Nephrotoxicity etiology

Two of the natural CDs are known to be parenterally unsafe due to nephrotoxic effects [9], The etiology of the nephrotoxicity of a- and P-CD is unknown but is believed to be related to either CD uptake by kidney tubule cells resulting in disruption of intracellular function or the extraction of lipid membrane components by the CDs. The latter is suggested to be of validity since there seems to be a linear correlation between the ability of some CDs to disrupt cellular membranes and kidney nephrotoxicity [2, 6], The ability of CDs to cause red blood cell hemolysis and membrane irritation seems also to correlate with their ability to extract lipid membrane components cholesterol and phospholipids [10,11],... 

It is well established that toxic nephropathies are not restricted to a single type of renal injury. Some chemicals target one discrete anatomical region of the kidney and may affect only one cell type. Chemical insult to the kidney may result in a spectrum of nephropathies that are indistinguishable from those that do not have a chemical etiology. Nephrotoxicity and neural disorders in animals and humans have occurred due to prolonged exposure to chemical substances. These may be broadly categorized as ... 

Other protease inhibitors have also been rarely associated with kidney injury. A single case of interstitial nephritis and reversible AKI in a patient treated with atazanavir has also been reported [153] Acute kidney injury attributed to ritonavir has been reported in several patients [154-157], the majority of whom were receiving concomitant nephrotoxic medications, while others had preexisting kidney disease or were volume depleted. In several patients, AKI recurred upon ritonavir rechallenge. Kidney biopsies were not performed, so histopathologic correlates and etiology of kidney injury were not precisely defined. 

Cousins MJ, Mazze Rl, Kosek JC, Elitt BA, Eove EV. The etiology of methoxyflurane nephrotoxicity. J Pharmacol Exp Ther 1974 190(3) 530-41. 

In the search for a role for such exposure, the following questions need to be answered (i) does occupational/environmental exposure to a potential nephrotoxic substance play a direct etiological role in the induction of a particular renal disease, (ii) does the exposure correlate with an increased risk for the progression of renal damage already present in patients with glomerulonephritis, diabetic nephropathy, hypertensive renal disease etc. (iii) dobothpossibihties have to be considered concomitantly or separately ... 

Several patients have also been reported with acute renal failure attributed to ritonavir [126-129]. Most of these patients were on other potentially nephrotoxic medications, and some had volume depletion or preexisting kidney disease. In several patients, ARF recurred upon rechallenge with ritonavir. None of the patients had renal biopsies performed, so there is no information on the histopafhologic correlates and etiology of the renal failure. 

Although the EDTA test has been shown to be safe even in the presence of renal failure [77], the cumulative nephrotoxicity of prolonged EDTA therapy in patients with markedly reduced glomerular filtration rates is unknown. Reports that CaNa2EDTA therapy has been followed by deterioration of renal function warrant careful follow-up of treated patients [78]. Despite these caveats, it may be appropriate to perform EDTA lead-mobilization tests in individuals with gout or hypertension and renal failure or interstitial nephritis of unknown etiology since a positive test may provide the best available indication of etiology. 

The earlier literature on the association between human exposure to ochratoxin A and the occurrence of Balkan endemic nephropathy and associated urinary tract tumours was summarized in the previous evaluation (Annex 1, reference 153. Contrary to the clear causal evidence of ochratoxin A-induced nephrotoxicity and kidney carcinogenicity in rodents, the significance of ochratoxin A for human health remains unclear from the available epidemiological evidence. Moreover, ochratoxin A exposure is only one of several hypotheses concerning an environmental etiology for Balkan endemic nephropathy. 

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