Skip to main content
Top
Published in: Critical Care 1/2021

Open Access 01-12-2021 | Acute Kidney Injury | Research

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

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

Published in: Critical Care | Issue 1/2021

Login to get access

Abstract

Background

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.

Methods

Prospective, 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.

Results

Patients 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.

Conclusions

In a broad cohort of critically ill patients, serum renin measured early in the ICU admission is associated with MAKE at discharge, particularly mortality.
Appendix
Available only for authorised users
Literature
1.
go back to reference Bitker L, Burrell LM. Classic and nonclassic renin-angiotensin systems in the critically ill. Crit Care Clin. 2019;35(2):213–27.CrossRef Bitker L, Burrell LM. Classic and nonclassic renin-angiotensin systems in the critically ill. Crit Care Clin. 2019;35(2):213–27.CrossRef
2.
go back to reference Bellomo R, Wunderink RG, Szerlip H, English SW, Busse LW, Deane AM, Khanna AK, McCurdy MT, Ostermann M, Young PJ, et al. Angiotensin I and angiotensin II concentrations and their ratio in catecholamine-resistant vasodilatory shock. Crit Care. 2020;24(1):43.CrossRef Bellomo R, Wunderink RG, Szerlip H, English SW, Busse LW, Deane AM, Khanna AK, McCurdy MT, Ostermann M, Young PJ, et al. Angiotensin I and angiotensin II concentrations and their ratio in catecholamine-resistant vasodilatory shock. Crit Care. 2020;24(1):43.CrossRef
3.
go back to reference Reddy R, Asante I, Liu S, Parikh P, Liebler J, Borok Z, Rodgers K, Baydur A, Louie SG. Circulating angiotensin peptides levels in acute respiratory distress syndrome correlate with clinical outcomes: a pilot study. PLoS ONE. 2019;14(3):e0213096.CrossRef Reddy R, Asante I, Liu S, Parikh P, Liebler J, Borok Z, Rodgers K, Baydur A, Louie SG. Circulating angiotensin peptides levels in acute respiratory distress syndrome correlate with clinical outcomes: a pilot study. PLoS ONE. 2019;14(3):e0213096.CrossRef
4.
go back to reference du Cheyron D, Fradin S, Ramakers M, Terzi N, Guillotin D, Bouchet B, Daubin C, Charbonneau P. Angiotensin converting enzyme insertion/deletion genetic polymorphism: its impact on renal function in critically ill patients. Crit Care Med. 2008;36(12):3178–83.CrossRef du Cheyron D, Fradin S, Ramakers M, Terzi N, Guillotin D, Bouchet B, Daubin C, Charbonneau P. Angiotensin converting enzyme insertion/deletion genetic polymorphism: its impact on renal function in critically ill patients. Crit Care Med. 2008;36(12):3178–83.CrossRef
5.
go back to reference Chappell MC. Biochemical evaluation of the renin-angiotensin system: the good, bad, and absolute? Am J Physiol Heart Circ Physiol. 2016;310(2):H137-152.CrossRef Chappell MC. Biochemical evaluation of the renin-angiotensin system: the good, bad, and absolute? Am J Physiol Heart Circ Physiol. 2016;310(2):H137-152.CrossRef
6.
go back to reference Gleeson PJ, Crippa IA, Mongkolpun W, Cavicchi FZ, Van Meerhaeghe T, Brimioulle S, Taccone FS, Vincent JL, Creteur J. Renin as a marker of tissue-perfusion and prognosis in critically ill patients. Crit Care Med. 2019;47(2):152–8.CrossRef Gleeson PJ, Crippa IA, Mongkolpun W, Cavicchi FZ, Van Meerhaeghe T, Brimioulle S, Taccone FS, Vincent JL, Creteur J. Renin as a marker of tissue-perfusion and prognosis in critically ill patients. Crit Care Med. 2019;47(2):152–8.CrossRef
7.
go back to reference Nguyen M, Denimal D, Dargent A, Guinot PG, Duvillard L, Quenot JP, Bouhemad B. Plasma renin concentration is associated with hemodynamic deficiency and adverse renal outcome in septic shock. Shock. 2019;52(4):e22–30.CrossRef Nguyen M, Denimal D, Dargent A, Guinot PG, Duvillard L, Quenot JP, Bouhemad B. Plasma renin concentration is associated with hemodynamic deficiency and adverse renal outcome in septic shock. Shock. 2019;52(4):e22–30.CrossRef
8.
go back to reference Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12.CrossRef Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12.CrossRef
