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As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant(More)
The Family Investigation of Nephropathy and Diabetes (FIND) was initiated to map genes underlying susceptibility to diabetic nephropathy. A total of 11 centers participated under a single collection protocol to recruit large numbers of diabetic sibling pairs concordant and discordant for diabetic nephropathy. We report the findings from the first-phase(More)
BACKGROUND Tubulo-interstitial nephropathy (TIN) is a common cause of chronic kidney disease (CKD). Consumption of an adenine-containing diet causes the accumulation of 2,8-dihydroxyadenine in the renal tubules triggering intense chronic TIN and progressive CKD in rats. CKD in this model is associated with, and largely driven by, oxidative stress and(More)
RATIONALE Diabetes mellitus is frequently complicated by cardiovascular disease, such as vascular calcification and endothelial dysfunction, which have been associated with bone morphogenetic proteins (BMPs). OBJECTIVE To determine whether hyperglycemia in vitro and diabetes in vivo promote vascular BMP activity and correlate with vascular calcification.(More)
Many studies have investigated the regulation of the Na+/ Ca2+ exchanger, NCX1, but limited data exist on transcriptional regulation of the NCX1 gene. We have identified the transcription start sites of three tissue-specific alternative promoters of NCX1 transcripts from rat heart, kidney, and brain. We have characterized the cardiac NCX1 promoter, from(More)
The cardiac sarcolemmal Na(+)/Ca(2+) exchanger plays a primary role in Ca(2+) efflux and is important in regulating intracellular Ca(2+) and beat-to-beat contractility. Of the three Na(+)/Ca(2+) exchanger genes cloned (NCX1, NCX2, and NCX3), only NCX1 is expressed in cardiac myocytes. NCX1 has alternative promoters for heart, kidney, and brain(More)
BACKGROUND Researchers have long been interested in counting the number of cells within the glomerulus. Investigators using different techniques have yielded conflicting results. The most direct method is to count the cells in serial sections from the entire glomerulus. This Exhaustive Count method is not usually practical. The disector/fractionator method(More)
OBJECTIVE African Americans (AAs) and Hispanics have higher diabetes and end-stage renal disease but similar or lower early chronic kidney disease (CKD) compared with whites. Inflammation plays a critical role in the pathogenesis of diabetes-related CKD. We postulated that in contrast to the general population, AAs and Hispanics have a higher prevalence of(More)
BACKGROUND Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with type 1 and type 2 diabetes. The multicenter FIND consortium aims to identify genes for DN and its associated quantitative traits, e.g. the urine albumin:creatinine ratio (ACR). Herein, the results of whole-genome linkage analysis and a sparse association scan(More)
The podocyte depletion hypothesis has emerged as an important unifying concept in glomerular pathology. The estimation of podocyte number is therefore often a critical component of studies of progressive renal diseases. Despite this, there is little uniformity in the biomedical literature with regard to the methods used to estimate this important parameter.(More)