ACE I/D and AGT Met235Thr Polymorphisms Distinctly Affect Biomarker Levels and Risk of AKI and Exertional Rhabdomyolysis After Intense Exercise

Author(s)

Cruz, Ayexa ; Gomes, Diego ; Verdan, Cintia ; Branquinho, Jessica ; Xavier, Michele ; Kirsztajn, Gianna ; Dos Santos, Maj Caleb Guedes Miranda ; Pesquero, Joao Bosco ; Carneiro, Andreia

• Document type: Journal article
• Source: MILITARY MEDICINE; v. N/A, p. 9-pg., 2025-02-20.

Abstract

Introduction Exertional rhabdomyolysis (ER) is one of the severe complications attributable to prolonged and repeated muscle exercises and is most commonly seen in military personnel and elite athletes. In military personnel, ER usually results from the long and strenuous nature of military training and may sometimes result in severe outcomes, such as acute kidney injury (AKI) and cardiac arrhythmias. Besides, muscle tissue injuries impair physical function, decreasing strength and flexibility and delaying muscle soreness and inflammation. The existing literature has studied genetic polymorphisms related to the renin-angiotensin-aldosterone system, such as AGT*Met235Thr (rs699) and ACE I/D (rs1799752), and clinical chemistry-related markers about their influence on athletic performance and injury prevention from exercise-induced trauma. The present study aimed to evaluate the association between the ACE (rs1799752) and AGT (rs699) gene polymorphisms and the increased susceptibility to exertional rhabdomyolysis risk (ERR) and AKI induced by strenuous exercise in military personnel.Materials and Methods Sixty-four male volunteers from the Brazilian Marine Corps who were sent on the Sandstorm mission in 2017, 2018, 2019, and 2022 were enrolled in the study. Blood and urine samples were collected from the participants before and immediately after the mission.Results After physical exercise, 54 of 64 individuals (84%) were positive for ER. Of these, 13 participants (24%) were positive for AKI, representing 20% of the whole group. AKI was more frequent in T allele carriers, as 13 of 14 positive findings belonged to the MT + TT group, while only one case occurred in MM (approaching significance at P = .063). A significant postexercise increase in serum creatinine (CRE) levels was observed for carriers of I (II + ID) and T (MT + TT) alleles (P = .008 and P = .028, respectively), with a significantly higher Delta CRE in the (II + ID) group compared to the DD group (P = .001).Conclusion These findings suggest that the ACE I/D and AGT M235T polymorphisms might be related to an increased risk for AKI following intensive, mixed-type exercise in military personnel. (AU)

• FAPESP's process: 14/27198-8 - Establishment of a center of genetic and molecular research for clinical challenges
• Grantee: João Bosco Pesquero
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/14635-1 - Modeling of monogenic diseases for physiopathological studies and pharmacological tests using specialized cells derived from iPSCs
• Grantee: João Bosco Pesquero
• Support Opportunities: Research Projects - Thematic Grants