Cynthia Kendrick

Disparate Estimates of Hypertension Control From Ambulatory and Clinic Blood Pressure Measurements in Hypertensive Kidney Disease

Ambulatory blood pressure (ABP) monitoring provides unique information about day-night patterns of blood pressure (BP). The objectives of this article were to describe ABP patterns in African Americans with hypertensive kidney disease, to examine the joint distribution of clinic BP and ABP, and to determine associations of hypertensive target organ damage with clinic BP and ABP. This study is a cross-sectional analysis of baseline data from the African American Study of Kidney Disease Cohort Study. Masked hypertension was defined by elevated daytime (≥135/85 mm Hg) or elevated nighttime (≥120/70 mm Hg) ABP in those with controlled clinic BP (<140/90 mm Hg); nondipping was defined by a ≤10% decrease in mean nighttime systolic BP; reverse dipping was defined by a higher nighttime than daytime systolic BP. Of the 617 participants (mean age: 60.2 years; 62% male; mean estimated glomerular filtration rate: 43.8 mL/min per 1.73 m2) with both clinic BP and ABP, 498 participants (80%) had a nondipping or reverse dipping profile. Of the 377 participants with controlled clinic BP (61%), 70% had masked hypertension. Compared with those with controlled clinic BP or white-coat hypertension, target organ damage (proteinuria and left ventricular hypertrophy) was more common in those with elevated nighttime BP, masked hypertension, or sustained hypertension. In conclusion, clinic BP provides an incomplete and potentially misleading assessment of the severity of hypertension in African Americans with hypertensive kidney disease, in large part because of increased nighttime BP. Whether lowering nighttime BP improves clinical outcomes is unknown but should be tested given the substantial burden of BP-related morbidity in this population.

Effects of frequent hemodialysis on measures of CKD mineral and bone disorder.

More frequent hemodialysis sessions and longer session lengths may offer improved phosphorus control. We analyzed data from the Frequent Hemodialysis Network Daily and Nocturnal Trials to examine the effects of treatment assignment on predialysis serum phosphorus and on prescribed dose of phosphorus binder, expressed relative to calcium carbonate on a weight basis. In the Daily Trial, with prescribed session lengths of 1.5-2.75 hours six times per week, assignment to frequent hemodialysis associated with both a 0.46 mg/dl decrease (95% confidence interval [95% CI], 0.13-0.78 mg/dl) in mean serum phosphorus and a 1.35 g/d reduction (95% CI, 0.20-2.50 g/d) in equivalent phosphorus binder dose at month 12 compared with assignment to conventional hemodialysis. In the Nocturnal Trial, with prescribed session lengths of 6-8 hours six times per week, assignment to frequent hemodialysis associated with a 1.24 mg/dl decrease (95% CI, 0.68-1.79 mg/dl) in mean serum phosphorus compared with assignment to conventional hemodialysis. Among patients assigned to the group receiving six sessions per week, 73% did not require phosphorus binders at month 12 compared with only 8% of patients assigned to sessions three times per week (P<0.001). At month 12, 42% of patients on nocturnal hemodialysis required the addition of phosphorus into the dialysate to prevent hypophosphatemia. Frequent hemodialysis did not have major effects on calcium or parathyroid hormone concentrations in either trial. In conclusion, frequent hemodialysis facilitates control of hyperphosphatemia and extended session lengths could allow more liberal diets and freedom from phosphorus binders.

Risk of hyperkalemia in nondiabetic patients with chronic kidney disease receiving antihypertensive therapy

BACKGROUND The incidence and factors associated with hyperkalemia in patients with chronic kidney disease (CKD) treated with angiotensin converting enzyme inhibitors (ACEIs) and other antihypertensive drugs was investigated using the African American Study of Kidney Disease and Hypertension (AASK) database. METHODS A total of 1094 nondiabetic adults with hypertensive CKD (glomerular filtration rate [GFR], 20-65 mL/min/1.73 m(2)) were followed for 3.0 to 6.4 years in the AASK trial. Participants were randomly assigned to ACEI, beta-blocker (BB), or dihydropyridine calcium channel blocker (CCB). The outcome variables for this analysis were a serum potassium level higher than 5.5 mEq/L (to convert to millimoles per liter, multiply by 1.0), or a clinical center initiated hyperkalemia stop point. RESULTS A total of 6497 potassium measurements were obtained, and 80 events in 51 subjects were identified (76 events driven by a central laboratory result and 4 driven by a clinical center-initiated hyperkalemia stop point). Compared with a GFR higher than 50 mL/min/1.73 m(2), after multivariable adjustment, the hazard ratio (HR) for hyperkalemia in patients with a GFR between 31 and 40 mL/min/1.73 m(2) and a GFR lower than 30 mL/min/1.73 m(2) was 3.61 (95% confidence interval [CI], 1.42-9.18 [P = .007]) and 6.81 (95% CI, 2.67-17.35 [P < .001]), respectively; there was no increased risk of hyperkalemia if GFR was 41 to 50 mL/min/1.73 m(2). Use of ACEIs was associated with more episodes of hyperkalemia compared with CCB use (HR, 7.00; 95% CI, 2.29-21.39 [P < .001]) and BB group (HR, 2.85; 95% CI, 1.50-5.42 [P = .001]). Diuretic use was associated with a 59% decreased risk of hyperkalemia. CONCLUSIONS In nondiabetic patients with hypertensive CKD treated with ACEIs, the risk of hyperkalemia is small, particularly if baseline and follow-up GFR is higher than 40 mL/min/1.73 m(2). Including a diuretic in the regimen may markedly reduce risk of hyperkalemia.

