# REstrictive versus LIberal rate of Extracorporeal Volume removal Evaluation in Acute Kidney Injury (RELIEVE-AKI)

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $328,766

## Abstract

Abstract
Two-thirds of critically ill patients with acute kidney injury have a fluid overload at the time of initiation of kidney
replacement therapy in the intensive care unit. Although “net ultrafiltration (UFNET),” also known as net fluid
removal during kidney replacement therapy, has been used in the treatment of fluid overload for more than
seven decades, the optimal rate of UFNET remains uncertain, complications such as hypotension and cardiac
arrhythmias occur frequently, and more than 40% of critically ill patients die. Emerging evidence from
observational studies suggests a “J” shaped association between UFNET rate and mortality in critically ill
patients with acute kidney injury and treated with kidney replacement therapy. Higher UFNET rates are
associated with an increased risk of death compared with moderate and lower UFNET rates. Understanding the
causal effects of UFNET rate on outcomes is critical to design interventions to reduce mortality, develop
evidence-based clinical practice guidelines, and implement quality measures for UFNET. In the absence of such
knowledge, optimizing UFNET to improve outcomes will remain problematic. Thus, we will conduct a pilot clinical
trial entitled REstrictive versus LIberal rate of Extracorporeal Volume removal Evaluation in Acute Kidney Injury
(RELIEVE-AKI) to examine the feasibility of restrictive compared with a liberal UFNET rate strategy. The study is
a stepped-wedge cluster-randomized trial involving 144 critically ill patients with acute kidney injury and treated
with continuous kidney replacement therapy in six intensive care units across two hospital systems. The
intensive care units will be randomized 1:1 in which patients will receive either a restrictive or a liberal UFNET
rate strategy. Both strategies are standards of care and are commonly used in current clinical practice. In the
restrictive group, the UFNET rate will be titrated and maintained between 0.5-1.5 mL/kg/h. In the liberal group,
the UFNET rate will be titrated and maintained between of 2.0-5.0 mL/kg/h. The primary feasibility outcomes are
between-group differences in patient mean delivered UFNET rates, protocol adherence, and rate of patient
recruitment (Aim 1). We will also explore the effects of alternative UFNET rate strategies on secondary
outcomes including hypotensive episodes, and cardiac arrhythmias; emergent use of rescue UFNET rates
higher than the assigned treatment arm for fluid overload; duration of kidney replacement therapy and
mechanical ventilation; intensive care unit and hospital length of stay, and independence from kidney
replacement therapy and hospital mortality (Aim 2). This pragmatic clinical trial will be used to support the
rationale, assess feasibility, and design a phase III multicenter randomized trial to examine the effects of
alternative UFNET rate strategies on patient-centered clinical outcomes. Our study will have a direct impact on
the care of critically ill patients with acute kidney ...

## Key facts

- **NIH application ID:** 10364868
- **Project number:** 1R01DK128100-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Kianoush B Kashani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $328,766
- **Award type:** 1
- **Project period:** 2021-09-30 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364868

## Citation

> US National Institutes of Health, RePORTER application 10364868, REstrictive versus LIberal rate of Extracorporeal Volume removal Evaluation in Acute Kidney Injury (RELIEVE-AKI) (1R01DK128100-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10364868. Licensed CC0.

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