Nephrotoxicity

Nephrotoxicity is toxicity to the kidneys resulting from exposure to drugs, toxins, or endogenous substances. It can manifest as acute kidney injury (AKI) or contribute to chronic kidney disease (CKD) with repeated or sustained injury. The condition is a common cause of AKI in hospitalized patients and arises from various mechanisms affecting renal cells and perfusion.

Common nephrotoxic agents include aminoglycoside antibiotics (for example, gentamicin), platinum-based chemotherapies (such as cisplatin), nonsteroidal anti-inflammatory drugs, calcineurin inhibitors (cyclosporine, tacrolimus), amphotericin B, and radiographic iodinated contrast media. Other contributors include heavy metals, solvents, herbals, and intra-arterial injections. Mechanisms of injury range from tubular epithelial cell toxicity and interstitial inflammation to glomerular injury and ischemia due to altered renal blood flow. Oxidative stress, mitochondrial dysfunction, and impaired repair processes often participate in the injury.

Risk factors for nephrotoxicity include advanced age, preexisting CKD, dehydration, hypotension, diabetes, hypertension, sepsis, and concurrent exposure to multiple nephrotoxins. Diagnosis typically relies on a rise in serum creatinine or a decline in estimated glomerular filtration rate after exposure, with supportive urinalysis findings such as granular casts or proteinuria. Additional biomarkers (for example, NGAL, KIM-1) are being studied but are not yet universally used in routine practice.

Prevention focuses on risk assessment, dose adjustment for kidney function, adequate hydration, minimizing radiographic contrast dose, and avoidance or staggered use of nephrotoxins. Treatment emphasizes stopping the offending agent, providing supportive care, correcting electrolytes, and, in severe cases, initiating renal replacement therapy. Prognosis varies with the agent and promptness of intervention, ranging from full recovery to progression to CKD.