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Abstract: PO2095

Early GFR Decline with Intensive BP Lowering and the Risk of Death and ESKD: Mediation Analysis of AASK Study

Session Information

Category: Hypertension and CVD

  • 1402 Hypertension and CVD: Clinical, Outcomes, and Trials

Authors

  • Beddhu, Srinivasan, Division of Nephrology & Hypertension, University of Utah School of Medicine, Salt Lake City, Utah, United States
  • Shen, Jincheng, Division of Biostatistics, University of Utah School of Medicine, Salt Lake City, Utah, United States
  • Chertow, Glenn Matthew, Division of Nephrology, Stanford University School of Medicine, Palo Alto, California, United States
  • Whelton, Paul K., Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States
  • Wei, Guo, Division of Nephrology & Hypertension, University of Utah School of Medicine, Salt Lake City, Utah, United States
  • Boucher, Robert E., Division of Nephrology & Hypertension, University of Utah School of Medicine, Salt Lake City, Utah, United States
  • Cheung, Alfred K., Division of Nephrology & Hypertension, University of Utah School of Medicine, Salt Lake City, Utah, United States
  • Greene, Tom, Division of Biostatistics, University of Utah School of Medicine, Salt Lake City, Utah, United States
Background

Intensive BP lowering decreased the risk of death in CKD in SPRINT but there are concerns that its acute, hemodynamic kidney effects might increase ESKD risk.

Methods

AASK Study (N =1094) was a RCT of low vs. usual mean arterial pressure (≤ 92 vs.102 to 107 mmHg) on kidney outcomes. Using the change in measured iothalamate GFR from baseline to the average of months 3 and 6 (early GFR change), we examined the acute effect of the intervention on subequent death/ESKD in a mediation analysis. We partitioned the total effect of BP intervention on death/ESKD that was mediated through early GFR change (indirect effect) and independent of early GFR change (direct effect). We also used SIMEX method to access the impact of measurement error in early GFR change on the findings.

Results

We included 976 AASK participants with GFR measurements at baseline, 3 and 6 months. Mean baseline GFR was 55±11 ml/min/1.73m2. There were 223 deaths, 293 ESKD events and 445 death/ESKD events during an average of 7.2± 3.3 years of follow-up. BP separation was maintained through the trial (Fig 1, panel A) with an early decline in GFR in the lower BP group but GFRs in the two arms that were similar at the end of the trial (Fig 1, panel B). After adjustment for covariates listed in the footnote to Fig 2, we observed a borderline significant beneficial total effect of the BP intervention on death/ESKD and a slightly stronger direct effect (Fig 2). The HR for the indirect effect was slightly > 1, consistent with the possibility of a small adverse effect of early GFR change.

Conclusion

Intensive BP lowering appears to have a largely beneficial direct effect and a small deleterious indirect effect on death/ESKD in CKD.

Funding

  • NIDDK Support