Effect of Intensive Blood Pressure Lowering on Kidney Tubule Injury: Findings From the ACCORD Trial Study Participants

Abstract

Randomization to intensive blood pressure lowering (SBP<120 mm Hg) compared to a less intensive BP target (SBP <140 mm Hg) in the ACCORD-BP trial resulted in a more rapid decline in the estimated glomerular filtration rate (eGFR). Whether this reflects hemodynamic effects or intrinsic kidney damage is unknown. Longitudinal analysis of a sub-group of clinical trial participants. A subgroup of 529 participants in ACCORD-BP. Urine biomarkers of tubular injury (kidney injury molecule 1 [KIM-1], interleukin 18 [IL-18]), repair (YKL-40) and inflammation (monocyte chemoattractant protein 1 [MCP-1]) at baseline and year 2. Changes in eGFR from baseline to 2 years. We compared changes in biomarkers and changes in eGFR across participants treated to an intensive vs. less intensive BP goal using analysis of covariance. Of the 529 participants, 260 had been randomized to the intensive and 269 to the standard blood pressure arm. Mean age was 62 ± 6.5 and eGFR 90 ml/min/1.73m 2 . Baseline clinical characteristics, eGFR, urinary albumin-to-creatinine ratio (ACR), and urinary biomarkers were similar across BP treatment groups. Compared to less intensive BP treatment, eGFR was 9.2 ml/min/1.73m 2 lower in the intensive BP treatment group at year 2. Despite the eGFR reduction, within this treatment group ACR was 30% lower and 4 urinary biomarkers were unchanged or lower at year 2. Also within this group, participants with largest declines in eGFR had greater reductions in urinary IL-18 and YKL-40. In a subgroup analysis of participants developing incident CKD (sustained 30% decline and eGFR < 60 ml/min/1.73 m 2 , n=77), neither ACR nor 4 biomarkers increased in the intensive treatment group, whereas one biomarker, IL-18, increased in the less intensive treatment group. Few participants with advanced baseline CKD. Comparisons across treatment groups do not represent comparisons of treatment arms created solely through randomization. Among a subset of ACCORD-BP trial participants, intensive BP control was associated reductions of eGFR but not with an increase in injury markers. These findings support that eGFR decline observed with intensive BP goals in ACCORD participants may predominantly reflect hemodynamic alterations.