Acute Renal Failure

Acute Kidney Injury

(ARF and AKI)

History
„ More than 35 definitions in literature
… Ischuriarenalis, in 1802
… Acute Bright’s disease, William Osler’s Textbook for
Medicine (1909)
… War nephritis, World War I
… Crush syndrome, World War II
… Acute renal failure, The Kidney–Structure and
Function in Health and Disease (1951)
… Acute kidney injury (AKI) - RIFLE, 2004
… Modified version of the RIFLE- AKIN, 2007
Definition

„ Acute renal failure (ARF) is an abrupt

decrease in kidney function that results in
accumulation of nitrogenous solutes and
severe derangements in electrolyte and acid
base physiology.
… Oliguric
… Nonoliguric (urine output is normal or increased
while solute clearance is markedly decreased)
Definitions

„ Azotemia – silent
„ Uremia – symptomatic
„ Oliguria - < 400 mL/24
„ Anuria - < 100 mL/24 h
„ Nonoliguric ARF - > 400 ml / 24 h
Mortality in AKI

Liano et al, 1996

AKI and Mortality (Brigham and Womens, 9210 adults
Multivariable Odds Ratio for Death

„ AKI (Δ in SCr >0.5) 6.5 <0.0001

„Age (per 10 yr) 1.7 <0.0001
„CKD 2.5 <0.0001
„CV dis. 1.5 <0.04
„Respiratory dis 3 <0.0001
„GI dis. 2.4 <0.001
„Cancer 2.9 <0.0001
„Infection 7.5 <0.0001
Chertow et al, JASN 16:3365-70;
2005
Classification

40-70% 10-50%

10%
Etiology-Prerenal
„ Hypovolemia
… Hemorrhage
… Skin losses (burns, sweating)
… Gastrointestinal losses (diarrhea, vomiting)
… Renal losses (diuretics, glycosuria)
… Extravascular pooling (peritonitis, burns)
„ Ineffective arterial volume
… Congestive heart failure
… Neurogenic hypotension
… cardiac arrhythmias
… sepsis
… anaphylaxis
… liver failure
„ Vascular disease:
… Renal artery stenosis
Intrinsic Renal Azotemia
„ Large Renal Vessel Disease
Thrombo-embolic disease
„ Renal Microvasculature and Glomerular Disease
Inflammatory: glomerulonephritis, allograft rejection
Vasospastic: malignant hypertension, scleroderma crisis, pre-
eclampsia, contrast
Hematologic: HUS-TTP, DIC
„ Tubulo-interestitial Disease
Acute Interestitial Nephritis (AIN), Acute cellular allograft rejection,
viral (HIV, BK virus), infiltration (sarcoid)
„ Intratubular Obstruction
myoglobin, hemoglobin, myeloma light chains, uric acid, tumor lysis,
drugs (indinavir, acyclovir, foscarnet, oxalate in ethylene glycol
toxicity)
Etiology-Intrarenal/Intrinsic
„ Intrinsic parenchymal damage of kidney

Acute Tubular Necrosis (ATN)

„ Ischemia to the renal parenchyma
„ Nephrotoxic drugs
Etiology-Intrarenal/Intrinsic
„ Acute Tubular Necrosis (ATN)
… Vascular
… Glomerulus
… Tubuluar injury
… Ischemia
… Endogenous proteins
… Intratubular crystals
Etiology-Postrenal
„ Upper urinary tract (proximal to the bladder)
„ Lower urinary tract (obstruction occurring at
the bladder outlet or urethra)
… Stones

… Blood clots
… Prostate disease
… Bladder disease
 80
GFR
(mL/min)
40

6
Serum
4
Creatinine
(mg/dL)
2

0
0 7 14 21 28
Days
Figure: The abrupt drop in GFR but the S.Cr. does not start going up
for 24 or 36 hours after the acute insult .
the Acute Dialysis Quality Initiative group(2004)
Continuum of the renal injury

STAGEI I
STAGE STAGEIIII
STAGE
STAGEIIIIII
STAGE STAGEIV
STAGE IV STAGEVV
STAGE
LOSS
LOSS ESRD
ESRD
INJURY
INJURY FAILURE
FAILURE (L)
(L) (E)
(E)
RISK
RISK (I)
(I) (F)
(F)
(R)
(R)

Severity Outcome
RIFLE criteria/staging system
Definition of AKI based on “Acute Kidney
Injury Network” (AKIN-2007)

Stage Increase in Serum Creatinine Urine Output

1 1.5-2 times baseline <0.5 ml/kg/h for >6 h
OR
0.3 mg/dl increase from baseline
2 2-3 times baseline <0.5 ml/kg/h for >12 h

3 3 times baseline OR <0.3 ml/kg/h for >24 h

0.5 mg/dl increase if baseline>4mg/dl OR
OR Anuria for >12 h
Any RRT given
Correlation between the definition
grade and observed mortality
 PaO2
50 mm of Hg

PaO2
20 mm of Hg

PaO2
10 mm of Hg

Schrier, R (Comprehensive Clinical Nephrology,2003)

