Velvie A. Pogue

Intensive blood-pressure control in hypertensive chronic kidney disease.

BACKGROUND In observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients. METHODS We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years. RESULTS During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive-control group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P=0.27). However, the effects differed according to the baseline level of proteinuria (P=0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P=0.01). CONCLUSIONS In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.)

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.

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.

Assessment and Management of Hypertension in Patients on Dialysis

Hypertension is common, difficult to diagnose, and poorly controlled among patients with ESRD. However, controversy surrounds the diagnosis and treatment of hypertension. Here, we describe the diagnosis, epidemiology, and management of hypertension in dialysis patients, and examine the data sparking debate over appropriate methods for diagnosing and treating hypertension. Furthermore, we consider the issues uniquely related to hypertension in pediatric dialysis patients. Future clinical trials designed to clarify the controversial results discussed here should lead to the implementation of diagnostic and therapeutic techniques that improve long-term cardiovascular outcomes in patients with ESRD.

Cocain-associated acute myoglobinuric renal failure

PURPOSE Abuse of cocaine is associated with serious medical complications involving the heart, central nervous system, and gastrointestinal tract. Renal complications appear to be uncommon. We describe herein four patients with rhabdomyolysis and acute myoglobinuric renal failure temporally related to cocaine use. CASE REPORTS Acute cocaine intoxication was the most common presentation and rhabdomyolysis was an unexpected finding. Renal failure progressed rapidly in all patients, necessitating dialysis in two. The prognosis was good, and all patients survived. The mechanism of cocaine injury is unclear; possibilities include increased muscle activity, muscle compression, hyperthermia, and vasospasm with muscle ischemia. CONCLUSION Rhabdomyolysis with acute renal failure should be recognized as a possible complication of cocaine abuse.

Relationship between Ambulatory BP and Clinical Outcomes in Patients with Hypertensive CKD

BACKGROUND AND OBJECTIVES Abnormal ambulatory BP (ABP) profiles are commonplace in CKD, yet the prognostic value of ABP for renal and cardiovascular outcomes is uncertain. This study assessed the relationship of baseline ABP profiles with CKD progression and subsequent cardiovascular outcomes to determine the prognostic value of ABP beyond that of clinic BP measurements. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Between 2002 and 2003, 617 African Americans with hypertensive CKD treated to a clinic BP goal of <130/80 mmHg were enrolled in this prospective, observational study. Participants were followed for a median of 5 years. Primary renal outcome was a composite of doubling of serum creatinine, ESRD, or death. The primary cardiovascular outcome was a composite of myocardial infarction, hospitalized congestive heart failure, stroke, revascularization procedures, cardiovascular death, and ESRD. RESULTS Multivariable Cox proportional hazard analysis showed that higher 24-hour systolic BP (SBP), daytime, night-time, and clinic SBP were each associated with subsequent renal (hazard ratio, 1.17-1.28; P<0.001) and cardiovascular outcomes (hazard ratio, 1.22-1.32; P<0.001). After controlling for clinic SBP, ABP measures were predictive of renal outcomes in participants with clinic SBP <130 mmHg (P<0.05 for interaction). ABP predicted cardiovascular outcomes with no interaction based on clinic BP control. CONCLUSIONS ABP provides additional information beyond that of multiple clinic BP measures in predicting renal and cardiovascular outcomes in African Americans with hypertensive CKD. The primary utility of ABP in these CKD patients was to identify high-risk individuals among those patients with controlled clinic BP.

