A Prompt REstart Study of Renin-Angiotensin System Inhibitors After Acute Kidney Injury (APRES-AKI)

The goal of this pilot clinical trial is to learn if early restart of renin-angiotensin system inhibitor (RASi) medications is feasible and well-tolerated in hospitalized patients with acute kidney injury (AKI). Researchers will compare early RASi restart to usual care.

Study participants will restart RASi per study protocol, obtain a lab test in 1-2 weeks if RASi restarted in the hospital and not collected as part of routine care, and answer questions at the 90-day follow-up.

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Drug: Usual Care; Drug: Early RASi restart strategy

Detailed Description

Among at-risk patients with heart failure and chronic kidney disease, use of RASi medications decreases the subsequent risk of adverse events such as cardiovascular death and kidney disease progression. However, RASi treatment is often stopped when AKI is detected in the hospital based on the notion that restoring an intact renin-angiotensin system in the context of hypovolemia or hypotension may be helpful to maintain perfusion to the glomeruli and thus support the glomerular filtration rate.

In observational studies, restart of RASi medications among at-risk patients after AKI has been associated with decreased subsequent rates of mortality, cardiovascular events, and kidney disease progression. However, there is no rigorous evidence from randomized trials to guide optimal strategy of RASi restart after AKI.

This is a pilot trial among hospitalized patients with AKI whose RASi were held to investigate the feasibility and tolerability of a strategy of early RASi restart (n=30) compared to usual care (n=30). This pilot trial will provide valuable data critical to inform the design of a larger definitive trial.

The study hypothesis is that the strategy of early RASi restart after AKI is feasible and well-tolerated. This pilot trial will inform the design of a larger definitive trial to determine whether early RASi restart can increase rates of RASi use at 90 days compared to usual care.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yuenting D Kwong, MD MAS; Phone Number: 415-514-7371; Email: diana.kwong@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Contact: Yuenting D Kwong, MD MAS; Phone Number: 415-514-7371; Email: diana.kwong@ucsf.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Pre-admission RASi use for Class I indication (e.g., heart failure, kidney disease)
• RASi stopped in the setting of AKI (defined by ≥1.5x baseline SCr)
• AKI in recovery (defined by a decrease in SCr by ≥0.3mg/dL from peak)

Exclusion Criteria:

• RASi allergy or contraindication (i.e., angioedema, bilateral renal artery stenosis)
• Ongoing dialysis requirement
• Pregnant or breastfeeding
• Prisoner
• Palliative or hospice care involvement
• Unable to consent
• No enteral route of medication administration
• Clinician judgment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual care; RASi restart will be deferred to the study participant's providers.	Drug: Usual Care; RASi restart will be deferred to the study participant's providers.
Experimental: Early RASi restart strategy; The early restart strategy is to resume RASi as soon as the serum creatinine (SCr) downtrends by ≥0.3mg/dL from peak. In addition, the following criteria must be met: most recent potassium ≤5mEq/L, SCr-based eGFR reported as ≥15 mL/min/1.73m2, and average systolic blood pressure≥120mmHg 12 hours prior to restart. If the study participant is discharged from the hospital before the RASi restart criteria are met, management of RASi restart would be deferred to the discretion of longitudinal outpatient healthcare team.	Drug: Early RASi restart strategy; The early restart strategy is to resume RASi as soon as the serum creatinine (SCr) downtrends by ≥0.3mg/dL from peak. In addition, the following criteria must be met: most recent potassium ≤5mEq/L, CKD-EPI SCr-based eGFR reported as ≥15 mL/min/1.73m2, and average SBP ≥120mmHg 12 hours prior to restart. If the study participant is discharged from the hospital before the RASi restart criteria are met, management of RASi restart would be deferred to the discretion of longitudinal outpatient healthcare team.; Other Names: renin-angiotensin system inhibitors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility- RASi use separation	Proportion of patients in the early RASi restart arm and the usual care arm who restart RASi within 72 hours of SCr downtrending by ≥0.3mg/dL from peak SCr and at hospital discharge	From date of enrollment until date of hospital discharge or up to 90 days if remains in the hospital

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability- 90 day follow up completion	Proportion of participants who complete 90 day follow up	Up to 90 days
Tolerability- Lab evaluation post RASi	Proportion with potassium and SCr evaluations within 1-2 weeks of RASi restart	Up to 2 weeks post hospital discharge or 90 days if patient remains in the hospital
Tolerability- SCr evaluation after hospital discharge	Proportion with SCr evaluation after hospital discharge	Up to 90 days
Tolerability- Proteinuria evaluation	Proportion with proteinuria evaluation after hospital discharge	Up to 90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Screening-to-recruitment ratio	Number of patients screened divided by the number of patients enrolled	Total study duration, anticipated 2.5 years, up to 4 years total
Adverse events	Total number of adverse events and number of adverse events attributable to study intervention. Adverse events include: hyperkalemia (>5.5mEq/L and >6mEq/L), recurrent AKI (minor (30-<50% decline) versus major (>=50% decline) in eGFR), symptomatic hypotension or hypertension, emergency room visits, hospitalizations, increase index hospital length of stay	Up to 90 days
90 day RASi use	Proportion with RASi use at 90 days	Up to 90 days
Cumulative RASi exposure	Number of days with RASi use	Up to 90 days
Days to RASi restart	Days to RASi restart from day of peak SCr	Up to 90 days

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Yuenting D Kwong, MD MAS, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: July 16, 2026
• First Submitted That Met QC Criteria: July 23, 2026
• First Posted (Actual): July 29, 2026

Study Record Updates

• Last Update Posted (Actual): September 8, 2026
• Last Update Submitted That Met QC Criteria: September 4, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Acute kidney injury
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: 25-45052; K23DK139456 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data collected after deidentification
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No