Schrier, R (Comprehensive Clinical Nephrology,2003)
Pathology and Pathophysiology
„ Vasoconstriction of the arteriole
„ Tubule cell denaturalization and
necrosis

The urine sediment of a patient

with acute intrinsic renal failure
from sepsis
Goldman: Cecil Textbook of
Medicine, 21st ed
 RBC cast

Hyaline cast Granular cast

Granular cast
Granular cast
WBC cast

Oval fat body WBC cast

and Hyaline cast
ATN

Sloughed Tubular Epithelial Cells

Normal renal tubules
Intratubular casts
Clinical manifestation
Oliguric and Anuria phase

„ Average, 10 to 14 days , main phase of

the AKI
„ Urine findings: RBC casts, granular
casts, RBCs, WBCs, proteinuria
Clinical manifestation
Oliguric and Anuria phase
„ Imbalance of water, acid-base and electrolytes
… Water intoxication: weight gain and tissue edema, heart failure,
hypertension, brain edema
… Hyperkalemia: most serious consequences of ARF, can cause
arrhythmias
… Hypermagnesemia: be always accompanied by hyperkalemia
… Hyperphosphatemia, hypocalcemia-- nervous irritability
… Hyponatremia
… Hypochloremia: be accompanied by hyponatremia
… Metabolic acidosis
Clinical manifestation
Oliguric and Anuria phase

„ Accumulate of metabolic products:

… Increase of serum BUN and creatinine
… Azotemia (means the accumulation of
nitrogenous waste products)

„ Disorders of coagulation and bleeding

abnormalities
Clinical manifestation
Diuretic phase
„ Urine volume will increase gradually after
1-2 weeks of oliguric and anuria phase
…Increase to 1500ml/d or more abruptly
…Increase to 200-500ml/d gradually
…Increase slowly, up to 500ml/d than stop
„ Decrease of BUN and creatinine
Clinical manifestation
Recovery phase
„ Several months
…anemia
…weakness
…Wasting
Diagnosis
„ History and etiology
„ Urinalysis :volume, nature, specific gravity and cast
„ Renal function:
… BUN, serum Cr (increased)
… Urinary sodium (mEq/L)
… Urinary osmolality (mOsm/kg H2 O)
… Urinary/plasma creatinine ratio
… Fractional sodium excretion
„ Serum electrolytes and arterial blood gas analysis
„ Fluid challenge (typically 500-1000 ml normal saline is
infused over 30-60 minutes )
Prevention of Acute Renal Failure

„ Identify Patient at Risk

… Elderly patients
… Patients with abnormal renal function and/or diabetics
… Patients who are volume depleted
… Following vascular surgery
… Following trauma
„ Avoid Nephrotoxic Agents
„ Specific Prevention Strategies
… Contrast media
… Rhabdomyolysis
… Tumor lysis syndrome
… Surgical procedures
… Avoid multiple insults
Prevention of Acute Renal Failure

„ Correct Intravascular Volume Depletion

„ Correct electrolytes and acid-base
imblance
„ Alkalinization of Urine and Use of Mannitol
to maintain the volume of urine after
rhabdomyolysis
„ Diuretic drugs therapy
Treatment- Oliguric and Anuria phase
„ Fluid intake Limited. Patients can be given fluids
according to his output
„ Management of disorder of electrolytes and acid-
base imbalance
„ If K>5.5mmol/L， [HCO3-]<15mmol/L,it requires
immediate medical therapy
„ Nutritional support
„ Prevent and control infection
„ Renal replacement therapies
Technique of Dialysis

„ Classification
… Hemodialysis
… Hemofiltration
„ Continuous venovenous hemofiltration (CVVH)
„ Continuous arteriovenous hemofiltration
(CAVH)
„ Continuous arteriovenous hemodiafiltration
(CAVHD)
… Peritoneal dialysis
Indication

„ Serum Cr>442μmol/L
„ Serum K+>6.5mmol/L；
„ Water intoxication
„ Azotemia
„ Serious metabolic acidosis
 Hemodialysis Hemofiltration Peritoneal
dialysis
Assessment Rapid- Slow- Slow-
intermittent continuous intermittent
Vascular A、V A、V Abdominal
access catheter
Anticoagulation Usually required None required
required
Solute removal excellent excellent excellent

Fuild removal excellent excellent good

Hemodynamic Critical ill None None

instability patients
Risk of Hypotension Hypovolumia Infection
procedure hemorrhage hemorrhage peritonitis,
Treatment- Diuretic phase

„ Supplement of fluid ， adjust it under

monitor of CVP or Pawp
„ Supplement of electrolytes
„ Anti-infection
„ Nutritional support
MODS
„ ARDS
„ ARF/AKI
„ DIC
„ AHF
„ Stress ulcer
„ Definition
„ Pathophysiology
„ ARDS/ALI criteria, PEEP
„ ARF/AKI causes, ATN, clinical
manifestation and treatments
Thank you