"According to the recent discussion, acute kidney injury (AKI) significantly increases the risk of chronic kidney disease and severity while, duration and frequency of AKI seems to be important predictors of further disease development   . "
[Show abstract][Hide abstract] ABSTRACT: Strong indications have been presented that dietary poisoning with aristolochic acids (AA) is responsible for Endemic Nephropathy (EN) and AA associated cancer of the upper urinary tract (UUTC). Our recent investigation showed drastic urinary proteome changes in AA treated mice. This study was designed to identify proteome changes associated with AA nephrotoxicity in experimental animal model. The DBA and C57BL mice, which differ in AA sensitivity, were exposed to AA for 4days. The strategy for urinary, plasma and kidney tissue proteome study of AA exposed and control mice integrated gel-based and in-solution tryptic digestion combined with LC-ESI-MS/MS. To maximize proteome coverage, plasma fractionation scheme was developed and MS compatible sequential tissue extraction procedure was established. Proteomic analyses of urinary, plasma and kidney tissue tryptic digests resulted in identification of several cytoskeletal proteins, as well as proteins involved in kidney development and inflammatory response, that are differentially expressed in both AA exposed and control mice. These proteins are consistent with renal pathogenesis of endotoxicity and cancer. This proteomic strategy could be effectively translated for unbiased discovery of potential biomarkers for EN and associated UUTC in humans. At the same time, these results highlight the significance of AA exposure with EN. This article is part of a Special Issue entitled: Integrated omics.
Journal of proteomics 07/2012; 76. DOI:10.1016/j.jprot.2012.06.026 · 3.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the past two decades, a substantial increase in the incidence of acute kidney injury (AKI) and kidney injury requiring dialysis has occurred in North America. This increase has coincided with an increase in the incidence of end-stage renal disease (ESRD), which has exceeded that expected based upon the prevalence of chronic kidney disease (CKD). In order to better understand the association between these conditions, there has been a proliferation of studies that have examined the risks of incident and progressive CKD following AKI. Animal studies have shown that failed differentiation of epithelial cells following renal ischaemia-reperfusion injury might lead to tubulointerstitial fibrosis, supporting a biological mechanism linking AKI and CKD. Strong and consistent associations between AKI and incident CKD, progression of CKD and incident ESRD have also been shown in epidemiological studies. In this Review, we summarize the wealth of available data on the relationship between AKI and CKD, and discuss the implications of these findings for the long-term clinical management of patients following AKI. We also identify areas of active investigation and future directions for research.
[Show abstract][Hide abstract] ABSTRACT: The incidence rate of AKI is increasing across the spectrum of hospitalized children and adults. Given the increased morbidity and mortality associated with AKI, significant research effort has been appropriately focused on standardizing AKI definitions, identifying risk factors, and discovering and validating novel, earlier structural biomarkers of kidney injury. In addition, a growing body of evidence demonstrates that AKI is a risk factor for the future development or accelerated progression of CKD. Unfortunately, prospective observational studies have not consistently followed survivors of episodes of AKI for longitudinal outcomes after hospital discharge, which could lead to ascertainment bias in terms of over- or underestimation of CKD development. Furthermore, data show that clinical follow-up of AKI survivors is low. This lack of systematic study and clinical follow-up represents a potential missed opportunity to prevent chronic disease after an acute illness and improve outcomes. Therefore, prospective study of transitions of care after episodes of AKI is needed to identify which patients are at risk for CKD development and to optimally target therapeutic interventions.
Clinical Journal of the American Society of Nephrology 03/2013; 8(3):476-83. DOI:10.2215/CJN.12101112 · 4.61 Impact Factor
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