Kwak Yooujin, Lee Jun Young, Kim Jae Seok, Yang Jae Won, Hwang Kyu-Hee, Cha Seung-Kuy, Eom Minseob
Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
Division of Nephrology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
Kidney Res Clin Pract. 2024 Sep;43(5):626-634. doi: 10.23876/j.krcp.23.342. Epub 2024 Aug 7.
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.
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.
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.
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.
糖尿病肾病（DN）的靶向治疗尚缺乏，部分原因在于其不可逆性。钙库操纵性钙通道Orai1在DN中的作用仍存在争议，动物模型中关于其对蛋白尿影响的证据相互矛盾。我们旨在阐明Orai1表达与DN患者临床病理参数的功能相关性。
在本研究中，我们纳入了2009年至2019年间诊断为DN的93例患者。对石蜡包埋的肾脏切片进行Orai1免疫组织化学染色。通过使用Pearson相关系数和单因素逻辑回归分析Orai1表达与DN病理及临床参数的相关性，评估其在人类DN中的意义。
与对照组相比，DN患者中Orai1显著过表达。观察到Orai1表达增加与更高的肾脏病理学会DN分级、增强的间质纤维化和肾小管萎缩评分之间存在强相关性。注意到与血清肌酐水平以及根据肾小球滤过率（GFR）和蛋白尿类别得出的慢性肾脏病（CKD）预后呈正相关，但估计的GFR与Orai1表达呈负相关。在多因素逻辑回归分析中，即使在调整混杂变量后，Orai1与晚期CKD阶段的关联仍然存在。
Orai1表达与DN的组织学和临床严重程度密切相关，表明其作为疾病进展和预后预测生物标志物的潜力。这些发现为DN中针对Orai1的治疗干预提供了新的视角。
