The kidneys can be damaged by a large number of therapeutic agents. The aim of this article is to discuss the pathological features of drug-induced renal disease as diagnosed by kidney biopsy. The literature is reviewed and cases seen by the authors that have a known drug association are analysed. Mechanisms of injury are varied and all renal structures may be affected. The tubulointerstitial compartment is most frequently involved, but glomerular and vascular lesions are seen in a significant proportion of cases.
Humans ; Kidney Diseases ; chemically induced ; pathology

Aristolochic Acids ; adverse effects ; Humans ; Kidney Diseases ; chemically induced

Melamine (Tripolycyanamide) and its derivatives have recently become a public concern on food safety. To better understand melamine and its major derivative cyanuric acid.literature on their chemical properties, metabolism, biological effects, relevant toxicology studies, and the detection methods is reviewed. Studies indicate that the acute toxicity of melamine and cyanuric acid is low. In mammalian, these compounds are hardly metabolized in vivo and are rapidly eliminated in the urine. When used in large dosage,these compounds demonstrate marked renal toxicity,as well as toxic effect towards heart. The renal toxicity is exemplified by the calculi formation, acute renal failure, and subsequently induced carcinomas of the urinary bladder. Among the tested species, male cats and rats are more prone to be affected by the compounds. The HPLC/MS/MS is becoming the mainstay of the detection methods. Despite of the achieved knowledge on melamine and cyanuric acid, further research is warranted to unveil the mechanism of underlying susceptibility of kidney, to develop better analytic methods,and to explore possible biomarkers for better clinical diagnosis.
Animals ; Carcinogens ; toxicity ; Cats ; Female ; Kidney Diseases ; chemically induced ; Male ; Rats ; Species Specificity ; Triazines ; toxicity ; Ureteral Calculi ; chemically induced

Angiotensin II ; metabolism ; Cisplatin ; adverse effects ; Humans ; Kidney ; drug effects ; Kidney Diseases ; chemically induced ; metabolism

OBJECTIVETo lessen the occurrence of contrast-induced nephropathy (CIN), the preventive measures of CIN were reviewed.

DATA SOURCESThe data used in this review were from PubMed with relevant English articles and from Chinese Knowledge Information (CNKI) published from 1989 to 2009. The search terms were "contrast medium", "contrast-induced nephropathy" and "prevention". Articles involved in prevention of CIN were selected.

STUDY SELECTIONCIN is the third most common cause of acute kidney injury and is associated with an unfavorable prognosis. The best treatment is prophylaxis because CIN can not be reversed or ameliorated.

RESULTSThirty articles were included. Among various preventive measures, pericatheterization hydration is almost universally accepted as an appropriate and safe measure to prevent CIN, although there is no agreement as to composition, amount, and timing of hydration. Based on the use of concomitant nephrotoxic agents or high doses of contrast medium (CM) is one of risk factors for CIN, discontinuation of potentially nephrotoxic drugs 2 - 3 days before and after the procedure until renal function recover, and using the lowest possible dose of CM can decrease the risk of CIN. It is promising that removing the majority of CM from the coronary sinus, before it enters the systemic circulation, during coronary angiography can reduce the risk for CIN in animal studies and in limited clinical trials. Inconsistent data exist with respect to application of some vasodilators (endothelin antagonists and adenosine antagonists) and antioxidants (N-acetylcysteine and statins) in preventing CIN in high-risk patients, and new vasodilators and antioxidants continue to be tested.

CONCLUSIONSPericatheterization hydration, discontinuation of nephrotoxic drugs, and using the lowest possible dose of CM are effective measures to lessen the risk for CIN. Other prophylactic strategies and some drugs are promising, but further confirmation is required.

Contrast Media ; adverse effects ; Humans ; Iodine ; adverse effects ; Kidney Diseases ; chemically induced ; prevention & control

Anti-Bacterial Agents ; adverse effects ; Humans ; Integrative Medicine ; Kidney Diseases ; chemically induced ; therapy

