dept.of Nephrology Qian Ying

CRF Definition: final stage of numorous renal diseases resulting from progressive loss of glomerular, tubular and endocrine function in both kidneys. This leads to disturbed excretion of end products of metabolism disturbed elimination of electrolytes and water disturbed secretion of hormones(eg. Erythropoietin, renin, prostaglandins, active form of vitamin D)

CRF Regional and racial incidence of CRF Britain 70-80/per million China 100/per million USA 60-70/per million

CRF overseas china Etiology diabetic nephropathy, hypertensive glomerular sclerosis, chronic GN chronic GN, obstructive nephropathy, diabetic nephropathy overseas china

CRF Pathogenesis (unknown) uremic toxins small molecular weight: urea, creatinine, uric acid, guanidine, phenol, amines, indoles middle molecular weight: PTH large molecular weight: 2-MG

CRF Major hypothesis intact nephron hypothesis final common pathway (hemodynamically mediated glomerular injury)

CRF glomerular injury adaptive single nephron hyperfiltration glomerular capillary plasma flow,  hydraulic pressure Intact nephron hypertrophy and sclerosis

CRF Trade-off hypothesis CRF  Calcium phostate PTH  SHPT  bone,heart,blood,nerves injury Hypertension and compensatory hypertrophy of glomeruli Hypermetabolism of renal tubuli cytokines and lipid disturbances

CRF Stage 1: the normal stage of renal function GFR>70 ml/min, BUN<6.5 mmol/L, Scr<110 umol/L Stage 2:imcompensation stage of renal GFR 50-70 ml/min, 6.5 <BUN< 9 mmol/L, 110 <Scr< 178 umol/L no any signs and symptoms except for the underlying disorders

CRF Stage 3: azotemic stage GFR<50 ml/min,BUN>9 mmol/L Scr>178 umol/L there may be slight fatigue,anorexia and anemia Stage 4: uremic stage GFR<25 ml/min,BUN>20 mmol/L Scr>445 umol/L a constellation of uremic syndrome may appear in this stage

CRF Signs and symptoms of uremia General Gastrointestinal tract Neuropathy Bone Blood Electrolyte disorders Heart Skin Muscles Infection Lung Endocrine and metabolic

CRF

CRF Cardiovascular disorders Hypertension 80% Water and sodium retention Alterations of RAAS Glomerular capillary pressure> systemic arterial pressure

CRF Atherosclerosis hypertriglycerid, hypercholesterolemia vascular calcification inadequate perfusion of the limbs

CRF Pericarditis Signs and symptoms Uremic Dialysis associated Chest pain Friction rub Pericardial effusion and tamponade

CRF Hematologic disorders Causes: Anemia, bleeding, granulocyte, platelet dysfunction Causes: Relative deficiency of erythropoietin Decreased erythropoietin production Reduced red cell survival Increased blood loss Folate and Iron deficiency Hypersplenism

CRF Neuropathy Central nervous system Tiredness, insomnia, agitation, irritability, depression, regression, rebellion Peripheral nervous system Restless leg syndrome the patient’s legs are jumpy during the night, painful paresthesis of extremities, twitching, loss of deep tendon reflexes , musclar weakness, sensory deficits

CRF Renal osteodystrophy Type I: high turn-over bone disease Type II: low turn-over bone disease Type III: mixture

CRF Causes of renal osteodystrophy 1, 25(OH)2D3 calcium phosphate  SHPT malnutrition iron and aluminum overload

CRF

CRF Water, electrolyte and acid-base disturbances potassium  sodium  calcium phosphate  Metabolic acidosis magnesium 

CRF Diagnosis of hyperkalemia Plasma K>5.5mmol/L Plasma K>7.0mmol/L cardiac arrest

CRF

CRF Causes of hyperkalemia Increased intake: rapid adminstration of K by mouth or intravenously Drugs containing K(chinese medical herbs) Impaired excretion Chronic renal failure(GFR<15ml/min)

CRF Causes of hyperkalemia Shift of K out of cells Metabolic acidosis Tissue breakdown Bleeding into soft tissues, GI tract or body cavities Hemolysis Catabolic states

CRF Diagnosis: Case history Physical examination Laboratory studies including urinalysis , renal function tests , biochemical analysis of blood X-ray, ultrosound and radiorenogram

CRF Treatment of CRF Non-dialysis dialysis

CRF Non-dialysis Diet therapy Treatment of reversible factors Treatment of the underlying disease Treatment of complcations of uremia Chinese medical herbs

CRF Diet therapy Protein restriction (0.5-0.8mg/kg/d) Adequte intake of calories(30-35kcal/kg/d) Fluid intake:urine volume +500ml Low phosphate diet(600-1000mg/d) Supplement of EAA(ketosteril)

CRF Reversible factors in CRF Hypertension Reduced renal perfusion (renal artery stenosis, hypotension , sodium and water depletion, poor cardiac function) Urinary tract obstruction Infection Nephrotoxic medications Metabolic factors(calcium phosphate products )

CRF Management of complications of uremia Hyperkalemia Identify treatable causes Inject 10-20ml 10% calcium gluconate 50% gluconate 50-100ml i.v.+insulin 6-12u Infusion 250ml 5% sodium bicarbonate Use exchage resin Hemodialysis or peritoneal dialysis

CRF Cardiac complications Diuretics Digitalis Treat hypertension dialysis

CRF Antihypertensive therapy Target blood pressure 130/85mmHg ACE inhibitors Angiotension II receptor antagonists Calcium antagonists -blockers vesodialators

CRF Treatment of anemia Recombinant human erythropoietin(rhEPO) 2000-3000u BIW H Target hemoglobin 10-12g/L hemotocrit 30-33%

CRF Side effects of rhEPO Hypertension Hypercoagulation Thrombosis of the AVF

CRF rhEPO resistant Iron deficiency Active inflamation Malignancy Secondary hyperparathyroid Aluminum overload Pure red cell aplasia

CRF Treatment of renal osteodystropy Low phosphate diet Calcium carbonate (1-6g/d) Vitamin D (0.25ug/d for prophylactic, 0.5ug/d for symptomatic, pulse therapy 2-4ug/d for severe cases) parathyroidectomy

CRF Renal replacement therapy Hemodialysis Peritoneal dialysis Renal transplantation

CRF Indications of HD GFR<10ml/min the uremic syndrome hyperkalemia acidosis fluid overload

Hemodialysis

Hemodialysis 弥散 Diffussion 渗透 Dialysis

Hemodialysis 超滤 Ultrofiltration 负压 正压 对流 Conduction

Contraindications of HD Shoke Severe caidioc complications Severe bleeding malignency , sepsis poor condition in vascular system

CRF Indications of CAPD child old people with cardiovascular disease dibetic nephropathy trouble of AVF

Cardiovascular disease 治疗 Choice of HD or CAPD poor better Ecnomic situation good Vascular condition Bleeding No bleeding Blood yes no Cardiovascular disease eldly young Age PD HD

CRF Indications of RT maitenance dialysis patients without contraindications of RT age<60 years

CRF Prognosis 5-year survival Home HD 80% RT 60% Hospital HD 60% CAPD 50%

CRF Drug dosing in CRF Redused dose and adminstration interval Ccr(ml/min)=[(140-years old)×body weight(kg)]/[72×Scr(mg/dl)] for female: ×0.85

Acute heart failure in uremia (key treatment?) Diuretics Digitalis Treat hypertension dialysis

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