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

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

doi:10.1186/s13054-021-03725-z

Cited by 28 publications

(29 citation statements)

References 28 publications

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“…Among others, Gleeson et al observed a significant association between direct renin measurement and mortality in a prospective observational study of critically ill adults [7]. Consistently, Flannery et al demonstrated that serum renin measured early after ICU admission was significantly and independently associated with mortality and major adverse kidney events, including kidney replacement therapy or reduced estimated glomerular filtration rate [8]. The prognostic value of renin and the importance of renin trajectory were recently confirmed in patients undergoing cardiac surgery [9].…”

Section: What We Know From Studies In Adult Patientsmentioning

confidence: 86%

“…The assay used by Stanski et al measured not only renin but also its precursor prorenin, whose plasma concentration in healthy subjects is significantly higher than that of its active form. Although renin production in stressful states exceeds prorenin release by 50-100-fold and prorenin is more stimulated by longer stimuli than by acute events, new low cross-reactivity assays for prorenin will be required in future trials, such as in some recent studies in adult patients [8]. Some concerns have been raised in the past about possible factors influencing renin levels in critically ill patients, but recent studies have clearly demonstrated that renin levels are not impacted by diurnal variation, medications, or continuous kidney replacement therapy (CKRT) [7].…”

Section: Measurement Techniquementioning

confidence: 99%

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Critically ill children with septic shock: time to rediscover renin?

Guzzo

Paglialonga

2023

Pediatr Nephrol

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Acute kidney injury (AKI) and sepsis are both associated with morbidity and mortality in critically ill patients. In detail, critically ill children with severe AKI (KDIGO stage 2 or 3) had a higher 28-day mortality than children without severe AKI (11% vs. 2.5%) and sepsis-associated AKI (SA-AKI) was independently associated with increased odds of mortality in a large cohort of children with septic shock [1,2]. Furthermore, the incidence of SA-AKI has increased over the past two decades, affecting mortality, hospitalization, and costs in this population [3]. Thus, early recognition of children at higher risk of developing SA-AKI could potentially be effective in improving septic patients' management and outcomes.In a recent paper in Pediatric Nephrology, Stanski and colleagues presented the results of a secondary analysis of a large, prospective, observational study, looking at the impact of elevated serum renin + prorenin concentration as a predictor of persistent AKI and mortality in children with septic shock [4]. In a cohort of 233 critically ill children with septic shock, an elevated renin + prorenin concentration at day 1 was predictive of severe persistent AKI in the first week of pediatric intensive care unit (ICU) stay. Similarly, persistence of renin + prorenin elevation at day 3 (as quantified by day 3:day 1 renin + prorenin ratio above an optimal cutoff) was predictive of 28-day mortality [4]. Therefore, the authors suggested that renin may be a valuable prognostic and predictive biomarker in pediatric critically ill patients with septic shock, which, if confirmed by further studies, may potentially guide therapy and improve outcomes in this population.

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Section: What We Know From Studies In Adult Patientsmentioning

confidence: 86%

Section: Measurement Techniquementioning

confidence: 99%

Critically ill children with septic shock: time to rediscover renin?

Guzzo

Paglialonga

2023

Pediatr Nephrol

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“…Limitations: The study is limited by the fact that serum renin was used as a surrogate for intrarenal RAS. Both plasma and serum renin have been analysed in other studies as measures of renal RAS [ 22 , 34 , 46 , 47 ], although it remains a proxy for actual intrarenal renin production. Although there are many advantages of investigating a pediatric population and providing new insights (e.g.…”

Section: Discussionmentioning

confidence: 99%

Urinary epidermal growth factor reflects vascular health in boys with either obesity or type 1 diabetes. A role for renin, or beyond?

