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Declining Mortality in Patients

with Acute Renal Failure, 1988 to

2002Sushrut S. Waikar, Gary C. Curhan, Ron Wald,

Ellen P. Mc Carthy, and Glenn M. Chertow

J Am Soc Nephrol 17: 1143-1150, 2006. doi: 10.1681 / ASN.2005091017

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J Am Soc Nephrol 17: 1143-1150, 2006

Declining Mortality in Patients with ARF

0

5

10

15

20

25

30

35

40

45

50

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

Mo

rtality(

Acute Renal Failure

Acute Renal Failure

Requiring Dialysis

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Acute Renal Failure

History, physical examination, and blood urine studies

Suggestive history and physicalfindings, fractional excreation of

sodium of < 1%. Urine osmolality

of > 500 mOsm, bland urine

sediment

Suggestive history and physicalfindings, fractional excreation of

sodium of < 3%. Urine osmolality

of 250 to 300 mOsm, active

urine sediment

Suggestive history and physicalfindings, anuria, elevated

postvoid residual,

hydronephrosis

Prerenal acute renal failure Intrinsic acute renal failure Postrenal acute renal failure

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TABLE 1

Key Symptoms and Physical

Findings in Patients with Acute

Renal Failure and Uremia*

SymptomsAnorexia

Fatigue

Mental status changes

Nausea and vomiting

Pruritus

Seizures (if blood urea nitrogen level is

very high)Shortness of breath (if volume overloadis present)

Physical findings

Asterixis and myoclonus

Pericardial or pleural rub

Peripheral edema (if volume overload is

present)Pulmonary rales (if volume overload ispresent)

Elevated right atrial pressure (if volumeoverload is present)

*--Clinical findings depend on the stage at

which acute renal failure is diagnosed.

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TABLE 5

Differential Diagnosis of Acute Renal Failure

Types of acute renalfailure andunderlying problem Possible disorders

Prerenal acute renal

failure

True intravasculardepletion

Sepsis, hemorrhage, overdiuresis, poor fluid intake, vomiting, diarrhea

Decreased effective

circulating volume to

the kidneys

Congestive heart failure, cirrhosis or hepatorenal syndrome, nephrotic syndrome

Impaired renal blood

flow because of

exogenous agents

Angiotensin-converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs

Intrinsic acute renal

failure

Acute tubular

necrosis

Ischemia

Toxins: drugs (e.g., aminoglycosides), contras agents, pigments (myoglobin or hemoglobin)

Glomerular disease Rapidly progessive glomerulonephritis: systemic lupus erythematosus, small-vessel vasculitis

(Wegeners granulomatosis or polyarteritis nodosa), Henoch-Schonlein purpura (immunoglobulin A

nephropathy), Goodpastures syndrome

Acute proliferative glomerulonephritis: endocarditis, poststreptococcal infection, postpneumococcal

infection

Vascular disease Microvascular disease: atheroembolic disease (cholesterol-plaque microembolism), thromboticthrombocytopenic purpura, hemolytic uremic syndrome, HELLP syndrome or postpartum acute renal

failure

Macrovascular disease: renal artery occlusion, severe abdominal aortic disease (aneurysm)

Interstitial disease Allergic reaction to drugs, autoimmune disease: (systemic lupus erythematosus or mixed connective

tissue disease), pyelonephritis, infiltrative disease (aneurysm)

Postrenal acute renal

failure

Benign prostatic hypertrophy or prostate cancer, cervical cancer, retroperitoneal disorders,

intratubular obstruction (crystals or myeloma light chains), pelvic mass or invasive pelvic malignancy,

intraluminal bladder mass (clot, tumor or fungus ball), neurogenic bladder, urethal strictures

HELLP = hemolysis, elevated liver enzymes, and low platelets.Information from references 2,3 and 6.

