BP and Renal Outcomes in Diabetic Kidney Disease: The Veterans Affairs Nephropathy in Diabetes Trial

Abstract

Background and objectives: Proteinuric diabetic kidney disease frequently progresses to ESRD. Control of BP delays progression, but the optimal BP to improve outcomes remains unclear. The objective of this analysis was to evaluate the relationship between BP and renal outcomes in proteinuric diabetic kidney disease.

Design, setting, participants, & measurements: BP data from all 1448 randomized participants in the Veterans Affairs Nephropathy in Diabetes Trial were included in a post hoc analysis. The associations of mean on-treatment BP with the primary end point (decline in eGFR, ESRD, or death), renal end point (decline in eGFR or ESRD), rate of eGFR decline, and mortality were measured.

Results: The median (25th, 75th percentile) follow-up time was 2.2 (1.2, 3.0) years. There were 284 primary end points. In univariate analyses, both mean systolic and mean diastolic BPs were strongly associated (P<0.001) with the primary end point. After multivariate adjustment, the hazard of developing the primary end point became progressively higher as mean systolic BP rose from <120 to ≥ 150 mmHg (P=0.02), with a significantly higher hazard ratio for 140-149 versus 120-129 mmHg (1.51 [1.06, 2.15]; P=0.02). There was also a significant association of mean diastolic BP with the hazard of developing the primary end point (P<0.01), with a significantly higher hazard ratio when mean diastolic BP was 80-89 versus 70-79 mmHg (1.54 [1.05, 2.25]; P=0.03); there was also a strong trend when mean diastolic BP was <60 mmHg. Associations between BP and both renal end point and rate of eGFR decline were similar to those with the primary end point. No association of BP with mortality was observed, possibly because of the limited number of mortality events.

Conclusions: In patients with proteinuric diabetic kidney disease, mean systolic BP ≥ 140 mmHg and mean diastolic BP ≥ 80 mmHg were associated with worse renal outcomes.

Keywords: blood pressure; diabetes mellitus; diabetic nephropathies; end-stage renal disease; follow-up studies; glomerular filtration rate; humans; kidney failure, chronic; progression of chronic kidney disease; proteinuria.

Figure 1.

BP among patients who did and did not reach the primary end point. The figures depict the (A) systolic BP (SBP) and (B) diastolic BP (DBP) at baseline (Pre), at randomization (Rand), and during the course of the study in patients who did and did not develop the primary end point. The error bars denote means and 95% confidence intervals.

Figure 2.

Univariate hazard ratios of the primary end point, secondary end point, and mortality for categorical mean systolic BP (SBP) and diastolic BP (DBP). (A) Mean SBP: P<0.001 for equal hazard of primary end point among all SBP groups, P<0.001 for equal hazard of secondary end point among all SBP groups, and P=0.11 for equal hazard of mortality among all SBP groups. (B) Mean DBP: P<0.001 for equal hazard of primary end point among all DBP groups, P<0.001 for equal hazard of secondary end point among all DBP groups, and P=0.22 for equal hazard of mortality among all DBP groups. The error bars denote 95% confidence intervals of the hazard ratios.

Figure 3.

Summary of eGFR at randomization (Rand) and during the course of the study for categorical mean systolic BP (SBP) and diastolic BP (DBP). (A) SBP. (B) DBP. The error bars denote the 95% confidence intervals of the means.