Zinc‐α2‐glycoprotein is Associated with Non‐albuminuric Chronic Kidney Disease Progression in Type 2 Diabetes: a Retrospective Study with 4‐year Follow‐up

Aim To investigate the association between baseline plasma zinc-alpha 2-glycoprotein and non-albuminuric chronic kidney disease progression in type 2 diabetes. Methods Adults with normoalbuminuria at entry (n=341; age 57 +/- 10 years, 52% men) were analysed. Chronic kidney disease progression was defined as a decrease in chronic kidney disease stage and a decline of >= 25% in estimated GFR from baseline. Baseline plasma zinc-alpha 2-glycoprotein levels were quantified by immunoassay, and analysed either as a continuous variable or by tertiles in Cox proportional hazards models. Model discrimination was assessed using Harrell's C-index. A sensitivity analysis was performed on a subset of individuals who maintained normoalbuminuria during follow-up. Results Chronic kidney disease progression occurred in 54 participants (16%). Zinc-alpha 2-glycoprotein levels were elevated in chronic kidney disease progressors (P = 0.011), and more progressors were assigned to the higher zinc-alpha 2-glycoprotein tertile than non-progressors. In the unadjusted Cox model, zinc-alpha 2-glycoprotein, both as a continuous variable (hazard ratio 1.72, 95% CI 1.08-2.75) and tertile 3 (vs tertile 1; hazard ratio 2.14, 95% CI 1.10-4.17), predicted chronic kidney disease progression. The association persisted after multivariable adjustment. The C-index of the Cox model increased significantly after incorporation of zinc-alpha 2-glycoprotein into a base model comprising renin-angiotensin system antagonist usage. Sensitivity analysis showed that zinc-alpha 2-glycoprotein independently predicted chronic kidney disease progression among individuals who maintained normoalbuminuria during follow-up. Conclusions Plasma zinc-alpha 2-glycoprotein is associated with chronic kidney disease progression, and may serve as a useful early biomarker for predicting non-albuminuric chronic kidney disease progression in type 2 diabetes.