Intensive Blood-Pressure Control in Hypertensive Chronic Kidney Disease

Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD 21205-2223, USA.
New England Journal of Medicine (Impact Factor: 55.87). 09/2010; 363(10):918-29. DOI: 10.1056/NEJMoa0910975
Source: PubMed


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.
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.
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).
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.)

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Available from: Otelio S Randall, Oct 01, 2015
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    • "This distinction is clinically important because the renal benefits of ACEi/ARBs in non-diabetic CKD primarily accrue in severely albuminuric patients [43,44] and the debated benefits of lower targeted blood pressure in CKD also primarily apply to albuminuric/proteinuric patients [45,46]. The under appreciation of the significance of albuminuria may be due in part to the greater emphasis on eGFR in the 2002 KDOQI guidelines. "
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    ABSTRACT: Most non-dialysis dependent chronic kidney disease (CKD) patients are cared for by their primary care physicians (PCPs). Studies suggest many CKD patients receive suboptimal care. Recently, CKD clinical practice guidelines were updated with additional emphasis on albuminuria. We performed an internet-based, cross-sectional survey of active PCPs in the United States using the American Medical Association Physician Masterfile. We explored CKD guideline familiarity, self-reported practice behaviors, and attitudinal and external barriers to implementing guideline recommendations, including albuminuria testing. Of 12,034 PCPs targeted, 848 opened a study email, 165 (19.5%) responded. Most respondents (88%) spent >=50% of their time in clinical care. Respondents were generally in private practice (46%). Most PCPs (96%) felt that eGFR values were helpful. Approximately, 75% and 91% of PCPs reported testing for albuminuria in non-diabetic hypertensive patients with an eGFR > 60 ml/min/1.73 m2 and < 60 ml/min/1.73 m2, respectively. Barriers to albuminuria testing included a lack of effect on management, limited time, and the perceived absence of guidelines recommending testing. While PCPs expressed high levels of agreement with the definition of CKD, 30% were concerned with overdiagnosis in older adults with an eGFR in the CKD stage 3a range. Most PCPs felt that angiotensin converting enzyme inhibitor (ACEi)/ angiotensin II receptor blockers (ARBs) improved outcomes in CKD, though agreement was lower with severe vs. moderate albuminuria (78% vs. 85%, respectively, p = 0.03). Many PCPs (51%) reported being unfamiliar with CKD guidelines, but were receptive to systematic interventions to improve their CKD care. PCPs generally agree with CKD clinical practice guidelines regarding CKD definition and albuminuria testing. However, future interventions are necessary to improve PCPs' familiarity with CKD guidelines, overcome barriers to albuminuria testing and, assist PCPs in targeting ACEi/ARBs to the patients most likely to benefit.
    BMC Nephrology 04/2014; 15(1):64. DOI:10.1186/1471-2369-15-64 · 1.69 Impact Factor
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    • "Specifically, the prognostic power of residual proteinuria seems to outweigh that of blood pressure since a graded relationship between the degree of proteinuria and the risk of reaching ESRD was observed for each systolic blood pressure strata [20]. Furthermore, better long-term renal survival in patients with overt proteinuria assigned to more intensive blood pressure reduction was confirmed by recently published data from the AASK study [21]. A similar relationship between albuminuria and renal outcome has been shown to apply also to earlier stages of the disease as indicated by an association of albuminuria reduction with better preservation of GFR in the STENO-2 study carried out on patients with type 2 diabetes [22]. "
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    ABSTRACT: The prevalence of chronic kidney disease, currently estimated to vary between 8 and 12 % in the general population, is steadily rising due to aging and to the ongoing epidemic of hypertension and type 2 diabetes. Even in its early stages, chronic kidney disease entails a greater risk for cardiovascular mortality, and its prevention and treatment is rapidly becoming a key medical issue for many health care systems worldwide. Adequate blood pressure control and reduction of urine protein excretion, preferably obtained by the use of renin-angiotensin-aldosterone system inhibitors, have traditionally been considered the mainstay of therapeutic strategies in patients with renal disease. Given the pivotal role of renin-angiotensin-aldosterone system activity in the pathogenesis and progression of renal and cardiovascular damage, a more profound inhibition of the system, either by the use of multiple agents or by a single agent at high dosage has recently been advocated, especially in the presence of proteinuria. Recent trials, however have failed to confirm the usefulness of this therapeutic approach, at least in unselected patients. This article will critically review the current literature and will discuss the clinical implications of targeting the renin-angiotensin-aldosterone system in order to provide the greatest renal protection.
    High Blood Pressure & Cardiovascular Prevention 10/2013; 20(4). DOI:10.1007/s40292-013-0027-y
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    • "The data, however, provides an excellent opportunity for a secondary analysis to evaluate the impact of time-dependent changes in arterial properties and cardiovascular remodeling, specifically, spontaneous or unintentional changes in a nonmonitored BP component, PP, over a specified time period, during which minimum changes in therapy occurred. Recently, we found that there may be differential effects of intensive blood-pressure control on kidney disease progression in patients with and those without baseline proteinuria [29]. The purpose of this observational study thus was to examine (i) the association between unit changes of PP on composite CV outcomes, (ii) the association of unit changes of PP with new detection of LVH, (iii) the effect of intensive blood-pressure control on time-dependent changes of the arterial system and/or CV remodeling characterized by rate of change in PP, "
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    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 09/2013; 2013(5):120167. DOI:10.1155/2013/120167
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