et al. 2023

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An increased blood pressure is a known comorbidity of both type 1 diabetes (T1DM) and obesity in children. Increasing evidence suggests a subtle interplay between epidermal growth factor (EGF) and renin along the juxtaglomerular system, regulating the impact of blood pressure on kidney health and the cardiovascular system. In this study, we investigated the relation between urinary EGF, serum renin and blood pressure in children with obesity or T1DM. 147 non-obese children with T1DM and 126 children with obesity, were included. Blood pressure was measured and mean arterial pressure (MAP) and the pulse pressure (PP) were calculated. Serum renin and urinary EGF levels were determined with a commercial ELISA kit. Partial Spearman rank correlation coefficients and multiple linear regression models were used to study the association between renin, the urinary EGF/urinary creatinine ratio and blood pressure parameters. The urinary EGF/urinary creatinine ratio is correlated with the SBP and the MAP in boys with obesity as well as in boys with T1DM. Multiple regression analysis showed that sex and pulse pressure in male subjects were found to be independently associated with renin. Sex, the presence of diabetes, age, the glomerular filtration rate and both pulse pressure and mean arterial pressure in male subjects were independently associated with urinary EGF/urinary creatinine. In conclusion, in boys with either obesity or diabetes, pulse pressure and mean arterial pressure are negatively associated with the functional integrity of the nephron, which is reflected by a decreased expression of urinary EGF.

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“…We conducted a multicenter, prospective study of critically ill patients admitted to the ICU at two large academic medical centers: the University of Texas Southwestern (UTSW) and the University of Kentucky (UKY) [ 23 , 24 ]. Inclusion criteria consisted of adult ICU patients (≥ 18 years old) with a known baseline eGFR ≥ 60 ml/min/1.73 m 2 .…”

Section: Methodsmentioning

confidence: 99%

Serum IL-17 levels are higher in critically ill patients with AKI and associated with worse outcomes

Collett

Ortiz-Soriano

et al. 2022

Crit Care

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Background Interleukin-17 (IL-17) antagonism in rats reduces the severity and progression of AKI. IL-17-producing circulating T helper-17 (TH17) cells is increased in critically ill patients with AKI indicating that this pathway is also activated in humans. We aim to compare serum IL-17A levels in critically ill patients with versus without AKI and to examine their relationship with mortality and major adverse kidney events (MAKE). Methods Multicenter, prospective study of ICU patients with AKI stage 2 or 3 and without AKI. Samples were collected at 24–48 h after AKI diagnosis or ICU admission (in those without AKI) [timepoint 1, T1] and 5–7 days later [timepoint 2, T2]. MAKE was defined as the composite of death, dependence on kidney replacement therapy or a reduction in eGFR of ≥ 30% from baseline up to 90 days following hospital discharge. Results A total of 299 patients were evaluated. Patients in the highest IL-17A tertile (versus lower tertiles) at T1 had higher acuity of illness and comorbidity scores. Patients with AKI had higher levels of IL-17A than those without AKI: T1 1918.6 fg/ml (692.0–5860.9) versus 623.1 fg/ml (331.7–1503.4), p < 0.001; T2 2167.7 fg/ml (839.9–4618.9) versus 1193.5 fg/ml (523.8–2198.7), p = 0.006. Every onefold higher serum IL-17A at T1 was independently associated with increased risk of hospital mortality (aOR 1.35, 95% CI: 1.06–1.73) and MAKE (aOR 1.26, 95% CI: 1.02–1.55). The highest tertile of IL-17A (vs. the lowest tertile) was also independently associated with higher risk of MAKE (aOR 3.03, 95% CI: 1.34–6.87). There was no effect modification of these associations by AKI status. IL-17A levels remained significantly elevated at T2 in patients that died or developed MAKE. Conclusions Serum IL-17A levels measured by the time of AKI diagnosis or ICU admission were differentially elevated in critically ill patients with AKI when compared to those without AKI and were independently associated with hospital mortality and MAKE.

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

Cited by 28 publications

References 28 publications

Critically ill children with septic shock: time to rediscover renin?

Critically ill children with septic shock: time to rediscover renin?

Urinary epidermal growth factor reflects vascular health in boys with either obesity or type 1 diabetes. A role for renin, or beyond?

Serum IL-17 levels are higher in critically ill patients with AKI and associated with worse outcomes

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