Fibroblast growth factor 23 (FGF23) targets tubular epithelial cells to promote phosphaturia and it has been associated with adverse outcomes in chronic kidney disease (CKD). Emerging data suggest that FGF23 plays a specific role in type 2 diabetes (T2D). We evaluated intact FGF23 (iFGF23) levels (plasma EDTA; chemiluminescence immunoassay) in 182 T2D subjects with no-DKD (n = 46), with albuminuria alone (ACR ≥30 mg/g; DKD stages 1-2, n = 48), with eGFR <60 ml/min/1.73m2 alone (Alb-DKD; n = 42) and with both albuminuria and eGFR <60 (Alb+DKD; n = 46). There was no difference in ACR between DKD stages 1-2 and Alb+DKD (97 [IQR 49-329] and 268 [62-736] mg/g); eGFR (CKD-EPI formula based on creatinine [eGFRcreat = 49 [45-54] and 45 [35-52] ml/min/1.73m2] or based on creatinine and cystatin-C) did not differ between Alb-DKD and Alb+DKD. Age, DD, HbA1c, triglycerides, uric acid and fibrinogen increased across DKD groups, while HDL cholesterol decreased, with no other significant difference in clinical and laboratory parameters. BP-lowering agents, RAS blockers and lipid-lowering drugs were slightly more frequent in albuminuric groups. Alb+DKD had the highest levels of inflammatory biomarkers: uric acid, hs-CRP and fibrinogen. In the whole cohort, iFGF23 was significantly and directly correlated with these 3 biomarkers. iFGF23 increased steeply (p<0.0001) across DKD groups (no DKD: 48.2 [IQR 37.3-61.5] pg/ml; DKD stages 1-2: 53.0 [42.5-61.4]; Alb-DKD: 60.4 [45.1-73.4] and Alb+DKD 76.6 [60.1-96.3]), with iFGF23 of Alb+DKD higher as compared to no-DKD (p<0.0001), DKD stages 1-2 (p<0.0001), and also Alb-DKD (p=0.008). In the whole cohort, iFGF23 was mildly associated with ACR (r = 0.260; p=0.001) and more strongly inversely related with eGFRcreat (r = -0.483, p<0.0001). Our results suggest that, for the same degree of eGFR reduction, higher iFGF23 levels in Alb+DKD as compared to Alb-DKD might be expression of more advanced renal damage and/or of an overwhelming inflammation.
M. Garofolo: Consultant; Self; Eli Lilly and Company. C. Pelosini: None. D. Lucchesi: None. P. Falcetta: None. M. Sessa: None. S. Del prato: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Sanofi. G. Penno: Advisory Panel; Self; Eli Lilly and Company.