Chronic Renal Failure

1
Chronic Renal Failure
2
Chronic Renal Failure

• General introduction
• Etiology
• Pathogenesis
• Clinical findings
• Complications
• Diagnosis D.D.
• Treatment

3
General introduction

• 1. CRF is defined as a progressive and
  irreversible loss of renal function. It is a
  serious stage of renal insufficiency.

4
General introduction

• Eliminate wastes and excess water
• maintain water,electrolyte and
• acid-base balance----homeostasis
• strong bone
• RBC formation(erythropoietin)
• control blood pressure(RAAS)

5
General introduction

• Renal function declines
• retention of metabolite
• imbalance of fluid
• electrolyte and acid-base disorder
• harms to other organs(almost every system)

6
General introduction

• CRF is artificially divided into 3
  stages according to glomerular filtration rate
  (GFR NR 80120ml/min).
• Serum creatinine , BUN may reflect GFR in
  some extent.

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stage GFR Scr BUN CM (ml/min) (umol/L ) (mmol/L) (mg/dl) (mg/dl )
Compensatory stage diminished renal reserve Azotemia early renal failure Uremia late RF end-stage RF primary ?50 ?178(?2) ?9(?20) diseases 25-50 ?178(?2) ?9(?20)   GIT symptoms lt 445(lt 5) lt20(lt55) anemia ?25 ? 445(? 5) ?20(?55) uremic ? 10 ? 707 symptoms
8
Etiology

• Any urinary system disease that can impair the
  structure and function of the kidney may cause
  CRF.

9
Causes
Primary GN Secondary nephropathy Obstructive
renal diseases Chronic interstitial
nephropathy Renal vascular diseases Congenital or
genetic renal diseases Unknown reason
10
Causes

• China
• Primary CGN
• Obstructive nephropathy
• Diabetic nephropathy
• Lupus nephritis
• Hypertensive nephropathy
• Policystic disease

• Western
• Diabetic nephropathy
• Hypertensive nephropathy
• Primary CGN
• Policystic disease

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Pathogenesis

• Progressive deterioration of renal function
• chronic renal disease is rarely reversable
  and leads to progressive decline in renal
  function.this occur even after an inciting event
  has been removed.
• Mechanism of uremic symptoms

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Pathogenesis
Progressive deterioration of renal function

• Intact nephron hypothesis
• The trade off hypothesis
• Glomerular hyperfiltration hypothesis
• Tubular hypertrophy hypothesis
• Otherslipid disorder,Coagulation disorder,etc.

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Pathogenesis
Progressive deterioration of renal function

• Intact nephron hypothesis
• considerable amount of nephrons has been
  impaired,remaining nephrons still work,but
  reduction in renal mass leads to hypertrophy of
  the remaining nephrons to meet the bodys need.
  Unfortunately these adaptations place a burden on
  the remaining nephrons and leads to progressive
  glomerular sclerosis and interstitial fibrosis.

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Pathogenesis
Progressive deterioration of renal function

•    The trade off hypothesis

The trade off hypothesis is to be considered
together with the intact nephron
hypothesis,i.e,the concept that adaptations
arising in chronic renal failure may control one
abnormality,but only in such a way as to produce
other changes characteristic of the uremic
syndrome.
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Pathogenesis
Progressive deterioration of renal function
   The trade off hypothesis example

• GFR

serum phosphate
Metastatic calcification Nervous
diseases Impotence Myopathy And so on
regulation
PTH harmful
serum phosphate normal (phosphate rising
corrected)
16
Pathogenesis
Progressive deterioration of renal function

• Glomerular hyperfiltration hypothesis

• hypertrophy of the remaining nephrons
  high filtration, high perfusion and high pressure
  in glomeruli which will lead to glomerular
  sclerosis and injure the remaining nephrons.

17
Pathogenesis
Progressive deterioration of renal function

• Tubular hypertrophy hypothesis
• although this adaptive mechanism can be
  beneficial in maintaining fluid, electrolyte and
  acid-base balance, long term consequence is
  perpetuation of tubular damage. Tubular
  hypertrophy is usually associated with increased
  energy expenditure and high metabolism.

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Pathogenesis
Progressive deterioration of renal function

• Others
• lipid disorder
• Coagulation disorder
• etc.

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Pathogenesis
Mechanism of uremic symptoms
Water electrolyte disorder
Acid-base imbalance
Uremic toxins
Uremic symptoms
Uremic toxins Decreased depletion of metabolic
products. Urea,creatinine,phosphate,sulphate,guani
dines,products of nucleic acid metabolism(UA,cAMP
),phenol compounds,hormones(PTH),middle molecules
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Clinical findings
Symptoms and signs

• The symptoms of CRF often develop slowly and are
  nonspecific.Individuals can remain asymptomatic
  until renal failure is far-advanced.(GFRlt1015ml/m
  in )
• In any patient with renal failure,it is important
  to identify and correct all reversible causes.

