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Showing papers by "Jackson T. Wright published in 2013"


Journal ArticleDOI
TL;DR: Renal risk variants in APOL1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status.
Abstract: Methods In two studies, we examined the effects of variants in the gene encoding apolipoprotein L1 (APOL1) on the progression of chronic kidney disease. In the African American Study of Kidney Disease and Hypertension (AASK), we evaluated 693 black patients with chronic kidney disease attributed to hypertension. In the Chronic Renal Insufficiency Cohort (CRIC) study, we evaluated 2955 white patients and black patients with chronic kidney disease (46% of whom had diabetes) according to whether they had 2 copies of high-risk APOL1 variants (APOL1 high-risk group) or 0 or 1 copy (APOL1 low-risk group). In the AASK study, the primary outcome was a composite of end-stage renal disease or a doubling of the serum creatinine level. In the CRIC study, the primary outcomes were the slope in the estimated glomerular filtration rate (eGFR) and the composite of end-stage renal disease or a reduction of 50% in the eGFR from baseline. Results In the AASK study, the primary outcome occurred in 58.1% of the patients in the APOL1 high-risk group and in 36.6% of those in the APOL1 low-risk group (hazard ratio in the high-risk group, 1.88; P<0.001). There was no interaction between APOL1 status and trial interventions or the presence of baseline proteinuria. In the CRIC study, black patients in the APOL1 high-risk group had a more rapid decline in the eGFR and a higher risk of the composite renal outcome than did white patients, among those with diabetes and those without diabetes (P<0.001 for all comparisons). Conclusions Renal risk variants in APOL1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.)

630 citations


Journal ArticleDOI
TL;DR: In this paper, the effects of two antihypertensive drug dose schedules (PM dose and add-on dose) on nocturnal blood pressure (BP) in comparison with usual therapy (AM dose) in blacks with hypertensive chronic kidney disease and controlled office BP were determined.
Abstract: The objective of our study was to determine the effects of 2 antihypertensive drug dose schedules (PM dose and add-on dose) on nocturnal blood pressure (BP) in comparison with usual therapy (AM dose) in blacks with hypertensive chronic kidney disease and controlled office BP. In a 3-period, crossover trial, former participants of the African American Study of Kidney Disease were assigned to receive the following 3 regimens, each lasting 6 weeks, presented in random order: AM dose (once-daily antihypertensive medications taken in the morning), PM dose (once-daily antihypertensives taken at bedtime), and add-on dose (once-daily antihypertensives taken in the morning and an additional antihypertensive medication before bedtime [diltiazem 60–120 mg, hydralazine 25 mg, or additional ramipril 5 mg]). Ambulatory BP monitoring was performed at the end of each period. The primary outcome was nocturnal systolic BP. Mean age of the study population (n=147) was 65.4 years, 64% were men, and mean estimated glomerular filtration rate was 44.9 mL/min per 1.73 m 2 . At the end of each period, mean (SE) nocturnal systolic BP was 125.6 (1.2) mm Hg in the AM dose, 123.9 (1.2) mm Hg in the PM dose, and 123.5 (1.2) mm Hg in the add-on dose. None of the pairwise differences in nocturnal, 24-hour, and daytime systolic BP was statistically significant. Among blacks with hypertensive chronic kidney disease, neither PM (bedtime) dosing of once-daily antihypertensive nor the addition of drugs taken at bedtime significantly reduced nocturnal BP compared with morning dosing of antihypertensive medications.

72 citations


Journal ArticleDOI
TL;DR: In this large chronic kidney disease cohort without heart failure, NT-proBNP had strong associations with prevalent LVH and LV systolic dysfunction, and significantly reclassified participants' likelihood of having LVH.
Abstract: We evaluated the cross-sectional associations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with cardiac structural and functional abnormalities in a cohort of patients with chronic kidney disease without clinical heart failure, the Chronic Renal Insufficiency Cohort (n = 3,232). The associations of NT-proBNP with echocardiographically determined left ventricular (LV) mass and LV systolic and diastolic function were evaluated using multivariate logistic and linear regression models. Reclassification of participants' predicted risk of LV hypertrophy (LVH), systolic and diastolic dysfunction was performed using a category-free net reclassification improvement index that compared a clinical model with and without NT-proBNP. The median NT-proBNP was 126.6 pg/ml (interquartile range 55.5 to 303.7). The greatest quartile of NT-proBNP was associated with a nearly threefold odds of LVH (odds ratio 2.7, 95% confidence interval [CI] 1.8 to 4.0) and LV systolic dysfunction (odds ratio 2.7, 95% CI 1.7 to 4.5) and a twofold odds of diastolic dysfunction (odds ratio 2.0, 95% CI 1.3 to 2.9) in the fully adjusted models. When evaluated alone as a screening test, NT-proBNP functioned modestly for the detection of LVH (area under the curve 0.66) and LV systolic dysfunction (area under the curve 0.62) and poorly for the detection of diastolic dysfunction (area under the curve 0.51). However, when added to the clinical model, NT-proBNP significantly reclassified participants' likelihood of having LVH (net reclassification improvement 0.14, 95% CI 0.13–0.15; p

57 citations


Journal ArticleDOI
TL;DR: Several loci associated with CAC in CKD that also relate to MI in a general population sample are identified and may provide a useful setting for discovery of novel CHD genes and pathways.

40 citations


Journal ArticleDOI
TL;DR: In this article, the authors carried out a prespecified subgroup analysis of 15 638 women and 17 719 men in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) to determine whether an angiotensin-converting enzyme inhibitor (lisinopril) or calcium channel blocker (amlodipine) is superior to a diuretic (chlorthalidone) in reducing cardiovascular disease incidence in sex subgroups.
Abstract: To determine whether an angiotensin-converting enzyme inhibitor (lisinopril) or calcium channel blocker (amlodipine) is superior to a diuretic (chlorthalidone) in reducing cardiovascular disease incidence in sex subgroups, we carried out a prespecified subgroup analysis of 15 638 women and 17 719 men in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Total follow-up (active treatment + passive surveillance using national administrative databases to ascertain deaths and hospitalizations) was 8 to 13 years The primary outcome was fatal coronary heart disease or nonfatal myocardial infarction Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (coronary heart disease death, nonfatal myocardial infarction, stroke, angina, coronary revascularization, heart failure [HF], or peripheral vascular disease), and end-stage renal disease In-trial rates of HF, stroke, and combined cardiovascular disease were significantly higher for lisinopril compared with chlorthalidone, and rates of HF were significantly higher for amlodipine compared with chlorthalidone in both men and women There were no significant treatment sex interactions These findings did not persist through the extension period with the exception of the HF result for amlodipine versus chlorthalidone, which did not differ significantly by sex For both women and men, rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary coronary heart disease outcome or any other cardiovascular disease outcome, and chlorthalidone-based treatment resulted in the lowest risk of HF Neither lisinopril nor amlodipine is superior to chlorthalidone for initial treatment of hypertension in either women or men Clinical Trial Registration- clinicaltrialsgov; Identifier: NCT00000542

35 citations