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Kidney Week

Abstract: PO0779

Clinical and Pathological Significance of Orai1 Expression in Human Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Kwak, Yooujin, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)
  • Shin, Hanwul, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)
  • Lee, Jun Young, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)
  • Kim, Jae seok, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)
  • Yang, Jae Won, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)
  • Cha, Seung-Kuy, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)
  • Eom, Minseob, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)
Background

Diabetic nephropathy (DN) causes about half of ESRD. The attempts for targeted therapy for DN have been lacking to date. Store-operated Ca entry (SOCE) is a primary Ca influx mechanism in non-excitable cells that is mediated by pore-forming subunit Orai1. Currently, it has been argued whether Orai1 overexpression protects against renal pathologies. Here, we investigate the significance of Orai1 expression in human DN.

Methods

Ninety-three DN patients from 2009 to 2019 were enrolled. The paraffin blocks were used to perform immunohistochemical staining for Orai1 (figure). Renal Pathology Society DN classification (RPS) and clinical parameters were compared with Orai1 expression. The results were compared by dividing them into a glomerulus (G) and tubulo-interstitium (T-I).

Results

In T-I, Orai1 was overexpressed in DN, and Orai1 expression was significantly correlated with the higher RPS and interstitial fibrosis & tubular atrophy score (p < 0.001). While Orai1 expression was correlated with serum Cr and CKD stages, eGFR and HbA1c were inversely associated with Orai1 expression (p < 0.001). By logistic regression, Orai1 expression was significantly correlated with the higher RPS and the advanced CKD stage. Moreover, Orai1 expression was strongly associated with the advanced CKD stage by the multivariate logistic regression (p = 0.002) (table). The result of G was similar to that of T-I.

Conclusion

It is suggested that Orai1 is a valuable biomarker for predicting the progression and prognosis of DN, that provides new perspectives on therapeutic targets for DN.

The correlation between Orai-1 expression and CKD stage in DN (Multivariate logistic regression)
AdjustmentsParametersOdds ratio95% Confidence intervalp-value
Lower limitUpper limit
Age, Sex, BMI, HbA1c, DM duration, and HTNOrai-1 (G)11.2082.59048.4970.001
Orai-1 (T-I)13.8762.69471.4760.002

BMI, body mass index; HTN, hypertension; G, glomerulus; T-I, tubulo-interstitium

Funding

  • Government Support – Non-U.S.