Review and Meta-Analysis to Assess Renal Outcomes with Intensive Blood Pressure Control

Patients with chronic kidney disease face increased risk of diabetes, cardiovascular morbidity, and mortality; nondiabetic CKD accounts for most of the incidence worldwide. Hypertension is strongly associated with the development of progression of nondiabetic CKD, and control of blood pressure can decrease the risk of decline in renal function and cardiovascular mortality. However, according to Wan-Chuan Tsai, MD, and colleagues in Taiwan, the optimal blood pressure target for the prevention of kidney disease progression is unclear.

Current guidelines suggest a target blood pressure of less than 140/90 mm Hg for patients with nondiabetic CKD; some suggest a reduction of that target to less than 130/80 mm Hg for patients with proteinuria. Results from the SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated that intensive blood pressure did not result in reduction of the risk of dialysis or decline in renal function in patients with nondiabetic CKD, but rather increased the risk of acute kidney injury. Dr. Tsai et al. recently conducted a systemic review and meta-analysis of results from randomized controlled trials to examine the effects of intensive treatment to lower blood pressure on major renal outcomes and mortality in patients with nondiabetic CKD. Results of the review were reported online in JAMA Internal Medicine [doi:10.1001/jamainternmed.2017.0197].

The researchers conducted literature searches of PubMed, MEDLINE, Embase, and the Cochrane Library from the earliest available date of indexing through March 24, 2016. They also hand searched the reference lists of identified publications for additional studies. The review included randomized controlled trials that compared different blood pressure targets in primarily nondiabetic CKD patients >18 years of age.

To be eligible for the review, the studies had to report at least one of the outcomes of interest: changes in glomerular filtration rate (GFR), doubling of serum creatinine level, 50% reduction in GFR, progression to end-stage renal disease (ESRD), or all-cause mortality. ESRD was defined as the need for dialysis therapy or kidney transplantation. Eligible studies were required to be published as full-length articles in peer-reviewed journals.

There were 1158 articles retrieved initially. Of those, 328 were excluded because of duplicate publication and 816 were excluded on the basis of titles and abstracts. Of the remaining 14 articles that underwent full-text evaluation, 10 met the inclusion criteria and were included in the review.

The 10 eligible articles reported on nine randomized controlled trials, enrolling a total of 8127 participants. Median length of in-trial follow-up was 3.3 years, mean age of participants was 55 years, and 58% were men. Six of the studies included mostly white participants, two had mostly black participants, and one included mostly Asians. Most of the studies excluded all patients with diabetes; two excluded patients with poorly controlled diabetes and a small percentage of each study population had diabetes. The studies had similar baseline blood pressure between the intensive and standard treatment groups.

During the in-trial follow-up period, 194 patients had doubling of serum creatinine level or decline in GFR by 50%, 314 progressed to ESRD, 306 reached the composite renal outcomes, and 111 died. Compared with standard strategy to lower blood pressure, participants in groups treated with intensive blood pressure strategies did not exhibit a significant difference in the annual rate of change in GFR (mean difference, 0.07; 95% confidence interval [CI], –0.16 to 0.29 mL/min/1.73 m2 per year), doubling of serum creatinine or 50% reduction in GFR (risk ratio [RR], 0.99; 95% CI, 0.76-1.29), ESRD (RR, 0.96; 95% CI, 0.78-1.18), composite renal outcome (RR, 0.99; 95% CI, 0.81-1.21) or all-cause mortality (RR, 0.95; 95% CI, 0.66-1.37).

Results were similar following omission of studies with imputed missing data for the annual rate of change in GFR (mean difference, 0.09; 95% CI, –0.38 to 0.55 mL/min/1.73 m2 per year). In sensitivity analyses that omitted results of the two trials that included small percentage of patients with diabetes, results were also similar.

Univariable meta-regression analyses found that the annual rate of decline in GFR with intensive blood pressure control tended to be faster among blacks compared with nonblacks (b value, –0.44; 95% CI, –0.96 to 0.07 mL/min/1.73 m2 per year; P=.09). In subgroup analyses, there was a trend of faster decline in GFR for intensive blood pressure control in studies that included mostly black participants (mean difference, –0.26; 95% CI, –0.70 to 0.18 mL/min/1.73 m2 per year) and a slower decline in GFR in studies with nonblack participants (mean difference, 0.18; 95% CI, –0.08 to 0.45; P for interaction=.09).

The only outcomes that could be assessed by different levels of proteinuria were annual rate of change in GFR and progression to ESRD. There were no significant differences in the effects of intensive blood pressure control among patients with different levels of proteinuria. There was, however, a trend for intensive blood pressure control to slow the rate of decline of GFR level among patients with proteinuria higher than 1 g/d (mean difference, 0.75; 95% CI, –0.40-1.89 mL/min/1.73 m2 per year), and a trend for lower risk of ESRD among patients with proteinuria level higher than 0.5 g/d (RR, 0.92; 95% CI, 0.70-1.21).

The researchers cited some limitations to the review, including between-study variability due to varying patient characteristics and trial designs, most of the included studies had follow-up time less than 4 years, and the review was limited to published studies.

“Targeting blood pressure below the current standard did not provide additional benefit for renal outcomes compared with standard treatment during a follow-up of 3.3 years in patients with CKD without diabetes. However, nonblack patients or those with higher levels of proteinuria might benefit from the intensive blood pressure lowering and the risk of adverse events are mostly similar among different blood pressure targets,” the researchers said.

Takeaway Points

  • There are few data on the optimal blood pressure target in patients with chronic kidney disease without diabetes; researchers in Taiwan conducted a systematic review and meta-analysis to compare intensive blood pressure control with standard control on major renal outcomes.
  • There was no significant difference on the annual rate of change in glomerular filtration rate (GFR) with intensive versus standard blood pressure control, or on doubling of serum creatinine level or 50% reduction in GFR.
  • In nonblack participants and in patients with higher levels or proteinuria, there was a trend of lower risk of kidney disease progression to end-stage renal disease with intensive blood pressure control.