Persistent Serum Renin Elevation is Associated With Acute Kidney Injury in Pediatric Septic Shock
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Sepsis, Renal, Pediatrics, 2022
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INTRODUCTION/HYPOTHESIS: Sepsis-associated acute kidney injury (SA-AKI) is associated with poor outcomes in critically ill children. The pathophysiology of SA-AKI is poorly understood, limiting treatment strategies. Adult studies highlight the potential role of the renin-angiotensin-aldosterone system (RAAS), by correlating renin levels >59 pg/ml with development of AKI. This concept has not yet been examined in children. METHODS: A secondary analysis of 379 children admitted to a PICU from a multi-center study of pediatric septic shock. A subset of 69 patients were selected based on availability of Day1 (D1) and Day3 (D3) serum samples, and the presence or absence of D3 severe SA-AKI (primary outcome, defined as ≥KDIGO stage 2). Serum renin concentrations were measured on D1 and D3 by Luminex® assay; these values, and their trend (D3:D1 ratio), were assessed for associations with SA-AKI and provision of renal replacement therapy (RRT). Risk stratified analyses were also performed using the previously validated Renal Angina Index (RAI) and the recently derived PERSEVERE-II Model. RESULTS: 26/69 (38%) subjects developed D3 severe SA-AKI and 12 (17%) received RRT. Median D1 renin value was 4751 pg/ml (IQR 1926-10307), with no D1 differences between subjects with vs. without SA-AKI or RRT. Median D3 renin values were higher for those with D3 severe SA-AKI (5250 pg/ml vs. 2153 pg/ml, p=0.035) and who required RRT (7514 pg/ml vs. 2221 pg/ml, p=0.014). These subjects also had higher median D3:D1 renin ratios (D3 severe SA-AKI: 0.99 vs 0.41, p=0.003; RRT: 1.1 vs. 0.51, p=0.014). In patients at high risk for D3 severe SA-AKI by either the RAI or PERSEVERE-II Model, the median D3:D1 renin ratio discriminated between true positives (those who developed severe SA-AKI) and false positives (those who did not) (RAI: 0.99 vs 0.41, p=0.016; PERSEVERE-II: 0.95 vs 0.41, p=0.023). CONCLUSIONS: Children with septic shock have very elevated renin levels on presentation, and persistent elevation at D3 is associated with severe SA-AKI and provision of RRT. This persistence also discriminates between true positives and false positives in high-risk patients identified by existing SA-AKI predictive tools. These data suggest a potential role of RAAS in SA-AKI pathophysiology that should be further explored.
Meta Tag
Content Type Presentation
Knowledge Area Sepsis
Knowledge Area Renal
Knowledge Area Pediatrics
Knowledge Level Advanced
Learning Pathway Sepsis Resources
Membership Level Select
Tag Shock
Tag Renal
Tag Pediatrics
Year 2022
renin elevation
acute kidney injury
sepsis-associated AKI
pediatric septic shock
angiotensin II therapy
Sepsis Resources


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