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Organ/system symptoms
signs
General fatigue weakness
Sallow-appearing chronically ill
Skin pruritus easy
bruisability pallor ecchymoses
excoriations

edema xerosis
ENT
pale conjuctiva
Pulmonary shortness of breath
rales pleural effusion
Cardiovascular dyspnea on exertion
hypertension cardiomegaly
pain on inspiration
friction rub
Genitourinary nocturia impotence
isosthenuria
Neuromuscular restless legs numbness
and cramps in legs
Neurologic generalized irritability
stupor asterixis myoclonus
and inability to concentrate
peripheral neuropathy
decreased libido
22
GFR
corrected
years
Reversible causes
Nephrotoxins Hypertension Congestive HF
Hypercalcemia Pregnancy e.t.c.
Urinary tract infections Obstruction Extracellular
volume depletion
23
Clinical findings
Laboratory findings

• Urinalysis early in the course of chronic renal
  failure provide valuable information,but late in
  renal failure urinary abnormalities are less
  conspicuous.

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Clinical findings
Laboratory findings

• Proteinuria
• Red cells
• Casts red cell casts
• granular and hyaline
  casts
• large chronic RF
  cast(wax)
• glycosuria

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Clinical findings
imaging

• The findings of small echogenic kidneys
  bilaterally(lt10cm) by UCG supports a diagnosis of
  CRF
• Though normal or even large kidneys can be seen
  with CRF caused by adult polycystic kidney
  disease,DN,multiple myeloma,amyloidosis and
  obstructive uropathy.
• Radiologic evidence of renal osteodystrophy is
  another helpful findings.

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Complications

• Water,electrolyte disorder
• Acid-base disorder
• Cardiovascular complications
• Hematologic complications
• Gastrointestinal complications
• Musculo-skeletal problems
• Skin
• Endocrine
• Metabolic disorder
• Immune system

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Water,electrolyte disorder

• Water retention or dehydration
• hyponatremia or hypernatremia
• Hyperkalemia or hypokalemia
• Hypocalcemia
• Hyperphosphatemia
• magnesium

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Hyperkalemia
Water,electrolyte disorder

• Risk of hyperkalemia (NR 3.55.5mmol/L)
• cardiac conduction system inhibition
• bradycardia,AVB,escape rhythm,heart arrest
• Potassium balance generally remains intact in CRF
  until GFR is less than 10ml/min.However,certain
  states pose an increased risk of hyperkalemia at
  higher GFRs.

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Hyperkalemia (normal distridution )
Water,electrolyte disorder

• Decreased potassium excretion
• Acidosis.
• Blood transfusion.
• Increased potassium intake.
• Drugs---spironolactone

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case

• 58ys Female,DM for 15ys ,BP for 5 ys
• severe edema ,urine output decreased for 2Ms
• Diagnosis DM DN CRF(uremia)
• Refuse to accept dialysis
• Conservative treatment, symptom not released
• Felt weakness HR45bpm,BP90/40mmHg
• Cardiac monitor

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Emergency!

• ECGjunctional escape rhythm
• Serum K6.8mmol/L,Na125mmol/L
• HCO311mmol/L

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Hyperkalemia Treatment

• Cardiac monitoring, decrease K intake
• 1.Correct acidosis
• 2.Calcium chloride (act against the inhibition on
  cardiac conduction system)
• 3.Insulin administration with glucose
• 4.An orally or rectally administered ion exchange
  resin(sodium potassium exchange)
• 5.!Kgt6.5mmol/L urgent dialysis

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Acid-base disorder (death rate)

• Filtration of titratable acid decreased
• Tubular H secretion decreased
• NH4 formation decreased
• Osteodystrophy
• Hyperkalemia
• Uremic symptoms(GIT,cardiovascular,pulmonary)

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Acid-base disorder

• Deep breath(kussmauls breath),bad appetite vomit
  ,weakness,coma, HF, BP decrease
• PH ,CO2CP HCO3-

Treatment HCO3- should be maintained at
1820mmol/l Sodium bicarbonate ivdrip or po
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Cardiovascular complications

• Hypertension
• Pericarditis
• Congestive heart failure
• Othersatherosclerosis

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Cardiovascular complications

• Hypertension
• Most common complication of ESRD must be
  properly controlled.
• due to
• Salt and water retention
• Hyperreninemic states(RAS)

37
Cardiovascular complications

• Treatment
• A.salt water restriction(case)
• a mildly decreased salt diet(46g/d)
• if hypertension persists, reduced to
  2g/d
• B. Drug therapy
• ACE inhibitors ARB are the first
  recommendation if serum potassium and GFR permit.
• CCB agents,diuretics,and ß-blocking
  agents.
• adjunctive drugs that are often needed
  reflect the difficulty of achieving and
  maintaining hypertensive control in these
  patients.