Drug-induced nephrotoxicity is very common in both new drug development and clinic practice. Various drugs can induce kidney injuries, including tubulointerstitial, glomerular and renal vascular disease. To investigate the mechanism of drug induced nephrotoxicity is important for risk reduction of new drug development, reasonable drug usage, early discovery and effective prevention/treatment of adverse effects in clinics.
Acute Kidney Injury ; chemically induced ; Animals ; Anti-Infective Agents ; adverse effects ; Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; Antineoplastic Agents ; adverse effects ; Humans ; Immunosuppressive Agents ; adverse effects ; Kidney Diseases ; chemically induced ; Kidney Tubular Necrosis, Acute ; chemically induced ; Nephritis, Interstitial ; chemically induced ; Renal Insufficiency ; chemically induced

Adult ; Female ; Humans ; Ketamine ; adverse effects ; Kidney ; drug effects ; physiopathology ; Kidney Diseases ; chemically induced ; complications ; Substance-Related Disorders ; complications

OBJECTIVETo investigate the nephrotoxic effects of methyl cantharidimide tablets on urinary protein and enzymes in Beagle dogs.

METHODBeagle dogs were randomly divided into negative control group(blank tablet), methyl cantharidimide tablets group (6.11,12.21, 24.42 mg x kg(-1)), continuously 30 days of oral adminiStration, once a day. The drug and control group were collected and determined fresh urine in 1, 2, 3 and 4 weeks of the administration; Serum urea nitrogen (BUN), creatinine (Crea), total protein (TP) and albumin (ALB) as well as sodium, potassium, chloride electrolyte were determined on 15 and 30 days of the administration; Urine albumin (mAlb), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin( NGAL), N-acetyl-beta-D-glucosaminidase (NAG), clusterin, beta2-microglobulin (beta2-MG), alpha1-microglobulin (alpha1-MG), alanine aminopeptidase( AAP) and im- munoglobulins IgG were tested on 15 and 30 days of the administration.

RESULTCompared with the control group, urine protein and white blood cells was significantly increased in each dose group. On 15 days of the administration, mAlb were higher in each dose group, KIM-1, NGAL, clusterin, NAG and AAP were significantly higher in high-dose group, while the middle and low dose group had no significant difference, as well as blood SCr and BUN no obvious abnormalities. On 30 days, mAlb, KIM-1, clusterin, NAG, AAP were increased in each dose group, appearing dose-effect relationship, beta2-MG and NGAL levels were significantly increased in high-dose group. Contents above indicators were increased with significant dose and time relationship, and serum BUN, Scr were correlated, suggesting that urine mAlb, KIM-1, clusterin, NAG and AAP indicators that can sensitively respond the changes of proteins and enzymes in urine.

CONCLUSIONMethyl cantharidimide tablets has a renal toxicity, urine mAlb, KIM-1, clusterin, NAG and AAP can be used as the early nephrotoxic biomarkers of methyl cantharidimide tablets.

Animals ; Biomarkers ; urine ; Dogs ; Female ; Kidney ; drug effects ; Kidney Diseases ; chemically induced ; Male ; Proteins ; metabolism ; Tablets ; adverse effects ; Urine ; chemistry

OBJECTIVEWe tested whether melamine nephrotoxicity was exacerbated by urate (a typical component of renal stones in humans) in rats with hyperuricemiainduced by the uricase inhibitor, potassium oxonate (Oxo).

METHODSRats were exposed to melamine or Oxo alone or combinations of melamine (200-400 mg/kg) and Oxo (200-600 mg/kg) for 3 consecutive days. Kidney injury was evaluated by renal biochemical functions, histomorphology, and lipid peroxidation. Kidney crystals were analyzed for their composition.

RESULTSNephrotoxicity was minimal in animals administered melamine or Oxo alone, but it was demonstrable in animals administered at least 800 mg/kg of the two compounds combined. All rats in the 400+600 (melamine+Oxo) and 400+400 mg/kg groups and 4 out of 6 in the 200+600 mg/kg group died within 3 days; no rat died in the 200+400 or 200+200 mg/kg group. Dose-dependent renal damage resembling clinical findings in affected patients was observed in rats administered the two compounds. Crystal composition determination revealed the existence of melamine and uric acid in the affected kidneys, resembling human stones.

CONCLUSIONOur findings suggest that uric acid plays a key role in melamine-related kidney injury in humans. Future studies should consider uric acid together with melamine when examining adverse effects in humans.

Animals ; Disease Models, Animal ; Hyperuricemia ; chemically induced ; complications ; Kidney Diseases ; chemically induced ; Lipid Peroxidation ; drug effects ; Male ; Oxonic Acid ; Rats, Wistar ; Triazines ; toxicity