Metabolic syndrome, proteinuria, and the risk of progressive CKD in hypertensive African Americans.

BACKGROUND: 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. DESIGN & PARTICIPANTS: 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. PREDICTORS: Metabolic syndrome was defined according to the modified National Cholesterol Education Program guidelines. OUTCOMES: 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. RESULTS: 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). LIMITATIONS: Lack of waist circumference as a better surrogate of abdominal obesity. CONCLUSIONS: In summary, metabolic syndrome is associated with proteinuria in hypertensive African Americans, but is not independently associated with CKD progression.

Angiotensin-converting enzyme gene polymorphism predicts the time-course of blood pressure response to angiotensin converting enzyme inhibition in the AASK trial.

OBJECTIVE: It has yet to be determined whether genotyping at the angiotensin-converting enzyme (ACE) locus is predictive of blood pressure response to an ACE inhibitor. METHODS: Participants from the African American Study of Kidney Disease and Hypertension trial randomized to the ACE inhibitor ramipril (n = 347) were genotyped at three polymorphisms on ACE, just downstream from the ACE insertion/deletion polymorphism (Ins/Del): G12269A, C17888T, and G20037A. Time to reach target mean arterial pressure (

Validation of creatinine-based estimates of GFR when evaluating risk factors in longitudinal studies of kidney disease.

Whereas much research has investigated equations for obtaining estimated GFR (eGFR) from serum creatinine in cross-sectional settings, little attention has been given to validating these equations as outcomes in longitudinal studies of chronic kidney disease. A common objective of chronic kidney disease studies is to identify risk factors for progression, characterized by slope (rate of change over time) or time to event (time until a designated decline in kidney function or ESRD). The relationships of 35 baseline factors with eGFR-based outcomes were compared with the relationships of the same factors with iothalamate GFR (iGFR)-based outcomes in the African American Study of Kidney Disease and Hypertension (AASK; n = 1094). With the use of the AASK equation to calculate eGFR, results were compared between time to halving of eGFR or ESRD and time to halving of iGFR or ESRD (with effect sizes expressed per 1 SD) and between eGFR and iGFR slopes starting 3 mo after randomization. The effects of the baseline factors were similar between the eGFR- and iGFR-based time-to-event outcomes (Pearson R = 0.99, concordance R = 0.98). Small but statistically significant differences (P < 0.05, without adjustment for multiple analyses) were observed for seven of the 35 factors. Agreement between eGFR and iGFR was somewhat weaker, although still relatively high for slope-based outcomes (Pearson R = 0.93, concordance R = 0.92). Effects of covariate adjustment for age, gender, baseline GFR, and urine proteinuria also were similar between the eGFR and iGFR outcomes. Sensitivity analyses including death in the composite time-to-event outcomes or using the Modification of Diet in Renal Disease equation instead of the AASK equation provided similar results. In conclusion, the data from the AASK provide tentative support for use of outcomes that are based on an established eGFR formula using serum creatinine as a surrogate for measured iGFR-based outcomes in analyses of risk factors for the progression of kidney disease.

Differing effects of antihypertensive drugs on the incidence of diabetes mellitus among patients with hypertensive kidney disease.

