[show abstract][hide abstract] ABSTRACT: Pulse pressure (PP), a marker of arterial system properties, has been linked to cardiovascular (CV) complications. We examined (a) association between unit changes of PP and (i) composite CV outcomes and (ii) development of left-ventricular hypertrophy (LVH) and (b) effect of mean arterial pressure (MAP) control on rate of change in PP. We studied 1094 nondiabetics with nephrosclerosis in the African American Study of Kidney Disease and Hypertension. Subjects were randomly assigned to usual MAP goal (102-107 mmHg) or a lower MAP goal (≤92 mmHg) and randomized to beta-blocker, angiotensin converting enzyme inhibitor, or calcium channel blocker. After covariate adjustment, a higher PP was associated with increased risk of CV outcome (RR = 1.28, CI = 1.11-1.47, P < 0.01) and new LVH (RR = 1.26, CI = 1.04-1.54, P = 0.02). PP increased at a greater rate in the usual than in lower MAP groups (slope ± SE: 1.08 ± 0.15 versus 0.42 ± 0.15 mmHg/year, P = 0.002), but not by the antihypertensive treatment assignment. Observations indicate that control to a lower MAP slows the progression of PP, a correlate of cardiovascular remodeling and complications, and may be beneficial to CV health.
International journal of nephrology. 01/2013; 2013:120167.
[show abstract][hide abstract] ABSTRACT: African Americans have a disproportionate burden of chronic kidney disease (CKD), which tends to have an earlier onset and a more rapid progression in this population. Many of the factors responsible for the rapid progression of CKD in African Americans are detectable by screening and are modifiable with prompt therapy.
Cleveland Clinic Journal of Medicine 10/2012; 79(10):726-34. · 3.40 Impact Factor
[show abstract][hide abstract] ABSTRACT: Disadvantaged populations across the globe exhibit a disproportionate burden of chronic kidney disease (CKD) because of differences in CKD occurrence and outcomes. Although many CKD risk factors can be managed and modified to optimize clinical outcomes, the prevailing socioeconomic and cultural factors in disadvantaged populations, more often than not, militate against optimum clinical outcomes. In addition, disadvantaged populations exhibit a broader spectrum of CKD risk factors and may be genetically predisposed to an earlier onset and a more rapid progression of chronic kidney disease. A basic understanding of the vulnerabilities of the disadvantaged populations will facilitate the adaptation and adoption of the kidney disease treatment and prevention guidelines for these vulnerable populations. The purpose of this paper is to examine recent discoveries and data on CKD occurrence and outcomes in disadvantaged populations and explore strategies for the prevention and treatment of CKD in these populations based on the established guidelines.
International journal of nephrology. 01/2012; 2012:469265.
[show abstract][hide abstract] ABSTRACT: Chronic kidney disease (CKD) is more likely to progress to end-stage renal disease (ESRD) in African Americans while the reasons for this are unclear. The metabolic syndrome is a risk factor for the development of diabetes, cardiovascular disease, and has been recently linked to incident CKD. Historically, fewer African Americans meet criteria for the definition of metabolic syndrome, despite having higher rates of cardiovascular mortality than Caucasians. The presence of microalbuminuria portends increased cardiovascular risks and has been shown to cluster with the metabolic syndrome. We recently reported that proteinuria is a predictor of CKD progression in African American hypertensives with metabolic syndrome. In this review we explore the potential value of including CKD markers--microalbuminuria/proteinuria or low glomerular filtration rate (GFR)-in refining the cluster of factors defined as metabolic syndrome, ie, "cardiorenal metabolic syndrome."
[show abstract][hide abstract] ABSTRACT: Chronic kidney disease (CKD) is a serious threat to African-American public health. In this population CKD progresses to end-stage renal disease (ESRD) at quadruple the rate in Caucasians. Factors fueling progression to ESRD include diabetes and hypertension, which show high prevalences and accelerated renal damage in African- Americans, as well as possible nutritional, socioeconomic, and genetic factors. Anemia, a common and deleterious complication of CKD, is more prevalent and severe in African-American than Caucasian patients at each stage of the disease. Proactive management of diabetes, hypertension, anemia, and other complications throughout the course of CKD can prevent or delay disease progression and alleviate the burden of ESRD for the African-American community. Currently, African-Americans with CKD are less likely than Caucasian patients to receive anemia treatment before and after the onset of dialysis. Although African-Americans often require higher doses of erythropoiesis-stimulating agents, this may result from late treatment initiation, lower hemoglobin levels, or the presence of comorbidities such as diabetes and inflammation, although racial differences in response cannot be excluded. This review explores racial-specific challenges and potential solutions in renal anemia management to improve outcomes in African-American patients.
