Abstract: FR-OR118

The Effect of Intensive Blood Pressure Lowering on Kidney Tubule Injury among Participants with CKD in the SPRINT Trial

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • Malhotra, Rakesh, UCSD, San Diego, California, United States
  • Ix, Joachim H., UCSD, San Diego, California, United States
  • Shlipak, Michael, San Francisco VA Medical Center, San Francisco, California, United States
  • Craven, Timothy, Wake Forest, Winston-Salem, North Carolina, United States
  • Ambrosius, Walter T, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States
  • Killeen, Anthony Alexander, University of Minnesota, Minneapolis, Minnesota, United States
  • Haley, William E., Mayo Clinic, Jacksonville, Florida, United States
  • Cheung, Alfred K., University of Utah, Salt Lake City, Utah, United States
  • Chonchol, Michel, University of Colorado, Aurora, Colorado, United States
  • Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States
  • Parikh, Chirag R., Yale University , New Haven, Connecticut, United States
Background

Randomization to the intensive (SBP<120 mm Hg) arm in SPRINT resulted in more rapid decline in estimated glomerular filtration rate (eGFR) than in the standard arm (SBP <140 mm Hg). Whether this change reflects hemodynamic effects or accelerated intrinsic kidney damage is unknown.

Methods

In a subset of SPRINT with CKD (eGFR<60 ml/min/1.73m2), we compared changes in kidney tubule biomarkers over 4 years between the intensive and standard arms. Among these 978 participants (519 in intensive and 459 in the standard arm), we measured urine biomarkers of tubule cell injury (KIM-1, IL-18), repair (YKL-40) and inflammation (MCP-1) at baseline, year 1 and year 4. Biomarkers were assayed en bloc in multiplex panels. Biomarker changes were evaluated using linear mixed-effects models in an intention-to-treat design.

Results

Mean age was 72± 8.6 and eGFR 46.1 ± 9.4. Clinical characteristics, eGFR, urinary albumin-to-creatinine ratio (ACR), and all 4 biomarkers were similar between arms at baseline. Compared to the standard arm, eGFR was 2.9 and 3.3 ml/min/1.73m2 lower in the intensive arm at year 1 and year 4, and ACR was also lower in the intensive arm. All urinary biomarkers, except YKL-40, were significantly lower at year 1 in the intensive arm, and none differed between arms at year 4 (Figure 1).

Conclusion

Among CKD participants in SPRINT, intensive BP control reduced eGFR but did not increase urine markers of tubule cell injury. These findings may support the hypothesis that eGFR decline in the intensive arm of SPRINT reflects hemodynamic changes.

Figure 1. Unadjusted least-square means and standard error of eGFR, urinary ACR and urinary biomarkers at baseline and the 4-year follow-up

Funding

  • NIDDK Support