Limitations of Analyses Based on Achieved Blood Pressure: Lessons From the African American Study of Kidney Disease and Hypertension Trial

Blood pressure (BP) guidelines that set target BP levels often rely on analyses of achieved BP from hypertension treatment trials. The objective of this paper was to compare the results of analyses of achieved BP to intention-to-treat analyses on renal disease progression. Participants (n=1,094) in the African-American Study of Kidney Disease and Hypertension Trial were randomized to either: (1) usual BP goal defined by a mean arterial pressure (MAP) goal of 102–107 mmHg or (2) lower BP goal defined by a MAP goal of ≤ 92 mmHg. Median follow-up was 3.7 years. Primary outcomes were rate of decline in measured glomerular filtration rate (GFR) and a composite of a decrease in GFR by > 50% or >25 ml/min/1.73m2, requirement for dialysis, transplantation, or death. Intention-to-treat analyses showed no evidence of a BP effect on either the rate of decline in GFR or the clinical composite outcome. In contrast, the achieved BP analyses showed that each 10 mm Hg increment in mean follow-up achieved MAP was associated with a 0.35 (95% CI 0.08 – 0.62, p = 0.01) ml/min/1.73m2 faster mean GFR decline and a 17% (95% CI 5% – 32%, p = 0.006) increased risk of the clinical composite outcome. Analyses based on achieved BP lead to markedly different inferences than traditional intention-to-treat analyses, due in part to confounding of achieved BP with co- morbidities, disease severity and adherence. Clinicians and policy makers should exercise caution when making treatment recommendations based on analyses relating outcomes to achieved BP.Blood pressure (BP) guidelines that set target BP levels often rely on analyses of achieved BP from hypertension treatment trials. The objective of this article was to compare the results of analyses of achieved BP to intention-to-treat analyses on renal disease progression. Participants (n=1094) in the African-American Study of Kidney Disease and Hypertension Trial were randomly assigned to either usual BP goal defined by a mean arterial pressure goal of 102 to 107 mm Hg or lower BP goal defined by a mean arterial pressure goal of ⩽92 mm Hg. Median follow-up was 3.7 years. Primary outcomes were rate of decline in measured glomerular filtration rate and a composite of a decrease in glomerular filtration rate by >50% or >25 mL/min per 1.73 m2, requirement for dialysis, transplantation, or death. Intention-to-treat analyses showed no evidence of a BP effect on either the rate of decline in glomerular filtration rate or the clinical composite outcome. In contrast, the achieved BP analyses showed that each 10-mm Hg increment in mean follow-up achieved mean arterial pressure was associated with a 0.35 mL/min per 1.73 m2 (95% CI: 0.08 to 0.62 mL/min per 1.73 m2; P=0.01) faster mean glomerular filtration rate decline and a 17% (95% CI: 5% to 32%; P=0.006) increased risk of the clinical composite outcome. Analyses based on achieved BP lead to markedly different inferences than traditional intention-to-treat analyses, attributed in part to confounding of achieved BP with comorbidities, disease severity, and adherence. Clinicians and policy makers should exercise caution when making treatment recommendations based on analyses relating outcomes to achieved BP.

Relationship Between Body Mass Index and Proteinuria in Hypertensive Nephrosclerosis: Results From the African American Study of Kidney Disease and Hypertension (AASK) Cohort

BACKGROUND Few studies have examined the association between obesity and markers of kidney injury in a chronic kidney disease population. We hypothesized that obesity is independently associated with proteinuria, a marker of chronic kidney disease progression. STUDY DESIGN Observational cross-sectional analysis. SETTING & PARTICIPANTS Post hoc analysis of baseline data for 652 participants in the African American Study of Kidney Disease (AASK). PREDICTORS Obesity, determined using body mass index (BMI). MEASUREMENTS & OUTCOMES Urine total protein-creatinine ratio and albumin-creatinine ratio measured in 24-hour urine collections. RESULTS AASK participants had a mean age of 60.2 ± 10.2 years and serum creatinine level of 2.3 ± 1.5 mg/dL; 61.3% were men. Mean BMI was 31.4 ± 7.0 kg/m(2). Approximately 70% of participants had a daily urine total protein excretion rate <300 mg/d. In linear regression analyses adjusted for sex, each 2-kg/m(2) increase in BMI was associated with a 6.7% (95% CI, 3.2-10.4) and 9.4% (95% CI, 4.9-14.1) increase in urine total protein-creatinine and urine albumin-creatinine ratios, respectively. In multivariable models adjusting for age, sex, systolic blood pressure, serum glucose level, uric acid level, and creatinine level, each 2-kg/m(2) increase in BMI was associated with a 3.5% (95% CI, 0.4-6.7) and 5.6% (95% CI, 1.5-9.9) increase in proteinuria and albuminuria, respectively. The interaction between older age and BMI was statistically significant, indicating that this relationship was driven by younger AASK participants. LIMITATIONS May not generalize to other populations; cross-sectional analysis precludes statements regarding causality. CONCLUSIONS BMI is associated independently with urine total protein and albumin excretion in African Americans with hypertensive nephrosclerosis, particularly in younger patients.

