SUrvey of renal Biopsy registry database and Anticancer dRUg therapy in Japan (SUBARU-J study)

Abstract

Background Kidney complications associated with anticancer-drug therapy have greatly increased recently. We aimed to investigate the real-world clinical outcomes of anticancer-drug therapy-associated renal complications in Japan, using the national kidney biopsy database, Japan Renal Biopsy Registry (J-RBR). Methods From 2018 to 2021, 449 cases from 49 facilities, identified as ‘drug-induced’ histopathology in the J-RBR were screened, of which a total of 135 were confirmed as anticancer-drug-related cases and included in the analysis. Overall survival rates were estimated using Kaplan–Meier method, and compared by log-rank test. Cox regression model was used to evaluate the association between variables and deaths. Results Most common primary sites of malignancies were lung (33.3%), followed by gastrointestinal (16.3%), and gynecological (11.1%) cancers. Tubulointerstitial nephritis (TIN; 47.4%) and thrombotic microangiopathy (TMA; 35.6%) were the most frequent diagnoses. All IgA nephropathy, minimal change disease, and crescentic glomerulonephritis (CrGN) cases were immune-checkpoint inhibitor-related. All CrGN cases were ANCA-negative. Antibiotics were most frequently used concomitantly with anticancer drugs in TMA cases among subgroups (TMA vs. others: 62.5 vs. 27.5%, P < 0.001). Among TMA cases, serum LDH level tended to be higher in cytotoxic agent-associated TMA (CTx-TMA) than in other TMA, but not significant between groups (415.5 vs. 219.0 U/L, P = 0.06). Overall survival was worse in CTx-TMA than in other TMA (P = 0.007). Cox model demonstrated proton-pump inhibitor (PPI) use (HR 2.49, P = 0.001) as a significant prognostic factor as well as metastasis presense and serum albumin level. Conclusions Our registry analysis highlighted various presentations of biopsy-proven kidney complications associated with anticancer-drug therapy. Clinicians should be aware of worse outcomes associated with CTx-TMA and prognostic role of PPI use.