Multi-Marker Detection of Diabetic Kidney Disease and Risk of Incident Diabetic Retinopathy in a Multi-Ethnic Asian Population.

Background/Objectives: Cystatin C-based and combined creatinine-cystatin C estimated glomerular filtration rate (eGFR) equations improve early chronic kidney disease (CKD) detection and prediction of adverse outcomes compared to creatinine alone. However, their role in predicting microvascular complications such as diabetic retinopathy (DR) is less clear. We examined the association between diabetic kidney disease (DKD), defined using creatinine-, cystatin C-, and combined eGFR measures, as well as albuminuria, and the risk of incident DR among Asian adults in Singapore. Methods: We analysed 1135 Chinese and Indian adults with diabetes aged ≥40 years from a population-based cohort study with baseline (2007-2011) and 6-year follow-up (2013-2017) data. DR was graded from retinal photographs, and incident DR was defined as new-onset at follow-up. DKD was defined as eGFR < 60 mL/min/1.73 m2 using eGFRcr, eGFRcys, combined eGFRcr-cys, and albuminuria (UACR ≥ 30 mg/g), assessed individually and jointly. Modified Poisson regression models adjusted for age, sex, ethnicity, diabetes duration, HbA1c, and systolic blood pressure were used to estimate relative risks (RRs). Results: Overall, incident DR occurred in 13.0% of participants. Among those with DKD, incidence was 18.2% (eGFRcr), 16.7% (eGFRcys), 23.7% (eGFRcr-cys), and 18.3% (albuminuria). eGFRcr-DKD (RR = 2.18, 95% CI 1.33-3.58), eGFRcys-DKD (2.38 [1.51-3.78]), and eGFRcr-cys-DKD (3.15 [1.94-5.12]) were independently associated with incident DR, whereas albuminuria alone was not. Risk increased with increasing number of markers,2.00 (1.02-3.92) by dual and 4.91 (2.50-9.65) by triple markers. Conclusions: DKD defined using multiple kidney markers, particularly combined creatinine-cystatin C, was strongly associated with incident DR. These findings support the use of multiple kidney function markers to improve risk stratification for developing DR.