Background: The risk of the development and progression of diabetic kidney disease (DKD) was increased by abnormal calcium release. However, it is still unknown whether calcium signal pathway-related proteins are changed in urinary exosomes. This study aims to explore the changes in urinary exosomal proteins, which may provide novel biomarkers for diagnosing DKD.
Methods: Urinary exosomes were isolated from 132 participants by size exclusion chromatography method and 72 participants were tested by LC-MS/MS (Discovery phase). Correlation and multivariate logistics analysis were applied to evaluate selected urinary proteins. Western blot and ELISA were used to validate the selected protein (Validation phase: n = 60). The diagnostic performance of the selected biomarker was evaluated by receiver operating characteristic curve analyses between the discovery and validation phases.
Results: Sixteen calcium signal pathway-related proteins were identified, however, only Calmodulin-1(CALM1) was continuously increased. Different expression of CALM1 was found in patients with different level of estimated glomerular filtration rate (eGFR) in two cohorts. The level of CALM1 was correlated with eGFR and serum creatinine levels in two cohorts. Multivariate analysis revealed that serum albumin (ALB) levels and CALM1 were independent risk factors for DKD. A diagnostic model based on CALM1 and serum ALB levels that could significantly distinguish DKD was established and validated.
Conclusions: Significant changes in calcium signal pathway-related urinary exosomal proteins were observed. The CALM1 may serve as an early noninvasive biomarker for diagnosing DKD.
Keywords: Biomarker; CALM1; Calcium signal pathway; Diabetic kidney disease; Urinary exosomes.
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