Beyond glomeruli: interstitial fibrosis and tubular atrophy predict poor renal outcomes in lupus nephritis

Abstract Objectives To evaluate the prevalence, associated factors, and prognostic performance of NIH activity index–defined interstitial inflammation (NIH-TII) and interstitial fibrosis and tubular atrophy (IFTA) in lupus nephritis (LN). Methods This retrospective cohort study analyzed 195 renal biopsy episodes from 135 LN patients. Tubulointerstitial lesions were graded according to histopathological severity. NIH-TII was assessed semiquantitatively using the interstitial inflammation component of the modified NIH activity index. Results Among 195 renal biopsies, class IV LN was most frequent (49.2%). Tubulointerstitial involvement was present in 74.3% of cases, with isolated NIH-TII in 14.4%, isolated IFTA in 15.9%, and both in 44.1%. Moderate-to-severe NIH-TII and IFTA were observed in 11.3% and 15.9% of biopsies, respectively. Patients with moderate-to-severe NIH-TII were older, had worse renal function, and more frequently exhibited moderate-to-severe IFTA. Moderate-to-severe IFTA was associated with older age, longer SLE duration, prior LN episodes, higher chronicity index, and impaired renal function, and was strongly associated with non-renal response and ESRD progression. In multivariable logistic regression, prior LN episodes (OR 8.4) and moderate-to-severe IFTA (OR 4.92) predicted non-renal response. In multivariable Cox regression, prior LN episodes (HR 8.55), moderate-to-severe IFTA (HR 8.93), and thrombotic microangiopathy (HR 12.99) predicted ESRD progression. Longitudinal analyses showed frequent progression of IFTA over time with increasing chronicity index. Conclusions Moderate-to-severe IFTA was a strong predictor of renal non-response and ESRD progression. TII defined according to the NIH activity index, which does not include systematic assessment of tubulitis or total cortical inflammatory burden, was not independently associated with outcomes.