Genomic biomarkers for chronic kidney disease
Division of Nephrology, Department of Internal Medicine, University of Michigan, 1150 W. Medical Center Drive, Ann Arbor, MI 48109-0680, USA.
Translational research : the journal of laboratory and clinical medicine
04/2012; 159(4):290-302. DOI: 10.1016/j.trsl.2012.01.020
Chronic kidney disease (CKD) remains a major challenge in nephrology and for public health care, affecting 14% to 15% of the adult US population and consuming significant health care resources. In the next 20 years, the number of patients with end stage renal disease is projected to increase by 50%. Ideal biomarkers that allow early identification of CKD patients at high risk of progression are urgently needed for early and targeted treatment to improve patient care. Recent success of integrating molecular approaches for personalized management of neoplastic diseases, including diagnosis, staging, prognosis, treatment selection, and monitoring, has strongly encouraged kidney researchers to pursue molecular definitions of patients with kidney disease. Challenges for molecular marker identification in CKD are a high degree of cellular heterogeneity of the kidney and the paucity of human tissue availability for molecular studies. Despite these limitations, potential molecular biomarker candidates have been uncovered at multiple levels along the genome--phenome continuum. Here we will review the identification and validation of potential genomic biomarker candidates of CKD and CKD progression in clinical studies. The challenges in predicting CKD progression, as well as the promises and opportunities resulting from a molecular definition of CKD will be discussed.
Available from: PubMed Central
- "Non-invasive, cost-effective biomarkers that allow frequent and accurate monitoring of graft function are needed in kidney transplantation [88,89]. As a biofluid, urine allows repeated and non-invasive collection, and its molecular composition highly reflects intrarenal events . "
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ABSTRACT: Although kidney transplantation has been an important means for the treatment of patients with end stage of renal disease, the long-term survival rate of the renal allograft remains a challenge. The cause of late renal allograft loss, once known as chronic allograft nephropathy, has been renamed "interstitial fibrosis and tubular atrophy" (IF/TA) to reflect the histologic pattern seen on biopsy. The mechanisms leading to IF/TA in the transplanted kidney include inflammation, activation of renal fibroblasts, and deposition of extracellular matrix proteins. Identifying the mediators and factors that trigger IF/TA may be useful in early diagnosis and development of novel therapeutic strategies for improving long-term renal allograft survival and patient outcomes. In this review, we highlight the recent advances in our understanding of IF/TA from three aspects: pathogenesis, diagnosis, and treatment.
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ABSTRACT: Here we report a metabolomics discovery study conducted on blood serum samples of patients in different stages of chronic kidney disease (CKD). Metabolites were monitored on a quality controlled holistic platform combining reversed-phase liquid chromatography coupled to high-resolution quadrupole time-of-flight mass spectrometry in both negative and positive ionization mode and gas chromatography coupled to quadrupole mass spectrometry. A substantial portion of the serum metabolome was thereby covered. Eighty-five metabolites were shown to evolve with CKD progression of which 43 metabolites were a confirmation of earlier reported uremic retention solutes and/or uremic toxins. Thirty-one unique metabolites were revealed which were increasing significantly throughout CKD progression, by a factor surpassing the level observed for creatinine, the currently used biomarker for kidney function. Additionally, 11 unique metabolites showed a decreasing trend.
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