BACKGROUND: The African American Study of Kidney Disease and Hypertension was a multicenter trial of African Americans with hypertensive kidney disease randomized to an angiotensin-converting enzyme inhibitor (ramipril), a beta-blocker (metoprolol succinate), or a calcium channel blocker (amlodipine besylate). We compared the incidence of type 2 diabetes mellitus (DM) and the composite outcome of impaired fasting glucose or DM (IFG/DM) for the African American Study of Kidney Disease and Hypertension interventions. METHODS: Cox regression models were used to evaluate (post hoc) the association of the randomized interventions and the relative risk (RR) of DM and IFG/DM and to assess the RR of DM and IFG/DM by several prerandomization characteristics. RESULTS: Among 1017 participants, 147 (14.5%) developed DM; 333 (42.9%) of 776 participants developed IFG/DM. Respective DM event rates were 2.8%, 4.4%, and 4.5% per patient-year in the ramipril-, amlodipine-, and metoprolol-treated groups. The RRs of DM with ramipril treatment were 0.53 (P = .001) compared with metoprolol treatment and 0.49 (P = .003) compared with amlodipine treatment. Respective IFG/DM event rates were 11.3%, 13.3%, and 15.8% per patient-year in the ramipril-, amlodipine-, and metoprolol-treated groups. The RRs of IFG/DM with ramipril treatment were 0.64 (P<.001) compared with metoprolol treatment and 0.76 (P = .09) compared with amlodipine treatment. The RRs of DM and IFG/DM with amlodipine treatment compared with metoprolol treatment were 1.07 (P = .76) and 0.84 (P = .26), respectively. CONCLUSION: Ramipril treatment was associated with a significantly lower risk of DM in African Americans with hypertensive kidney disease than amlodipine or metoprolol treatment.

Glomerular filtration rate can be accurately predicted using lean mass measured by dual-energy X-ray absorptiometry.

BACKGROUND: Accurate assessment of renal function is important in the management of patients with kidney disease yet is often difficult to obtain. Formulae, designed for clinical use, have been developed to predict glomerular filtration rate (GFR) utilizing serum creatinine (Scr). Additional parameters are included in these formulae to account for variations in Scr due to differences in total body lean mass in kg (LM). Therefore, the purpose of this study was to derive a simple formula to predict GFR based on Scr and direct quantification of LM. METHODS: Ten subjects with a wide range of renal function had GFRs determined by [125I]iothalamate clearance and LM determined by dual-energy X-ray absorptiometry as well as fasting measurements of Scr, serum and 24 h urine urea nitrogen, and albumin. RESULTS: The following formula was derived using LM (kg) and Scr (mg/dl): predicted GFR=(2.4xLM)-(0.75xLMxScr). The correlation coefficient for this formula was 0.97, when compared with [125I]iothalamate clearances, and similar to the MDRD formulae (R=0.87-0.95). CONCLUSION: Although further validation is necessary, these findings suggest that total body non-invasive measurement of LM along with Scr can be used to accurately predict GFR.

Blood pressure control, drug therapy, and kidney disease.

The African American Study of Kidney Disease and Hypertension examined the effect on renal function decline of 2 blood pressure (BP) goals (low mean arterial pressure [MAP] < or =92 versus usual MAP 102 to 107 mm Hg) and 3 antihypertensives (ramipril versus amlodipine versus metoprolol). We previously reported that in all drug groups combined the BP intervention had similar effects on the primary outcome of glomerular filtration rate (GFR) slope or the main secondary clinical composite outcome of end-stage renal disease (ESRD), death, or GFR decline by 50% or 25 mL/min per 1.73 m2. This report examines the effect of the BP intervention separately in the 3 drug groups. The BP effect was similar among the drug groups for either GFR slope or the main clinical composite. However, the BP effect differed significantly among the drug groups for the composite of ESRD or death (P=0.035) and ESRD alone (P=0.021). Higher event rates for amlodipine patients assigned to the usual BP goal (0.087 per patient-year for ESRD or death and 0.064 per patient-year for ESRD) were seen compared with the remaining groups of the factorial design (range, 0.041 to 0.050 for ESRD or death; and range, 0.027 to 0.036 for ESRD). The low BP goal was associated with reduced risk of ESRD or death (risk reduction 51%; 95% confidence interval, 13% to 73%) and ESRD (54%; 8% to 77%) for amlodipine patients, but not for patients assigned to the other drug groups. These secondary analyses suggest a benefit of the low BP goal among patients assigned to amlodipine, but they must be interpreted cautiously.

Prevalence, treatment, and control of hypertension among African Americans and Caucasians at primary care sites for medically under-served patients.

