Nephrotoxic tubular and interstitial lesions: morphology and classification

Nephrotoxic renal injury, and especially drug nephrotoxicity is now a common cause of acute renal failure. The most common patterns of renal injury produced by nephrotoxins, tubular damage, and interstitial nephritis, are discussed here. Toxic agents which are primarily tubular toxins include certain antibiotics, cisplatinum, anesthetics, and radiocontrast agents. In tubules injured by toxins, alterations range from subtle ultrastructural abnormalities to extensive tubular necrosis. Mechanisms of tubular injury include direct tubular cell toxicity, and alterations in intrarenal blood flow producing secondary tubular damage. Other commonly used therapeutic agents, including the penicillins, other antibiotics, and non-steroidal anti-inflammatory agents, produce renal dysfunction by inducing interstitial nephritis. Long-term analgesic abuse is associated with a particularly striking interstitial damage with frank papillary necrosis. Criteria for differentiating primary tubular injury with inflammation and primary interstitial nephritis with tubular injury are discussed. Individual commonly-used therapeutic agents are considered in some detail, with discussion of both clinical and morphological aspects of drug nephrotoxicity.