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Kidney Week

Abstract: PO0619

Tubulointerstitial Fibrosis and Markers of Kidney Tubule Secretion

Session Information

  • CKD Mechanisms - 1
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Garimella, Pranav S., University of California San Diego, La Jolla, California, United States
  • Katz, Ronit, University of Washington, Seattle, Washington, United States
  • Waikar, Sushrut S., Boston Medical Center, Boston, Massachusetts, United States
  • Srivastava, Anand, Northwestern University, Evanston, Illinois, United States
  • Schmidt, Insa Marie, Boston Medical Center, Boston, Massachusetts, United States
  • Hoofnagle, Andrew N., University of Washington, Seattle, Washington, United States
  • Stillman, Isaac Ely, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Palsson, Ragnar, Landspitali, Reykjavik, Capital, Iceland
  • Rennke, Helmut G., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Wang, Ke, University of Washington, Seattle, Washington, United States
  • Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
  • Ix, Joachim H., University of Washington, Seattle, Washington, United States
Background

Tubular secretion plays an important role in the efficient elimination of endogenous solutes and medications, and lower secretory clearance is associated with risk of kidney function decline. We evaluated whether the biopsy measurement of tubular damage atrophy and interstitial fibrosis was associated with lower tubular secretory clearance in persons undergoing kidney biopsy.

Methods

The Boston Kidney Biopsy Cohort is a prospective cohort study of persons undergoing native kidney biopsies for clinical indications. Trained pathologists scored interstitial fibrosis and tubular atrophy (IFTA) on a semi-quantitative scale. We measured plasma and urine concentrations of nine endogenous secretory solutes using a targeted liquid chromatography mass-spectroscopy assay. We used linear regression to test associations of urine to plasma ratios (UPR) of these solutes with IFTA score after controlling for estimated GFR (eGFR) and albuminuria.

Results

Among 418 persons, the mean age was 53 years, 51% were women, 64% were White and 18% were African American. The mean eGFR was 50 ml/min/1.73m2 and median album/creatinine ratio was 890 mg/g. Compared to individuals with no IFTA, those with >50% IFTA had 27 to 76% lower UPR for the all 9 secretory markers. After adjusting for age, sex and race, these associations remained essentially unchanged. After further adjusting for eGFR and albuminuria this association were attenuated [Image] but the trend across groups remained statistically significant (p for trend <0.05) for all 9 solutes. For example, persons with >50% IFTA had, on average, 44% lower (95% CI 12% - 65% lower) UPR of p-cresol sulfate, a highly protein bound secretory solute, compared to persons with no IFTA. A composite secretory index incorporating UPR for all 9 secretory solutes using the min-max method showed similar results.

Conclusion

Greater IFTA severity is associated with lower tubular clearance of endogenous solutes clearance even after adjusting for eGFR and albuminuria.

Funding

  • NIDDK Support