title: Phosphate, fibroblast growth factor 23 and retinopathy in chronic kidney disease: the Chronic Renal Insufficiency Cohort Study.
abstract: BACKGROUND
  Elevated circulating concentrations of phosphate and fibroblast growth factor 23 (FGF23) contribute to the pathogenesis of cardiovascular disease in chronic kidney disease (CKD). Retinopathy is a common manifestation of microvascular disease in CKD, but its associations with phosphate and FGF23 have not been studied. We tested the hypothesis that higher serum phosphate is associated with more severe retinopathy in individuals with CKD, independent of FGF23 and known risk factors for retinopathy.
  
  
  METHODS
  We tested the associations of serum phosphate and plasma FGF23 with retinopathy in a cross-sectional analysis of 1800 participants in the Chronic Renal Insufficiency Cohort Study who underwent fundus photography. Retinopathy severity was graded according to the Early Treatment of Diabetic Retinopathy Severity score, and retinal venous and arterial diameters were measured.
  
  
  RESULTS
  Mean estimated glomerular filtration rate (eGFR) was 46.5 ± 15.4 mL/min/1.73 m(2), mean serum phosphate was 3.7 ± 0.6 mg/dl and median plasma C-terminal FGF23 was 133 RU/mL (interquartile range 87.2, 217.8 RU/mL). In multivariable ordinal logistic regression models, higher serum phosphate was associated with greater retinopathy severity independent of hypertension, diabetes, CKD severity and FGF23 [adjusted odds ratio of being in one higher category of retinopathy severity: 1.19 per 1 standard deviation increase; 95% confidence interval (CI) 1.05, 1.36; P = 0.007]. Presence of diabetes or hypertension did not modify the results. Higher serum phosphate was also independently associated with greater retinal venous diameter (multivariable-adjusted 1.70 µm increase per 1 standard deviation increase in phosphate; 95% CI 0.46, 2.93; P = 0.007). FGF23 levels were not independently associated with retinopathy severity or retinal venous diameter, and neither FGF23 nor phosphate was associated with retinal arterial diameter.
  
  
  CONCLUSIONS
  Among individuals with moderate-to-severe CKD, higher serum phosphate but not FGF23 was independently associated with more severe retinopathy and microvascular retinal venous dilatation.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine and Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Rupal
authors.initials: R
authors.lastname: Mehta
authors.affiliation: University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Gui Shuang
authors.initials: GS
authors.lastname: Ying
authors.affiliation: Willis Eye Hospital, Philadelphia, PA, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Houston
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine and Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Isakova
authors.affiliation: University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Nessel
authors.affiliation: University of Michigan, Ann Arbor, MI, USA.
authors.forename: Akinlolu
authors.initials: A
authors.lastname: Ojo
authors.affiliation: Kaiser Permanente, Oakland, CA, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Go
authors.affiliation: University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Lash
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
authors.forename: John
authors.initials: J
authors.lastname: Kusek
authors.affiliation: University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Grunwald
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine and Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D003430:Cross-Sectional Studies; D003930:Diabetic Retinopathy / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000097:blood*; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D012161:Retinal Artery / Q000473:pathology; D012169:Retinal Vein / Q000473:pathology; D012307:Risk Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: CKD; FGF-23; phosphate; retinopathy; vascular disease