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Kidney Week

Abstract: FR-PO310

Circulating Interleukin-6 Level Predicts Decline in Kidney Function in Autosomal Dominant Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidney

  • 801 Cystic Kidney Diseases

Authors

  • Gitomer, Berenice Y., Div. Renal Diseases and Hypertension,, Aurora, Colorado, United States
  • Wang, Wei, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Nowak, Kristen L., University of Colorado Denver: Anschutz Medical Campus, Aurora, Colorado, United States
  • Hopp, Katharina, University of Colorado Denver, AMC, Aurora, Colorado, United States
  • You, Zhiying, UC Denver, Aurora, Colorado, United States
  • Brosnahan, Godela M., None, Aurora, Colorado, United States
  • Harris, Peter C., Mayo Clinic, Rochester, Minnesota, United States
  • Torres, Vicente E., Mayo Clinic, Rochester, Minnesota, United States
  • Chapman, Arlene B., University of Chicago, Chicago, Illinois, United States
  • Perrone, Ronald D., Tufts Medical Center, Boston, Massachusetts, United States
  • Steinman, Theodore I., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Yu, Alan S.L., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Abebe, Kaleab Z., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Bae, Kyongtae Ty, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Chonchol, Michel, University of Colorado, Aurora, Colorado, United States
Background

There is significant variability in the rate of kidney function decline among patients with autosomal dominant polycystic kidney disease (ADPKD). Resultant from the growth of cysts, several processes contribute to kidney injury including inflammation and consequent fibrosis. We hypothesized that the level of the circulating pro-inflammatory cytokine interleukin-6 (IL-6) may indicate kidney inflammation and predict the rate of kidney function decline.

Methods

Serum from 407 subjects who participated in the HALT clinical trial and had a PKD1 mutation were utilized in the study. IL-6 level was measured by a high sensitivity ELISA assay in the 24 month samples which were treated as baseline. Kidney function was assessed by eGFR using the CKD-EPI equation. Due to skewed distribution IL-6 was log transformed for analysis. Linear regression and mixed effects models were used to assess the association between circulating IL-6 and subsequent kidney function decline. Analyses were adjusted for age, sex, race, randomization group, systolic blood pressure and urinary albumin excretion.

Results

The mean age of included subjects was 40 ± 10 years and eGFR was 62 ± 27 ml/min/1.73m2. In cross-sectional analysis when stratified by the median level, higher Ln IL-6 was significantly negatively associated with lower eGFR in the fully adjusted model (β -6.315, 95%CI -10.517,-2.109; p = 0.003). In longitudinal analysis, higher circulating IL-6 measured at baseline was independently associated with a greater decrease in eGFR in the fully adjusted model (β -10.207, 95% CI -11.315,-9.10; p = < 0.0001).

Conclusion

Inflammation indicated by higher IL-6 level at baseline predicts kidney function decline. This suggests that measurement of serum IL-6 or other inflammatory mediators at baseline may represent a predictive biomarker of kidney disease progression in ADPKD. Future validation of IL-6 as a biomarker of ADPKD progression in additional cohorts will be necessary to confirm these results.

Funding

  • NIDDK Support