Abstract
Rationale & Objective: 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 histopathologic quantification of interstitial fibrosis and tubular atrophy (IFTA) is associated with lower tubular secretory clearance in persons undergoing kidney biopsy. Study Design: Cross-sectional. Settings & Participants: The Boston Kidney Biopsy Cohort is a study of persons undergoing native kidney biopsies for clinical indications. Exposures: Semiquantitative score of IFTA reported by 2 trained pathologists. Outcomes: We measured plasma and urine concentrations of 9 endogenous secretory solutes using a targeted liquid chromatography/mass spectrometry assay. We used linear regression to test associations of urine-to-plasma ratios (UPRs) of these solutes with IFTA score after controlling for estimated glomerular filtration rate (eGFR) and albuminuria. Results: Among 418 participants, mean age was 53 years, 51% were women, 64% were White, and 18% were Black. Mean eGFR was 50 mL/min/1.73 m2, and median urinary albumin-creatinine ratio was 819 mg/g. Compared with individuals with ≤25% IFTA, those with >50% IFTA had 12%-37% lower UPRs for all 9 secretory solutes. Adjusting for age, sex, race, eGFR, and urine albumin and creatinine levels attenuated the associations, yet a trend of lower secretion across groups remained statistically significant (P < 0.05 for trend) for 7 of 9 solutes. A standardized composite secretory score incorporating UPR for all 9 secretory solutes using the min-max method showed similar results (P < 0.05 for trend). Limitations: Single time point and spot measures of secretory solutes. Conclusions: Greater IFTA severity is associated with lower clearance of endogenous secretory solutes even after adjusting for eGFR and albuminuria.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 709-716 |
| Number of pages | 8 |
| Journal | American Journal of Kidney Diseases |
| Volume | 79 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2022 |
Funding
Pranav S. Garimella, MD, MPH, Ronit Katz, PhD, Sushrut S. Waikar, MD, MPH, Anand Srivastava, MD, MPH, Insa Schmidt, MD, MPH, Andrew Hoofnagle, MD, PhD, Ragnar Palsson, MD, Helmut G. Rennke, MD, Isaac E. Stillman, MD, Ke Wang, MD, Bryan R. Kestenbaum, MD, MS, and Joachim H. Ix, MD, MAS. Concept and design of study: PSG, BRK, KW, JHI; data acquisition: PSG, SSW, AH, IS, AS, BRK, RP, HGR, IES, JHI; interpretation of results: PSG, RK, SSW, BRK, JHI. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual's own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate. This study is supported by National Institutes of Health grants K23DK114556 to PSG, R01DK095374 to SW, K24DK103986 to BRK, and R01DK098234, K24DK110427, and AHA 14EIA18560026 to JHI. The funders had no role in the study design, data collection, analysis, reporting or the decision to submit for publication. The authors declare that they have no relevant financial interests. We thank the members of the laboratory of SSW for their invaluable assistance in the Boston Kidney Biopsy Cohort. Part of this work was presented as a poster at the 2020 American Society of Nephrology Kidney Week Reimagined Virtual Poster Session, October 19-25, 2021. Received February 16, 2021. Evaluated by 2 external peer reviewers, with direct editorial input from a Statistics/Methods Editor and an Associate Editor, who served as Acting Editor-in-Chief. Accepted in revised form August 13, 2021. The involvement of an Acting Editor-in-Chief was to comply with AJKD's procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies. This study is supported by National Institutes of Health grants K23DK114556 to PSG, R01DK095374 to SW, K24DK103986 to BRK, and R01DK098234, K24DK110427, and AHA 14EIA18560026 to JHI. The funders had no role in the study design, data collection, analysis, reporting or the decision to submit for publication.
Keywords
- IFTA score
- Kidney tubule
- acute tubular injury (ATI)
- biomarker
- biopsy
- clearance
- fibrosis
- interstitial fibrosis and tubular atrophy (IFTA)
- renal function
- secretion
- solute
- tubular atrophy
- tubule cell dysfunction
- vascular sclerosis
ASJC Scopus subject areas
- Nephrology