Aminopeptidasic Enzymes As Early Biomarkers of Cardiac Surgery-Associated Acute Kidney Injury and Long-Term Events

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2024 Sep 28

PMID 39334816

Authors

Noelia Risquez Chica

Elisa Pereira

Francisco Manzano

Maria Mar Jimenez Quintana

Antonio Osuna

Maria Carmen Ruiz Fuentes

Rosemary Wangensteen

Affiliations

Soon will be listed here.

Abstract

Background: Diagnosis of acute kidney injury (AKI) relies on serum creatinine (SCr) changes. This study investigated if urinary aminopeptidases are early and predictive biomarkers of cardiac surgery-associated AKI (CSA-AKI).

Methods: Glutamyl aminopeptidase (GluAp), alanyl aminopeptidase (AlaAp), dipeptidyl peptidase-4 (DPP4), proteinuria, albuminuria, N-acetyl-β--glucosaminidase (NAG), and neutrophile gelatinase-associated lipocalin (NGAL) were measured in urine samples from 44 patients at arrival in the intensive care unit (ICU) after cardiac surgery. Sensitivity, specificity, and positive and negative predictive value for diagnosis of stages 1, 2, and 3 of AKI were analyzed for the highest quartile of each marker. We also studied the relationship with SCr after surgery, 6- and 12-month glomerular filtration rates (GFRs), and other long-term events over the next 5 years.

Results: GluAp diagnosed the maximal number of patients that developed stage 2 or 3 of AKI, increasing diagnostic sensitivity from 0% to 75%. In addition, GluAp and DPP4 were related to the decrease in GFR at 6 or 12 months after surgery.

Conclusions: Urinary aminopeptidases are a potential tool for the early diagnosis of CSA-AKI, with GluAp being the most effective marker for diagnosing stage 2 or 3 of AKI at ICU admission. GluAp and DPP4 serve as predictive biomarkers for a decrease in GFR.

References

Mao H, Katz N, Ariyanon W, Blanca-Martos L, Adybelli Z, Giuliani A . Cardiac surgery-associated acute kidney injury. Cardiorenal Med. 2014; 3(3):178-199. PMC: 3884176. DOI: 10.1159/000353134. View

Lisowska-Myjak B . Serum and urinary biomarkers of acute kidney injury. Blood Purif. 2010; 29(4):357-65. DOI: 10.1159/000309421. View

Antonio Lopes J, Jorge S . The RIFLE and AKIN classifications for acute kidney injury: a critical and comprehensive review. Clin Kidney J. 2016; 6(1):8-14. PMC: 5094385. DOI: 10.1093/ckj/sfs160. View

Westhuyzen J, Endre Z, Reece G, Reith D, Saltissi D, Morgan T . Measurement of tubular enzymuria facilitates early detection of acute renal impairment in the intensive care unit. Nephrol Dial Transplant. 2003; 18(3):543-51. DOI: 10.1093/ndt/18.3.543. View

Kenny A, Booth A, George S, Ingram J, Kershaw D, Wood E . Dipeptidyl peptidase IV, a kidney brush-border serine peptidase. Biochem J. 1976; 157(1):169-82. PMC: 1163828. DOI: 10.1042/bj1570169. View

Nistala R, Savin V . Diabetes, hypertension, and chronic kidney disease progression: role of DPP4. Am J Physiol Renal Physiol. 2017; 312(4):F661-F670. DOI: 10.1152/ajprenal.00316.2016. View

Lisa A, Carbone F, Liberale L, Montecucco F . The Need to Identify Novel Markers for Early Renal Injury in Cardiorenal Syndrome. Cells. 2024; 13(15. PMC: 11311518. DOI: 10.3390/cells13151283. View

Song L, Ye M, Troyanovskaya M, WILK E, Wilk S, Healy D . Rat kidney glutamyl aminopeptidase (aminopeptidase A): molecular identity and cellular localization. Am J Physiol. 1994; 267(4 Pt 2):F546-57. DOI: 10.1152/ajprenal.1994.267.4.F546. View

E Hobson C, Yavas S, Segal M, Schold J, Tribble C, Layon A . Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery. Circulation. 2009; 119(18):2444-53. DOI: 10.1161/CIRCULATIONAHA.108.800011. View

10.

Xie S, Song S, Liu S, Li Q, Zou W, Ke J . (Pro)renin receptor mediates tubular epithelial cell pyroptosis in diabetic kidney disease via DPP4-JNK pathway. J Transl Med. 2024; 22(1):26. PMC: 10768114. DOI: 10.1186/s12967-023-04846-5. View

11.

Montoro-Molina S, Quesada A, Zafra-Ruiz P, OValle F, Vargas F, de Gracia M . Immunological detection of glutamyl aminopeptidase in urine samples from cisplatin-treated rats. Proteomics Clin Appl. 2014; 9(5-6):630-5. DOI: 10.1002/prca.201400096. View

12.

Kenny A, MAROUX S . Topology of microvillar membrance hydrolases of kidney and intestine. Physiol Rev. 1982; 62(1):91-128. DOI: 10.1152/physrev.1982.62.1.91. View

13.

Lambeir A, Durinx C, Scharpe S, De Meester I . Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci. 2003; 40(3):209-94. DOI: 10.1080/713609354. View

14.

Pickkers P, Darmon M, Hoste E, Joannidis M, Legrand M, Ostermann M . Acute kidney injury in the critically ill: an updated review on pathophysiology and management. Intensive Care Med. 2021; 47(8):835-850. PMC: 8249842. DOI: 10.1007/s00134-021-06454-7. View

15.

Bonventre J, Vaidya V, Schmouder R, Feig P, Dieterle F . Next-generation biomarkers for detecting kidney toxicity. Nat Biotechnol. 2010; 28(5):436-40. PMC: 3033582. DOI: 10.1038/nbt0510-436. View

16.

Perez-Abud R, Rodriguez-Gomez I, Villarejo A, Manuel Moreno J, Wangensteen R, Tassi M . Salt sensitivity in experimental thyroid disorders in rats. Am J Physiol Endocrinol Metab. 2011; 301(2):E281-7. DOI: 10.1152/ajpendo.00690.2010. View

17.

Liangos O, Perianayagam M, Vaidya V, Han W, Wald R, Tighiouart H . Urinary N-acetyl-beta-(D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. J Am Soc Nephrol. 2007; 18(3):904-12. DOI: 10.1681/ASN.2006030221. View

18.

Samra M, Abcar A . False estimates of elevated creatinine. Perm J. 2012; 16(2):51-2. PMC: 3383162. DOI: 10.7812/tpp/11-121. View

19.

Haase-Fielitz A, Bellomo R, Devarajan P, Story D, Matalanis G, Dragun D . Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery--a prospective cohort study. Crit Care Med. 2008; 37(2):553-60. DOI: 10.1097/CCM.0b013e318195846e. View

20.

Englberger L, Suri R, Li Z, Casey E, Daly R, Dearani J . Clinical accuracy of RIFLE and Acute Kidney Injury Network (AKIN) criteria for acute kidney injury in patients undergoing cardiac surgery. Crit Care. 2011; 15(1):R16. PMC: 3222049. DOI: 10.1186/cc9960. View