American Journal of Nephrology 05/2008; 28(5):732-43. · 2.62 Impact Factor
[show abstract][hide abstract] ABSTRACT: Chronic kidney disease (CKD) is more likely to progress to kidney failure (end-stage renal disease) in African Americans, although the reasons for this are unclear. Metabolic syndrome is a risk factor for the development of diabetes and cardiovascular disease and recently was linked to incident CKD. The purpose of this study is to examine whether metabolic syndrome is associated with kidney disease progression in hypertensive African Americans.
The current study design is a secondary analysis of the African-American Study of Hypertension and Kidney Disease, a randomized controlled trial of blood pressure goal and agents in hypertensive African Americans with CKD.
Metabolic syndrome was defined according to the modified National Cholesterol Education Program guidelines.
Decrease in glomerular filtration rate of 50% or 25 mL/min/1.73 m(2), end-stage renal disease (initiation of dialysis therapy or transplantation), death, or a composite outcome of all 3.
842 subjects were included in this analysis, and 41.7% met criteria for metabolic syndrome. Subjects meeting criteria for metabolic syndrome had greater levels of proteinuria. Cox regression analyses adjusted for age, sex, glomerular filtration rate, and other significant covariates except for proteinuria indicated a 31% increased risk, with a 95% confidence interval of 1.03 to 1.7 (P = 0.03) for time to reach the composite outcome in those with metabolic syndrome. Adjusting for proteinuria, the effect was abated to 16% (95% confidence interval, 0.9 to 1.5), no longer remained significant (P = 0.2), and was unchanged by adjusting randomized treatment group (blood pressure goal or antihypertensive drug).
Lack of waist circumference as a better surrogate of abdominal obesity.
In summary, metabolic syndrome is associated with proteinuria in hypertensive African Americans, but is not independently associated with CKD progression.
American Journal of Kidney Diseases 05/2008; 51(5):732-40. · 5.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: African-Americans have, in comparison with Caucasians, excess hypertension and end-stage renal disease, which has been presumed to be due to hypertension. However, systematic renal biopsy assessment of lesions in this population and verification of this clinical impression have not been done. During the pilot phase of the AASK trial, 46 hypertensive (diastolic BP > 95 mmHg) non-diabetic African-American patients between the ages of 18–70 years, with glomerular filtration rate (GFR) between 25 and 70 mL/min per 1.73m2 and without marked proteinuria were therefore biopsied to assess underlying lesions. Adequate biopsy material was obtained in 39 (29 men and 10 women), on average 53.0 ± 11.0 years old, with MAP of 109 ± 15 mmHg and GFR 51.7 ± 13.6 mL/min per 1.73 m2. of these 39 biopsies, 38 showed arteriosclerosis and/or arteriolosclerosis, severity on average 1.5 ± 0.9 and 1.5 ± 0.8, respectively, on a 0–3+ scale. Interstitial fibrosis was moderate, 1.3 ± 0.9 (0–3+ scale). Segmental glomerulosclerosis was present in five biopsies, and in one patient, biopsy and clinical findings were consistent with idiopathic focal segmental glomerulosclerosis. Additional lesions included mesangiopathic glomerulonephritis in one patient, basement membrane thickening suggestive of diabetic nephropathy in one, and cholesterol emboli in two cases. Arteriolar and arterial sclerosis were tightly linked, and correlated with interstitial fibrosis and the reciprocal of serum creatinine. Global glomerulosclerosis was extensive, involving on average 43 ± 26% of glomeruli. the extent of this lesion did not correlate with degree of arteriolar or arterial thickening, but did correlate with systolic blood pressure (P 0.0174), the reciprocal of serum creatinine (P= 0.0009), serum cholesterol (P= 0.0129) and interstitial fibrosis (P < 0.0001). These data underscore that the clinical diagnosis of hypertensive nephrosclerosis based on strict clinical criteria in non-diabetic African-Americans with mild to moderate renal insufficiency without marked proteinuria is strongly correlated with renal biopsy vascular lesions consistent with this clinical diagnosis. However, the mechanism(s) for this clinicopathologic constellation remains undetermined. Current studies are focused on possible genetic contributions to the development of hypertension and renal lesions in this population.
