Acute Renal Failure

Qiu bo
May, 2009
 General considerations
 Rapid decline in the GFR over days to
weeks.
 Inability to maintain fluid and
electrolyte and to excrete
nitrogenous wastes
 Cr increases by 88.4-132.6umol/L
daily
 GFR <10mL/min, or <25% of normal
 Definitions
Anuria: urine<100ml/d
Oliguria: urine<400 mL/d
Azotemia: Incr Cr, BUN
 May be prerenal, renal, postrenal

Chronic Renal Insufficiency

 Deterioration over months-years

 GFR 10-20 mL/min, or 20-50% of

normal
ESRD = GFR <5% of normal
 Etiology
 Separation to three broad categories is
of great clinical utility
 Preranal faiture:
a.ture volume
depletion(diarrhea,vomiting,or other
hemorrhage)
b.effective circulatory volume depletion
 Postrenal faiture
is due to urinary tract
obstruction(stone)
multisclrosis
 Intrinsic acute renal failure
acute tubular necrosis(ATN) accounts
for 85%
Causes of ARF in hospitalized

45% ATN
 Ischemia, Nephrotoxins

21% Prerenal
 chronic heart failure (CHF), volume

depletion, sepsis
10% Urinary obstruction
4% Glomerulonephritis or vasculitis
2% acute interstitial nephritis (AIN)
Etiology of ARF among Outpatients

Prerenal (70%)
Intrarenal (11%)
Obstruction(17%)
idiopathic(2%)
Etiology of ARF among Inpatients

ATN (45%)

Prerenal (21%)

ARF on CKD (13%)

Obstruction (10%)

GN/vasc (4%)

AIN (2%)

Atheroemboli (1%)
Acute Renal Failure

pathogenesis
 pathogenesis
 The course of ischemic ARF is
typically characterized by three
phases:
1. initiation
2.maintenance
3. recovery
 Initiation phase
 Renal hypoperfusion, and glomerular
ultrafiltration rate reduce
 Cause:
1.glomerualr ultrafiltration pressure is
reduced as a result of the fall in renal flow
2.the flow of glomerular filtrate with in the
tubule is obstructed by casts comprised of
epithelial cells and necrotic debris
3.backleak of glomerualr filtrate through
injured tubular epithelium
 initiation
 Importantly, renal injury can be
limited by restoration of renal blood
flow during this period
 maintenance
 Duration is about 1-2 weeks
 Renal cells injury are established
 GFR is stabilized at 5-10 ml/min
 Urinary output become lowest
 Serum concentration of Cr and BUN
are elevated
 Recovery phase
 Chracterized by renal parenchymal cells
and epithelial cells injury are repaired, and
a gradual return of GFR
 Complicated by marked diuretic phase due
to excretion of retained salt and water and
other solutes
 The epithelial cells ability to reabsorption
of salt and water are subnormal relative to
glomerular filtration
 ARF: Signs and Symptoms
 Hyperkalemia (cause arrhythmias)
 Nausea/Vomiting
 Malaise
 Pericardial effusion
 Pulmonary edema
 bleeding
 Encephalopathy
 ARF: Focused History
 Nausea? Vomiting? Diarrhea?
 History of heart disease, liver disease,
previous renal disease, kidney stones, benign
prostate hypertrophy(BPH)?
 Any recent illnesses?
 Any edema, change in
urination?
 Any new medications?
 Any recent radiology studies?
 Rashes?
 Physical Exam
 Mucosa and skin
rashes, pale
 Volume Status
• Mucus membranes (edma), orthostatic hypotension
 Cardiovascular
• Heart rate, rhythm,extant of cardiac outline, friction
rubs
 Pulmonary
• Decreased breath sounds
• Rales
 Rash or pain on the flank (Allergic interstitial nephritis)
 Large prostate palpation (size and rigidity)
 Laboratory findings
 Serum analysis
a.Creatinine and urea rise rapidly
b.anemia: usually mild
c.hyperkalemia,hyperphosphatemia,hy
pocalcemia,and elevation in serum
uric acid and creatine kinase
d.Metabolic
acidosis:PH<7.35,bicarbonate<20m
mol/l
 Laboratory findings
 Urinalysis
a.Oliguric or anuria
b.sediment:muddy browm granular casts or
containing tubule epithelial cell, microscopic
hematuria and proteinuria
c.gravity<1.015
d.Urine sodium concentration >20mmol/l
e.Urine osmolality<300mosmol/kg H2O
f.Urine creatinine to plasma creatinine ratio<20
g.Urine urea nitrogen to plasma ratio<3
h.Fractional excretion of sodium>1
 Laboratory findings
 Radiological findings
 Ultrasonography tomography and
magnetic resonance imaging are useful to
exclude postrenal ARF
 Retrograde or anterograde pyelography
are definitive investigation in complex
cases and provide precise localization of
the obstruction
 Doppler ultrasonography and MRI are
useful for assessment of renal arteries and
veins with suspected vascular obstruction
 Laboratory findings
 Renal biopsy
a.be reserved for patients in whom prerenal
and postrenal ARF have been excluded
and the cause of intrinsic renal ARF is
unclear
b.Particularly useful when clinical
assessment suggest diagnoses other than
ischemic or nephrotoxic injury that may
repond to disease-specific therapy
 Diagnosis
 Acute? Or chronic?
 Anema , neuropathy, and radiologic
evidence of renal osteodystrophy or
small scarred kidneys
 nail creatinine indicate the level of
creatinine 2-3months before
suggest chronic renal failure
 Prerenal causes
 Intravascular volume depletion
• Hemorrhage
• Vomiting, diarrhea
• “Third spacing”
• Diuretics
 Reduced Cardiac output
• Cardiogenic shock, CHF, tamponade, huge
PE....
 Systemic vasodilation
• Sepsis
• Anaphylaxis( 过敏反应） , Antihypertensive
drugs
 ATN Prerenal

