Kidney Blood Flow and Renin-Angiotensin-Aldosterone System Measurements Associated With Kidney and Cardiovascular Dysfunction in Pediatric Shock

Abstract

Importance: Pediatric acute kidney injury (AKI) is a prevalent and morbid complication of shock. Its pathogenesis and early identification remain elusive.

Objectives: We aim to determine whether renal blood flow (RBF) measurements by point-of-care ultrasound (POCUS) and renin-angiotensin-aldosterone system (RAAS) hormones in pediatric shock associate with vasoactive requirements and AKI.

Design, setting, and participants: This is a single-center prospective, noninterventional observational cohort study in one tertiary PICU in North American from 2020 to 2022 that enrolled children younger than 18 years with shock without preexisting end-stage renal disease.

Main outcomes and measures: RBF was measured by POCUS on hospital days 1 and 3 and plasma RAAS hormone levels were measured on day 1. The primary outcome was the presence of AKI by Kidney Disease Improving Global Outcomes criteria at first ultrasound with key secondary outcomes of creatinine, blood urea nitrogen (BUN), Vasoactive-Inotrope Score (VIS), and norepinephrine equivalent dosing (NED) 48 hours after first ultrasound.

Results: Fifty patients were recruited (20 with AKI, mean age 10.5 yr, 48% female). POCUS RBF showed lower qualitative blood flow (power Doppler ultrasound [PDU] score) and higher regional vascular resistance (renal resistive index [RRI]) in children with AKI (p = 0.017 and p = 0.0007). Renin and aldosterone levels were higher in the AKI cohort (p = 0.003 and p = 0.007). Admission RRI and PDU associated with higher day 3 VIS and NED after adjusting for age, day 1 VIS, and RAAS hormones. Admission renin associated with higher day 3 creatinine and BUN after adjusting for age, day 1 VIS, and the ultrasound parameters.

Conclusions and relevance: In pediatric shock, kidney blood flow was abnormal and renin and aldosterone were elevated in those with AKI. Kidney blood flow abnormalities are independently associated with future cardiovascular dysfunction; renin elevations are independently associated with future kidney dysfunction. Kidney blood flow by POCUS may identify children who will have persistent as opposed to resolving AKI. RAAS perturbations may drive AKI in pediatric shock.

Figure 1.

Outcomes by presence of acute kidney injury (AKI) on study day 1. Box and whiskers plots demonstrating differences in renal resistive index (RRI), power Doppler ultrasonography, and renin, aldosterone in patients grouped as AKI vs. no AKI on study day 1. Day 1 and day 3 renal ultrasound parameters were also compared between cohorts with and without AKI on day 1, detailing that day 3 RRI was higher in those with day 1 AKI compared with those without day 1 AKI. *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 2.

Kidney function and renin-angiotensin-aldosterone system (RAAS) hormone variables by normal or abnormal power Doppler ultrasonography (PDU) at day 1. Box and whiskers plots demonstrating differences in renin, aldosterone, creatinine, and blood urea nitrogen (BUN) by abnormal vs. normal PDU score on study day 1. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

Figure 3.

Global and regional vascular resistance by normal or abnormal power Doppler ultrasonography (PDU) at day 1. Box and whiskers plots demonstrating differences in renal resistive index (RRI), Vasoactive-Inotrope Score (VIS), and norepinephrine equivalent dosing (NED) by abnormal vs. normal PDU score on study day 1. Day 1 and day 3 hemodynamics were compared between cohorts with normal and abnormal PDU on day 1. *p < 0.05, **p < 0.01, ***p < 0.001.