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TABLE 6

Finding on Urinalysis in the Broad Categories of Acute Renal Failure

Types of renal failure Findings on urinalysis

Prerenal acute renal

failure

Scant; few hyaline casts

Postrenal acute renal

failure

Scant; few hyaline casts, possible red cells

Acute tubular

necrosis

Epithelial cells, muddy-brown, coarsely granular casts, white blood cells, low-grade

proteinuria

Allergic interstitial

nephritis

White blood cells, red blood cells, epithelial cells, eosinophils, possible white blood cell

cast, low to moderate proteinuria

Glomerulonephritis Red blood cell casts, dysmorphic red cells, moderate to severe proteinuria

Adapted with permission from Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med

1996;334:1448-60.

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Type of renal

failureBUN-to-

creatinin ratio

Urine

osmolality

Excretion of

sodium*

Prerenal acuterenal failure >20:1 >500mOsm

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Vasoconstriction in response to :

endothelin, adenosine,

angiotensin II, thromboxane A2,

leukotrienes, sympathetic nerveactivity

Vasodilation in response to :

nitric oxide, PGE2, acetylcholine

brady kinin

Endothelial and vascular smooth

muscle cell structural damage

Leukocyte-Endothelial adhesion

vascular obstruction, leukocyte

activation, and inflammation

Cytoskeletal breakdown

Loss of polarity

Apoptosis and Necrosis

Desquamation of viable

and necrotic cells

Tubular obstruction

Backleak

Inflammantory

And

Vasoactive

mediators

O2

Figure 1. Interacting microvascular and tubular events contributing to the pathophysiology of ischemicacute renal failure (ARF)

Pathophysiology of Ischemic Acute Renal Failure

MICROVASCULAR TUBULAR

Glomerular Medullary

J Am Soc Nephrol 14: 2199-2210, 2003

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Category GFR Criteria Urine Output (UO)

Criteria

Risk Increased creatinin x 1.5of GFR decrease > 25%

UO < 0.5 ml/kg/h x 6 hr High

Sensitivity

Injury Increased creatinine x2 or

GFR decrease > 50%

UO < 0.5 ml/kg/h x 12 hr

Failure Increase creatinine x3 orGFR decrease > 75%

UO < 0.3 ml/kg/h x 24 hr or

Anuria x 12 hrs

High

Specicity

Loss Persistent ARF = complete loss of kidney function > 4weeks

ESKD End Stage Kidney Disease (> 3 months)

RIFLE Criteria for Acute Renal Dysfunction

GFR; Glomerular Filtration Rate

ARF; Acute Renal Failure

ESKD; End Stage Kidney Disease

References :

Bellomo R, Kellum JA, Mehta R, Palevsky PM, Ronco C. Acute Dialysis Quality Initiative II :

the Vicenza conference. Curr Opin Crit Care. 2002 Dec; 8(6):505-8.[Medline]

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Decreased effective intravascular volume

Congestive heart failure,

cirrhosis, nephrosis, peritonitis

Figure 2. Conditions That Lead to Ischemic Acute Renal Failure

Intravascular volume depletion and hypotension

Gastrointestinal, renal, and dermal losses;

Hemorrhage; shock

NEJM Thadhani et al. 334(22): 1448, Figure 2 May 30, 1996

Generalized

or looalized reduction inRenal blood flow

Ischemic

acute renal failure

Medications

Cylosporine, tecrolimus,

Angiotensin-converting-enzyme inhibitors,

Nonsteroidal antiinflammatory drugs,

Radiocontrast agents, amphotericin B

Hepatorenal syndrome Sepsis

Large-vessel renal vascular disease

Renal-artery thrombosis or embolism,

Operative arterial cross-clamping,

renal-artery stenosis

Small-vessel renal vascular disease

Vasculitis, atheroembolism, hemolytic-

uremic syndrome, malignant hypertension,

scleroderma, preeclampsia

sickle cell anemia, hypercalcemia,

transplant rejection

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History

Physical examination

Serum chemistriesUrea, creatinine, electrolytes, abnormal serologyc tests (see text)