A trial of 2 strategies to reduce nocturnal blood pressure in blacks with chronic kidney disease

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 m2. 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.

Malnutrition-Inflammation Modifies the Relationship of Cholesterol with Cardiovascular Disease

In moderate and severe CKD, the association of cholesterol with subsequent cardiovascular disease (CVD) is weak. We examined whether malnutrition or inflammation (M-I) modifies the risk relationship between cholesterol levels and CVD events in African Americans with hypertensive CKD and a GFR between 20 and 65 ml/min per 1.73 m². We stratified 990 participants by the presence or absence of M-I, defined as body mass index <23 kg/m² or C-reactive protein >10 mg/L at baseline. The primary composite outcome included cardiovascular death or first hospitalization for coronary artery disease, stroke, or congestive heart failure occurring during a median follow-up of 77 months. Baseline total cholesterol (212 ± 48 versus 212 ± 44 mg/dl) and overall incidence of the primary CVD outcome (19 versus 21%) were similar in participants with (n = 304) and without (n = 686) M-I. In adjusted analyses, the CVD composite outcome exhibited a significantly stronger relationship with total cholesterol for participants without M-I than for participants with M-I at baseline (P < 0.02). In the non-M-I group, the cholesterol-adjusted hazard ratio (HR) for CVD increased progressively across cholesterol levels: HR = 1.19 [95% CI; 0.77, 1.84] and 2.18 [1.43, 3.33] in participants with cholesterol 200 to 239 and ≥240 mg/dl, respectively (reference: cholesterol <200). In the M-I group, the corresponding HRs did not vary significantly by cholesterol level. In conclusion, the presence of M-I modifies the risk relationship between cholesterol level and CVD in African Americans with hypertensive CKD.

Relationship of Left Ventricular Hypertrophy and Diastolic Function With Cardiovascular and Renal Outcomes in African Americans With Hypertensive Chronic Kidney Disease

African Americans with hypertension are at high risk for adverse outcomes from cardiovascular and renal disease. Patients with stage 3 or greater chronic kidney disease have a high prevalence of left ventricular (LV) hypertrophy and diastolic dysfunction. Our goal was to study prospectively the relationships of LV mass and diastolic function with subsequent cardiovascular and renal outcomes in the African American Study of Kidney Disease and Hypertension cohort study. Of 691 patients enrolled in the cohort, 578 had interpretable echocardiograms and complete relevant clinical data. Exposures were LV hypertrophy and diastolic parameters. Outcomes were cardiovascular events requiring hospitalization or causing death; a renal composite outcome of doubling of serum creatinine or end-stage renal disease (censoring death); and heart failure. We found strong independent relationships between LV hypertrophy and subsequent cardiovascular (hazard ratio, 1.16; 95% confidence interval, 1.05–1.27) events, but not renal outcomes. After adjustment for LV mass and clinical variables, lower systolic tissue Doppler velocities and diastolic parameters reflecting a less compliant LV (shorter deceleration time and abnormal E/A ratio) were significantly (P<0.05) associated with future heart failure events. This is the first study to show a strong relationship among LV hypertrophy, diastolic parameters, and adverse cardiac outcomes in African Americans with hypertension and chronic kidney disease. These echocardiographic risk factors may help identify high-risk patients with chronic kidney disease for aggressive therapeutic intervention.

A Within-Patient Analysis for Time-Varying Risk Factors of CKD Progression

Recent data suggest that nonlinear GFR trajectories are common among patients with CKD, but the modifiable risk factors underlying these changes in CKD progression rate are unknown. Analyses relating baseline risk factors to subsequent GFR decline are suboptimal because these relationships often attenuate as follow-up time increases and these analyses do not account for temporal changes in risk factors. We identified 74 participants in the African American Study of Kidney Disease and Hypertension who had both a period of rapid GFR decline and an extended period of stability during a follow-up period of ≥12 years. We performed a within-patient comparison of time-varying risk factors measured during the periods of GFR decline and stability and identified several risk factors associated with faster GFR decline: more hospitalization episodes and hospitalization days per year; higher BP, serum phosphorus, and urine protein-to-creatinine ratio; lower serum albumin and urine sodium-to-potassium ratio; slower rate of decline of serum urea nitrogen, serum creatinine, serum uric acid, and serum phosphorus; and faster rate of decline of serum hematocrit and serum bicarbonate. By allowing each patient to serve as his or her own control, this novel, within-patient analytic approach holds considerable promise as a means to identify time-varying risk factors associated with stabilization of GFR or acceleration of GFR decline.

