The effect of interactions between proteinuria, activity of fibroblast growth factor 23 and serum phosphate on renal progression in patients with chronic kidney disease: a result from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease study
- Authors
- Kim, Hyoungnae; Park, Jimin; Nam, Ki Heon; Jhee, Jong Hyun; Yun, Hae-Ryong; Park, Jung Tak; Han, Seung Hyeok; Chung, Wookyung; Oh, Kook-Hwan; Park, Sue Kyung; Kim, Soo Wan; Kang, Shin-Wook; Choi, Kyu Hun; Ahn, Curie; Yoo, Tae-Hyun
- Issue Date
- Mar-2020
- Publisher
- OXFORD UNIV PRESS
- Keywords
- chronic kidney disease; FGF-23; phosphate; prognosis; proteinuria
- Citation
- NEPHROLOGY DIALYSIS TRANSPLANTATION, v.35, no.3, pp.438 - 446
- Journal Title
- NEPHROLOGY DIALYSIS TRANSPLANTATION
- Volume
- 35
- Number
- 3
- Start Page
- 438
- End Page
- 446
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/26090
- DOI
- 10.1093/ndt/gfy403
- ISSN
- 0931-0509
- Abstract
- Background. Recent experimental study reported that proteinuria increases serum phosphate by decreasing biologic activity of fibroblast growth factor 23 (FGF-23). We examined this relationship in a large chronic kidney disease (CKD) cohort and evaluated the combined effect of proteinuria, FGF-23 activity and serum phosphate on CKD progression. Methods. The activity of FGF-23, measured by the fractional excretion of phosphate (FEP)/FGF-23 ratio, was compared according to the degree of proteinuria in 1909 patients with CKD. Primary outcome was CKD progression defined as >= 50% decline of estimated glomerular filtration rate, doubling of serum creatinine and start of dialysis. Results. There was a negative relationship between 24-h urine protein (24-h UP) and FEP/FGF-23 ratio (gamma -0.07; P=0.005). In addition, after matching variables associated with serum phosphate, patients with more proteinuria had higher serum phosphate (P<0.001) and FGF-23 (P=0.012), and lower FEP/FGF-23 ratio (P=0.007) compared with those with less proteinuria. In the matched cohort, low FEP/FGF-23 ratio was an independent risk factor for CKD progression (hazard ratio 0.87 per 1 log increase; 95% confidence interval 0.79-0.95; P=0.002), and there was significant interaction between 24-h UP and FEP/FGF-23 ratio (P=0.039). Furthermore, 24-h UP and serum phosphate also had a significant interaction on CKD progression (P<0.001). Conclusions. Proteinuria is associated with decreased biologic activity of FGF-23 and increased serum phosphate. Furthermore, diminished activity of FGF23 is an independent risk factor for renal progression in proteinuric CKD patients.
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