Analysis of Physiopathology of Acute Kidney Injury Associated or Not with Diabetes Mellitus
Authors: de Ponte Mariana Charleaux , Cardoso Vanessa Gerolde , de Souza Maria Oliveira 
Published: June 2021

Introduction

Acute kidney injury (AKI) and diabetes mellitus (DM) are the major causes of chronic kidney disease (CKD). However, the pathophysiological mechanisms of AKI associated or not with diabetes are unclear. Thus, the aim of this study is to identify the pathophysiology of AKI in an experimental model of renal ischemia and reperfusion (I/R) associated or not with streptozotocin (STZ)‐induced diabetes.

Methods

The protocols are in agreement with CEUA (nº 12/2017). C57BL/6J mice, aged 60 days, were randomly grouped into: Control (CTL) ‐ vehicle and sham surgery; renal ischemia and reperfusion (I/R) ‐ vehicle and ischemia and reperfusion surgery; streptozotocin (STZ) ‐ STZ injection (55 mg/kg/day) for five consecutive days followed by sham surgery; STZ + I/R ‐ STZ injection (55 mg/kg/day) for five consecutive days followed by ischemia and reperfusion surgery. On the fifth day after the last injection of STZ, hyperglycemic animals (glycemia ≥ 250 mg/dL, monitored by glycosimeter) were considered diabetic. On the 12th day after the last STZ injection, the animals were submitted to surgical procedures and after 48 hours were submitted to euthanasia. Renal function was assessed by plasma creatinine and urea concentration. Proteinuria was assessed by commercial kit. Renal tissue was used for evaluation of gene expression by qPCR and protein expression by Western Blotting. Statistical analysis was performed by one‐way ANOVA, followed by Bonferroni post‐test. Values of p<0.05 were considered statistically significant.

Results

Renal ischemia followed by reperfusion resulted in increased plasma creatinine levels (p<0.05 vs CTL) and plasma urea levels (p<0.001 vs CTL); albuminuria (p<0.05 vs CTL); decreased nephrin mRNA expression (p<0.01 vs CTL), indicating glomerular injury and increased Kim‐1 mRNA expression (p<0.001 vs CTL), indicating tubular injury. Renal ischemia followed by reperfusion also induced inflammation, confirmed by the expression of mRNA for TNF‐α (p<0.01 vs CTL) and interleukin 1β (p<0.001 vs CTL), as well as the pro‐fibrotic response indicated by increased expression of collagen I (p<0.001 vs CTL), collagen III (p<0.001 vs CTL) and collagen IV (p<0.001 vs CTL). In the STZ‐treated group, the parameters described above were not altered because it is a condition of early diabetes. However, the diabetic group submitted to renal ischemia and reperfusion presented exacerbated responses in all parameters evaluated. In protein expression studies, renal ischemia followed by reperfusion decreased the expression of phosphorylated adenosine monophosphate‐activated protein kinase (AMPK) (p<0.01 vs CTL) and did not alter the protein expression of LC3A/B I (microtubule‐associated protein 1 light chain 3), indicating a loss of autophagic response.

Conclusion

AKI induces glomerular and tubular injury, inflammation, fibrosis and loss of autophagic response. DM behaves as an underlying disease that aggravates post‐ischemic AKI, primarily by accentuating tubular injury and inflammatory response.

Support or Funding Information

FAPESP (2016/12354‐0), CNPq (140182/2017‐9) and CAPES.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.