Pattern of Tubulo-Interstitial Injury and its Association with Post-Induction Therapy Response in Proliferative Lupus Nephritis

ObjectiveThe aim of the study was to assess the pattern of tubulo-interstitial injury and its association with post-induction therapy response in proliferative LN. MethodsThis multi-centered, prospective observational study was conducted from February 2020 – August 2021 (19 months). Class III and IV LN patients were included. With a total of 82 enrolled participants, we recorded the socio- demographic and histological characteristics and severity of injuries. Comparisons and associations between the therapy response and injuries were also evaluated.ResultsInterstitial Inflammation (84.1%) followed by Acute Tubular Injury (81.7%) were the most common types of tubulo-interstitial injuries. Furthermore, statistically significant association was found for all types of injuries, meaning, II (p=0.001); ATI (p=0.025) and interstitial fibrosis and tubular atrophy (p=0.003). Wire-loop lesion (p=0.012); global sclerosis (p=0.001) and fibrous crescent (p=0.001) were the types of glomerular lesions where statistically significant association was seen. Majority (64.5%) patients of mild II expressed complete response; 64.0% moderate category patients revealed deterioration; 51.6% patients of mild ATI showed complete response; 56.0% moderate and 24.0% severe interstitial fibrosis and tubular atrophy revealed deterioration. Statistically significant association was found in case of II (p=0.001) and IFTA (0.001).ConclusionTubulo-interstitial injuries, particularly II and IFTA, showed significant associations with both histopathological severity and treatment outcomes in proliferative LN. These findings highlight their prognostic value in guiding therapeutic decisions.Main points• Interstitial inflammation (II) and acute tubular injury (ATI) were the most common tubulo-interstitial injuries, present in 84.1% and 81.7% of cases, respectively.• A statistically significant association was observed between tubulo-interstitial injuries (II, ATI, IFTA) and LN class, particularly Class III and IV (p < 0.05).• II and IFTA showed strong correlations with glomerular lesions such as global sclerosis, wire-loop lesions, and crescents (p < 0.05).• Higher grades of IFTA were significantly associated with increased baseline and follow-up serum creatinine levels (p < 0.01), indicating prognostic relevance.• Patients with mild II and IFTA were more likely to achieve complete response to induction therapy, while ATI did not show a statistically significant impact on treatment response (p = 0.106).