N-acetylcysteine for the prevention of non-contrast media agent-induced kidney injury: from preclinical data to clinical evidence

Adriamycin nephropathy (AN) is a rodent model of chronic kidney disease that has been studied extensively and has enabled a greater understanding of the processes underlying the progression of chronic proteinuric renal disease. AN is characterized by podocyte injury followed by glomerulosclerosis, tubulointerstitial inflammation and fibrosis. Genetic studies have demonstrated a number of loci that alter both risk and severity of renal injury induced by Adriamycin. Adriamycin-induced renal injury has been shown in numerous studies to be modulated by both non-immune and immune factors, and has facilitated further study of mechanisms of tubulointerstitial injury. This review will outline the pharmacological behaviour of Adriamycin, and describe in detail the model of AN, including its key structural characteristics, genetic susceptibility and pathogenesis. © 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology.

Treatment failures following vancomycin therapy in patients with methicillin-resistant Staphylococcus aureus infections have led to the utilization of higher doses of this antibiotic to achieve the trough concentrations of 10-20 μg/mL recommended by the Infectious Diseases Society of America clinical practice guideline. However, many questions remain on the safety of such high doses of vancomycin, specifically their nephrotoxic effects. In this review, we have collected available evidence on the nephrotoxicity of vancomycin, particularly in terms of its mechanism, incidence, predisposing factors and special target populations. The data were collected by searching Scopus, PubMed, Medline, and Cochrane database systematic reviews. The key words used as search terms were "vancomycin", "nephrotoxicity", "renal failure", "renal damage", "risk factors", "infants", "children", "adult", "elderly" and "pregnancy". We have included all relevant animal and human studies up to the date of publication. Vancomycin-induced renal toxicity was reported in 10-20 % and 30-40 % of patients following conventional and high doses of vancomycin therapy, respectively .The most probable mechanism for its nephrotoxicity can be at least partially attributable to an increased production of reactive oxygen species and oxidative stress. There are a number of different risk factors which could accelerate or potentiate the occurrence of vancomycin-induced nephrotoxicity, with the most documented risk factors being high trough vancomycin level (especially >20 mg/L) or doses (>4 g/day), concomitant treatment with nephrotoxic agents, prolonged therapy (even more than 7 days), and admittance to an intensive care unit (especially prolonged stay). It is necessary to carry out more studies, especially those focused on the association between nephrotoxicity and high trough levels of vancomycin.

To perform a systematic review comparing the diagnostic accuracy of CysC with SCr. MEDLINE and EMBASE (January 1984-February 2006) were searched. Studies included i) evaluated CysC against a recognised 'gold standard' method for determining GFR using a receiver operating characteristics (ROC) curve analysis and ii) included data that could be extracted into a 2x2 table. The search identified 27 population groups in 24 studies (n=2007) that compared the diagnostic accuracy of CysC with SCr. The diagnostic odds ratios (DORs) (95% CI) of predicting renal dysfunction derived from a Moses-Littenberg linear regression model were 3.99 (3.41-4.57) for CysC and 2.79 (2.12-3.46) for SCr. The diagnostic accuracy for impaired renal function favours CysC. However, the confidence intervals for the pooled DORs for the biomarkers overlap. The ability of CysC (cut-off values between 0.9 and 1.4 mg/L) to rule in renal impairment (as measured by inulin-determined GFR of 60-79 mL/min/1.73 m2) in persons in whom this is suspected is large and conclusive.