[show abstract][hide abstract] ABSTRACT: In the randomized Hemodialysis (HEMO) Study, chronic high-flux dialysis, as defined by higher beta-2 microglobulin (beta(2)M) clearance, compared with low-flux dialysis did not significantly alter all-cause mortality in the entire cohort but was associated with lower mortality in long-term dialysis patients. This analysis examined the determinants of serum beta(2)M levels and the associations of serum beta(2)M levels or dialyzer beta(2)M clearance with mortality. In a multivariable regression model that examined 1704 patients, baseline residual kidney urea clearance and dialyzer beta(2)M clearance were strong predictors of predialysis serum beta(2)M levels at 1 mo of follow-up, with regression coefficients of -7.21 (+/-0.69 SE) mg/L per ml/min per 35 L urea volume (P < 0.0001) and -1.94 (+/-0.30) mg/L per ml/min (P < 0.0001),respectively. In addition, black race and baseline years on dialysis correlated positively whereas age, diabetes, serum albumin, and body mass index correlated negatively with serum beta(2)M levels (P < 0.05). In time-dependent Cox regression models, mean cumulative predialysis serum beta(2)M levels but not dialyzer beta(2)M clearance were associated with all-cause mortality (relative risk = 1.11 per 10-mg/L increase in beta(2)M level; 95% confidence interval 1.05 to 1.19; P = 0.001), after adjustment for residual kidney urea clearance and number of prestudy years on dialysis. This association is supportive of the potential value of beta(2)M as a marker to guide chronic hemodialysis therapy.
Journal of the American Society of Nephrology 02/2006; 17(2):546-55. · 8.99 Impact Factor
[show abstract][hide abstract] ABSTRACT: Similarities in patterns of renal disease in developing countries, and in minority and disadvantaged groups in developed countries, formed the basis of the International Society of Nephrology/Commission for the Global Advance- ment of Nephrology (ISN/COMGAN) initiative to explore how to share challenges and successes between these commu- nities. From these insights the ISN/COMGAN subcommittee that has focused on renal disease in indigenous populations and ethnic minority groups has evolved to become the ''Committee for Kidney Health in Disadvantaged Populations.'' The purpose of this evolution was to extend the focus beyond the renal problems of indigenous populations and ethnic minority groups to embrace similar communities within developing nations whose interests might otherwise go unrepresented.1 The strength of this committee over the last 10 years has been its willingness to embrace the particular problems of chronic kidney disease (CKD) within developing areas, and to bring together at successive meetings, with the aid of scholarship support, those who are working in nephrology in the developing world and those whose clinical practice and research skills have direct application to the needs of the former. These proceedings from the most recent satellite conference, linked to the Third World Congress on Nephrology in Singapore in June 2005, highlight several of the key themes explored during that meeting. The exchange of epidemiology, disease mechanisms and intervention strategies related to CKD, CKD risk factors, competing health issues, and diverse health care delivery systems led to a robust series of interactions and insights.2 Presentations included the identification of key strategies for improving the detection and prevention of renal disease and the newest findings on treatment and clinical outcomes of CKD among ethnic minority populations in developing nations. Additional sessions were designed to improve our understanding of not only the pathogenesis and pathophysiology of CKD, but the unique presentations, expressions, and key risk factors that contribute to the worldwide CKD pandemic. Finally, there was a series of discussions to recognize new research opportunities and to design and/or support programs to reduce the rising incidence of CKD to improve outcomes in at-risk communities. As developing countries are faced with increasing rates of chronic diseases3,4 including an explosion in the rate CKD, the opportunity to learn from successes and failures in developed countries can help shape public health policy and create innovate cost-effective CKD programs. Simultaneously, these innovative programs may have significant utility for developing countries as they try to copewith increasingly diverse communities with relatively unique genetic and environmental CKD risks immersed within a broad range of health beliefs and health practices, and often isolated from traditional Western allopathic healthcare systems. Ultimately, these efforts contrib- ute globally to help meet the US Healthy People 2010 goals on increasing quality and quantity of life, and reducing disparities in health outcomes.5
