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Abstract: TH-PO1098

The Interactions Between Proteinuria, Activity of Fibroblast Growth Factor 23, and Serum Phosphate on Renal Progression in Patients with CKD: A Result from the KNOW-CKD Study

Session Information

Category: CKD (Non-Dialysis)

  • 1902 CKD (Non-Dialysis): Clinical, Outcomes, and Trials


  • Kim, Hyoungnae, Soonchunhyang University Hospital, Seoul, Korea (the Republic of)
  • Nam, Ki Heon, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
  • Han, Seung Hyeok, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
  • Yoo, Tae-Hyun, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

Both of proteinuria and hyperphosphatemia are well known risk factors of CKD progression. 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 combined effect of proteinuria, FGF-23 activity, and serum phosphate on CKD progression.


This prospective longitudinal study was conducted with 1909 patients from CKD stage 1 to 5. The activity of FGF-23, measured by fractional excretion of phosphate (FEP)/FGF-23 ratio, was compared according to the degree of proteinuria. Primary outcome was CKD progression defined as ≥50% decline of estimated glomerular filtration rate (eGFR), doubling of serum creatinine, start of dialysis, or kidney transplantation.


The patients with more proteinuria had significantly higher serum phosphate levels from CKD stage 2 to 5 than those with less proteinuria. In addition, there was a negative relationship between 24 hour urine protein (24h 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 to those with less proteinuria. In the matched cohort, low FEP/FGF-23 ratio was a risk factor of CKD progression (hazard ratio, 0.86 per 1 log increase; 95% confidence interval, 0.79-0.94; P = 0.001), and there was significant interaction between 24h UP and FEP/FGF-23 ratio (P = 0.027). Furthermore, 24h UP and serum phosphate also had a significant interaction on CKD progression (P < 0.001).


Proteinuria is associated with decreased biologic activity of FGF-23 and serum phosphate. Furthermore, diminished activity of FGF23 is an independent risk factor for renal progression in proteinuric CKD patients.