Cr(mg/dl) increases at 0.3- increases

0.5 /day slower than
0.3 /day
U UNa>40 UNa<20
Na(mmol/l), FeNa >2% FeNa<1%
FeNa
UA epi cells, Normal
granular casts
Response to Cr won’t Cr improves
volume improve much with IVF
BUN/Cr 10-15:1 >20:1
A 22yo male with sickle cell anemia
and abdominal pain who has been
vomiting nonstop for 2 days.
BUN=45mmol/l,
Cr=2.2mg/dl(195umol/l).
A. ATN
B. Glomerulo-
nephritis
C. Prerenal ARF
D. AIN from
NSAIDs
Hyaline casts
 Intrinsic ARF

1. Tubular (ATN)
2. Interstitial (AIN)
3. Glomerular
(Glomerulonephritis)
4. Vascular
 Intrinsic ARF

• Glomerulonephritis is often accompanied

by hypertension and moderate edema
• Urine sediment is most helpful to
differentiate from prerenal causes, RBC,
WBC, and cellular casts are
characteristic of GN
• WBC or eosinophil of the urine always
indicate allergic interstitial nephritis
 ATN
 Muddy brown granular casts (last
slide)
 Renal tubular epithelial cell casts
 More ATN
•Broad casts (form in dilated, damaged tubules)
 ATN Causes
1. Hypotension
 Relative low BP

 May occur immediately after low BP

episode or up to 7 days later!

2. Infection or Ischemia
3. Crystal precipitation
4. Myoglobinuria
5. Aminoglycosides (10-26%)
 ATN
 Gravity 1.010, 5-10 renal tubular cells,
many granular casts, occasional renal
tubular cell casts, no eosinophil
 Dilute urine: failure to concentrate urine
 No RBC casts or WBC casts in ATN
RBC cast
WBC Casts

Cells in the cast

have nuclei （细胞
核）
(unlike RBC casts)

especially for Acute

Interstitial
Nephritis
 Acute Interstitial Nephritis

70% Drug hypersensitivity

 PCNs (Methicillin), Cephalosporins

 Sulfa drugs

 NSAIDs

 Allopurinol... （别嘌呤醇）

15% Infection
 Streptococcus, CMV, other bact/viruses

8% Idiopathic
6% Autoimmune
 AIN from Drugs
 Renal damage is NOT dose-dependent
May take place soon after initial exposure to low-
dose drug

 Fever (27%)
 Serum Eosinophilia (23%)
 papular rash (15%)

