Abstract
BACKGROUND: Diabetic retinopathy (DR) is a risk factor for diabetic kidney disease (DKD). Whether the duration, especially the short-term duration, of DR is associated with the development and progression of DKD remains unclear. MATERIALS AND METHODS: A retrospective study and two-sample Mendelian randomization (MR) analysis were conducted. Kidney disease was defined by the urinary albumin-to-creatinine ratio (ACR) and the estimated glomerular filtration rate (eGFR). DR was diagnosed by an expert ophthalmologist by using a digital fundus camera. Binary and ordinal logistic regression analyses were performed. A restricted cubic spline was utilized to detect nonlinear associations. Summary statistics for DR- and DKD-associated single-nuclear polymorphisms (SNPs) were extracted from the FinnGen and the UK Biobank consortia. RESULTS: A total of 2674 patients with type 2 diabetes mellitus (T2DM) and type 2 diabetic kidney disease (T2DKD) were included. The prevalence and mean duration of DR increased with elevation of ACR and decline in eGFR. Renal function was significantly reduced in patients with DR in the fifth year of life. Binary and ordinal logistic regression showed that each 1-year increase in DR duration was associated with a 19% risk increase in the development of DKD, 16% in the elevation of ACR, and 21% in the decline of renal function. MR estimates indicated that DR was causally associated with DKD development, with an odds ratio of 2.89. CONCLUSIONS: DR and the duration of DR were independent risk factors for the development and progression of DKD. The short-term duration of DR may be associated with DKD development. DR had a statistically significant effect on DKD.