Sex modulates the association of fibroblast growth factor 21 with end‐stage renal disease in Asian people with Type 2 diabetes: a 6.3‐year prospective cohort study

Aim To study whether plasma fibroblast growth factor 21 independently predicts the risk of end‐stage renal disease in Asian people with Type 2 diabetes. Methods In this prospective cohort study, 1700 Asian people with Type 2 diabetes were followed for a mean of 6.3 years in a regional hospital in Singapore. Incident end‐stage renal disease was identified by linkage with a national renal registry. The association of baseline fibroblast growth factor 21 levels with risk of progression to end‐stage renal disease was studied using survival analyses. Results Participants were aged 60 ± 10 years, with an average diabetes duration of 12 years. Their estimated GFR was 73 ± 28 ml/min/1.73 m2 and 62% had albuminuria at baseline. A total of 179 incident end‐stage renal disease cases were identified. Plasma fibroblast growth factor 21 interacted with sex in its association with end‐stage renal disease (Pinteraction = 0.003). A 1‐sd increment in fibroblast growth factor 21 (natural log‐transformed) was associated with a 1.32‐fold (95% CI 1.05–1.66, P = 0.02) increased hazard for end‐stage renal disease in women, after adjustment for traditional risk factors including estimated GFR and albuminuria. Taking death as a competing risk did not materially change the outcome [sub‐distribution hazard ratio 1.35 (95% CI 1.11–1.66, P = 0.003)]. Fibroblast growth factor 21 did not predict end‐stage renal disease risk in men after adjustment for baseline estimated GFR and albuminuria [hazard ratio 1.07 (95% CI 0.89–1.28, P = 0.49)]. Conclusions Plasma fibroblast growth factor 21 level independently predicted risk of progression to end‐stage renal disease in women with Type 2 diabetes. The pathophysiological relationships among FGF21, sex and renal progression warrant further study. What's new? To our knowledge, this is the first study to show the association of fibroblast growth factor 21 (FGF21) with end‐stage renal disease (ESRD) in people with Type 2 diabetes. Sex modulates the association of FGF21 with ESRD. This is the first study reporting sex dimorphism in the association of FGF21 with renal outcome. Our data could prompt further studies on the role of FGF21 in the pathophysiological mechanisms of ESRD.