Introduction:
The frequency of consultations for renal complications associated with anti-cancer drug therapy has greatly increased in recent years, but the actual situations remain yet to be fully understood. We aimed to investigate the clinical outcomes of anti-cancer 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 (OS) 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 cancers 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 nephrotic syndrome, 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 cases with TIN, their OS in the subgroups of targeted therapy (Tx), and the combination with Tx and conventional cytotoxic agents (Combi) seemed to be worse than that of cytotoxic agents alone (CTx); it may be due to more cases in the Tx and Combi subgroups with treatment response category of progressive disease (by RECIST criteria). In contrast, among TMA cases, OS in each of the three subgroups of Tx, CTx, and Combi seemed to be overlapped, suggesting the prognostic impact of TMA on OS. Among TMA cases, serum LDH level was higher in cytotoxic agent-associated TMA (CTx-TMA) than in other TMA (415.5 vs. 219.0 U/L, p=0.06). OS 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 and serum albumin.
Conclusions:
Our registry analysis highlighted a snapshot and various presentations of biopsy-proven kidney complications associated with anticancer-drug therapy. Higher LDH in CTx-TMA cases may be associated with systemic TMA, probably leading to the poor prognosis. To explore the detail of anti-cancer drug-associated TMA and other complications, further research employing more sample size is warranted in the future. Besides, clinicians should be aware of worse outcomes associated with CTx-TMA and prognostic role of PPI use.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.