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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
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
Water, electrolyte and acid-base disturbances
• potassium sodium • calcium phosphate • Metabolic acidosis
• magnesium
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
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
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
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
Indications of HD
• GFR<10ml/min
• the uremic syndrome
• hyperkalemia
• acidosis
• fluid overload
Contraindications of HD
• Shoke
• Severe caidioc complications
• Severe bleeding
• malignency , sepsis
• poor condition in vascular system
Choice of HD or CAPD
poorbetterEcnomic situation
poorgoodVascular condition
BleedingNo bleedingBlood
yesnoCardiovascular disease
eldlyyoungAge
PDHD
治疗
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