Urine chemistries

Na, FENa urea, FEUr creatinine

24-hour clearence: creatinine, urea, protein

Urinalysis

Dipstick determinations

MicroscopySulfosalicylic acid

Urine culture/Gram stain

Hemodynamic monitoring

Ultrasound imaging

Radiography

KUB, IVP, tomography, CT scan, MRI

Invasive radiography

Renal arteriography (selective, digital substraction)

Retrograde pyelography

Percutaneous antegrade pyelography

Nuclear scanning

Split function studies and renal flow (DTPA, MAG-3)

Galium scan

Enal biopsy

Table 13-1. Renal Assessment

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Creatinine or urea clearance can be calculated as follows :

Creatinine clearance

(mL/min)

Serum Ur(mg/dL)

Urine Cr(mg/dL)xUrine volume(mL/min)

Serum Cr(mg/dL)

Urea clearance

(mL/min)

Urine Ur(mg/dL)xUrine volume(mL/min)

=

=

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CardiovascularEdemaAnasarcaHypertensionCongestive heart failurePulmonary edemaArrhythmiasMyocardial infarction

PericarditisHematologic

AnemiaPlatelet dysfunctionGastrointestinal BleedingInadequate wound hemostasis

InfectiousSepticemiaPneumoniaCatheter-related infections

Urinary tract infectionsWound infectionsMetabolic

HyperkalemiaHyponatremiaHypocalcemiaHyperphosphatemiaHyphophosphatemia(parenteral hyperalimentation)HypermagnesemiaHypomagnesemiaAcidosis

Alkalosis(vomiting, nasogastric tube losses)Hypoglycemia(decreased insulin catabolism)

NeurologicNeuromuscular irritabilitySomnolenceComaConvulsions

GastrointestinalNauseaVomitingGastritis

Table 13-3. Complications associated with acute renal failure.1

1Modified from Brezis M, Rosen S, Epstein FH: Acute renal failure. In : TheKidney, 4th ed. Brenner B, Rector FC(editors). Saunders, 1991

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ESSENTIALS OF DIAGNOSIS

BUN : creatinine ratio > 20:1

Dicreased urine output (unless renal losses are

primary)

FENa < 1% and FEUr < 35%

Urine sediment may show a few granular casts

but absence of inflammantory cells and red andwhite cells casts.

No evidence of urinary tract obstruction

PRERENAL RENAL FAILURE

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Dilated renal pelvis on ultrasound

Enlarged, palpable bladder (if obstruction to

bladder outflow)

POSTRENAL RENAL FAILURE

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Nephritic urine sediment with red cells, white

cells, and red cell casts.

Proteinuria (variable, sometimes in nephrotic

range:>3.5 g/d)

1. Glomerulonephritis

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Interstitial nephritis :

History of drug sensitivity, infection, or toxin

ingestion.

Flank pain (occasionally).

Kidney size normal or increased.

Allergic interstitial nephritis :

Fever, rash, peripheral blood eosinophilia. Sterile pyuria, hemturia, white cell casts, tubular

epithe

2. Acute Interstitial Nephritis

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Hematuria

Proteinuria(variable)

In thrombocytopenic purpura-hemolytic uremic syndrome

and disseminated intravascular coagulation:thrombocytopenia and microangiopathic hemolytic

anemia.

In cryoglobulinemia: cryoglobulin present in serum,

purpura (variable), and hypertension (variable)

In cholesterol embolization : hypertension, signs of

peripheral vascular occlusive disease (claudication), skin

discoloration (livedo reticularis, purpletoes), eosinophilia,

and a history of recent intraaortic catheterization.

3. Microcapillary & Glomerular Occlusion

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History of exposure to nephrotoxic drugs or hypotension

Oliguria in ischemic ATN but absence of oliguria in toxic

ATN

FENa> 1% Urinalysis:tubular epithelial cells, and muddy brown

casts.

