Serum renin and major adverse kidney events in critically ill patients: a multicenter prospective study

Alexander H Flannery,Fabiola G Gianella,Orson W Moe,Victor Ortiz-Soriano,Xilong Li,Javier A Neyra,Prasad Devarajan,Stuart L Goldstein,Robert D Toto

doi:10.1186/s13054-021-03725-z

Abstract

BackgroundPreliminary studies have suggested that the renin-angiotensin system is activated in critical illness and associated with mortality and kidney outcomes. We sought to assess in a larger, multicenter study the relationship between serum renin and Major Adverse Kidney Events (MAKE) in intensive care unit (ICU) patients.MethodsProspective, multicenter study at two institutions of patients with and without acute kidney injury (AKI). Blood samples were collected for renin measurement a median of 2 days into the index ICU admission and 5–7 days later. The primary outcome was MAKE at hospital discharge, a composite of mortality, kidney replacement therapy, or reduced estimated glomerular filtration rate to ≤ 75% of baseline.ResultsPatients in the highest renin tertile were more severely ill overall, including more AKI, vasopressor-dependence, and severity of illness. MAKE were significantly greater in the highest renin tertile compared to the first and second tertiles. In multivariable logistic regression, this initial measurement of renin remained significantly associated with both MAKE as well as the individual component of mortality. The association of renin with MAKE in survivors was not statistically significant. Renin measurements at the second time point were also higher in patients with MAKE. The trajectory of the renin measurements between time 1 and 2 was distinct when comparing death versus survival, but not when comparing MAKE versus those without.ConclusionsIn a broad cohort of critically ill patients, serum renin measured early in the ICU admission is associated with MAKE at discharge, particularly mortality.

Highlights

Preliminary studies have suggested that the renin-angiotensin system is activated in critical illness and associated with mortality and kidney outcomes
Given the potential of renin to serve as a novel biomarker for adverse kidney outcomes and mortality in critically ill patients, we conducted a multicenter prospective study to examine the association of serum renin with mortality and adverse kidney events in a larger and heterogeneous cohort of critically ill adult patients
Neutrophil gelatinase-associated lipocalin (NGAL), per 1-log unit eGFR estimated glomerular filtration rate, ICU intensive care unit, UK University of Kentucky, UTSW University of Texas Southwestern, APACHE II Acute Physiology and Chronic Health Evaluation II, NGAL neutrophil gelatinase-associated lipocalin a Fixed model developed using hypothesized predictors of outcome and clinically relevant imbalances in renin tertiles remained significantly and independently associated with Major Adverse Kidney Events (MAKE) (OR 1.19 for 1-log unit higher serum renin) (Additional file 1: Table S4)

Summary

Introduction

Preliminary studies have suggested that the renin-angiotensin system is activated in critical illness and associated with mortality and kidney outcomes. We sought to assess in a larger, multicenter study the relationship between serum renin and Major Adverse Kidney Events (MAKE) in intensive care unit (ICU) patients. The renin-angiotensin system (RAS) is increasingly recognized to be perturbed during critical illness The complexity of this system, including circulatory, tissue-level, and intra-cellular actions, as well as both traditional and Flannery et al Crit Care (2021) 25:294 respectively, in critically ill patients. Given the potential of renin to serve as a novel biomarker for adverse kidney outcomes and mortality in critically ill patients, we conducted a multicenter prospective study to examine the association of serum renin with mortality and adverse kidney events in a larger and heterogeneous cohort of critically ill adult patients

Methods

Results

Discussion

Conclusion