4B

Differential Diagnosis of Acute Renal Failure

: (Intern, : B8601076)

Definition
 Acute renal failure (ARF) is defined as a precipitous and significant (>50%) decrease in glomerular filtration rate (GFR) over a period of hours to days, with an accompanying accumulation of nitrogenous wastes in the body.

Prerenal Disease
True volume depletion Advanced liver disease Congestive heart failure Renal arterial disease
Perinatal or Neonatal hemorrhage Perinatal asphyxia and hyaline membrane disease Gastroenteritis Congenital and acquired heart diseases
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Prerenal Disease
 A reduction in renal blood flow - the most common cause of acute renal failure.  Occur from true volume depletion or from selective renal ischemia (as in bilateral renal artery stenosis).  Causes of prerenal azotemia: true volume depletion, advanced liver disease, and congestive heart failure.
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Prerenal Azotemia Caused by True Volume Depletion

 In severe cases the patient may be in hypovolemic shock.  Oliguria is present in most individuals  Normal or increased urine output indicates that an osmotic agent or other diuretic agent is acting, or that there is tubular dysfunction such as ATN.
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Prerenal Azotemia Caused by Advanced Liver Disease

Liver disease:  sodium retention, initially manifested as ascites  a progressive decline in GFR. Both humoral and hemodynamic factors play a primary role in the development of these problems.
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Prerenal Azotemia Caused by Congestive Heart Failure

CHF is associated with two major alterations in renal function:  Sodium retention early in the course of the disease and a decline in GFR as cardiac function worsens.  Neurohumeroral factors and certain therapies may contribute to these problems.
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Prerenal Azotemia Caused by Renal arterial disease

Renal arterial disease - Renal arterial stenosis (atherosclerotic, fibromuscular dysplasia), embolic disease (septic, cholesterol)

Prerenal ARF of Newborns and Infants

The most common cause of ARF is prerenal etiologies. Prerenal ARF: Perinatal hemorrhage - Twin-twin transfusion, complications of amniocentesis, abruptio placenta, birth trauma Neonatal hemorrhage - Severe intraventricular hemorrhage, adrenal hemorrhage
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Prerenal ARF of Newborns and Infants Perinatal asphyxia and hyaline membrane disease (newborn respiratory distress syndrome) both may result in preferential blood shunting away from kidneys (ie, prerenal) to central circulation.

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Prerenal ARF of Children The most common cause of ARF is prerenal etiologies. Prerenal ARF: The most common cause of hypovolemia in children is gastroenteritis. Congenital and acquired heart diseases are also important causes of decreased renal perfusion in this age group.
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Symptoms and Signs of Prerenal Failure Patients commonly present with symptoms related to hypovolemia, including thirst, decreased urine output, dizziness, and orthostatic hypotension. Look for a history of excessive fluid loss via hemorrhage, GI losses, sweating, or renal sources.
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Symptoms and Signs of Prerenal Failure

Patients with advanced cardiac failure leading to depressed renal perfusion may present with orthopnea and paroxysmal nocturnal dyspnea.

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Intrinsic Renal Failure

Tubular diseases Interstitial diseases Glomerular diseases Vascula diseases Nephrotoxins Allergic interstitial nephritis
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Intrinsic Renal Failure Glomerular diseases: Nephritic syndrome of hematuria, edema, and HTN is synonymous with a glomerular etiology of ARF.

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Intrinsic Renal Failure Tubular diseases: ATN should be suspected in any patient presenting after a period of hypotension secondary to cardiac arrest, hemorrhage, sepsis, drug overdose, or surgery.
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Intrinsic Renal Failure

Interstitial diseases - Acute interstitial nephritis, drug reactions, autoimmune diseases (eg, systemic lupus erythematosus [SLE]), infiltrative disease (sarcoidosis, lymphoma), infectious agents (Legionnaire disease, hantavirus) Vascular diseases - Hypertensive crisis, polyarteritis nodosa, vasculitis
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Intrinsic Renal Failure A careful search for exposure to nephrotoxins should include a detailed list of all current medications and any recent radiologic examinations (ie, exposure to radiologic contrast agents).
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Intrinsic Renal Failure Allergic interstitial nephritis should be suspected with recent drug ingestion, fevers, rash, and arthralgias.

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Acute Tubular Necrosis

Renal insults, including  renal ischemia  exposure to exogenous or endogenous nephrotoxins. The net effect is a rapid decline in renal function that may require a period of dialysis before spontaneous resolution occurs.
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Acute Tubular Necrosis

There are two major histiologic changes that take place in ATN: (1) tubular necrosis with sloughing of the epithelial cells (2) occlusion of the tubular lumina by casts and by cellular debris
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Acute Tubular Necrosis

In addition of the tubular obstruction, two other factors appear to contribute to the development of renal failure in ATN:  across the damaged tubular epithelia backleak of filtrate and  a primary reduction in glomerular filtration.
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Acute Tubular Necrosis

 The decrease in glomerular filtration results both from arteriolar vasoconstriction and from mesangial contraction.  The decline in renal function begins abruptly following a hypotensive episode, rhabdomyolysis, or the administration of a radiocontrast media.  When aminoglycosides are the cause, the onset is more insidious, with the first rise in creatinine being at seven or more days.
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Major Causes of Acute Tubular Necrosis

 Renal Ischemia: * Severe prerenal disease from any cause.  Exposure to Nephrotoxins: * Amphotericin B * Aminoglycosides * Heme Pigments * NSAID's (hemoglobinuria/myoglobinura)
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Intrinsic ARF of Children

Hemolytic uremic syndrome (HUS) often is cited as the most common cause of ARF in children. The most common form of the disease is associated with a diarrheal prodrome caused by Escherichia coli 0157:H7.  These children usually present with microangiopathic anemia, thrombocytopenia, colitis, mental status changes, and renal failure.
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PostPost-renal ARF


Diseases causing urinary obstruction from the level of the renal tubules to the urethra
acid, calcium oxalate, acyclovir, sulfonamide, methotrexate, myeloma light chains) Ureteral obstruction - Retroperitoneal tumor, retroperitoneal fibrosis (methysergide, propranolol, hydralazine), urolithiasis, papillary necrosis
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Tubular obstruction from crystals (eg, uric

PostPost-renal ARF
Urethral obstruction - Benign prostatic hypertrophy; prostate, cervical, bladder, colorectal carcinoma; bladder hematoma; bladder stone; obstructed Foley catheter; neurogenic bladder; stricture

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FeNa
Calculation of fractional excretion of sodium (FeNa) FeNa = (urine Na/plasma Na)/(urine creatinine/plasma creatinine) FeNa <1 % = prerenal ARF FeNa >1% = ATN
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FeNa
Exceptions (intrinsic renal failure with FeNa <1%) Urinary tract obstruction Acute glomerulonephritis Hepatorenal syndrome Radiologic contrast induced ATN Myoglobinuric and hemoglobinuric ARF Renal allograft rejection Drug-related alterations in renal hemodynamics (eg, captopril, NSAIDs)
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Urine output
Anuria

(<100 mL/d)
Oliguria Non-

Urinary tract obstruction, renal artery obstruction, rapidly progressive glomerulonephritis, bilateral diffuse renal cortical necrosis (100-400 mL/d) Prerenal failure, hepatorenal syndrome (>400 mL/d) Acute interstitial nephritis, acute glomerulonephritis, partial obstructive nephropathy, nephrotoxic and ischemic ATN, radiocontrast-induced ARF, and 30 rhabdomyolysis

oliguria

Urinalysis
Granular casts RBC casts WBC casts ATN, glomerulonephritis, interstitial nephritis Glomerulonephritis, malignant HTN Acute interstitial nephritis, pyelonephritis

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Urinalysis
Eosinophiluria Crystalluria Normal Acute allergic interstitial nephritis, atheroembolism Acyclovir, sulfonamides, methotrexate, ethylene glycol toxicity, radiocontrast agents prerenal and postrenal failure, HUS/thrombotic thrombocytopenic purpura (TTP), preglomerular vasculitis, or atheroembolism
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Complete blood count

Leukocytosis common in ARF Leukopenia and SLE or TTP thrombocytopenia Anemia and multiple myeloma rouleaux formation

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Complete blood count

Microangiopathic TTP or atheroemboli anemia Eosinophilia allergic interstitial nephritis, polyarteritis nodosa, or atheroemboli Coagulation liver disease or disturbances hepatorenal syndrome.
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Blood chemistry
Creatine phosphokinase (CPK) elevations Elevations in liver transaminases Hypocalcemia (moderate) Hyperkalemia rhabdomyolysis and myocardial infarction rapidly progressive liver failure and hepatorenal syndrome common complication of ARF
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Urine indices
Urine specific gravity
Urine osmolality (mOsm/kg H2O) Urine sodium (mEq/L) Plasma BUN/creatinine ratio Urine/plasma creatinine ratio

prerenal ARF >1.018 >500 <15-20 >20 >40

ATN <1.012 <500 >40 <10-15 <20

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Laboratory Findings in the Differential Diagnosis of Acute Renal Failure:

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Laboratory Findings in the Differential Diagnosis of Acute Renal Failure:

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References
1 Liano F, Pascual J: Epidemiology of acute renal failure: a prospective, multicenter, communitybased study. Madrid Acute Renal Failure Study Group. Kidney Int 1996 Sep; 50(3): 811-8 Klahr S, Miller SB: Acute oliguria. N Engl J Med 1998 Mar 5; 338(10): 671-5 Akposso K, Hertig A, Couprie R, et al: Acute renal failure in patients over 80 years old: 25years' experience [In Process Citation]. Intensive Care Med 2000 Apr; 26(4): 400-6 Druml W: Prognosis of Acute Renal Failure. 39 Nephron 1996; 53: 8-15

References

5 Moghal NE, Brocklebank JT,

Meadow SR: A review of acute renal failure in children: incidence, etiology and outcome. Clin Nephrol 1998 Feb; 49(2): 91-5 6 Ragaller MJ, Theilen H, Koch T: Volume replacement in critically ill patients with acute renal failure. J Am Soc Nephrol 2001 Feb; 12 Suppl 17: S33-9
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References

7 San A, Selcuk Y, Tonbul Z, Soypacaci Z:

Etiology and prognosis in 438 patients with acute renal failure. Ren Fail 1996 Jul; 18(4): 593-9 Renal Failure, AcuteSeptember 17, 2002 eMedicine.com, Inc.

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