4. Acute Tubular Necrosis

J Am Soc Nephrol 14: 2199 2210 2003

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Vasoconstriction in response to :

endothelin, adenosine,

angiotensin II, thromboxane A2,

leukotrienes, sympathetic nerve

activity

Vasodilation in response to :

nitric oxide, PGE2, acetylcholine

brady kinin

Endothelial and vascular smooth

muscle cell structural damageLeukocyte-Endothelial adhesion

vascular obstruction, leukocyte

activation, and inflammation

Cytoskeletal breakdown

Loss of polarity

Apoptosis and Necrosis

Desquamation of viable

and necrotic cells

Tubular obstruction

Backleak

Inflammantory

And

Vasoactive

mediators

O2

Figure 1. Interacting microvascular and tubular events contributing to the pathophysiology of ischemicacute renal failure (ARF)

Pathophysiology of Ischemic Acute Renal Failure

MICROVASCULAR TUBULAR

Glomerular Medullary

J Am Soc Nephrol 14: 2199-2210, 2003

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Category GFR Criteria UO Criteria

Risk Increased creatinin x1.5 of GFR decrease

> 25%

UO < 0.5 ml/kg/h x 6hr HighSensitivity

Injury Increased creatinine

x2 or GFR decrease

> 50%

UO < 0.5 ml/kg/h x 12

hr

Failure Increase creatinine

x3 or GFR decrease

> 75%

UO < 0.3 ml/kg/h x 24

hr or Anuria x 12 hrs

High

Specicity

Loss Persistent ARF = complete loss of kidney

function > 4 weeks

ESKD End Stage Kidney Disease (> 3 months)

RIFLE Criteria for Acute Renal Dysfunction

GFR=Glomerular Filtration Rate ARF; Acute Renal Failure

UO = Urine Output ESKD; End Stage Kidney Disease

References :

Bellomo R, Kellum JA, Mehta R, Palevsky PM, Ronco C. Curr Opin Crit Care. 2002 Dec; 8(6):505-8.

NEJM Thadhani et al 334(22): 1448 Figure 2 May 30 1996

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Decreased effective intravascular volume

Congestive heart failure,

cirrhosis, nephrosis, peritonitis

Figure 2. Conditions That Lead to Ischemic Acute Renal Failure

Intravascular volume depletion and hypotension

Gastrointestinal, renal, and dermal losses;

Hemorrhage; shock

NEJM Thadhani et al. 334(22): 1448, Figure 2 May 30, 1996

Generalized

or looalized reduction inRenal blood flow

Ischemic

acute renal failure

Medications

Cylosporine, tecrolimus,

Angiotensin-converting-enzyme inhibitors,

Nonsteroidal antiinflammatory drugs,

Radiocontrast agents, amphotericin B

Hepatorenal syndrome Sepsis

Large-vessel renal vascular disease

Renal-artery thrombosis or embolism,

Operative arterial cross-clamping,

renal-artery stenosis

Small-vessel renal vascular disease

Vasculitis, atheroembolism, hemolytic-

uremic syndrome, malignant hypertension,

scleroderma, preeclampsia

sickle cell anemia, hypercalcemia,

transplant rejection

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History

Physical examination

Serum chemistriesUrea, creatinine, electrolytes, abnormal serologyc tests (see text)

Urine chemistries

Na, FENa urea, FEUr creatinine

24-hour clearence: creatinine, urea, protein

Urinalysis

Dipstick determinations

MicroscopySulfosalicylic acid

Urine culture/Gram stain

Hemodynamic monitoring

Ultrasound imaging

Radiography

KUB, IVP, tomography, CT scan, MRI

Invasive radiography

Renal arteriography (selective, digital substraction)

Retrograde pyelography

Percutaneous antegrade pyelography

Nuclear scanning

Split function studies and renal flow (DTPA, MAG-3)

Galium scan

Enal biopsy

Table 13-1. Renal Assessment

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Creatinine or urea clearance can be calculated as follows :

Creatinine clearance

(mL/min)

