AASK COHORT STUDY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The AASK Cohort Study is a study that is an extension of the AASK clinical trial. (GCRC SPID 0301) The AASK full scale trial tested the effects of 3 different medications used as first line anti-hypertensive therapy and 2 levels of blood pressure control a usual goal and a low goal. Of the 1,094 participants in AASK, it was anticipated that 650-750 individuals would enroll in the cohort study. At the start of the cohort study, 787 participants were alive and not on dialysis. Of these 691 enrolled in this phase of the AASK study. As of 03/13/06, 548 remain alive and not on dialysis; 482 of the 548 have had at least 1 BP measurement. The purpose of this longitudinal cohort study is to identify factors affecting the rate and pattern of renal function loss in African Americans with Chronic Kidney Disease attributed to hypertension and to determine the long-term effects of the AASK trial on chronic kidney disease progression; Since the last progress report, the AASK investigators have proposed five major hypotheses. Hypothesis 1 We plan to examine the association between inflammation and cardiovascular disease in African Americans with Chronic Kidney Disease (CKD); The investigators plan to relate factors ascertained at the beginning of the AASK trial to outcomes assessed both during the trial phase alone and during the trial and cohort phases combined. We plan to determine the cross sectional relationship between markers of inflammation (C-reactive protein (CRP), interleukin 6 (IL-6), Interleukin 18, (IL-18), VCAM-1, and kidney function determined by estimated glomerular filtration rate (eGFR) serum creatinine Scr, degree of proteinuria) 1. To determine the longitudinal relationship between baseline markers of inflammation and the risk of clinical renal outcomes (reduced glomerular filtration rate (GFR), Stage V CKD (ESRD,) and death we hypothesize that higher levels of pro-inflammatory markers at baseline will be associated with an increased risk of future clinical renal outcomes. Hypothesis 2 We plan to examine the relationship between N-terminal Pro BNP (NT-pro BNP), cardiovascular and all cause mortality and hypothesize that increased NT-pro BNP is independently associated with a greater risk of cardiovascular and all cause mortality. Hypothesis 3 We plan to determine the prospective relationship between level of nocturnal BP and renal disease progression and hypothesize that nocturnal BP elevation will be directly associated with progression of kidney disease. We will examine the relationship between dipping status and kidney disease progression and hypothesize that nocturnal BP elevation will directly be associated with progression of kidney disease; that individuals with abnormal dipping profiles will have a faster rate of progression; and that level of nocturnal dipping status will be a stronger predictor of kidney disease progression than categories of dipping status. Hypothesis 4 We will investigate a possible link between proteinuria and the acceleration in the rate of decline in renal function over time. We hypothesize that changes in the level of proteinuria are directly associated with change in the rate of decline in eGFR between the period prior to and subsequent to the change; additionally we hypothesize that association between the change in proteinuria and change in the rate of decline in eGFR is independent of other risk factors for disease progression Urine protein to creatinine ratios. The outcome variable, eGFR, will be calculated at from data that was obtained at 6 month intervals during the full scale trial and will be calculated from data obtained yearly in the cohort study. The main predictor variable, will be measured in AASK cohort subjects at 6 month intervals and annually. Hypothesis 5 Finally the Cohort investigators will compare in African Americans with CKD attributed to HTN Non-traditional risk factors as predictors of cardiovascular disease events to traditional risk factors. The investigators hypothesize that C-reactive protein (CRP), phosphate level, calcium level, calcium phosphate product, uric acid, lipoprotein(a) (Lpa), homocysteine, UP/Cr left ventricular mass index LVNI diastolic dysfunction, ambulatory systolic and diastolic hypertension, and anemia are associated with development of cardiovascular events independently of traditional CVD risk factors