 Bland sediment or WBCs, RBCs, non-nephrotic

proteinuria
 WBC Casts are pathognomonic!
 Urine eosinophils on Wright’s Stain
 AIN Management
 Remove offending agent
 Most patients recover full kidney
function in 1 year
 Poor prognostic factors
• ARF > 3 weeks
• Advanced age at onset
You evaluate a 32 yo woman with HTN, oliguria,
and rapidly increasing Cr, BUN. You spin her
urine:

A. ATN
B. Acute
glomerulonephriti
s
C. Acute interstitial
nephritis
D. Nephrotic
Syndrome
 Acute Glomerulonephritis
 RBC casts: cells have no nuclei
 Casts in urine: think INTRINSIC
renal disease
 If she has Lupus or have recent
viral prodrome, think Rapidly
Progressive Glomerulonephritis
 If she had a sore throat 10 days
ago, think Postinfectious
Proliferative Glomerulonephritis
 Rapidly Progressive Glomerulonephritis

Type 1: Anti-GBM dz
Type 2: Immune complex
 IgA nephropathy
 Postinfectious glomerulonephritis
 Lupus nephritis
 Mixed cryoglobulinemia
Type 3: Pauci-immune
 Necrotizing glomerulonephritis (often ANCA-positive, assoc.
w/vasculitis)

Can present with viral-like prodrome

 Myalgias, arthralgias, back pain, fever, malaise

Kidney bx : Extensive cellular crescents with or w/o immune

complexes
Can develop ESRD in days to weeks.
Treat w/glucocorticoids & cyclophosphamide.
 Postinfectious Proliferative
Glomerulonephritis
 Usually after strep infxn of upper
respiratory tract or skin – 8-14 day latent
period
 Hematuria, Hypertension, edema,
proteinuria
 Positive antistreptolysin O titer (90%
upper respiratory and 50% skin)
 Treatment is supportive
• Screen family members with throat culture
and treat with antibiotics if necessary
 Microvascular ARF
 TTP/HUS
 HELLP syndrome
 Platelets form thrombi and deposit in
kidneysGlomerular capillary
occlusion or thrombosis
 Plasma exchange, steroids
Why do his toes look like this?
 Post-Renal ARF

• Urethral obstruction: prostate, urethral

stricture.
• Bladder calculi or neoplasms.
• Pelvic or retroperitoneal neoplams.
• Bilateral ureteral obstruction
(neoplasm,
calculi).
• Retroperitoneal fibrosis.
 treatement
 Aim:hastening recovery and avoiding
complication
 Avoiding volume overload and
hyperkalemia
 Dopamine “renal dose” 0.001-
0.003ug/kg.min can increase renal blood
flow but also potentiate arrhythmias and
myocardial ischemia
 Furosemide(20-160mg/d) convert oliguric
to nonoliguric renal failure
 treatement
 Nutritional support:dietary protein
restriction of 0.6g/kg.d to prevent
metabolic acidosis
 Restriction of salt and water
salt 2-4g/d, water intake=urine
volume+500ml
 Treatment of heart failure
restriction of water and salt, digoxin,
diuritics, dialysis
 treatement
 Control hypocalcemia and hyperphosphatemia:aluminum
hydroxide and calcium carbonate can be used
 Treatment of anemia and haemorrhage
a.Hb<70g/l, blood transplant should be do
b.found out gastrointestinal hemorrhage as early as possible
 Treatment of infection
a.the leading cause for death
b.select antibiotics according to culture and microbe
sensitivity
c. and no nephrotoxic
 Dosages must be adjusted according to the estimated
degree of renal impairment for drugs eliminated by the
kidney
 Indications for acute dialysis
 Acidosis (metabolic)
hydrocarbonate<13mmol/l, PH<7.25
 Life threatening Electrolytes (hyperkalemia)
>6.5mmol/l
 Cr>442umol/l, BUN>21.4mmol/l
 Anuria>2d, or oliguria>4d
 Volume overload (fluid)
acute heart failure, pulmonary edema
 Uremia
vomit complications(encephalopathy,pericarditis)
 prognosis
 Nonoliguric acute tubular necrosis has a
better outcome
 Mortality rate is 20-50% in medical illness
and up to 70% in a surgical setting.
 Increased mortality is associated with
:advanced age,severe underlying
disease,and multisystem organ failure
 Leading cause of death are infection.
 Mortality rate have not changed
significantly over 20 years