Factors Contributing to Nephrotoxicity

TABLE 29.1. Factors Influencing Susceptibility of the Kidney to Toxicants 

Concentration of chemicals in intraluminal fluid Reabsorption and/or secretion of chemicals through tubular cells Biotransformtion of protoxicants to reactive intermediates 

active transport processes within the proximal tubule may further raise the intracellular concentration of an actively transported toxicant. During active secretion and/or reabsorption, substrates generally accumulate in proximal tubular cells in much higher concentrations than present in either luminal fluid or peritubular blood. 

Fourth, certain segments of the nephron have a capacity for metabolic bioactivation. For example, the proximal and distal tubules contain isozymes of the cytochrome P450 monooxygenase system that may mediate intrarenal bioactivation of several protoxicants. Additionally, prostaglandin synthetase activity in medullary and papillary interstitial cells may be involved in cooxidation of protoxicants, resulting in selective papillary injury. 

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Diuretics have been shown to have variable effects in relationship to urinary calcium excretion and supersaturation, most notably including loop diuretic induced hypercalciuria and attenuation of urinary calcium excretion by thiazide diuretics. The factors contributing to nephrotoxicity are most commonly associated with multiple factors that favor calcium salt or uric acid deposition at the tubulo-interstitial level. Management of renal stone formation and nephrocalcinosis therefore presents a unique clinical challenge, balancing factors that increase risk for abnormal calcium salt deposition or crystallization, and factors that reduce this risk. 

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