Diabetic Kidney Disease

Chronic kidney disease (CKD) and end stage renal diseases (ESRD) represent an enormous burden in the United States and worldwide. Diabetic kidney disease (DKD) is the single largest cause of CKD and ESRD. DKD is progressive and few therapies are able to alter its course. Currently, clinical risk assessment of DKD depends upon measures of estimated GFR (eGFR) and glomerular injury (albuminuria). However, these two markers fall short of providing sufficient risk stratification for progression to advanced DKD, ESRD and cardiovascular (CV) events. Development of prognostic biomarkers to identify patients with a high risk of progression will aide future clinical trials by serving to enrich the enrollment with patients with a higher event rate, thereby allowing for a reduced sample size to detect an intervention with a given relative risk reduction. Moreover, there is an urgent need to identify the subgroups of patients that are most likely to drive benefit from various forms of intensive therapy (predictive biomarkers) and to identify better surrogate endpoints. By leveraging the data and stored blood and urine samples from three large clinical trials in patients with type 2 diabetes (VA- NEPHRON-D, ACCORD, and Sun-MACRO), we will measure blood and urine biomarkers from diverse pathways including inflammatory, glomerular, tubule injury, and tubulointerstitial fibrosis markers.

There are three principal aims of this project:

• Aim 1 - To derive and validate biomarker panels for prognosis of renal endpoints (GFR progression and dialysis)
• Aim 2 - To derive and validate biomarker panels for prognosis of cardiovascular events and death
• Aim 3 - To test for effect modification by biomarkers to determine if there were sub-groups that demonstrated benefit with various interventions employed in the trials (specifically, dual renin angiotensin aldosterone blockade, intensive glycemic control, or lower systolic blood pressure targets)

Funding Information for this Project

Funding for this project comes from the NIH/NIDDK (U01DK106962, “Leveraging Clinical Trials of Diabetic Kidney Disease to Advance Biomarkers”) and utilizes blood and urine samples from two large clinical trials: VA- NEPHRON-D and ACCORD

• VA-NEPHRON-D (ClinicalTrials.gov Identifier: NCT00555217)
• ACCORD (ClinicalTrials.gov Identifier: NCT00000620)

PubMed

Diabetic Kidney Disease