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Kidney Week

Abstract: SA-PO507

Serum Micro RNA Levels and Disease Progression in ADPKD

Session Information

  • ADPKD: Clinical Studies
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidney

  • 1001 Genetic Diseases of the Kidney: Cystic

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
  • Tan, Aik choon, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • You, Zhiying, UC Denver, 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
  • Brosnahan, Godela M., University of Colorado Denver, 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
  • Bae, Kyongtae Ty, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Abebe, Kaleab, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Chonchol, Michel, University of Colorado, Aurora, Colorado, United States
Background

The rate of kidney disease progression is highly variable among patients with autosomal dominant polycystic kidney disease (ADPKD). Unfortunately, there is currently no biomarker that accurately predicts disease progression especially in the early stages of disease while kidney function is normal. Changes in circulating micro RNA (miR) levels occur in patients with chronic kidney disease and also in patients with acute kidney injury. We hypothesized that a signature of miRs may distinguish ADPKD patients at increased risk for faster kidney disease progression.

Methods

Forty-six serum samples from HALT ADPKD study participants were analyzed, 23 from fast progressors (eGFR decline > 3.4 ml/min/1.73m2/year) and 23 from slow/normal progressors (eGFR decline ≤ 3.4 ml/min/1.73m2/year). Subjects were matched by sex, gene mutation, mutation type and age (± 5 years). Serum miRs were analyzed by RNASeq and human mature miRNA sequences were mapped to miRBase 21.

Results

The baseline characteristics and eGFR decline rate for both groups are shown in Table 1. The differentially expressed miRs in the fast compared to slow progressors included miR 1246, miR 6785-5p and miR 323a-3p which were significantly up-regulated in the fast progressors while miR 93, miR 451a and miR 106-5p were down regulated . Pathways associated with up-regulated miRs included adherens junction, renal cell carcinoma and AMP kinase signaling and those associated with down-regulated miRs included TGF-β and mTOR signaling, focal adhesion and extracellular matrix interaction.

Conclusion

The results indicate that aberrant expression of serum miRs occurs in ADPKD patients with fast disease progression. These may indicate further disruption of key pathways in patients with faster kidney disease progression. Future validation in a large cohort will be necessary to fully chracterize the key signature of discriminatory miRs.

Table 1 Characteristics of ADPKD Population for RNAseq
CharacteristicFast progressorsSlow progressors
Baseline age years (SD)35 (8)40 (8)
Baseline eGFR (SD) (ml/min/1.73m2)67.6 (22.5)92.7 (22.9)
Decrease in eGFR/year (SD) (ml/min/1.73m2)-9.2 (3.9)-1.3 (2.0)

Funding

  • NIDDK Support