Nephrotoxins

Nephrotoxins are substances that cause damage to the kidneys. They include drugs, environmental chemicals, metals, and certain biological or endogenous toxins. Exposure can result in acute kidney injury or contribute to chronic kidney disease, depending on dose, duration, and individual susceptibility.

Damage from nephrotoxins occurs through several mechanisms. Direct cellular toxicity can injure renal tubular cells or glomerular structures. Inflammation and immune-mediated reactions can cause interstitial nephritis. Altered renal blood flow may reduce filtration, and crystal formation within tubules can obstruct flow. The proximal tubule is particularly vulnerable, but injuries can involve other nephron segments and the interstitium, leading to acute tubular necrosis, acute interstitial nephritis, or, less commonly, glomerulopathy.

Common nephrotoxins include:

- Aminoglycoside antibiotics (e.g., gentamicin, amikacin) causing acute tubular necrosis.

- Cisplatin and other platinum-based chemotherapies causing proximal tubular injury.

- Amphotericin B and certain antifungals causing tubular dysfunction.

- Nonsteroidal anti-inflammatory drugs and calcineurin inhibitors (cyclosporine, tacrolimus) causing hemodynamic injury or interstitial nephritis.

- Radiographic contrast media causing contrast-induced nephropathy.

- Heavy metals (lead, mercury, cadmium) causing tubular and glomerular injury.

- Ethylene glycol and methanol poisoning, with fomepizole as an antidote.

- Aristolochic acid-containing herbal preparations causing nephropathy.

- Myoglobin from rhabdomyolysis or severe dehydration can injure renal tubules.

Clinical approach involves identifying exposure, stopping the offending agent, and providing supportive care. Hydration and correction of electrolyte disturbances are central, along with avoidance of additional nephrotoxins. Renal replacement therapy may be required in severe cases. Antidotes or chelating agents are used for select toxins (e.g., fomepizole for ethylene glycol/methanol; EDTA or other chelators for certain metals). Prevention, especially in at-risk patients, is essential.