Chronic Renal Failure(CRF)

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

2. 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)

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

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

5. 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

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

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

8. 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

9. CRF • Stage 1: the normal stage of renal function GFR>70ml/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

10. 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

11. CRFSigns and symptoms of uremia • General • Gastrointestinal tract • Neuropathy • Bone • Blood • Electrolyte disorders • Heart • Skin • Muscles • Infection • Lung • Endocrine and metabolic

12. CRF

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

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

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

16. CRF Hematologic disorders • 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

17. 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

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

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

20. CRF

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

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

23. CRF

24. 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)

25. 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

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

27. CRF Treatment of CRF • Non-dialysis • dialysis

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

29. 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)

30. 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 )

31. 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

32. CRF Cardiac complications • Diuretics • Digitalis • Treat hypertension • dialysis

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

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

35. CRF Side effects of rhEPO • Hypertension • Hypercoagulation • Thrombosis of the AVF

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

37. 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

38. CRF Renal replacement therapy • Hemodialysis • Peritoneal dialysis • Renal transplantation

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

40. Hemodialysis

41. Hemodialysis 弥散 Diffussion 渗透 Dialysis

42. Hemodialysis 超滤 Ultrofiltration 负压 正压 对流 Conduction

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

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

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

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

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

48. 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

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

50. Thank You!