Journal of translational medicine · 2026
Serum cystatin C as a biomarker for diabetic retinopathy and its role in diabetic retinopathy-diabetic kidney disease comorbidity.
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Chen Xiaosi, Yuan Weichen, Zeng Yiyun, Wu Hanyu, Pi Linghui, Yang Yang, Gu Xinming, Zhang Xinyuan
Аннотация
BACKGROUND: To investigate whether serum cystatin C (CysC) can serve as a biomarker for diabetic retinopathy (DR), and explore the comorbidity between DR and diabetic kidney disease (DKD).
METHODS: This study used a nested case-control design with Mendelian randomization (MR) analysis. A total of 128 type 2 diabetic patients were categorized into no DR (DM), non-proliferative DR (NPDR), and proliferative DR (PDR) groups with age- and sex- matched controls. Biochemical and renal biomarkers were assessed, including the absolute difference (abdiff) eGFRabdiff (eGFRCysC-eGFRScr) and relative difference (rediff) eGFRrediff (eGFRCysC/eGFRScr). Instrumental variables for renal function and DR subtypes were selected from the UK Biobank and FinnGen consortium. Genetic associations were primarily derived using the inverse-variance weighted approach, with sensitivity analyses and multivariable MR adjusting for confounders.
RESULTS: Multivariable logistic analysis demonstrated that CysC levels were significantly associated with DM patients (OR=13.22, P=0.001) compared to healthy controls, and with NPDR patients (P=0.016) compared to DM patients, after adjusting for confounding variables; while eGFRCysC was a protective factor for DM (PDM vs. Normal=0.002); NPDR (PNPDR vs. DM=0.025) and PDR (PPDR vs. NPDR=0.013). Receiver operating characteristic (ROC) analysis confirmed the superior diagnostic efficacy of CysC and eGFRCysC for both DM and NPDR, eGFRrediff and urine Albumin-to-Creatinine Ratio (UACR) had superior predictive value for PDR compared to other renal biomarkers. Each standard deviation increases in serum CysC levels elevated the risks of DM (P=0.011), NPDR (P=0.00067), and PDR (P=0.042) by MR analysis.
CONCLUSIONS: The renal dysfunction biomarkers CysC and eGFRCysC were identified as key biomarkers for NPDR, while eGFRrediff and UACR were predictive for PDR. MR analyses confirmed CysC as a strong risk factor for DR susceptibility, particularly in the early stages.
METHODS: This study used a nested case-control design with Mendelian randomization (MR) analysis. A total of 128 type 2 diabetic patients were categorized into no DR (DM), non-proliferative DR (NPDR), and proliferative DR (PDR) groups with age- and sex- matched controls. Biochemical and renal biomarkers were assessed, including the absolute difference (abdiff) eGFRabdiff (eGFRCysC-eGFRScr) and relative difference (rediff) eGFRrediff (eGFRCysC/eGFRScr). Instrumental variables for renal function and DR subtypes were selected from the UK Biobank and FinnGen consortium. Genetic associations were primarily derived using the inverse-variance weighted approach, with sensitivity analyses and multivariable MR adjusting for confounders.
RESULTS: Multivariable logistic analysis demonstrated that CysC levels were significantly associated with DM patients (OR=13.22, P=0.001) compared to healthy controls, and with NPDR patients (P=0.016) compared to DM patients, after adjusting for confounding variables; while eGFRCysC was a protective factor for DM (PDM vs. Normal=0.002); NPDR (PNPDR vs. DM=0.025) and PDR (PPDR vs. NPDR=0.013). Receiver operating characteristic (ROC) analysis confirmed the superior diagnostic efficacy of CysC and eGFRCysC for both DM and NPDR, eGFRrediff and urine Albumin-to-Creatinine Ratio (UACR) had superior predictive value for PDR compared to other renal biomarkers. Each standard deviation increases in serum CysC levels elevated the risks of DM (P=0.011), NPDR (P=0.00067), and PDR (P=0.042) by MR analysis.
CONCLUSIONS: The renal dysfunction biomarkers CysC and eGFRCysC were identified as key biomarkers for NPDR, while eGFRrediff and UACR were predictive for PDR. MR analyses confirmed CysC as a strong risk factor for DR susceptibility, particularly in the early stages.