Nephrotoxicity

There has been a growing awareness that nephrotoxicity represents a key factor in human nephropathies, where, irrespective of the causative agent, only a few clinical end-effects are diagnosed. Thus nephropathies are generally classified as acute or chronic renal failure, malignancies or immunological changes. The weaknesses in diagnosing nephropathies arises because of the effective role the kidney plays in maintaining homeostasis, despite the fact that it has been extensively damaged. The frequencies of some type of chemically-induced acute renal failure is well documented, but the causes of chronic renal failure, malignancy, and other nephropathies are far more difficult to associate with a chemical aetiology. Many of the new therapeutic agents have important beneficial effects, but they are found to have marked nephrotoxic effects. Thus there is a growing urgency to increase the stringency of chemical safety evaluation for their potential nephrotoxic effects. This is strongly countered by the increased financial pressure to identify potentially nephrotoxic chemicals earlier in their development and humanitarian considerations to more closely relate animal test to the clinical situation. Part of the challenge may be achieved by the increasing use of in vitro techniques.

Inhalt
Species differences in renal structure and function Applications to the assessment of nephrotoxicity in man.- Lead induced nephrotoxicity: kidney calcium as an indicator of tubular injury.- Predicting the kidney burden of toxic metals.- A prospective study of proteinuria in cadmium workers.- Red blood cell negative charges as an index of the glomerular polyanion in chronic cadmium poisoning.- Some considerations on critical concentration of cadmium for renal toxicity in rats.- Historical perspective on cadmium-induced nephrotoxicity.- Cadmium may predispose mice to immune complex-mediated renal injury: another possible mechanism for cadmium-induced nephrotoxicity.- Nephrotoxicity of cadmium in chickens.- Differential effects of cadmium and mercury on lysosomal enzymes in the kidney of Myxine glutinosa.- The effects of cadmium and adriamycin on the isolated perfused glomerulus of Myxine glutinosa (Cyclostomata).- Protective effect of low concentrations of mercury against mercuric chloride-induced nephrotoxicity.- Induction of antinuclear antibodies by mercuric chloride in mice.- Analysis of unscheduled DNA synthesis and S-phase synthesis in F344 rat kidney after in vivo treatment with mercuric chloride.- In vitro and in vivo mercuric chloride-induced nephrotoxicity assessed by tubular enzymes release.- Prevention and reversal of mercuric chloride-induced increases in renal vascular resistance by captopril.- Regioselective acute tubular necrosis in renal cortical slices following mercuric chloride and potassium dichromate: localization and transport studies.- In-vivo bone lead measurements and renal effects.- Early indicators of lead nephropathy.- Nephrotoxicity of uranyl fluoride and reversibility of renal injury in the rat.- Low molecular weight proteins in thekidney of copper-loaded rats.- Gold nephropathy effect of gold on immune response to renal tubular basement membrane (TBM) antigen in mice.- Drug induced renal effects of cyclosporine, aminoglycoside antibiotics and lithium: extrapolation of animal data to man.- Lithium-induced distal nephron dilatation in young rabbits with associated encephalitazoan cuniculi related interstitial fibrosis.- Urinary phospholipids patterns after treatment with aminoglycoside antibiotics and cis-platinum.- Comparative uptake and lysosomal phospholipidosis induced by gentamicin components C1, C1a and C2.- Uptake and subcellular distribution of poly-L-aspartic acid, a protectant against aminoglycoside-induced nephrotoxicity, in rat kidney cortex.- Aminoglycoside antibiotics inhibit the phophatidylinositol cascade in renal proximal tubular cells : possible role in toxicity.- Silymarin ameliorates gentamicin nephrotoxicity.- Possible role of the renin-angiotensin system in the development of gentamicin nephrotoxicity in the rat.- Effect of furosemide and verapamil on gentamicin nephrotoxicity.- Renal phospholipidosis in rats after gentamicin and pefloxacin coadministration at low doses.- Morphological and functional impairments of the developing rat kidney exposed to gentamicin in utero.- Morphological and functional effects in rat neonates of aminoglycosides given to the mother during gestation.- Gentamicin-stimulated increase in para-aminohippurate uptake in renal cortical slices and isolated proximal tubular cells.- Investigation of gentamicin nephrotoxicity using renal brush border membrane vesicles.- Time dependent nephrotoxicity of amikacin.- Effect of latamoxef [Moxalactam] on tobramycin binding to kidney brush border membranes in rats.- Amphotericin-B nephrotoxicity is decreasedby intravenous flucytosine in the rat.- Apparent amoxapine nephrotoxicity: dependence on rhabdomyolysis and acidosis.- Mechanisms of cyclosporin A nephrotoxicity rat to man.- The effects of cyclosporin A on the urine excretion of specific proteins in humans.- Renal tubular function in experimental and clinical cyclosporin nephrotoxicity.- The effect of biliary cannulation or ligation on cyclosporin A (CsA) nephrotoxicity in the rat.- Cyclosporine A-induced lipid peroxidation in rat renal microsomes and effect on glucose uptake by renal brush border membrane vesicles.- Chronic renal tubular damage caused by cyclosporin A.- Effects of acute and chronic cyclosporine administration on glomerular haemodynamics in rats.- Intracellular localization of cyclosporin A in the rat kidney.- Distribution of platinum amongst the subcellular organelles of the rat kidney after oral administration of cisplatin.- Alpha-methylglucose uptake by isolated rat kidney proximal tubular cells as a parameter for cell integrity in vitro.- Lipid peroxidation as a mechanism of cisplatin-induced nephrotoxicity.- Renal toxicity of cis-dichlorodiammine platinum in rats.- Uptake of cisplatin (195mpt) into LLCPK1 cells in the presence of diethyldithiocarbamate, (DDTC) mercaptoethane-sulphate (MESNA) and amiloride.- The effect of amiloride on cisplatin induced nephrotoxicity and the renal uptake of cisplatin (195mpt) in male Wistar rats.- The response of the pig kidney to a combination of cisplatin and irradiation.- The effect of acetazolamide and furosemide on lithium clearance and cisplatin nephrotoxicity in the rat.- Sensitivity of in vitro ion accumulation, gluconeogenesis and other parameters as indicators of cisplatin-induced renal toxicity.- Assessment of nephrotoxicity by analysis of arandomised multi-centre comparative study regarding the previous extent of kidney damage.- Drug pharmacokinetics in renal failure influence of disease type.- Analgesic related renal injury in man.- Progression of renal failure in analgesic associated nephropathy.- The renal reponse of a nonhuman primate (baboon) to certain nonsteroidal anti-inflammatory drugs.- Morphological changes in the pig kidney associated with an acutely induced renal papillary necrosis.- Upper urothelial carcinoma, using N-butyl-N-(4-hydroxybutyl)-nitrosamine and an acute papillary necrosis.- High resolution microscopic changes in an acutely induced renal papillary necrosis: morphology and enzyme histo-chemistry.- Cannulation of the bile duct protects against para-aminophenol-induced nephrotoxicity in the Fischer 344 rat.- Effects of antidotes on the hepato- and nephro-toxicity of paracetamol in the rat.- Celiptium induced lipid peroxidation and toxicity in rat renal cortex.- Nephrotoxicity of ifosfamide in combination chemotherapy.- Risk evaluation of muzolimine and furosemide in experimental models of nephrotoxicity.- The role of oxidative stress in cephaloridine nephrotoxicity.- Studies on the mechanism of radiological contrast media induced renal failure.- Radiocontrast nephrotoxicity in diabetes: clinical considerati…