Chronic kidney disease (CKD) affects more than one in ten Americans. CKD does progress to end stage kidney disease (ESKD) in some, but not all patients, despite 'optimal'management. Biomarkers that 'predict'the risk and/or rate of progression in individual CKD patients sufficiently to guide preventive interventions are currently not available. Thus, discovery of 'predictive'biomarkers for CKD progression is an important unmet need and the goal of the proposed New York CKD Biomarker Discovery Program. The Program will bring together an interdisciplinary team of nephrologists, laboratory medicine specialists, pathologists, and statisticians to achieve this goal, in collaboration and with guidance from the NIDDK CKD Biomarker Consortium. In preliminary discovery work by our groups, 78 candidate biomarkers, including neutrophil gelatinaseassociated lipocalin (LCN2 or NGAL), a urinary biomarker for acute kidney injury, were identified by genomewide transcriptional profiling and systems biology analysis in kidney tissue of a range of murine models with diabetic, immune-mediated, and glomemlar renal diseases.
In Aim 1 (Qualification Phase) we propose to examine the urinary excretion profiles of up to 20 top candidates, selected from the 78 candidate CKD biomarkers, and including NGAL, in few selected 'gold standard'cases of advanced CKD, and controls by systematic western blotting. Next, we will establish and characterize commercially available ELISA for candidates that passed the western blot screen.
In Aim 2 (Verification Phase), the top candidate biomarkers will be measured by ELISA in urine samples of patients with progressive or non-progressive CKD that have been followed in well-characterized, longterm cohorts, including the African-American Study of Kidney Disease in Hypertension (AASK), the Modification of Diet in Renal Disease (MDRD), and the Diabetes Control And Complications Trial/Epidemiology Of Diabetes Intervention And Complications (DCCT/EDIC), together with samples from patients without CKD. Statistical analysis will be applied to assess the candidate CKD biomarker as 'predictors'of progression of CKD. Intrarenal expression of highly credentialed candidates (anticipated 2 to 4) delivered in Aim 2, will be assessed by immunohistochemistry at the Renal Pathology Laboratory at Columbia University. The long-term goal of the proposed New York CKD Biomarker Program is to work collaboratively with the emerging NIDDK CKD Biomarker Consortium to discover and develop promising 'predictive'CKD biomarkers towards clinical application.
Biomarkers that 'predict'the risk and/or rate of progression in individual CKD patients sufficiently to guide preventive interventions are currently not available. Thus, discovery of 'predictive'biomarkers for CKD progression is an important unmet need and the goal of the proposed New York CKD Biomarker Discovery Program.
|Bottinger, Erwin P (2010) Lights on for aminopeptidases in cystic kidney disease. J Clin Invest 120:660-3|