[show abstract][hide abstract] ABSTRACT: Among the 1846 patients in the HEMO Study, chronic high-flux dialysis did not significantly affect the primary outcome of the all-cause mortality (ACM) rate or the main secondary composite outcomes, including the rates of first cardiac hospitalization or ACM, first infectious hospitalization or ACM, first 15% decrease in serum albumin levels or ACM, or all non-vascular access-related hospitalizations. The high-flux intervention, however, seemed to be associated with reduced risks of specific cardiac-related events. The relative risks (RR) for the high-flux arm, compared with the low-flux arm, were 0.80 [95% confidence interval (CI), 0.65 to 0.99] for cardiac death and 0.87 (95% CI, 0.76 to 1.00) for the composite of first cardiac hospitalization or cardiac death. Also, the effect of high-flux dialysis on ACM seemed to vary, depending on the duration of prior dialysis. This report presents secondary analyses to further explore the relationship between the flux intervention and the duration of dialysis with respect to various outcomes. The patients were stratified into a short-duration group and a long-duration group, on the basis of the mean duration of dialysis of 3.7 yr before randomization. In the subgroup that had been on dialysis for >3.7 yr, randomization to high-flux dialysis was associated with lower risks of ACM (RR, 0.68; 95% CI, 0.53 to 0.86; P = 0.001), the composite of first albumin level decrease or ACM (RR, 0.74; 95% CI, 0.60 to 0.91; P = 0.005), and cardiac deaths (RR, 0.63; 95% CI, 0.43 to 0.92; P = 0.016), compared with low-flux dialysis. No significant differences were observed in outcomes related to infection for either duration subgroup, however, and the trends for beneficial effects of high-flux dialysis on ACM rates were considerably weakened when the years of dialysis during the follow-up phase were combined with the prestudy years of dialysis in the analysis. For the subgroup of patients with <3.7 yr of dialysis before the study, assignment to high-flux dialysis had no significant effect on any of the examined clinical outcomes. These data suggest that high-flux dialysis might have a beneficial effect on cardiac outcomes. Because these results are derived from multiple statistical comparisons, however, they must be interpreted with caution. The subgroup results that demonstrate that patients with different durations of dialysis are affected differently by high-flux dialysis are interesting and require further study for confirmation.
Journal of the American Society of Nephrology 12/2003; 14(12):3251-63. · 8.99 Impact Factor
[show abstract][hide abstract] ABSTRACT: The African American Study of Kidney Disease and Hypertension (AASK) is a multicenter randomized clinical trial designed to test the effectiveness of three anti-hypertensive drug regimens and two levels of BP control on the progression of hypertensive kidney disease. Participants include African-American men and women aged 18 to 70 yr who have hypertensive kidney disease and GFR between 20 and 65 ml/min per 1.73 m(2). The three anti-hypertensive drug regimens include an angiotensin converting enzyme inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine) or a beta-blocker (metoprolol) as initial therapy. The BP control levels are a lower goal (mean arterial pressure, </=92 mmHg) and a usual goal (mean arterial pressure, 102 to 107 mmHg inclusive). The primary outcome is rate of change in renal function as measured by GFR, assessed by (125) I-iothalamate clearance. The main secondary patient outcome is a composite including the following events: (1) reduction in GFR by 50%, (2) end-stage renal disease, or (3) death.
Journal of the American Society of Nephrology 07/2003; 14(7 Suppl 2):S154-65. · 8.99 Impact Factor
[show abstract][hide abstract] ABSTRACT: An interim analysis of the AASK trial at three years demonstrates a renoprotective effect [slower decline in glomerular filtration rate (GFR), delayed onset of significant decrease in GFR, end-stage renal disease (ESRD) or death, and a decrease in urinary protein excretion] of the angiotensin converting enzyme (ACE) inhibitor, ramipril, as compared to the dihydropyridine calcium channel blocker (DHP-CCB), amlodipine, in patients with mild-to-moderate renal insufficiency. The beneficial effect occurred in the presence of similar levels of blood pressure control and was apparent in patients with proteinuric (beyond the threshold of "dipstick positive" proteinuria, 300 mg/day) and non-proteinuric hypertensive nephrosclerosis. At the time of the interim analysis, the effectiveness of the beta-blocker metoprolol was not significantly different from that of the ACE inhibitor. The data suggest that DHP-CCBs should be used with caution in the presence of mild-to-moderate renal insufficiency.
[show abstract][hide abstract] ABSTRACT: Because cardiovascular disease is the leading cause of death and hypoalbuminemia predicts mortality, hypoalbuminemia may be associated with atherosclerosis.
In 1,411 patients enrolled in the HEMO study, associations of albumin with the presence of coronary artery disease (CAD), cerebrovascular disease (CVD), peripheral vascular disease (PVD), and any one of the three conditions at baseline were examined using multivariable logistic regression models.