N-Terminal Prohormone Brain Natriuretic Peptide as a Predictor of Cardiovascular Disease and Mortality in Blacks With Hypertensive Kidney Disease: The African American Study of Kidney Disease and Hypertension (AASK)

Background— Higher levels of N-terminal prohormone brain-type natriuretic peptide (NT-proBNP) predict cardiovascular disease (CVD) in several disease states, but few data are available in patients with chronic kidney disease or in blacks. Methods and Results— The African American Study of Kidney Disease and Hypertension trial enrolled hypertensive blacks with a glomerular filtration rate of 20 to 65 mL · min−1 · 1.73 m−2 and no other identified cause of kidney disease. NT-proBNP was measured with a sandwich chemiluminescence immunoassay (coefficient of variation 2.9%) in 994 African American Study of Kidney Disease and Hypertension participants. NT-proBNP was categorized as undetectable, low, moderate, or high. Proteinuria was defined as 24-hour urinary protein–creatinine ratio >0.22. A total of 134 first CVD events (CVD death or hospitalization for coronary artery disease, heart failure, or stroke) occurred over a median of 4.3 years. Participants with high NT-proBNP were much more likely to have a CVD event than participants with undetectable NT-proBNP after adjustment (relative hazard 4.0 [95% confidence interval [CI] 2.1 to 7.6]). A doubling of NT-proBNP was associated with a relative hazard of 1.3 (95% CI 1.0 to 1.6) for coronary artery disease, 1.7 (95% CI 1.4 to 2.2) for heart failure, 1.1 (95% CI 0.9 to 1.4) for stroke, and 1.8 (95% CI 1.4 to 2.4) for CVD death. The association of NT-proBNP with CVD events was significantly stronger (Pinteraction=0.05) in participants with than in those without proteinuria. Higher NT-proBNP was not associated with renal disease progression. Conclusions— These results suggest that elevated NT-proBNP levels are associated with higher CVD risk among blacks with hypertensive kidney disease. This association may be stronger in individuals with significant proteinuria.

BP Control and Long-Term Risk of ESRD and Mortality

We recently showed an association between strict BP control and lower mortality risk during two decades of follow-up of prior participants in the Modification of Diet in Renal Disease (MDRD) trial. Here, we determined the risk of ESRD and mortality during extended follow-up of the African American Study of Kidney Disease and Hypertension (AASK) trial. We linked 1067 former AASK participants with CKD previously randomized to strict or usual BP control (mean arterial pressure ≤92 mmHg or 102-107 mmHg, respectively) to the US Renal Data System and Social Security Death Index; 397 patients had ESRD and 475 deaths occurred during a median follow-up of 14.4 years from 1995 to 2012. Compared with the usual BP arm, the strict BP arm had unadjusted and adjusted relative risks of ESRD of 0.92 (95% confidence interval [95% CI], 0.75 to 1.12) and 0.95 (95% CI, 0.78 to 1.16; P=0.64), respectively, and unadjusted and adjusted relative risks of death of 0.92 (95% CI, 0.77 to 1.10) and 0.81 (95% CI, 0.68 to 0.98; P=0.03), respectively. In meta-analyses of individual-level data from the MDRD and the AASK trials, unadjusted relative risk of ESRD was 0.88 (95% CI, 0.78 to 1.00) and unadjusted relative risk of death was 0.87 (95% CI, 0.76 to 0.99) for strict versus usual BP arms. Our findings suggest that, during long-term follow-up, strict BP control does not delay the onset of ESRD but may reduce the relative risk of death in CKD.