9.
go back to reference Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2:1–138.CrossRef Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2:1–138.CrossRef
10.
go back to reference Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.CrossRef Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.CrossRef
11.
go back to reference Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818–29.CrossRef Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818–29.CrossRef
12.
go back to reference Billings FT, Shaw AD. Clinical trial endpoints in acute kidney injury. Nephron Clin Pract. 2014;127(1–4):89–93.CrossRef Billings FT, Shaw AD. Clinical trial endpoints in acute kidney injury. Nephron Clin Pract. 2014;127(1–4):89–93.CrossRef
13.
go back to reference Flannery AH, Bosler K, Ortiz-Soriano VM, Gianella F, Prado V, Lambert J, Toto RD, Moe OW, Neyra JA. Kidney biomarkers and major adverse kidney events in critically ill patients. Kidney360. 2021;2(1):26–32.CrossRef Flannery AH, Bosler K, Ortiz-Soriano VM, Gianella F, Prado V, Lambert J, Toto RD, Moe OW, Neyra JA. Kidney biomarkers and major adverse kidney events in critically ill patients. Kidney360. 2021;2(1):26–32.CrossRef
14.
go back to reference Haase M, Bellomo R, Albert C, Vanpoucke G, Thomas G, Laroy W, Verleysen K, Kropf S, Kuppe H, Hetzer R, et al. The identification of three novel biomarkers of major adverse kidney events. Biomark Med. 2014;8(10):1207–17.CrossRef Haase M, Bellomo R, Albert C, Vanpoucke G, Thomas G, Laroy W, Verleysen K, Kropf S, Kuppe H, Hetzer R, et al. The identification of three novel biomarkers of major adverse kidney events. Biomark Med. 2014;8(10):1207–17.CrossRef
15.
go back to reference Doerschug KC, Delsing AS, Schmidt GA, Ashare A. Renin-angiotensin system activation correlates with microvascular dysfunction in a prospective cohort study of clinical sepsis. Crit Care. 2010;14(1):R24.CrossRef Doerschug KC, Delsing AS, Schmidt GA, Ashare A. Renin-angiotensin system activation correlates with microvascular dysfunction in a prospective cohort study of clinical sepsis. Crit Care. 2010;14(1):R24.CrossRef
16.
go back to reference Peti-Peterdi J, Harris RC. Macula densa sensing and signaling mechanisms of renin release. J Am Soc Nephrol. 2010;21(7):1093–6.CrossRef Peti-Peterdi J, Harris RC. Macula densa sensing and signaling mechanisms of renin release. J Am Soc Nephrol. 2010;21(7):1093–6.CrossRef
17.
go back to reference Küllmar M, Saadat-Gilani K, Weiss R, Massoth C, Lagan A, Núñez Cortés M, Gerss J, Chawla LS, Fliser D, Meersch M, et al. Kinetic changes of plasma renin levels predict acute kidney injury in cardiac surgery patients. Am J Respir Crit Care Med. 2020;203(9):1119–26.CrossRef Küllmar M, Saadat-Gilani K, Weiss R, Massoth C, Lagan A, Núñez Cortés M, Gerss J, Chawla LS, Fliser D, Meersch M, et al. Kinetic changes of plasma renin levels predict acute kidney injury in cardiac surgery patients. Am J Respir Crit Care Med. 2020;203(9):1119–26.CrossRef
18.
go back to reference Campbell DJ, Nussberger J, Stowasser M, Danser AH, Morganti A, Frandsen E, Ménard J. Activity assays and immunoassays for plasma Renin and prorenin: information provided and precautions necessary for accurate measurement. Clin Chem. 2009;55(5):867–77.CrossRef Campbell DJ, Nussberger J, Stowasser M, Danser AH, Morganti A, Frandsen E, Ménard J. Activity assays and immunoassays for plasma Renin and prorenin: information provided and precautions necessary for accurate measurement. Clin Chem. 2009;55(5):867–77.CrossRef
19.
go back to reference Batenburg WW, Danser AH. (Pro)renin and its receptors: pathophysiological implications. Clin Sci (Lond). 2012;123(3):121–33.CrossRef Batenburg WW, Danser AH. (Pro)renin and its receptors: pathophysiological implications. Clin Sci (Lond). 2012;123(3):121–33.CrossRef
20.
