Zinc‐α2‐glycoprotein is associated with non‐albuminuric chronic kidney disease progression in type 2 diabetes: a retrospective study with 4‐year follow‐up

Abstract

Aim To investigate the association between baseline plasma zinc-a2-glycoprotein and non-albuminuric chronic kidney disease progression in type 2 diabetes. Methods Adults with normoalbuminuria at entry (n=341; age 57AE10 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-a2-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-a2-glycoprotein levels were elevated in chronic kidney disease progressors (P = 0.011), and more progressors were assigned to the higher zinc-a2glycoprotein tertile than non-progressors. In the unadjusted Cox model, zinc-a2-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-a2-glycoprotein into a base model comprising reninangiotensin system antagonist usage. Sensitivity analysis showed that zinc-a2-glycoprotein independently predicted chronic kidney disease progression among individuals who maintained normoalbuminuria during follow-up. Conclusions Plasma zinc-a2-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.

Serum Zinc-α2-glycoprotein Levels Are Associated with the Hepatorenal Function and Predict the Survival in Cases of Chronic Liver Disease

“…Xiao et al recently showed that the ZAG expression was decreased in NAFLD patient liver biopsy samples, obese mouse livers and palmitate-treated hepatocytes ( 7 ). In addition, increased serum ZAG levels were detected in individuals with CKD, indicating its usefulness as a biomarker for CKD progression ( 11 ). Although the ZAG/Cr predicted the patient prognosis in the entire and no-HCC groups, it did not predict the prognosis of patients with HCC.…”

Association of inflammation-related markers and diabetic retinopathy severity in the aqueous humor, but not serum of type 2 diabetic patients

“…It is thought to play diverse compartment-specific roles, the main one being to promote lipid mobilization [ 19 ]. ZAG has been discussed as a biomarker for early kidney disease [ 44 ], progression of diabetic nephropathy [ 45 , 46 ] and kidney disease-associated mortality [ 47 ]. Nevertheless, longitudinal data for its role in systemic micro- and macrovascular complications of diabetes have yet to be established.…”