38

• 28ys,female,headache for 2 months ,GIT disorder
• Hypertension found,200/130140mmHg,
• Family historynegative
• urine test blood 2, Pr 2 blood test Hb
  88g/L
• serum test Cr 596umol/L
• Kidney imagelength 88mm 92mmecho changes

Cr 600 400 200
BP 200/140
case
Main treatmentBP control Diet Six drugs were
taken
BP140/90
BP138/85
2 years
hospitalization
39

• 32ys, female,found hypertension in pregnancy
• urine Pr3,blood 3,gave birth after 8Ms
  pregnancy (infant died right after delivery)
• suffer ARF,got recovery,but renal lesion still
  exited.
• SCr 200umol/L,drugs taken for BP controlling.
• After hospitalization
• Ignore her desease, Drugs withdrawal
• 1.5 year later,back to hospital
  again,complained about anorexia,vomitting,fatigue,
  bad memory,cramp occasionally BP 170/100mmHg
• TestsHb 54g/L,BUN 55mmol/L,SCr 1002umol/L, K
  5.6mmol/L,Na128mmol/L,Ca2 1.7mmol/L,HCO3-
  12mmol/L.

case
40

• Failure to control BP can accelerate the
  progression of renal damage.

41
Cardiovascular complications

• hypertension
• retention of fluid
• uremic cardiomyopathy

Heart failure
treatment
Water salt intake (oliguria
auria) Dialysis(remove excess water) Diuretics Dig
oxin ACEI (is proved to be efficient)
42
Cardiovascular complications
Pericarditis

• retention of metabolic toxins
• prolonged bleeding time declined function of
  platelet and decreased amount of platelet.
• Chest pain,fever,signs of poor cardiac output a
  friction rub may be auscultated, X-ray,UCG
• Pericarditis is an absolute indication for
  initiation of hemodialysis.

43
Pulmonary effects

• A. pulmonary edema.
• B. Pneumonitis.
• C. Pleuritis.
• Dialysis is needed.

44
Hematologic complications

• Anemia
• Bleeding
• WBC dysfunction

45
Hematologic complications
anemia

• Normochromic and normocytic anemia
• decreased erythropoietin production
• Iron intake decreased
• Bleeding
• RBC life span shortened
• BM suppression

46
Hematologic complications
anemia
Iron, folic acid, VitB12
ingestion
GIT disorder
RBC life span 120days
Spleen old RBC disrupted
BM RBC formation EPO needed
RBC 80days
bleeding
EPO decreased BM suppression
47
Hematologic complications
Anemia treatment

• Recombinant EPO is used in patients
• 2050units/kg(10004000u/dose)
• subcutaneously injection or iv.
• three times a week.
• Iron stores must be adequate to ensure
  response.(folic acid,VitB12)

48
Hematologic complications

• Bleeding
• Bruising,epistaxis,menorrhagia,hemorrhagic
  pericardial effusion.
• It is mainly caused by platelet dysfunction.
• Treatmentdialysis
• WBC dysfunction prone to infection

49
Gastrointestinal effects

• Gastrointestinal disturbances are among the
  earliest and most common signs of the uremic
  syndrome.
• metabolic taste and loss of appetite Later,
  nausea and intermittent vomiting, even
  gastrointestinal bleeding may occur. Gastritis,
  peptic ulcer.

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Neuro-Muscular manifestations

• Early manifestations weakness insomnia
  concentration dysorder
• Late character changes,bad memory,
  dumps,cramp,jerk,delirium,convulsion, coma

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osteodystrophy

• Osteitis fibrosa
• Osteomalacia
• Osteoporosis
• Osteosclerosis
• Active VitD3 deficiency
• Secondary PTH
• Malnutrition
• others

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osteodystrophy
treatment

• Active VitD3 Osteitis fibrosa myopathy
• 0.25-1.0µg/d
• Surgery Osteomalacia Osteoporosis
• Osteosclerosis
• parathyroid

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skin

• Pruritus.
• Yellow pigmentation.

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Endocrine abnormalities

• A. Plasma renin concentration is normal or
  increased.
• B. EPO is decreased.
• C. 1,25-(OH)2VitD3 is decreased.
• D. Insulin, parathyroid hormone and glucagon
  are increased.
• E.  Hypogonadism.