go back to reference Toffelmire EB, Slater K, Corvol P, Menard J, Schambelan M. Response of plasma prorenin and active renin to chronic and acute alterations of renin secretion in normal humans. Studies using a direct immunoradiometric assay. J Clin Investig. 1989;83(2):679–87.CrossRef Toffelmire EB, Slater K, Corvol P, Menard J, Schambelan M. Response of plasma prorenin and active renin to chronic and acute alterations of renin secretion in normal humans. Studies using a direct immunoradiometric assay. J Clin Investig. 1989;83(2):679–87.CrossRef
21.
go back to reference Feldt S, Batenburg WW, Mazak I, Maschke U, Wellner M, Kvakan H, Dechend R, Fiebeler A, Burckle C, Contrepas A, et al. Prorenin and renin-induced extracellular signal-regulated kinase 1/2 activation in monocytes is not blocked by aliskiren or the handle-region peptide. Hypertension. 2008;51(3):682–8.CrossRef Feldt S, Batenburg WW, Mazak I, Maschke U, Wellner M, Kvakan H, Dechend R, Fiebeler A, Burckle C, Contrepas A, et al. Prorenin and renin-induced extracellular signal-regulated kinase 1/2 activation in monocytes is not blocked by aliskiren or the handle-region peptide. Hypertension. 2008;51(3):682–8.CrossRef
22.
go back to reference Ichihara A, Yatabe MS. The (pro)renin receptor in health and disease. Nat Rev Nephrol. 2019;15(11):693–712.CrossRef Ichihara A, Yatabe MS. The (pro)renin receptor in health and disease. Nat Rev Nephrol. 2019;15(11):693–712.CrossRef
23.
go back to reference Bellomo R, Forni LG, Busse LW, McCurdy MT, Ham KR, Boldt DW, Hästbacka J, Khanna AK, Albertson TE, Tumlin J, et al. Renin and survival in patients given angiotensin II for catecholamine-resistant vasodilatory shock. A clinical trial. Am J Respir Crit Care Med. 2020;202(9):1253–61.CrossRef Bellomo R, Forni LG, Busse LW, McCurdy MT, Ham KR, Boldt DW, Hästbacka J, Khanna AK, Albertson TE, Tumlin J, et al. Renin and survival in patients given angiotensin II for catecholamine-resistant vasodilatory shock. A clinical trial. Am J Respir Crit Care Med. 2020;202(9):1253–61.CrossRef
24.
go back to reference Leisman DE, Fernandes TD, Bijol V, Abraham MN, Lehman JR, Taylor MD, Capone C, Yaipan O, Bellomo R, Deutschman CS. Impaired angiotensin II type 1 receptor signaling contributes to sepsis induced acute kidney injury. Kidney Int. 2021;99(1):148–60.CrossRef Leisman DE, Fernandes TD, Bijol V, Abraham MN, Lehman JR, Taylor MD, Capone C, Yaipan O, Bellomo R, Deutschman CS. Impaired angiotensin II type 1 receptor signaling contributes to sepsis induced acute kidney injury. Kidney Int. 2021;99(1):148–60.CrossRef
25.
go back to reference Delgado C, Baweja M, Burrows NR, Crews DC, Eneanya ND, Gadegbeku CA, Inker LA, Mendu ML, Miller WG, Moxey-Mims MM, Roberts GV, St Peter WL, Warfield C, Powe NR. Reassessing the inclusion of race in diagnosing kidney diseases: an interim report from the NKF-ASN task force. J Am Soc Nephrol. 2021;32(6):1305–17.CrossRef Delgado C, Baweja M, Burrows NR, Crews DC, Eneanya ND, Gadegbeku CA, Inker LA, Mendu ML, Miller WG, Moxey-Mims MM, Roberts GV, St Peter WL, Warfield C, Powe NR. Reassessing the inclusion of race in diagnosing kidney diseases: an interim report from the NKF-ASN task force. J Am Soc Nephrol. 2021;32(6):1305–17.CrossRef
26.
go back to reference Conti S, Cassis P, Benigni A. Aging and the renin-angiotensin system. Hypertension. 2012;60(4):878–83.CrossRef Conti S, Cassis P, Benigni A. Aging and the renin-angiotensin system. Hypertension. 2012;60(4):878–83.CrossRef
27.
go back to reference Medina D, Mehay D, Arnold AC. Sex differences in cardiovascular actions of the renin-angiotensin system. Clin Auton Res. 2020;30(5):393–408.CrossRef Medina D, Mehay D, Arnold AC. Sex differences in cardiovascular actions of the renin-angiotensin system. Clin Auton Res. 2020;30(5):393–408.CrossRef
Metadata
Title
Serum renin and major adverse kidney events in critically ill patients: a multicenter prospective study
Authors
Alexander H. Flannery
Victor Ortiz-Soriano
Xilong Li
Fabiola G. Gianella
Robert D. Toto
Orson W. Moe
Prasad Devarajan
Stuart L. Goldstein
Javier A. Neyra
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2021
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-021-03725-z

Other articles of this Issue 1/2021

Critical Care 1/2021 Go to the issue