ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO303

Association of Serum FGF23 and Klotho with Long-Term Renal Outcomes of Polycystic Kidney Disease (PKD) in the Consortium for Radiologic Imaging Studies of PKD (CRISP) Cohort

Session Information

Category: Genetic Diseases of the Kidney

  • 801 Cystic Kidney Diseases

Authors

  • El Ters, Mireille, Mayo Clinic, Rochester, Minnesota, United States
  • Stubbs, Jason R., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Mahnken, Jonathan D., The University of Kansas Medical Center, Kansas City, Alabama, United States
  • Wallace, Darren P., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Yu, Alan S.L., University of Kansas Medical Center, Kansas City, Kansas, United States
Background

PKD is a slowly progressive disease leading to end-stage renal disease (ESRD). Levels of FGF23 are elevated in PKD out of proportion to kidney function, and circulating levels of its receptor, Klotho, decreased. Whether these are associated with long term renal outcomes is unknown.

Methods

CRISP is an observational cohort study of 241 PKD patients. Kidney function was serially measured with iothomalate clearance(iGFR) and height-adjusted total kidney volume(htTKV) measured by MRI. Intact FGF23 and soluble Klotho were measured on 191 available baseline serum samples and dichotomized into high/low FGF23 groups (cutoff 50 pg/ml) and high/low Klotho groups (cutoff 1000 pg/ml). The association of baseline FGF23 and Klotho level with follow-up log-htTKV and iGFR was tested using linear mixed models with random intercepts and adjusted for age, gender and Irazabal class. The risk of combined endpoint of ESRD and death was evaluated using a multivariable adjusted Cox proportional hazards model.

Results

Baseline serum FGF23 was 58±29 pg/ml and Klotho 918±925 pg/ml (mean ± SD). High FGF23 and low Klotho were both associated with higher baseline htTKV and lower baseline iGFR. Median follow-up was 13 years, during which 37 patients died or reached ESRD. High FGF23 was associated with faster growth of htTKV over the follow-up period and faster decline in iGFR (adjusted mean slope -3.04 vs -2.21 ml/min/y, p= 0.0013). Low Klotho also was associated with faster increase in htTKV and faster decline in iGFR (adjusted mean slope -2.97 vs -1.70 ml/min/y, p<0.01). High serum FGF23 was associated with increased risk of ESRD/death (adjusted HR=2.4, p=0.04). Low Klotho was also associated with increased risk however not when adjusted for baseline iGFR (Adjusted HR=0.4, p = 0.14 for Klotho).

Conclusion

Higher serum FGF23 and lower serum Klotho are associated with faster kidney growth and decline in renal function. Higher FGF23 was associated with increased risk of ESRD or death after adjustments for age, gender, Irazabal class and baseline iGFR.

Time to Death/ESRD

Funding

  • Other NIH Support