Total Tubulointerstitial Score: a simple and effective predictor of long-term mortality and adverse renal outcomes in lupus nephritis

Objective Most studies focused on glomerular lesions in lupus nephritis (LN). However, the predictive value for tubulointerstitial lesions remains less well understood and controversial. Here, we assessed the impact of tubulointerstitial lesions, quantified by Total Tubulointerstitial Lesions Score (TTS), on long-term renal outcomes and mortality in LN. Methods We conducted a cohort study of 832 patients with LN diagnosed from 1996 to 2018 at the First Affiliated Hospital of Sun Yat-sen University. Patients were stratified by the median of TTS (TTS ≤2 vs TTS >2 groups), which included the total score of tubulointerstitial inflammation, tubular atrophy and interstitial fibrosis by the 2018 ISN/RPS (International Society of Nephrology and Renal Pathology Society) classification semi-score. We used Kaplan-Meier survival curves and Cox regression models to analyse the associations between TTS and patient outcomes. Results Pearson’s correlation analysis revealed that TTS was negatively correlated with estimated glomerular filtration rate, haemoglobin and serum albumin levels, while positively correlated with proteinuria levels. TTS was significantly higher in patients with proliferative LN. Kaplan-Meier analysis showed that patients with higher TTS had a higher risk of all-cause mortality and adverse renal outcomes. Multivariate Cox analysis identified TTS >2 (HR=1.50, 95% CI=1.02 to 2.22, p=0.039) and higher tubulointerstitial inflammation and tubular atrophy as the independent predictor of all-cause mortality, and TTS >2 (HR=1.63, 95% CI=1.05 to 2.52, p=0.030) and severer tubulointerstitial inflammation, tubular atrophy and interstitial fibrosis were independently associated with adverse renal outcomes. Conclusions TTS provides a comprehensive assessment of renal tubulointerstitial lesions and is a simple and effective predictor of long-term mortality and adverse renal outcomes in LN.