Tubulointerstitial damage predicts end stage renal disease in lupus nephritis with preserved to moderately impaired renal function: A retrospective cohort study

Objectives The presence of tubulointerstitial damage (TID) on renal biopsy is considered to be a late sequela of lupus nephritis (LN). The objective of this study was to determine if TID predicts progression to end stage renal disease (ESRD) in LN patients without advanced kidney disease. Methods All SLE patients with an index biopsy consistent with LN between January 2005 and July 2015, and eGFR ≥ 30 mL/min/1.73 m² were included. Moderate-to-severe TID was defined as the presence of moderate-to-severe tubular atrophy and/or interstitial fibrosis. Time to ESRD was defined as time from the index biopsy date to incident ESRD date; non-ESRD patients were censored at the time of death or the last visit before December 2015. Time-dependent analyses were conducted to evaluate whether moderate-to-severe TID was predictive of ESRD progression. Results Of the 131 LN patients with eGFR ≥ 30 mL/min/1.73 m², 17 (13%) patients progressed to ESRD. Moderate-to-severe TID was present in 13% of biopsies with eGFR ≥ 60 mL/min/1.73 m² and in 33% of biopsies with eGFR between 30 and 60 mL/min/1.73 m². Moderate-to-severe TID was associated with a higher risk of ESRD progression: adjusted hazard ratio (HR) = 4.1, 95% CI: 1.4–12.1, p = 0.01 for eGFR ≥ 30 mL/min/1.73 m²; HR = 6.2, 95% CI: 1.7–23.2, p = 0.008 for eGFR ≥ 60 mL/min/1.73 m². There was no association between tubulointerstitial inflammation (TII) and ESRD progression. Conclusions Moderate-to-severe TID, but not TII, was a strong predictor of ESRD progression independent of eGFR or glomerular findings, therefore, providing an important window for potential early interventions.