Chronic Renal Failure(CRF)

Shanghai Ruijin Hospital affiliated to Shanghai Second Medical University,

Dept.of Nephrology

Qian Ying

CRFDefinition: final stage of numorous renal diseases resulting fr

om 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, pr

ostaglandins, 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

Etiology

diabetic nephropathy, hypertensive glomerular sclerosis, chronic GN

chronic GN, obstructive nephropathy, diabetic nephropathy

overseas

china

CRFPathogenesis (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)

CRFglomerular injuryglomerular injury

adaptive single nephron hyperfiltrationadaptive single nephron hyperfiltration

glomerular capillary plasma flow, hydraulic pressureglomerular capillary plasma flow, hydraulic pressure

Intact nephron hypertrophy and sclerosisIntact 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 t

his stage

CRFSigns 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, hypercholesterolemiahypertriglycerid, hypercholesterolemia

vascular calcificationvascular calcification

inadequate perfusion of the limbsinadequate perfusion of the limbs

CRF

Pericarditis• Uremic• Dialysis associated

Signs and symptoms• Chest pain• Friction rub• Pericardial effusion and tamponade

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

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 extre

mities, twitching, loss of deep tendon reflexes , musclar weakness, sensory deficits

CRF

Renal osteodystrophyType I: high turn-over bone diseaseType II: low turn-over bone diseaseType 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 b

y 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, hyp

otension , sodium and water depletion, poor cardiac function)

• Urinary tract obstruction• Infection• Nephrotoxic medications• Metabolic factors(calcium phosphate products )

CRFManagement 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 f

or 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

对流 Conduction

正压 负压

Contraindications of HD

• Shoke

• Severe caidioc complications

• Severe bleeding

• malignency , sepsis

• poor condition in vascular system

CRF

Indications of CAPDchildold people with cardiovascular diseasedibetic nephropathytrouble of AVF

Choice of HD or CAPD

poorbetterEcnomic situation

poorgoodVascular condition

BleedingNo bleedingBlood

yesnoCardiovascular disease

eldlyyoungAge

PDHD

治疗

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(k

g)]/[72×Scr(mg/dl)] for female: ×0.85

Acute heart failure in uremia (key treatment?)

• Diuretics

• Digitalis

• Treat hypertension

• dialysis