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Nephrol Dial Transplant. 2019 Jan 4. doi: 10.1093/ndt/gfy403. [Epub ahead of print]

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.

Author information

1
Division of Nephrology, Soonchunhyang University Hospital, Seoul, Republic of Korea.
2
Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Republic of Korea.
3
Department of Internal Medicine, College of Medicine, Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea.
4
Division of Nephrology and Hypertension, Department of Internal Medicine, Inha University College of Medicine, Incheon, Republic of Korea.
5
Department of Internal Medicine, Gil Medical Center, Gachon University of Medicine and Science, Incheon, Republic of Korea.
6
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
7
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
8
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.

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 (γ -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.

PMID:
30615179
DOI:
10.1093/ndt/gfy403

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