In the two-slope model, when albumin level was 3.6 g/dL (36 g/L) or greater, with each 1-g/dL (10-g/L) increase in albumin level the odds for CAD (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.17 to 0.59), PVD (OR, 0.39; 95% CI, 0.18 to 0.80), CVD (OR, 0.33; 95% CI, 0.15 to 0.73), and any one of the three conditions (OR, 0.23; 95% CI, 0.12 to 0.44) decreased. When albumin level was less than 3.6 g/dL (36 g/L), none of the conditions was statistically significantly associated with each 1-g/dL (10-g/L) increase in albumin level. When normal- and low-albumin groups were compared with each other, patients with albumin levels less than 3.6 g/dL (36 g/L) had a higher association with CAD (OR, 1.32; 95% CI, 1.03 to 1.70) and for any one of the three conditions (OR, 1.38; 95% CI, 1.07 to 1.78).
The odds for atherosclerosis linearly decreased as albumin level increased in the normal-albumin group, and a plateau was seen in the low-albumin group; however, the low-albumin group had significantly greater CAD. The nonlinearity of association of albumin level with prevalence of atherosclerosis might be due to the cross-sectional nature of the study of higher mortality with hypoalbuminemia.
American Journal of Kidney Diseases 11/2002; 40(4):721-7. · 5.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: The African American Study of Kidney Disease and Hypertension (AASK) is an ongoing trial to evaluate the effect of blood pressure and choice of antihypertensive drug on the rate of decline of renal function.
To present the success of the AASK in achieving the trial's rigorous blood pressure goals in an extremely challenging patient population.
The AASK participants included African American patients with hypertension (n = 1094), aged 18 to 70 years, with glomerular filtration rates between 20 and 65 mL/min per 1.73 m(2) and no other identified causes of renal insufficiency. Participants were randomized to a goal mean arterial blood pressure (MAP) of either 102 to 107 mm Hg (usual MAP goal) or 92 mm Hg or less (low MAP goal). Participants in each of these groups were also randomized (double-blind) to a regimen containing metoprolol succinate, ramipril, or amlodipine besylate. Additional agents were added, if required, in the following recommended order: furosemide, doxazosin mesylate, clonidine hydrochloride, or hydralazine hydrochloride (or minoxidil, if needed).
In participants randomized to the low MAP goal, the percentage of participants who achieved a blood pressure of less than 140/90 mm Hg increased from a baseline of 20.0% to 78.9% by 14 months after randomization. For usual MAP goal participants, the corresponding percentages increased from 21.5% to 41.8%. The difference in median levels of MAP between the 2 MAP goal groups increased and remained at approximately 12 mm Hg. Blood pressure reduction was similar regardless of age, sex, body mass index, education, insurance or employment status, income, or marital status.
The blood pressure goals set and achieved in AASK participants clearly demonstrate that adequate blood pressure control can be achieved even in hypertensive populations whose blood pressure is the most difficult to control.
Archives of Internal Medicine 08/2002; 162(14):1636-43. · 11.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: Renal function measurements were obtained in 1,703 African Americans with presumed hypertensive nephrosclerosis who were screened for entry into the African-American Study of Hypertension and Kidney Disease (AASK). We examined the effect of race on relationships involving renal variables by comparing African Americans enrolled into the AASK with non-African Americans enrolled into the Modification of Diet in Renal Disease (MDRD) study. We examined the effect of gender on renal variables by comparing African American men and women. We compared various methods for estimating glomerular filtration rate (GFR) with iodine 125-labeled ((125)I)-iothalamate GFR. AASK data were also used to derive a new formula for estimating GFR in African Americans. After adjusting for age, sex, and baseline GFR, African American patients on the AASK study were heavier and had larger body surface areas and body mass indices than either MDRD African Americans or non-African Americans. African Americans had greater serum creatinine levels and urinary creatinine excretions for any given level of GFR. Mean GFR was greater in African American men than African American women (59.7 versus 51.7 mL/min/1.73 m(2)), although serum creatinine levels were also greater in men (1.91 versus 1.73 mg/dL). Seventy-eight percent of women with serum creatinine levels between 1.2 and 1.5 mg/dL had GFRs less than 65 mL/min/1.73 m(2). For African Americans in the AASK, GFR was overestimated by the 24-hour creatinine clearance and underestimated by the Cockcroft-Gault formula. A prediction formula developed in the MDRD study more accurately predicted GFR in AASK patients than these measurements. AASK data were also used to derive a new five-term formula for estimating GFR that was slightly more accurate in the African Americans in the AASK than the MDRD formula (median percentage of error, 12.4% for the MDRD formula versus 12.1% for the AASK formula). Important differences exist in renal variables between African Americans and non-African Americans and between African American men and African American women. Formulas using demographic data and readily measured serum values estimate (125)I-iothalamate GFR.
American Journal of Kidney Diseases 11/2001; 38(4):744-53. · 5.29 Impact Factor