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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    • "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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    • "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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    • "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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