Effect of cuproptosis on acute kidney injury after cardiopulmonary bypass in diabetic patients

World J Diabetes. 2024 Oct 15;15(10):2123-2134. doi: 10.4239/wjd.v15.i10.2123.

Abstract

Background: Cardiopulmonary bypass (CPB) is a common procedure in cardiac surgery. CPB is a high-risk factor for acute kidney injury (AKI), and diabetes is also such a factor. Diabetes can lead to copper overload. It is currently unclear whether AKI after CPB in diabetic patients is related to copper overload.

Aim: To explore whether the occurrence of CPB-AKI in diabetic patients is associated with cuproptosis.

Methods: Blood and urine were collected from clinical diabetic and non-diabetic patients before and after CPB. Levels of copper ion, lactate, glucose, heat shock protein-70 (HSP-70), and dihydrolipoamide dehydrogenase (DLAT) were determined. A diabetic rat model was established and CPB was performed. The rats were assessed for the development of CPB-AKI, and for the association of AKI with cuproptosis by detecting copper levels, iron-sulfur cluster proteins and observation of mitochondrial structure by electron microscopy.

Results: CPB resulted in elevations of copper, lactate, HSP-70 and DLAT in blood and urine in both diabetic and non-diabetic patients. CPB was associated with pathologic and mitochondrial damage in the kidneys of diabetic rats. Cuproptosis-related proteins also appeared to be significantly reduced.

Conclusion: CPB-AKI is associated with cuproptosis. Diabetes mellitus is an important factor aggravating CPB-AKI and cuproptosis.

Keywords: Acute kidney injury; Cardiopulmonary bypass; Copper overload; Cuproptosis; Diabetes; Iron-sulfur cluster proteins.