CONTEXT: Hypertension is a major contributor to ethnic disparities in cardiovascular disease, especially among low-income African Americans in the southeast United States. OBJECTIVE: To assess differences between African Americans and Caucasians in the prevalence, treatment, and control of hypertension in outpatient clinics for under-served patients in South Carolina. DESIGN: A random sample of outpatient charts on 7795 adults was abstracted from 31 primary care clinics providing health care for approximately 180,000 medically under-served patients. Variables included visit dates, blood pressures (BP), diagnosis of hypertension, and medications. RESULTS: Data were abstracted from outpatient medical records on 4694 African Americans (1483 men, 3195 women, 16 gender unknown, age 46.8 +/- 0.3 years) and 2540 Caucasians (1031 men, 1492 women, 17 gender unknown, age 47.7 +/- 0.4 years). The prevalence of hypertension was greater in African Americans than Caucasians (47.6% vs 31.0%, P < .001). The percentages of hypertensive African Americans and Caucasians receiving BP medications were similar (83.4% vs 81.6%, P=NS). Although African-American hypertensives were more likely than Caucasian hypertensives to receive diuretics and calcium channel blockers and less likely to receive beta-blockers, the number of BP medications was similar for both groups (1.44 +/- 0.02 vs 1.40 +/- 0.04, P=NS). Despite comparable treatment, African Americans were less likely than Caucasians to have BP controlled to <140/90 mm Hg at the most recent clinic visit (40.9% vs 46.3%, P=.01). CONCLUSIONS: In healthcare settings for medically under-served patients, the greater prevalence and lesser control of hypertension, despite similar treatment intensity, may contribute to higher rates of cardiovascular disease among African Americans than Caucasians.

IgA antiglomerular basement membrane nephritis associated with Crohn's disease: a case report and review of glomerulonephritis in inflammatory bowel disease.

A case of glomerulonephritis in a 35-year-old man with Crohn's disease is described here. The patient presented with severe diarrhea, nephrotic range proteinuria, hematuria, microangiopathic hemolytic anemia, thrombocytopenia, hypocomplementemia, acute renal failure requiring hemodialysis, cryoglobulinemia, and extensive thrombotic gangrene of the distal upper and lower limbs. The patient did not respond to plasmapheresis and steroid therapy and died of upper gastrointestinal bleeding. Renal tissue obtained at autopsy showed IgA-mediated antiglomerular basement membrane crescentic glomerulonephritis. Linear staining of the glomerular basement membrane by non-IgG antibodies is quite unusual with only 11 cases previously reported in the worldwide literature, 8 caused by IgA. Glomerulonephritis is a rarely reported extraintestinal manifestation of inflammatory bowel disease, and there are only 24 previously described cases that are reviewed and summarized in this report. Glomerulonephritis occurred in the setting of active bowel inflammation in all cases, circulating immune complexes were found in nearly half the cases, and serum complements usually were normal. Renal insufficiency and nephrotic range proteinuria were typically present at the time of diagnosis of glomerulonephritis and most often improved in parallel with treatment of the gastrointestinal disorder. The histologic findings were varied and included membranoproliferative glomerulonephritis, mesangioproliferative glomerulonephritis, membranous nephropathy, IgA nephropathy, and IgM nephropathy. Thus, the authors present the first case of glomerulonephritis caused by antiglomerular basement membrane disease in association with inflammatory bowel disease.

Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial.

CONTEXT: Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD. OBJECTIVE: To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension. DESIGN: Randomized 3 x 2 factorial trial with enrollment from February 1995 to September 1998. SETTING AND PARTICIPANTS: A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years. INTERVENTIONS: Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n = 554) or 92 mm Hg or less (lower; n = 540), and to initial treatment with either a beta-blocker (metoprolol 50-200 mg/d; n = 441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n = 436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n = 217). Open-label agents were added to achieve the assigned BP goals. MAIN OUTCOME MEASURES: Rate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or > or =25 mL/min per 1.73 m2) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol. RESULTS: Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m2 per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 m2 per year; P =.24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group = 2%; 95% confidence interval [CI], -22% to 21%; P =.85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% (95% CI, 1%-38%; P =.04) and 38% (95% CI, 14%-56%; P =.004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups. CONCLUSIONS: No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline.