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Mr. T is 77-year-old man with acute renal failure (ARF).

What is the differential diagnosis of ARF? How would you frame the differential?

ARF is defined as an abrupt decrease in glomerular filtration rate (GFR), with a concomitant increase in serum creatinine, resulting in an inability to maintain fluid and electrolyte balance. It occurs over hours or days and can occur in the presence of previously normal renal function or in patients with chronic kidney disease (CKD). There is no standard definition, and criteria commonly used include an increase in serum creatinine of > 0.5 mg/dL, an increase of more than 20% above baseline, or a decrease in GFR of at least 50%.

The framework for the differential diagnosis is a combination of anatomic and pathophysiologic:

  1. Prerenal (due to renal hypoperfusion)

    1. Hypovolemia

      1. GI fluid loss

      1. Renal loss

      1. Hemorrhage

      1. Third spacing

      1. Decreased effective circulating volume

        1. Heart failure (HF)

        1. Cirrhosis

    1. Hypotension

      1. Sepsis

      1. Cardiogenic shock

      1. Anaphylaxis

      1. Anesthesia- and medication-induced

      1. Relative hypotension below patient's autoregulatory level

    1. Changes in renal hemodynamics

      1. Nonsteroidal antiinflammatory drugs (NSAIDs)/ cyclooxygenase (COX)-2 inhibitors

      1. ACE inhibitors/angiotensin receptor blockers (ARBs)

      1. Renal artery thrombosis or embolism

      1. Abdominal aortic aneurysm

  2. Intrarenal

    1. Vascular

      1. Vasculitis

      1. Malignant hypertension

      1. Cholesterol emboli

      1. Thrombotic microangiopathies

        1. Thrombotic thrombocytopenic purpura

        1. Hemolytic uremic syndrome

        1. Disseminated intravascular coagulopathy

    1. Glomerular

      1. Inflammatory

        1. Postinfectious glomerulonephritis (GN)

        1. Cryoglobulinemia

        1. Henoch-Schönlein purpura

        1. Systemic lupus erythematosus

        1. Antineutrophil cytoplasmic antibody associated GN

        1. Anti-glomerular basement membrane disease

      1. Thrombotic microangiopathies

    1. Tubular injury (acute tubular necrosis [ATN])

      1. Ischemic, due to prolonged renal hypoperfusion

      1. Toxin induced

        1. Medications (such as aminoglycosides)

        1. Radiocontrast media

        1. Heavy metals (cisplatinum)

        1. Intratubular pigments (myoglobin, hemoglobin), crystals (uric acid, oxalate), or proteins (myeloma)

    1. Interstitial

      1. Acute interstitial nephritis

      1. Bilateral pyelonephritis

      1. Infiltration (lymphoma, sarcoidosis)

  3. Postrenal

    1. Mechanical

      1. Ureteral (must be bilateral obstruction to cause ARF)

        1. Stones

        1. Tumors

        1. Hematoma

        1. Retroperitoneal adenopathy or fibrosis

      1. Bladder neck

        1. Benign prostatic hyperplasia (BPH) or prostate cancer

        1. Tumors

        1. Stones

      1. Urethral

        1. Strictures

        1. Tumors

        1. Obstructed indwelling catheters

    1. Neurogenic bladder

An algorithm outlining the diagnostic approach to acute renal failure appears at the end of the chapter.

Measuring Kidney Function

  1. GFR

    1. Best overall measure of kidney function

    1. Normal = 130 mL/min/1.73m2 in young men (120 mL/min/ 1.73m2 in women)

    1. Difficult to accurately measure in clinical practice

  2. Creatinine

    1. Generation determined by muscle mass and dietary intake

    1. Level varies with age, sex, race or ethnic group, muscle mass, diet, nutritional status

    1. The relationship between creatinine and GFR varies inversely and exponentially, so that relatively small changes in serum creatinine may reflect significant decreases in GFR (Figure 25–1).

  3. Creatinine clearance

    1. Creatinine is filtered by glomeruli and secreted by proximal tubule, so creatinine clearance exceeds GFR.

    1. Must be calculated with a 24-hour urine collection, which is inconvenient for patients and often incomplete.

  4. Cystatin C

    1. Freely filtered by glomerulus

    1. Less variable than creatinine

    1. Not yet in widespread use

  5. Estimating GFR

    1. Cockcroft-Gault formula (multiply by 0.85 for women):


      1. Systematically overestimates GFR

      1. Does not adjust for body surface ...

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