Serum Ur(mg/dL)

Urine Cr(mg/dL)xUrine volume(mL/min)

Serum Cr(mg/dL)

Urea clearance

(mL/min)

Urine Ur(mg/dL)xUrine volume(mL/min)

=

=

Table 13 3 Complications associated with acute renal failure 1

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CardiovascularEdemaAnasarcaHypertensionCongestive heart failurePulmonary edemaArrhythmiasMyocardial infarction

PericarditisHematologic

AnemiaPlatelet dysfunctionGastrointestinal BleedingInadequate wound hemostasis

InfectiousSepticemiaPneumoniaCatheter-related infectionsUrinary tract infectionsWound infections

MetabolicHyperkalemiaHyponatremiaHypocalcemiaHyperphosphatemiaHyphophosphatemia(parenteral hyperalimentation)HypermagnesemiaHypomagnesemiaAcidosis

Alkalosis(vomiting, nasogastric tube losses)Hypoglycemia(decreased insulin catabolism)Neurologic

Neuromuscular irritabilitySomnolenceComaConvulsions

GastrointestinalNauseaVomitingGastritis

Table 13-3. Complications associated with acute renal failure.1

1Modified from Brezis M, Rosen S, Epstein FH: Acute renal failure. In : TheKidney, 4th ed. Brenner B, Rector FC(editors). Saunders, 1991


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BUN : creatinine ratio > 20:1

Dicreased urine output (unless renal losses are

primary)

FENa < 1% and FEUr < 35%

Urine sediment may show a few granular casts

but absence of inflammantory cells and red andwhite cells casts.

No evidence of urinary tract obstruction



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Dilated renal pelvis on ultrasound

Enlarged, palpable bladder (if obstruction to

bladder outflow)


1 Gl l h iti

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Nephritic urine sediment with red cells, white

cells, and red cell casts.

Proteinuria (variable, sometimes in nephrotic

range:>3.5 g/d)

1. Glomerulonephritis

2 A t I t titi l N h iti

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Interstitial nephritis :

History of drug sensitivity, infection, or toxin

ingestion.

Flank pain (occasionally).

Kidney size normal or increased.

Allergic interstitial nephritis :

Fever, rash, peripheral blood eosinophilia. Sterile pyuria, hemturia, white cell casts, tubular

epithe

2. Acute Interstitial Nephritis

3 Mi ill & Gl l O l i

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Hematuria

Proteinuria(variable)

In thrombocytopenic purpura-hemolytic uremic syndrome

and disseminated intravascular coagulation:

thrombocytopenia and microangiopathic hemolytic

anemia.

In cryoglobulinemia: cryoglobulin present in serum,

purpura (variable), and hypertension (variable)

In cholesterol embolization : hypertension, signs of

peripheral vascular occlusive disease (claudication), skin

discoloration (livedo reticularis, purpletoes), eosinophilia,

and a history of recent intraaortic catheterization.

3. Microcapillary & Glomerular Occlusion

4 A t T b l N i

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History of exposure to nephrotoxic drugs or hypotension

Oliguria in ischemic ATN but absence of oliguria in toxic

ATN

FENa

> 1%

Urinalysis:tubular epithelial cells, and muddy brown

casts.

4. Acute Tubular Necrosis

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Treatment Prescription

Time-Averaged

Urea Clearance Protein Loss

mL/min L/d L/wk g/d2

Hemodialysis 3 x 4 h/wk7 x 4 h/wk

14.333.3

2148

144336

615

Peritoneal

dialysis

2 L/h 26.7 24 168 30

CAPD 2 L/6 h 6.9 10 70 10

CAVH 14 L/d 9.7 14 98 15

CAVHD 1-2 L/h 19-35 29-51 189-357 11

CVVH 1-3 L/h 17-50 24-72 168-504 18-38

CVVHD 1-3 L/h 19-52 27-75 189-525 18-36

Table 13-12. Renal replacement: Urea clearance and protein losses

comet arf

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