The effects of weight change on glomerular filtration rate

BACKGROUND Little is known about the effect of weight loss/gain on kidney function. Analyses are complicated by uncertainty about optimal body surface indexing strategies for measured glomerular filtration rate (mGFR). METHODS Using data from the African-American Study of Kidney Disease and Hypertension (AASK), we determined the association of change in weight with three different estimates of change in kidney function: (i) unindexed mGFR estimated by renal clearance of iodine-125-iothalamate, (ii) mGFR indexed to concurrently measured BSA and (iii) GFR estimated from serum creatinine (eGFR). All models were adjusted for baseline weight, time, randomization group and time-varying diuretic use. We also examined whether these relationships were consistent across a number of subgroups, including tertiles of baseline 24-h urine sodium excretion. RESULTS In 1094 participants followed over an average of 3.6 years, a 5-kg weight gain was associated with a 1.10 mL/min/1.73 m(2) (95% CI: 0.87 to 1.33; P < 0.001) increase in unindexed mGFR. There was no association between weight change and mGFR indexed for concurrent BSA (per 5 kg weight gain, 0.21; 95% CI: -0.02 to 0.44; P = 0.1) or between weight change and eGFR (-0.09; 95% CI: -0.32 to 0.14; P = 0.4). The effect of weight change on unindexed mGFR was less pronounced in individuals with higher baseline sodium excretion (P = 0.08 for interaction). CONCLUSION The association between weight change and kidney function varies depending on the method of assessment. Future clinical trials should examine the effect of intentional weight change on measured GFR or filtration markers robust to changes in muscle mass.

BP in Dialysis: Results of a Pilot Study

The optimal BP target for patients receiving hemodialysis is unknown. We randomized 126 hypertensive patients on hemodialysis to a standardized predialysis systolic BP of 110-140 mmHg (intensive arm) or 155-165 mmHg (standard arm). The primary objectives were to assess feasibility and safety and inform the design of a full-scale trial. A secondary objective was to assess changes in left ventricular mass. Median follow-up was 365 days. In the standard arm, the 2-week moving average systolic BP did not change significantly during the intervention period, but in the intensive arm, systolic BP decreased from 160 mmHg at baseline to 143 mmHg at 4.5 months. From months 4-12, the mean separation in systolic BP between arms was 12.9 mmHg. Four deaths occurred in the intensive arm and one death occurred in the standard arm. The incidence rate ratios for the intensive compared with the standard arm (95% confidence intervals) were 1.18 (0.40 to 3.33), 1.61 (0.87 to 2.97), and 3.09 (0.96 to 8.78) for major adverse cardiovascular events, hospitalizations, and vascular access thrombosis, respectively. The intensive and standard arms had similar median changes (95% confidence intervals) in left ventricular mass of -0.84 (-17.1 to 10.0) g and 1.4 (-11.6 to 10.4) g, respectively. Although we identified a possible safety signal, the small size and short duration of the trial prevent definitive conclusions. Considering the high risk for major adverse cardiovascular events in patients receiving hemodialysis, a full-scale trial is needed to assess potential benefits of intensive hypertension control in this population.

Left ventricular hypertrophy by electrocardiography and echocardiography in the African American Study of Kidney Disease Cohort Study

Although electrocardiographic criteria for diagnosing left ventricular hypertrophy have a low sensitivity in the general population, their test characteristics have not been evaluated in the high-prevalence group of American Americans with chronic kidney disease. The purpose of the current study was to evaluate these test characteristics among African Americans (n = 645) with hypertensive kidney disease as part of the African-American Study of Kidney Disease and Hypertension cohort. Electrocardiograms were read by 2 cardiologists at an independent core laboratory using the 2 Sokolow-Lyon criteria and the Cornell criteria. Left ventricular hypertrophy on echocardiography was defined as left ventricular mass index greater than 49.2 and greater than 46.7 g/m(2.7) in men and women, respectively. Sixty-nine percent of the population had left ventricular hypertrophy on echo, whereas 34% had left ventricular hypertrophy by any of the electrocardiographic criteria. Sensitivity by individual electrocardiographic criteria was 16.5% by Sokolow-Lyon-1, 19.3% by Sokolow-Lyon-2, and 24.7% by Cornell criteria, with specificity ranging from 89% to 92%. When using any of the 3 criteria, sensitivity increased to 40.4% with a decrease in specificity to 78.0%. Consistent with findings in a general population, left ventricular hypertrophy by electrocardiography had low sensitivity and high specificity in this cohort of African Americans with hypertensive kidney disease.