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: Rupal Mehta, Gui Shuang Ying, Samuel Houston, Tamara Isakova, Lisa Nessel, Akinlolu Ojo, Alan Go, Jim Lash, John Kusek, Juan Grunwald, Myles Wolf, CRIC Study Investigators
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 30 Issue 9 Pg. 1534-41 (Sep 2015) ISSN: 1460-2385 [Electronic] England
• PMID: 25910495 (Publication Type: Journal Article, Observational Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Chemical References

• Biomarkers
• FGF23 protein, human
• Phosphates
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23

Topics

• Adult
• Aged
• Biomarkers (blood)
• Cross-Sectional Studies
• Diabetic Retinopathy (blood, diagnosis, etiology)
• Female
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (blood)
• Glomerular Filtration Rate
• Humans
• Male
• Middle Aged
• Phosphates (blood)
• Prospective Studies
• Renal Insufficiency, Chronic (blood)
• Retinal Artery (pathology)
• Retinal Vein (pathology)
• Risk Factors
• Young Adult