Harrison's Principles of Internal Medicine, 21e >Acute Kidney Injury

Joseph Loscalzo, Anthony Fauci, Dennis Kasper, Stephen Hauser, Dan Longo, J. Larry Jameson+
TABLE 310-2Major Causes, Clinical Features, and Diagnostic Studies for Prerenal and Intrinsic Acute Kidney Injury

ETIOLOGY CLINICAL FEATURES LABORATORY FEATURES COMMENTS

History of poor fluid intake or fluid loss

(hemorrhage, diarrhea, vomiting, sequestration Low FeNa, high specific gravity and osmolality
into extravascular space); NSAID/ACE-I/ARB; may not be seen in the setting of CKD, diuretic
BUN/creatinine ratio above 20, FeNa <1%,
heart failure; evidence of volume depletion use; BUN elevation out of proportion to creatinine
Prerenal azotemia hyaline casts in urine sediment, urine specific
(tachycardia, absolute or postural hypotension, may alternatively indicate upper GI bleed or
gravity >1.018, urine osmolality >500 mOsm/kg
low jugular venous pressure, dry mucous increased catabolism. Response to restoration of
membranes), decreased effective circulatory hemodynamics is most diagnostic.
volume (cirrhosis, heart failure)

Positive culture from normally sterile body fluid or

Sepsis, sepsis syndrome, or septic shock; overt FeNa may be low (<1%), particularly early in the
other test confirming infection; urine sediment
Sepsis-associated AKI hypotension not always seen in mild to moderate course, but is usually >1% with osmolality <500
often contains granular casts, renal tubular
AKI mOsm/kg
epithelial cell casts

Systemic hypotension, often superimposed upon Urine sediment often contains granular casts,
Ischemia-associated AKI sepsis and/or reasons for limited renal reserve renal tubular epithelial cell casts; FeNa typically
such as older age, CKD >1%

Nephrotoxin-Associated AKI: Endogenous

Elevated myoglobin, creatine kinase; urine heme

Rhabdomyolysis Traumatic crush injuries, seizures, immobilization FeNa may be low (<1%)
positive with few red blood cells

Recent blood transfusion with transfusion FeNa may be low (<1%); evaluation for
Hemolysis Anemia, elevated LDH, low haptoglobin
reaction transfusion reaction

Hyperphosphatemia, hypocalcemia,
Tumor lysis Recent chemotherapy
hyperuricemia

Age >60 years, constitutional symptoms, bone Monoclonal spike in urine or serum
Multiple myeloma Bone marrow or renal biopsy can be diagnostic
pain electrophoresis; low anion gap; anemia

Nephrotoxin-Associated AKI: Exogenous

Characteristic course is rise in SCr within 1–2 d,

Contrast nephropathy Exposure to iodinated contrast FeNa may be low (<1%)
peak within 3–5 d, recovery within 7 d

Aminoglycoside antibiotics, cisplatin, tenofovir, Urine sediment often contains granular casts,
Tubular injury vancoycin, zoledronate, ethylene glycol, renal tubular epithelial cell casts. FeNa typically Can be oliguric or nonoliguric
aristolochic acid, and melamine (to name a few) >1%.

Other Causes of Intrinsic AKI

Variable (Chap. 314) features include skin rash,

arthralgias, sinusitis (AGBM disease), lung ANA, ANCA, AGBM antibody, hepatitis
hemorrhage (AGBM, ANCA, lupus), recent skin serologies, cryoglobulins, blood culture,
Glomerulonephritis/vasculitis infection or pharyngitis (poststreptococcal), complement abnormalities, ASO titer Kidney biopsy may be necessary
thrombotic microangiopathies including those (abnormalities of these tests depending on
related to drugs, such as cocaine, anti-VEGF etiology)
agents
 Nondrug-related causes include tubulointerstitial
Urine eosinophils have limited diagnostic
Interstitial nephritis nephritis-uveitis (TINU) syndrome, Legionella Eosinophilia, sterile pyuria; often nonoliguric
accuracy; kidney biopsy may be necessary
infection

“Typical HUS” refers to AKI with a diarrheal

prodrome, often due to Shiga toxin released from
Escherichia coli or other bacteria; “atypical HUS”
Neurologic abnormalities and/or AKI; recent is due to inherited or acquired complement
Schistocytes on peripheral blood smear, elevated
TTP/HUS diarrheal illness; use of calcineurin inhibitors; dysregulation. “TTP-HUS” refers to sporadic
LDH, anemia, thrombocytopenia
pregnancy or postpartum; spontaneous cases in adults. Diagnosis may involve screening
for ADAMTS13 activity, Shiga toxin–producing E.
coli, genetic evaluation of complement regulatory
proteins, and kidney biopsy.

Recent manipulation of the aorta or other large

vessels; may occur spontaneously or after Hypocomplementemia, eosinophiluria (variable),
Atheroembolic disease Skin or kidney biopsy can be diagnostic
anticoagulation; retinal plaques, palpable variable amounts of proteinuria
purpura, livedo reticularis, GI bleed

History of kidney stones, prostate disease,

No specific findings other than AKI; may have Imaging with computed tomography or
Postrenal AKI obstructed bladder catheter, retroperitoneal or
pyuria or hematuria ultrasound
pelvic neoplasm

Abbreviations: ACE-I, angiotensin-converting enzyme inhibitor-I; AGBM, antiglomerular basement membrane; AKI, acute kidney injury; ANA, antinuclear antibody; ANCA, antineutrophilic cytoplasmic antibody;
ARB, angiotensin receptor blocker; ASO, antistreptolysin O; BUN, blood urea nitrogen; CKD, chronic kidney disease; FeNa, fractional excretion of sodium; GI, gastrointestinal; LDH, lactate dehydrogenase; NSAID,
nonsteroidal anti-inflammatory drug; TTP/HUS, thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome.

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