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Objectives Lupus nephritis (LN) is a major complication in patients with systemic lupus erythematosus (SLE). Tubulointerstitial injury is an inflammatory process that, if not attenuated, can promote renal damage. Despite this, the 2003 ISN/RPS glomerulocentric classification did not include a score for tubulointerstitial injury. Aiming the limitations of this classification, a review of this system was published in 2018; however, this revision has not yet been officially approved by societies but is widely used and accepted. To validate these findings and to emphasize the importance of an approach based on the distinctive features of the renal biopsy we sought to establish predictors for tubulointerstitial injury and to determine their influence on renal outcomes.Methods This is a retrospective study of a cohort of 166 patients with biopsy-proven LN diagnosed in a Spanish referral center, with a median follow-up of 86 months. Chronic tubulointerstitial lesions were defined as interstitial fibrosis and tubular atrophy (IF/TA), whereas tubulointerstitial inflammation (TII) was defined as an acute interstitial lesion. Activity (0–24) and chronicity (0–12) indices were assigned. Composite outcome defined as advanced CKD or development of kidney failure.Results The prevalence of tubulointerstitial lesions was 69.3% (115 patients). Eighty-one (48.8%) of the biopsies had features of tubulointerstitial inflammation and only 6 of these 81 (7%) patients had moderate/severe tubulointerstitial inflammation. The incidence of interstitial fibrosis and tubular atrophy was 56.6% (94 patients). At univariate analysis, renal survival was shorter in patients with moderate/severe IF/TA as compared with absent/mild IF/TA (p = 0.008), and in patients with moderate/severe TII as compared with absent/mild TII (p = 0.004) after adjusting for hypertension or diabetes. As expected, concomitant arterial hypertension or diabetes was associated with shorter renal survival (p = 0.04). At multivariate analysis, extension of TII in the renal biopsy emerged as an independent predictor of renal survival after adjustment for IF/TA grade, hypertension or diabetes (p=0.014).Conclusions The extent of TII emerged as an independent predictor of renal survival. Since TII is potentially reversible, its identification can help identify high-risk LN patients who can benefit from early immunosuppression before the development of chronic damage.