Kidney Res Clin Pract.
2024 Sep;43(5):626-634. 10.23876/j.krcp.23.342.
Clinical and pathological significance of Orai1 channel expression in human diabetic nephropathy
- Affiliations
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- 1Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
- 2Division of Nephrology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
- 3Transplantation Center, Wonju Severance Christian Hospital, Wonju, Republic of Korea
- 4Center of Evidence-Based Medicine, Institute of Convergence Science, Yonsei University, Seoul, Republic of Korea
- 5National Health Big Data Clinical Research Institute, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
- 6Department of Convergence Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
- 7Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
- 8Department of Global Medical Science, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
- 9Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
- KMID: 2564669
- DOI: http://doi.org/10.23876/j.krcp.23.342
Abstract
- Background
Targeted therapies for diabetic nephropathy (DN) are lacking, partly due to their irreversible nature. The role of Orai1, a store-operated Ca2+ channel, in DN remains debated, with conflicting evidence on its effect on proteinuria in animal models. We aimed to elucidate the functional relevance of Orai1 expression for clinicopathological parameters in patients with DN. Methods: In this study, we included 93 patients diagnosed with DN between 2009 and 2019. Immunohistochemical staining for Orai1 was performed on paraffin-embedded kidney sections. The significance of Orai1 expression in human DN was assessed by examining its correlation with DN’s pathological and clinical parameters using Pearson’s correlation coefficient and univariate logistic regression. Results: Orai1 was significantly overexpressed in DN patients compared to control. A strong correlation was observed between increased Orai1 expression and higher Renal Pathology Society DN classification, enhanced interstitial fibrosis and tubular atrophy scores. Positive correlations with serum creatinine levels and prognosis of chronic kidney disease (CKD) by glomerular filtration rate (GFR) and albuminuria category were noted but the estimated GFR was inversely related to Orai1 expression. Orai1’s association with advanced CKD stages persisted even after adjusting for confounding variables in multivariate logistic regression analysis. Conclusion: Orai1 expression is closely associated with histological and clinical severities of DN, suggesting its potential as a predictive biomarker for disease progression and prognosis. These findings provide new perspectives on therapeutic interventions targeting Orai1 in DN.
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