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.

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.

Nurse-led disease management for hypertension control in a diverse urban community: a randomized trial.

BACKGROUND: Treated but uncontrolled hypertension is highly prevalent in African American and Hispanic communities. OBJECTIVE: To test the effectiveness on blood pressure of home blood pressure monitors alone or in combination with follow-up by a nurse manager. DESIGN: Randomized controlled effectiveness trial. PATIENTS: Four hundred and sixteen African American or Hispanic patients with a history of uncontrolled hypertension. Patients with blood pressure ≥150/95, or ≥140/85 for patients with diabetes or renal disease, at enrollment were recruited from one community clinic and four hospital outpatient clinics in East and Central Harlem, New York City. INTERVENTION: Patients were randomized to receive usual care or a home blood pressure monitor plus one in-person counseling session and 9 months of telephone follow-up with a registered nurse. During the trial, the home monitor alone arm was added. MAIN MEASURES: Change in systolic and diastolic blood pressure at 9 and 18 months. KEY RESULTS: Changes from baseline to 9 months in systolic blood pressure relative to usual care was -7.0 mm Hg (Confidence Interval [CI], -13.4 to -0.6) in the nurse management plus home blood pressure monitor arm, and +1.1 mm Hg (95% CI, -5.5 to 7.8) in the home blood pressure monitor only arm. No statistically significant differences in systolic blood pressure were observed among treatment arms at 18 months. No statistically significant improvements in diastolic blood pressure were found across treatment arms at 9 or 18 months. Changes in prescribing practices did not explain the decrease in blood pressure in the nurse management arm. CONCLUSIONS: A nurse management intervention combining an in-person visit, periodic phone calls, and home blood pressure monitoring over 9 months was associated with a statistically significant reduction in systolic, but not diastolic, blood pressure compared to usual care in a high risk population. Home blood pressure monitoring alone was no more effective than usual care.

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 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 m(2), 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 m(2) (95% CI: 0.08 to 0.62 mL/min per 1.73 m(2); 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.

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.)

Influence of concomitant prednisolone on trimethoprim-associated hyperkalaemia.

OBJECTIVES: Trimethoprim-sulfamethoxazole may cause hyperkalaemia by the amiloride-like effect of trimethoprim on sodium channels in the distal nephron. Hyperkalaemia usually occurs after 7-10 days and has been reported in 20%-50% of patients receiving trimethoprim-sulfamethoxazole. Patients with Pneumocystis jiroveci pneumonia and severe hypoxaemia benefit from the use of prednisolone as an adjuvant to trimethoprim-sulfamethoxazole. The addition of prednisolone may lower the incidence of trimethoprim-related hyperkalaemia due, in part, to its mineralocorticoid activity. We studied the effect of concomitant prednisolone on trimethoprim-related hyperkalaemia. PATIENTS: Thirty patients qualified for inclusion and were reviewed. Patients were divided into two groups: one group received trimethoprim-sulfamethoxazole plus prednisolone (18 patients); and the other group received trimethoprim-sulfamethoxazole alone (12 patients). RESULTS: The two groups were comparable at baseline, except for the severity of the P. jiroveci pneumonia. Hyperkalaemia developed in seven patients: all in the prednisolone and trimethoprim-sulfamethoxazole group. The greater incidence of hyperkalaemia in this group is surprising and was counter to our expectation. CONCLUSIONS: Although it is possible that there is an unexplained interaction between trimethoprim and prednisolone, we postulate that our observation is a result of the catabolic effect of prednisolone. The patients treated with trimethoprim-sulfamethoxazole plus prednisolone appear to be more likely to develop hyperkalaemia than patients treated with trimethoprim-sulfamethoxazole alone.

Proteinuria lowers the risk of amphotericin B-associated hypokalaemia.

OBJECTIVES: Amphotericin B-induced nephrotoxicity is frequent, severe and associated with an increased risk of death. Patients with underlying renal disease are considered to be at high risk for amphotericin B nephrotoxicity. Amphotericin B is a molecule that is highly protein bound over a wide range of protein and drug concentrations, including those seen in patients with >or= 3 + proteinuria. We hypothesized that amphotericin B treatment in patients with proteinuria will be associated with less hypokalaemia than patients with non-proteinuric renal disease. METHODS: Thirty-six subjects who received amphotericin B deoxycholate were studied retrospectively. Twenty-five patients with proteinuria < 3 g/L and 11 with proteinuria >or= 3 g/L were compared. RESULTS: Hypokalaemia (K+ < 3.5 mmol/L) developed in 47.2% (17/36) of our cohort of patients. There was a 64% (16/25) incidence of hypokalaemia in the group with < 3 g/L of proteinuria in contrast to an incidence of 9.1% (1/11) in the other group. CONCLUSIONS: In our study, heavy proteinuria appears to protect the tubular luminal membrane by decreasing the luminal concentration of free drug available to bind with the membrane. Our findings redefine the patient population deemed to be at risk of developing amphotericin B nephrotoxicity. This ensures the benefit of this important antifungal treatment option to patients with heavy proteinuria who might otherwise not be administered this drug due to the presence of pre-existing kidney disease.

Kidney disease physician workforce: where is the emerging pipeline?

A predicted increase in the number of patients with end-stage renal disease in coming years, coupled with significant numbers of qualified nephrologists reaching retirement age, will place great demands on the renal physician workforce. Action is required on several fronts to combat the predicted shortfall in full-time nephrologists. Of particular importance is the need to recruit and train greater numbers of physicians from ethnic minority groups. Changes in the demographics of kidney disease make it increasingly a disease of ethnic minorities and the poor. These demographic changes, together with the existing racial disparities in the diagnosis and treatment of kidney disease, highlight the specific need for nephrologists who are cognizant of the issues and barriers that prevent optimal care of high-risk minority populations. The current lack of academic role models and the drive by medical schools and residency programs to encourage minority group physicians to become primary care providers, rather than specialists, are issues that must be urgently addressed. Equally, changes in the training of renal fellows are required to merge the critical need for cutting edge research activity in renal science and with the insights and sensitivity to equip clinicians with the necessary skills for the team-based approach to patient care that increasingly characterizes the management and care of the patient with chronic kidney disease.