Drugs Causing Acute Tubular Necrosis

Acute tubular necrosis (ATN) is one of the causes of acute renal failure (ARF), occurring in 10% of cases of ARF in the outpatient setting and in 38-76% of ICU cases of ARF. Prerenal causes are the most common of ARF in the outpatient setting. We’ve all heard that drugs are one of the predominant causes of ATN, but why does this occur? First of all, you need to know what ATN is. ATN is acute tubular cell death caused by either ischemic injury or toxic injury. Ischemic ATN is basically in the same spectrum as prerenal disease, both cause by decreased renal blood flow. The causes of prerenal azotemia are the same as for ischemic ATN, but we will focus on drugs. NSAIDs decrease preglomerular arterial dilation resulting in ischemia. Drugs such as ACEIs or ARBs cause ischemia by decreasing postglomerular arteriolar constriction. Basically both of the above result in less blood being filtered through the glomerulus and the tubules suffer.

The other major mechanism of ATN is secondary to toxins. Drugs that cause ATN due to their toxic effects include aminoglycosides, cyclosporine, tacrolimus, cisplatin, ifosfamide, foscarnet, pentamidine, sulfa drugs, acyclovir, indinavir, and radiographic IV contrast. The two most important on this list for the ED setting are likely aminoglycosides and IV contrast, as we will likely be giving both, and in the wrong setting, this could tip the patient into ATN. Always be careful with the above medications. Also remember that toxins are not just drugs. Proteins from multiple myeloma, crystals (uric acid, calcium, etc.), and myoglobin are also nephrotoxic to varying degrees.

Erdbruegger U, Okusa M. Etiology and diagnosis of acute tubular necrosis and prerenal disease. Uptodate. June 14, 2011.

Gill N, Nally J, Fatica R. Acute Tubular Necrosis. Chest. 2005; 128: 2847-2863.

Lerma E. Acute Tubular Necrosis. Emedicine. June 28, 2011.

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