56
Metabolic disorders

• A. low temperature.
• B. Abnormality of glucose metabolism.
• a. Fasting blood sugar is high in some cases,
  because peripheral insulin resistance is
  increased.
• b. Diabetes patients have a decrease in their
  insulin requirements.
• C. Hyperuricemia.

57
Infection immune system

• Prone to infection
• Dysfunction of WBC
• Lower amount of WBC
• Decreased immune function

58
Diagnosis and differential diagnosis

• chronic renal failure(stage)
• Primary disease
• Risk factors(reversible)
• complications

59
Diagnostic route
CRF or not?
stage?
early
azotemia
late
ESRD
causes
Risk factors
complications
60
Treatment

• Primary diseases and risk factors.
• Dietary treatment
• ?-keto acid use
• BP control
• Complications
• Cautious about the side effect of drugs.
• Dialysis
• Renal transplantation

61
Causes
Primary GN Secondary nephropathy Obstructive
renal diseases Chronic interstitial
nephropathy Renal vascular diseases Congenital or
genetic renal diseases Unknown reason
62
Causes

• China
• Primary CGN
• Obstructive nephropathy
• Diabetic nephropathy
• Lupus nephritis
• Hypertensive nephropathy
• Policystic disease

• Western
• Diabetic nephropathy
• Hypertensive nephropathy
• Primary CGN
• Policystic disease

63
Risk factors
GFR
corrected
years
Reversible causes
Nephrotoxins Hypertension Congestive HF
Hypercalcemia Pregnancy e.t.c.
infections Obstruction Extracellular volume
depletion
64
Dietary treatment

• A.   Dietary protein restriction
• It can decrease BUN, plasma phosphate
  concentration and relieve acidosis. But if
  protein intake is too low, malnutration may
  occur. Generally, dietary protein should be
  restricted properly when GFR is lower than
  50ml/min.
• Pr amount 0.6g/kg
• high quality Pr(animal Pr)

65
Dietary treatment

• B. Diet must consist of enough calories and
  plenty of VitB, VitC and   lactate.
• C. Water and sodium must be restricted if
  patients have edema, HP, heat failure or
  oliguria
• D. potassium must be restricted when urine
  volume is less than 1L/d and phosphate should be
  restricted at azemia stage.

66
?-keto acid use

• ?-keto acid can combine with nitrogen to form EAA
  and EAA can combine with urea to synthesize
  protein, so, using ?-keto acid can decrease BUN.

67
BP control

• Systamic BP control
• Intraglomerular pressure control
• relieve hyperfiltration
• ACEI or ARB
• SCrgt350umol/L cautious

68
complications
69
Treatment

• Dialysis
• GFRlt10ml/min
• SCrgt707umol/L
• peritoneum D, haemodialysis
• Renal transplantation

70
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76
case

• 58ys Female,DM for 15ys ,BP for 5 ys
• severe edema ,urine output decreased for 2Ms
• Diagnosis DM DN CRF(uremia)
• Refuse to accept dialysis
• Conservative treatment, symptom not released
• Felt weakness HR45bpm,BP90/40mmHg
• Cardiac monitor

77
Emergency!

• ECGjunctional escape rythum
• Serum K6.8mmol/L,Na125mmol/L
• HCO311mmol/L

78
Case 1 Hu fenlan, female, 68ys

• Edema for 30ys, fatigue and anorexia for 2Ms
• 30ys ago, edema on legs was found when she was in
  pregnancy.10ys ago, HP was found. Nocturnal urine
  output has been increased for 3ys. 2Ms ago,
  suffered fatigue, anorexia, nausea and vomiting.
  Pruritus and arthralgia occurred.

79

• Physical examination p,92/min, uremic face,the
  cardiac dullness distending to the left, systolic
  murmurs heard on mitral area,percussion pain on
  right renal area.
• Lab tests
• renal functionBUN 27.8mmol/l, CRE 766?mol/l
• blood gas acidosis
• electrolytes plasma Na, k, Cl-, Ca2
  decreased.
• x rays left ventricle enlarged
• abnormalities of bone

80
Case 2 zhang tao, femal/ 34ys

• Fatigue, anorexia and menorrhagia for 4Ms.
• 4Ms ago, felt fatigue and dizziness accompanied
  by menorrhagia. And then, palpitation , dyspnea,
  anorexia and nausea occurred gradually. One week
  ago, Bp 170/110mmHg , BUN 22.6mmol/l, Cre 835
  ?mol/l.
• Physical examination the positivfindings were
  same as case 1.
• Lab tests plasma k P high, RBC and Hb low.