Evaluation of the association of serum glypican-4 with prevalent and future kidney function

Serum glypican-4 (GPC4) has been identified as an insulin-sensitizing adipokine serving as a marker for body mass index and insulin resistance in humans. The association of circulating GPC4 with kidney function is to date largely unexplored. Therefore, we aimed to evaluate the association between serum GPC4 and prevalent as well future kidney function in a prospective cohort study. The study included 456 Caucasian coronary angiography patients. After a median follow up period of 3.4 years, data on kidney function was reassessed in all patients. Chronic kidney disease (CKD) was defined by decreased estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² or albuminuria. At baseline, serum GPC4 was significantly associated with decreased eGFR (adjusted odds ratio (OR) per standard deviation = 4.75 [2.66-8.48]; P <  0.001), albuminuria (OR = 1.49 [1.15-1.92]; P = 0.002), and, accordingly, with CKD (OR = 1.75 [1.35-2.26]; P < 0.001). GPC4 levels also significantly and independently predicted the incidence of newly diagnosed decreased eGFR (OR = 2.74 [1.82-4.14]; P < 0.001, albuminuria (OR = 1.58 [1.01-2.46]; P = 0.043, and CKD (OR = 2.16 [1.45-3.23]; P < 0.001). ROC analysis indicated an additional predictive value of GPC4 to a basic prediction model for newly diagnosed CKD and eGFR < 60 mL/min/1.73 m². Our study, therefore, indicates that high serum GPC4 is associated with decreased prevalent and future kidney function.