# Acute declines in kidney function during blood pressure interventions in CKD

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $720,273

## Abstract

PROJECT ABSTRACT
Chronic kidney disease (CKD) is associated with significant morbidity and mortality: Medicare spent 98 billion
dollars for CKD care in 2017. To date, the two interventions that have been shown to improve cardiovascular
disease (CVD) risk or slow the progression of CKD are intensive lowering of systolic blood pressure (BP) to
<120 mmHg or use of renin-angiotensin system (RAS) blockers. However, during both interventions, acute
declines in estimated glomerular filtration rate (eGFR) occur in the majority of patients, especially if baseline
CKD is present. Traditionally, these acute declines in kidney function (e.g. serum creatinine increases of up to
30% during RAS blockade) have been thought to be benign, reversible, and not associated with long-term
sequelae, but more recent studies have questioned whether even smaller changes in kidney function during
these interventions could be associated with long-term CVD or renal risk. Few studies have systematically
quantified the magnitude of acute decline in eGFR during BP lowering or RAS initiation and if there is a
threshold that may be associated with higher risk of adverse renal or CVD outcomes. This question is
significant, since currently, achievement of appropriate BP control and use of RAS inhibitors is suboptimal in
patients with CKD despite the proven benefits of these interventions. Many providers may relax BP control or
stop RAS inhibitors in the face of acute declines in eGFR despite expert recommendations to tolerate these
changes. Our objective is to determine the long-term kidney and CVD implications of the acute changes in
eGFR during anti-hypertensive therapy. In Aim 1, we will assemble and harmonize data from completed
randomized trials of intensive BP control or RAS inhibition to examine this issue in an individual-level meta-
analysis of patients with baseline CKD and identify characteristics of patients at-risk for large acute declines in
kidney function during BP therapy. In Aim 2, we will evaluate the association between acute changes in eGFR
and risk of ESRD or CVD events following either intensive BP lowering or RAS initiation and explore if there is
a magnitude of change in eGFR that is associated with adverse outcomes. Next, we will determine whether
acute changes in eGFR modify or mediate the effect of either intensive BP lowering or RAS therapy on ESRD
or CVD risk (Aim 3). Finally, we will develop an innovative tool that will 1) predict further changes in eGFR
with continued anti-hypertensive therapy and 2) provide refined estimates of the risk of ESRD or CVD,
accounting for the changes in eGFR that occurred (Aim 4). This proposal is significant as it could guide
clinical decision-making: if acute declines in eGFR are not associated with adverse outcomes, then providers
should be encouraged to continue these therapies regardless of the acute eGFR changes that occur.
However, if acute declines in eGFR are associated with adverse outcomes (and the threshold wh...

## Key facts

- **NIH application ID:** 10155481
- **Project number:** 5R01DK121904-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Elaine Ku
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $720,273
- **Award type:** 5
- **Project period:** 2020-05-01 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155481

## Citation

> US National Institutes of Health, RePORTER application 10155481, Acute declines in kidney function during blood pressure interventions in CKD (5R01DK121904-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10155481. Licensed CC0.

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