Urinary albumin fraction and tubulointerstitial injury: an association shaped by diagnostic composition

Background: Urinary protein composition provides qualitative information not captured by total protein excretion alone. Prior studies have linked low urinary albumin fraction to tubulointerstitial diseases and lesions, but whether this reflects pathology itself or diagnostic composition remains unclear. We investigated the association of urinary albumin fraction with tubulointerstitial lesions and diagnostic composition. Methods: We conducted a multicenter cross-sectional study of patients who underwent kidney biopsy at three referral centers. Urinary albumin fraction was obtained by urinary protein fraction analysis. Associations with interstitial fibrosis/tubular atrophy (IFTA) and inflammatory cell infiltration were examined overall and by diagnostic group. We also evaluated diagnostic composition in low urinary albumin fraction subgroups and the diagnostic performance for identifying tubulointerstitial disease. Results: A total of 462 patients was included. In the overall cohort, urinary albumin fraction differed significantly across IFTA grades (ANOVA p <0.001). In linear regression, IFTA grade 4 was associated with a significantly lower urinary albumin fraction than IFTA grade 0 (β − 22.10, 95% CI − 29.77 to − 14.43, p <0.001), but this association was no longer evident after adjustment for diagnostic group (β 4.13, 95% CI − 2.98 to 11.23, p = 0.294). The low urinary albumin fraction subgroups included not only tubulointerstitial diseases but also a substantial number of vasculitis cases. Conclusion: In this study, the apparent association between low urinary albumin fraction and tubulointerstitial lesions was largely explained by diagnostic group composition. Low urinary albumin fraction may serve as a supplementary clue to tubulointerstitial disease, but is neither disease-specific nor interpretable in isolation.