# Long-term metabolic effects of kidney events with intensive SBP control

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $277,543

## Abstract

The Systolic Blood Pressure Intervention Trial (SPRINT), a landmark study demonstrated that intensive
systolic blood pressure (SBP) lowering (SBP target <120 versus <140 mmHg) reduced the risk of death and
major cardiovascular events in persons without diabetes but at high cardiovascular risk. In a recent publication,
we noted that intensive SBP lowering in SPRINT resulted in a relative mean decline in estimated glomerular
filtration rate (eGFR) (intensive versus standard) of −3.31 ± 0.30 mL/min/1.73 m2 by 6 months. The intensive
SBP group also had a 3.5-fold higher hazard of incident chronic kidney disease (CKD).
 The Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) trial used a 2 X 2
factorial design to test the same SBP intervention as SPRINT as well as intensive versus standard glycemic
control (glycated hemoglobin < 6% versus 7.0 to 7.8%) in persons with type 2 diabetes mellitus (T2DM). In our
analysis of ACCORD-BP data, comparisons of the intensive vs. standard SBP groups showed that the
intensive SBP intervention in ACCORD-BP led to an even more pronounced early mean eGFR decline and a
greater increase in the cumulative incidence of CKD relative to SPRINT (interaction p-value <0.001).
 It is possible that the decline in eGFR due to blood pressure lowering may have distinct clinical and public
health consequences compared with the decline in eGFR due to other conditions, which we have presumed to
be related to progression of intrinsic kidney disease. As the follow-up periods are too short to determine the
long-term effects of acute, early eGFR decline/incident CKD on hard endpoints, stored specimens from both
studies provide an opportunity to study parallel effects on metabolic markers reflecting key outcome domains
of inflammation/ iron metabolism and bone and mineral metabolism/ vascular calcification.
 Herein we propose to examine the long-term metabolic implications of acute, early eGFR decline/incident
CKD in SPRINT and ACCORD-BP. The analyses of Aim 1 will address consequences of acute changes in
eGFR and incident CKD that are due to the SBP interventions as well as consequences of changes in GFR
due to other factors including the natural course of kidney disease. Aim 2 will use modern causal modeling
techniques to address the consequences of acute changes in eGFR and incident CKD that are specifically due
to the intensive SBP intervention.
 The current proposal will clarify whether changes in eGFR and incident CKD noted with intensive SBP
lowering result in an altered metabolic milieu. Prior to SPRINT, there was no RCT level evidence that intensive
SBP control to a goal of <120 mm Hg prolongs survival and reduces the risk of cardiovascular events. While
SPRINT findings are novel and significant, there are concerns about the kidney effects of the SPRINT
intervention. This proposal seeks to address this knowledge gap in a topic of profound public health
significance.

## Key facts

- **NIH application ID:** 10223281
- **Project number:** 5R01DK118219-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** SRINIVASAN BEDDHU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $277,543
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10223281

## Citation

> US National Institutes of Health, RePORTER application 10223281, Long-term metabolic effects of kidney events with intensive SBP control (5R01DK118219-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10223281. Licensed CC0.

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