Renal Inflammation and Innate Immune Activation Underlie the Transition From Gentamicin-Induced Acute Kidney Injury to Renal Fibrosis

Author(s):Show less -

Albino, Amanda Helen ^[1] ; Fregnan Zambom, Fernanda Florencia ^[1] ; Foresto-Neto, Orestes ^[1] ; Oliveira, Karin Carneiro ^[1] ; Avila, Victor Ferreira ^[1] ; Alarcon Arias, Simone Costa ^[1] ; Seguro, Antonio Carlos ^[1] ; Avancini Costa Malheiros, Denise Maria ^[1] ; Saraiva Camara, Niels Olsen ^{[1, 2]} ; Fujihara, Clarice Kazue ^[1] ; Zatz, Roberto ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Clin Med, Fac Med, Renal Div, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Lab Transplantat Immunobiol, Inst Biomed Sci, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN PHYSIOLOGY; v. 12, JUL 7 2021.
• Web of Science Citations: 0

Abstract

Subjects recovering from acute kidney injury (AKI) are at risk of developing chronic kidney disease (CKD). The mechanisms underlying this transition are unclear and may involve sustained activation of renal innate immunity, with resulting renal inflammation and fibrosis. We investigated whether the NF-kappa B system and/or the NLRP3 inflammasome pathway remain activated after the resolution of AKI induced by gentamicin (GT) treatment, thus favoring the development of CKD. Male Munich-Wistar rats received daily subcutaneous injections of GT, 80 mg/kg, for 9 days. Control rats received vehicle only (NC). Rats were studied at 1, 30, and 180 days after GT treatment was ceased. On Day 1, glomerular ischemia (ISCH), tubular necrosis, albuminuria, creatinine retention, and tubular dysfunction were noted, in association with prominent renal infiltration by macrophages and myofibroblasts, along with increased renal abundance of TLR4, IL-6, and IL1 beta. Regression of functional and structural changes occurred on Day 30. However, the renal content of IL-1 beta was still elevated at this time, while the local renin-angiotensin system remained activated, and interstitial fibrosis became evident. On Day 180, recurring albuminuria and mild glomerulosclerosis were seen, along with ISCH and unabated interstitial fibrosis, whereas macrophage infiltration was still evident. GT-induced AKI activates innate immunity and promotes renal inflammation. Persistence of these abnormalities provides a plausible explanation for the transition of AKI to CKD observed in a growing number of patients. (AU)

• FAPESP's process: 17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/10926-5 - Pathogenesis and treatment of chronic kidney disease: role of innate immunity in glomerular, tubular and interstitial injury
• Grantee: Roberto Zatz
• Support Opportunities: Research Projects - Thematic Grants