The relentless progression of chronic kidney disease (CKD) in the setting of optimal blood pressure therapy and the increased risk of atherosclerotic cardiovascular disease (ASCVD) among persons with CKD are major public health concerns. Increasingly, it has been documented that CKD and ASCVD share common antecedents. Markers of inflammation have emerged as highly predictive of ASCVD events in persons without CKD. However, the prospective role of inflammation in the setting of moderately impaired renal function has received scant attention. In this proposal, we plan to assess the role of inflammation on CKD progression and on the occurrence of ASCVD events using specimens collected as part of the African- American Study of Kidney Disease and Hypertension (AASK) study. AASK is a completed randomized, controlled trial that tested the effects of specific blood pressure lowering medications (Angiotensin converting enzyme inhibitor, calcium channel blocker, beta blocker), as well as level of blood pressure control, on kidney disease progression in 1,094 African-Americans with hypertensive CKD.
The specific aims of the current proposal are: 1a. To determine the cross-sectional relationship between markers of inflammation and kidney function (GFR, serum creatinine, and degree of proteinuria), 1b. To determine the longitudinal relationship between baseline levels of markers of inflammation and the risk of future clinical renal outcomes (reduced glomerular filtration rate (GFR), end-stage renal disease (ESRD) or death), 2a. To determine the cross-sectional relationship between markers of inflammation and prevalent CVD, 2b. To determine the longitudinal relationship between baseline levels of markers of inflammation and the risk of clinical cardiovascular disease events., 3. To determine the effect of antihypertensive medications (randomized therapies: angiotensin converting enzyme inhibitor, dihydropyridine calcium- channel blocker, beta blocker) on markers of inflammation. In longitudinal analyses, we will also determine the potential for effect modification by randomized treatment groups for both kidney and CVD outcomes. Ultimately, results of this study should enhance our understanding of risk factors and processes that determine the progression of kidney disease and the risk of cardiovascular disease among African-Americans with hypertension. Such results might eventually lead to new strategies that delay or prevent end stage kidney disease and its complications. ? ?
