Clinical and pathological significance of Orai1 channel expression in human diabetic nephropathy

Background: Targeted therapies for diabetic nephropathy (DN) are lacking, partly due to their irreversible nature. The role of Orai1, a store-operated Ca 2+ channel, in DN remains debated, with conflicting evidence on its effect on proteinuria in animal models. We aimed to elucidate the functional r...

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Bibliographic Details
Published in:Kidney research and clinical practice 2024-09, Vol.43 (5), p.626
Main Authors: Yooujin Kwak, Jun Young Lee, Jae Seok Kim, Jae Won Yang, Kyu-hee Hwang, Seung-kuy Cha, Minseob Eom
Format: Article
Language:Korean
Subjects:
Biomarkers
Chronic renal insufficiency
Prognosis
STIM1
Store-operated Ca 2+ entry
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Summary:Background: Targeted therapies for diabetic nephropathy (DN) are lacking, partly due to their irreversible nature. The role of Orai1, a store-operated Ca 2+ 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.
ISSN:2211-9132