Association of overhydration and serum pigment epithelium-derived factor with CKD progression in diabetic kidney disease: A prospective cohort study

Abstract Aim Little is known about whether overhydration (OH), measured using bioimpedance assay (BIA), is associated with CKD progression in patients with type 2 diabetes mellitus (T2DM). We hypothesised that OH was a predictor, and pigment epithelium-derived factor (PEDF) was a modifiable risk factor of CKD progression. Methods We conducted a prospective cohort study of 1,065 patients with clinically euvolemic T2DM who attended the diabetes centre in a tertiary hospital or primary care clinic. CKD progression was defined as a combination of the worsening of the KDIGO defined CKD category by eGFR and a ≥ 25% decline in eGFR compared to baseline. Results Patients with T2DM in the highest tertile of OH and relative OH (OH/ extracellular water >7%) were positively associated with CKD progression (hazard ratio [HR] 1.45 [95% confidence interval (CI) 1.14–1.85; p=0.003 and HR 1.29 [95%CI 1.05–1.59; p=0.017]). There were positive associations between PEDF and CKD progression (β=1.10; p=0.001) and between OH and CKD progression (β=0.21; p=0.036). OH remained positively associated with CKD progression mediated by PEDF. Conclusions OH is an independent risk factor for CKD progression in patients with T2DM. Our study supports the novel definition of PEDF as a positive mediator between OH and CKD progression.