Renal disease toxic nephropathy

Immunological-mediated toxic-induced renal diseases are multifactorial Genetic control of metal-induced autoimmunity and nephropathy... 

Diseases of the kidney that are discussed in this section include (1) the uremic syndrome, (2) chronic kidney disease, (3) end-stage renal disease, (4) diabetic nephropathy, (5) hypertensive nephropathy, (6) glomerular diseases, (7) interstitial nephritis, (8) polycystic Iddney disease, (9) polycystic kidney disease, (10) toxic nephropathy, (11) obstructive uropathy, (12) tubular diseases, (13) renal calculi, and (14) cystinuria. In addition, this section also includes discussions on (1) prostaglandins and NS AIDS in kidney disease, (2) monoclonal light chains and kidney disease, and (3) urinary osmolality. 

Chaparral has also been associated with cystic renal disease in rats (Grice et al., 1968 Goodman et al., 1970 Evan et al., 1979) and humans (Smith et al., 1994 see Section 16.5). Toxicity studies revealed that cystic nephropathy could be reliably induced in rats fed a 2% by wt concentration of NDGA for 6 wk (Evan et al., 1979). Renal toxicity may stem from the accumulation of theo-quinone metabolite. NDGA is converted to this metabolite in the rat ileum and cecum, absorbed into the bloodstream, and excreted by the kidney, where it is reabsorbed by the epithelial cells of the proximal convoluted tubules. In the rat, tubular changes are thus confined to the tubules in the outer cortex (i.e., the proximal convoluted tubules) (Grice et al., 1968). 

Chronic renal failure as a result of toxic or environmental exposures usually involve progressive chronic interstitial nephropathy, which, in addition to prolonged analgesic abuse, may result from chronic lithium ingestion, heavy metal exposure or treatment with cyclosporine [2]. Exposure to hydrocarbons may accentuate the renal insufficiency in patients with preexisting renal disease or result in the appearance of the nephrotic syndrome or a form a rapidly progressive glomerulonephritis. 

Persons at greatest risk for NSAID hemodynamic nephropathy generally have pre-existing renal insufficiency, medical problems associated with high plasma renin activity (hepatic disease with ascites, decompensated congestive heart failure, or intravascular volume depletion), or systemic lupus erythematosus. Additional risk factors include atherosclerotic cardiovascular disease and diuretic therapy. The elderly are also at higher risk due to interaction of prevalent medical problems, multiple drug therapies, and reduced renal hemodynamics. Advanced age, however, has not been shown to be an independent risk factor for toxicity in limited trials in otherwise healthy elderly subjects. Combined NSAID and ACEl or ARB therapy is also a concern and should be avoided. 

Ochratoxin A was first evaluated by the Committee at its thirty-seventh meeting (Annex 1, reference 94). The key adverse effects noted involved toxicity to the kidney. The Committee established a provisional tolerable weekly intake (PTWI) of 112 ng/kg body weight (bw), on the basis of deterioration of renal function in pigs, for which the lowest-observed-effect level (LOEL) was 8 pg/kg bw per day, and application of a safety factor of 500. At that time, the Committee recommended that further studies be conducted to elucidate the role of ochratoxin A in causing nephropathy in pigs, the mode of action of ochratoxin A as a kidney carcinogen in rodents and the possible role of ochratoxin A in human disease. 

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