ESSENTIALS OF DIAGNOSIS
Acute renal failure occurs in 4.9% of hospitalized patients with renal insufficiency.
Fifty percent of patients experience nonoliguric acute renal failure.
Antibiotics, analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), contrast media, and angiotensin-converting enzyme (ACE) inhibitors are the most common causes of acute renal failure.
Impaired renal function, decreased volume status, exposure to contrast media, and aminoglycosides account for 79% of all cases of renal failure.
Although most therapeutic agents infrequently cause community-acquired kidney injury, a number of diagnostic and therapeutic agents can produce kidney injury and kidney failure among hospitalized patients. These kidney injuries may be caused either directly or indirectly by drugs or metabolites of these agents. Recent data suggest that kidney adverse effects caused by pharmaceutical agents may contribute to approximately 30% of acute kidney injury (AKI) incidents in hospitalized patients. Antibiotics, analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), contrast media, and angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers were the most commonly reported causes of AKI. A number of factors make the kidneys more susceptible to drug toxicity. First, the kidneys receive a high fraction (20–25%) of cardiac output relative to their weight, so drugs transit to the kidneys in large amounts. The kidneys represent only 0.4% of the body weight but receive 25% of resting cardiac output; therefore, kidneys are exposed to a significant concentration of therapeutic agents. Second, the kidneys are very sensitive to reductions in blood perfusion and oxygen deprivation. Third, the renal concentrating mechanisms also concentrate drugs and chemicals within the filtered tubular fluid. Thus, local concentrations of these substances in contact with renal epithelia may exceed that in peripheral blood. Finally, most drug-induced AKI occurs in patients with subclinical preexisting kidney dysfunction.
AKI associated with drug-induced nephropathy can be classified into six categories based on pathophysiologic injuries. These injuries include prerenal failure, acute tubular necrosis (ATN), acute tubulointerstitial disease (ATID), tubular obstruction (crystal-induced ARF), hypersensitivity (glomerulonephritis), and thrombotic microangiopathy. A list of common therapeutic agents associated with each of these injuries is provided in Table 14–1.
Table 14–1.Classification of various drugs based on pathophysiologic categories of acute renal failure. ||Download (.pdf) Table 14–1. Classification of various drugs based on pathophysiologic categories of acute renal failure.
NSAIDs, ACE inhibitors, cyclosporine, norepinephrine, angiotensin receptor blockers, diuretics, interleukins, cocaine, mitomycin C, tacrolimus, estrogen, quinine
Acute tubular necrosis
Antibiotics: Aminoglycosides, cephaloridine, cephalothin, amphotericin B, rifampicin, vancomycin, foscarnet, pentamide
NSAIDs, contrast media, acetaminophen, cyclosporine, cisplatin, intravenous immunoglobulin, dextran, maltose, sucrose, mannitol, heavy metals
Acute interstitial nephritis
Antibiotics: Ciprofloxacin, methicillin, penicillin G, ampicillin, cephalothin, oxacillin, rifampicin
NSAIDs, contrast media, sulfonamides, thiazides, phenytoin, furosemide, allopurinol, cimetidine, omeprazole, phenindione
Sulfonamides, methotrexate, methoxyflurane, triamterene, acyclovir, ethylene glycol, protease inhibitors
Penicillin G, ampicillin, sulfonamides
Mitomycin C, cyclosporine, oral contraceptives