The separation into three broad categories (prerenal, intrinsic renal, and postrenal failure) is of considerable clinical utility (Table 138-1). Prerenal failure is most common among hospitalized pts. It may result from true volume depletion (e.g., diarrhea, vomiting, GI or other hemorrhage) or “arterial underfilling,” i.e., reduced renal perfusion in the setting of adequate or excess blood volume. Reduced renal perfusion may be seen in congestive heart failure (CHF) (due to reduced cardiac output and/or potent vasodilator therapy), hepatic cirrhosis (due mostly to peripheral vasodilation and arteriovenous shunting), nephrotic syndrome and other states of severe hypoproteinemia (total serum protein <54 g/L [<5.4 g/dL]), and renovascular disease (because of fixed stenosis at the level of the main renal artery or large branch vessels). Several drugs can reduce renal perfusion, most notably NSAIDs. ACE inhibitors and angiotensin II receptor antagonists may reduce glomerular filtration rate but do not tend to reduce renal perfusion.

Causes of intrinsic renal failure depend on the clinical setting. Among hospitalized pts, especially on surgical services or in intensive care units, acute tubular necrosis (ATN) is the most common diagnosis. A well-defined ischemic event or toxic exposure (e.g., aminoglycoside therapy) may lead to in-hospital ATN. Alternatively, pts may be admitted to the hospital with ATN associated with rhabdomyolysis; common predisposing factors in rhabdomyolysis include alcoholism, hypokalemia, and various drugs (e.g., statins). Allergic interstitial nephritis, usually due to antibiotics (e.g., penicillins, cephalosporins, sulfa drugs, quinolones, and rifampin), or NSAIDs, may also be responsible. Radiographic contrast dyes may cause AKI in pts with preexisting kidney disease; the risk is substantially higher in diabetics with chronic kidney disease. Coronary angiography, other vascular procedures, thrombolysis, or anticoagulation may lead to atheroemboli, which cause AKI due to both hemodynamic and inflammatory effects; livedo reticularis, embolic phenomena with preserved peripheral pulses, and eosinophilia are important clues to this diagnosis. Acute glomerulonephritis (Chap. 142. Glomerular Diseases) and thrombotic microangiopathies may also cause AKI. Thrombotic microangiopathies can be clinically subdivided into renal-limited forms (e.g., Escherichia coli-associated hemolytic uremic syndrome [HUS]) and systemic forms (e.g., thrombotic thrombocytopenic purpura [TTP]). “Atypical HUS,” occurring in the absence of HUS-associated bacterial toxins, is associated with hereditary mutations in complement proteins or complement regulatory proteins, leading to exaggerated endothelial sensitivity to complement-mediated cytolysis. A variety of drugs can cause thrombotic microangiopathies, including calcineurin inhibitors (cyclosporine and tacrolimus), quinine, antiplatelet agents (e.g., ticlopidine), inhibitors of the action of vascular endothelial growth factor (VEGF), and chemotherapeutics (e.g., mitomycin C and gemcitabine). Important associated disorders in TTP include HIV infection, bone marrow transplantation, systemic lupus erythematosus (SLE), and antiphospholipid syndrome.

Postrenal failure is due to urinary tract obstruction, which is also more common among ambulatory rather than hospitalized pts. More common in men than women, it is most often caused by ureteral or urethral blockade. Occasionally, stones, sloughed renal papillae, or malignancy (primary or metastatic) may cause more proximal obstruction.