Related Experiment Video
Updated: Oct 19, 2025
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Early type 1 diabetes aggravates renal ischemia/reperfusion-induced acute kidney injury
Mariana Charleaux de Ponte1, Vanessa Gerolde Cardoso1, Guilherme Lopes Gonçalves1
1Laboratory of Renal Physiology, Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, SP, 05508-900, Brazil.
Abstract:
The present study aimed to investigate the interaction between early diabetes and renal IR-induced AKI and to clarify the mechanisms involved. C57BL/6J mice were assigned to the following groups: (1) sham-operated; (2) renal IR; (3) streptozotocin (STZ-55 mg/kg/day) and sham operation; and (4) STZ and renal IR. On the 12th day after treatments, the animals were subjected to bilateral IR for 30 min followed by reperfusion for 48 h, at which time the animals were euthanized. Renal function was assessed by plasma creatinine and urea levels, as well urinary protein contents. Kidney morphology and gene and protein expression were also evaluated. Compared to the sham group, renal IR increased plasma creatinine, urea and albuminuria levels and decreased Nphs1 mRNA expression and nephrin and WT1 protein staining. Tubular injury was observed with increased Havcr1 and Mki67 mRNA expression accompanied by reduced megalin staining. Renal IR also resulted in increased SQSTM1 protein expression and increased proinflammatory and profibrotic factors mRNA expression. Although STZ treatment resulted in hyperglycemia, it did not induce significant changes in renal function. On the other hand, STZ treatment aggravated renal IR-induced AKI by exacerbating renal dysfunction, glomerular and tubular injury, inflammation, and profibrotic responses. Thus, early diabetes constitutes a relevant risk factor for renal IR-induced AKI.
Insights
Early diabetes exacerbates kidney injury caused by renal ischemia-reperfusion (IR). This study reveals that diabetes worsens acute kidney injury (AKI) by increasing inflammation and fibrosis, highlighting diabetes as a significant AKI risk factor.
Area of Science:
- Nephrology
- Endocrinology
- Pathology
Background:
- Acute kidney injury (AKI) following renal ischemia-reperfusion (IR) is a significant clinical concern.
- The role of early-stage diabetes as a risk factor for renal IR-induced AKI remains incompletely understood.
Purpose of the Study:
- To investigate the interaction between early diabetes and renal IR-induced AKI.
- To elucidate the underlying mechanisms contributing to exacerbated kidney injury in diabetic conditions.
Main Methods:
- C57BL/6J mice were divided into sham-operated, renal IR, streptozotocin (STZ)-induced diabetes with sham operation, and STZ-induced diabetes with renal IR groups.
- Renal function, kidney morphology, and gene/protein expression (including markers for tubular injury, inflammation, and fibrosis) were assessed post-IR.
- STZ administration induced hyperglycemia, modeling early diabetes.
Main Results:
- Renal IR alone increased plasma creatinine, urea, and albuminuria, with decreased Nphs1 mRNA and nephrin/WT1 protein, indicating glomerular injury.
- Tubular injury markers (Havcr1, Mki67 mRNA, reduced megalin) and inflammation/fibrosis markers (SQSTM1, proinflammatory/profibrotic factors) were elevated post-IR.
- STZ-induced diabetes aggravated IR-induced AKI, worsening renal dysfunction, injury, inflammation, and fibrosis compared to IR alone.
Conclusions:
- Early diabetes significantly exacerbates renal IR-induced AKI.
- Diabetic conditions heighten inflammation and fibrotic responses following renal IR.
- Early diabetes is identified as a critical risk factor for developing severe renal IR-induced AKI.
Related Concept Videos
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:29Acute Kidney Injury II: Pathophysiology
01:22Acute Kidney Injury I: Introduction
01:22Diabetes Mellitus: Overview and Type I Subtype
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
01:20Acute Kidney Injury V: Interprofessional Care
01:25Chronic Kidney Disease I: Introduction