Richardson S.I.,Columbia University |
Freedman B.I.,Section on Nephrology |
Ellison D.H.,Oregon Health And Science University
Journal of the American Society of Hypertension | Year: 2013
The purpose of this review is to summarize the available information regarding salt sensitivity particularly as it relates to non-Hispanic blacks and Hispanics and to clarify possible etiologies, especially those that might shed light on potential treatment options. In non-Hispanic blacks, there is evidence that endothelial dysfunction, reduced potassium intake, decreased urinary kallikrein excretion, upregulation of sodium channel activity, dysfunction in atrial natriuretic peptide (ANP) production, and APOL1 gene nephropathy risk variants may cause or contribute to salt sensitivity. Supported treatment avenues include diets high in potassium and soybean protein, the components of which stimulate nitric oxide production. Racial heterogeneity complicates the study of salt sensitivity in Hispanic populations. Caribbean Hispanics, who have a higher proportion of African ancestry, may respond to commonly prescribed anti-hypertensive agents in a way that is characteristic of non-Hispanic black hypertensives. The low-renin hypertensive phenotype commonly seen in non-Hispanic blacks has been linked to salt sensitivity and may indicate an increased risk for salt sensitivity in a portion of the Hispanic population. In conclusion, increased morbidity and mortality associated with salt sensitivity mandates further studies evaluating the efficacy of tailored dietary and pharmacologic treatment in non-Hispanic blacks and determining the prevalence of low renin hypertension and salt sensitivity within the various subgroups of Hispanic Americans.
Freedman B.I.,Section on Nephrology
Nature Reviews Nephrology | Year: 2016
Unrelated disease processes commonly occur in non-diabetic individuals with mild-to-moderate hypertension and low level or absent proteinuria who present with chronic kidney disease: primary glomerulosclerosis in those with recent African ancestry, and arteriolar nephrosclerosis with resultant glomerular ischaemia potentially related to hypertension and vascular disease risk factors in other cases. Unfortunately, nephrologists often indiscriminately apply a diagnosis of 'hypertensive nephrosclerosis' to patients in either scenario, which implies that the hypertension is causative of their renal disease. Although nephropathies that are associated with variants in the apolipoprotein L1 gene (APOL1) often cause secondarily elevated blood pressure, they belong to the spectrum of focal segmental glomerulosclerosis and are not initiated by systemic hypertension. Because genetic testing for APOL1 variants and other glomerulosclerosis-associated gene variants is available and can provide a precise definition of disease pathogenesis, we believe that the term 'hypertensive nephrosclerosis' should now be abandoned and replaced with either gene-based (for example, APOL1-associated) glomerulosclerosis or arteriolar nephrosclerosis. Precision medicine will be key to improving diagnostic accuracy in this field. Discrimination of these disparate disorders has the potential to eradicate primary forms of glomerulosclerosis that are associated with APOL1 renal-risk variants. © 2016 Macmillan Publishers Limited.
Kovesdy C.P.,Memphis Medical Center |
Kovesdy C.P.,University of Tennessee Health Science Center |
Lu J.L.,University of Tennessee Health Science Center |
Molnar M.Z.,University of Tennessee Health Science Center |
And 5 more authors.
JAMA Internal Medicine | Year: 2014
IMPORTANCE The effect of strict blood pressure control on clinical outcomes in patients with chronic kidney disease (CKD) is unclear. OBJECTIVE To compare the outcomes associated with a treated systolic blood pressure (SBP) of less than 120mmHg vs those associated with the currently recommended SBP of less than 140mmHg in a national CKD database of US veterans. DESIGN, SETTING, AND PARTICIPANTS Historical cohort study using a nationwide cohort of US veterans with prevalent CKD, estimated glomerular filtration rate less than 60 mL/min/1.73 m2, and uncontrolled hypertension, who then received 1 or more additional blood pressure medications with evidence of a decrease in SBP. Propensity scores were calculated to reflect each individual's probability for future SBP less than 120 vs 120 to 139mmHg. MAIN OUTCOMES AND MEASURES The effect of SBP on all-cause mortalitywas evaluated by the log-rank test, and in Cox models adjusted for propensity scores. RESULTS Using a database of 651 749 patients with CKD, we identified 77 765 individuals meeting the inclusion criteria. A total of 5760 patients experienced follow-up treated SBP of less than 120mmHg and 72 005 patients had SBP of 120 to 139mmHg. During a median follow-up of 6.0 years, 19 517 patients died, with 2380 deaths in the SBP less than 120mm Hg group (death rate, 80.9/1000 patient-years [95%CI, 77.7-84.2/1000 patient-years]) and 17 137 deaths in the SBP 120 to 139mmHg group (death rate, 41.8/1000 patient-years [95% CI, 41.2-42.4/1000 patient-years]; P > .001). The mortality hazard ratio (95%CI) associated with follow-up SBP less than 120 vs 120 to 139mmHg was 1.70 (1.63-1.78) after adjustment for propensity scores. CONCLUSIONS AND RELEVANCE Our results suggest that stricter SBP control is associated with higher all-cause mortality in patients with CKD. Confirmation of these findings by ongoing clinical trials would suggest that modeling of therapeutic interventions in observational cohorts may offer useful guidance for the treatment of conditions that lack clinical trial data. © 2014 American Medical Association. All rights reserved.
Murea M.,Section on Nephrology
Advances in Chronic Kidney Disease | Year: 2012
Metabolic end products accumulate in kidney failure, including uric acid (UA), a terminal product of purine catabolism. Hyperuricemia (HUA) can cause gout and has been increasingly linked with cardiovascular (CV) morbidity and mortality, outcomes that are highly prevalent in patients with kidney disease. Serum UA levels rise as glomerular filtration declines, whereas the frequency of gouty attacks declines and the incidence of CV death rises precipitously. Herein, we review the kinetics of UA metabolism in CKD and dialysis and discuss the possible mechanisms of gout mitigation in kidney failure and the potential contribution of hyperuricemic milieu to CV outcomes in patients with kidney disease. © 2012 National Kidney Foundation, Inc.
Wright J.T.,Case Western Reserve University |
Williamson J.D.,Sticht Center on Aging |
Whelton P.K.,Tulane University |
Snyder J.K.,U.S. National Institutes of Health |
And 13 more authors.
New England Journal of Medicine | Year: 2015
BACKGROUND The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain. METHODS We randomly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. RESULTS At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensivetreatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensivetreatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P = 0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensivetreatment group than in the standard-treatment group. CONCLUSIONS Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group. © 2015 Massachusetts Medical Society.