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Kidney Week

Abstract: FR-PO295

Mediation Analysis of Proteinuria and Serum Phosphate: Insight from the KNOW-CKD Study

Session Information

Category: CKD (Non-Dialysis)

  • 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Jung, Ji Yong, Gachon University Gil Medical Center, Incheon, Korea (the Republic of)
  • Ro, Han, Gachon University Gil Medical Center, Incheon, Korea (the Republic of)
  • Oh, Yun Jung, Cheju Halla General Hospital, Jeju, Korea (the Republic of)
  • Lee, Chungsik, Cheju Halla General Hospital, Jeju, Korea (the Republic of)
  • Chang, Jae Hyun, Gachon University Gil Medical Center, Incheon, Korea (the Republic of)
  • Kim, Ae jin, Gachon University Gil Medical Center, Incheon, Korea (the Republic of)
  • Lee, Hyun Hee, Gachon University Gil Medical Center, Incheon, Korea (the Republic of)
  • Oh, Kook-Hwan, SNU College of Medicine, Seoul, Korea (the Republic of)
  • Ahn, Curie, Seoul National University Hospital, Seoul, Korea (the Republic of)
  • Chung, Wookyung, Gachon University Gil Medical Center, Incheon, Korea (the Republic of)
Background

Proteinuria and hyperphosphatemia are risk factors for cardiovascular disease in patients with chronic kidney disease (CKD). While experiencing the interaction between proteinuria and serum phosphate level, there is an insufficient mechanistic link between the two, particularly the extent to which is mediated by phosphate regulating factors. Therefore, we examined their association and potential mediators including circulating FGF23/Klotho and 24hr urinary excretion rate of phosphate to glomerular filtration rate (24hr EP/GFR) and 24hr tubular reabsorption rate of phosphate to GFR (24hr TRP/GFR).

Methods

We analyzed 1793 patients for whom 24hr urine protein and phosphate, serum phosphate, FGF23 and Klotho level were measured simultaneously using data from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD). Multivariable linear regression and mediation analyses were performed. Total, direct, and indirect effects were also estimated.

Results

The group of patients with high serum phosphate levels was likely to have higher proteinuria and FGF23 and lower Klotho levels. 24hr EP/GFR increased with increasing proteinuria and CKD progression, but 24hr TRP/GFR showed a tendency to decrease. Simple mediation analyses showed that 15.4% or 67.9% of the relation was mediated by FGF23/Klotho ratio or 24hr EP/GFR, respectively. In addition, 73.1% of the relation was mediated by two serial mediators.

Conclusion

These findings represents that proteinuria increases 24hr EP/GFR through FGF23/Klotho axis as a mechanism to regulate increased phosphate burden per unit nephron much earlier than reduction in renal function.

Mediation analyses of the effect of 24hr UPE on serum phosphate level.