Chapter 527 Toxic Nephropathy

Aberrant renal function often results from purposeful or accidental exposure to any number of agents that are potential or actual nephrotoxins. Iodinated radiocontrast agents are generally well tolerated by most patients without significant adverse consequences. In volume-depleted patients or patients with underlying chronic kidney disease, their use poses a serious risk for the development of acute kidney injury with significant attendant morbidity and mortality. Biologic nephrotoxins include venomous exposures from insects, reptiles, amphibians, and a wide variety of sea-dwelling animals. The most common forms of toxic nephropathy unfortunately relate to the purposeful exposure of children to pharmacologic agents, accounting for close to 20% of episodes of acute kidney injury occurring in children and adolescents. Age, underlying medical condition including surgical exposure, genetics, exposure dose, and the concomitant use of other drugs all influence the likelihood of developing acute kidney injury.

Agents that commonly cause acute kidney injury and some of their clinical manifestations are summarized in Table 527-1. Mechanisms of injury often help to explain the presentation; multiple toxic exposures in patients with complicated clinical histories often limit the ability to clearly establish clinical cause and effect. For example, diminished urine output may be the clinical hallmark of tubular obstruction cause by agents such as methotrexate or agents that cause acute tubular necrosis such as amphotericin B or pentamidine. Alternatively, nephrogenic diabetes insipidus may be the critical clinical manifestation of agents that cause interstitial nephritis such as lithium or cisplatin. Nephrotoxicity is often reversible if the noxious agent is promptly removed.

Clinically necessary potential nephrotoxins should be used judiciously, not summarily avoided. Necessity of exposure, dosing parameters, and the use of drug levels or pharmacogenomic data, when available, should always be considered. Caution is particularly critical for patients with complex medical conditions that include pre-existing renal disease, cardiac disease, diabetes, and/or complicated surgeries. Alternative modalities of care provision should be also be considered when possible. Imaging modalities such as ultrasonography, radionuclide scanning, or magnetic resonance imaging may be preferable to contrast studies in some patients. Alternatively, judicious volume expansion with or without the administration of N-acetylcysteine might offer renoprotection when radioiodinated contrast studies are critical. Pharmacologic agents with no known renal effects can often be substituted for known nephrotoxins with equal clinical efficacy. In all cases, simultaneous use of known nephrotoxins should be avoided whenever necessary.