Kidney Tubulointerstitial Fibrosis and Tubular Secretion

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 50mL/min/1.73m², and median urinary albumin-creatinine ratio was 819mg/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.

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.