- 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, contrast media, and angiotensin-converting enzyme 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 renal failure, a number of diagnostic and therapeutic agents can produce renal injury and renal failure among hospitalized patients. These renal injuries may be caused either directly or indirectly by drugs or metabolites of these agents in critically ill patients. Recent data suggest that renal adverse effects caused by pharmaceutical agents may contribute to approximately 30% of acute renal failure (ARF) incidents in hospitalized patients. Antibiotics, analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), contrast media, and angiotensin-converting enzyme (ACE) inhibitors were the most commonly reported causes of ARF (see Figure 9–2).
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, blood flow to the kidneys is rich in oxygen, and the kidneys are very sensitive to reduction in blood perfusion and oxygen deprivation. Third, the renal countercurrent concentrating mechanism for water also concentrates 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 renal failure occurs in patients with subclinical preexisting renal dysfunction.
Renal failure 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. |Favorite Table|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
NSAIDSs, 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