Ifosfamide is a commonly used chemotherapeutic known to have numerous adverse kidney manifestations. In this issue of Clinical Kidney Journal, Ensergueix et al. report a multicentric observational retrospective French study on 34 adult patients with tubular dysfunction and /or kidney dysfunction following ifosfamide treatment. Of these patients, 18% had isolated proximal tubular dysfunction, 14% had isolated acute kidney injury (AKI), 18% had isolated chronic kidney disease (CKD) and 50% had a combination of proximal tubular dysfunction and AKI. Concomitant treatment with cisplatin was identified as a risk factor for the development of AKI, and cisplatin and age were associated with estimated glomerular filtration rate at last follow-up. Interestingly, the cumulative dose of ifosfamide was not associated with renal outcomes. This report highlights the need for additional studies on the prevalence, spectrum and management of ifosfamide-associated nephrotoxicity and clearly demonstrates that patients who received ifosfamide should be followed long term to detect proximal tubular dysfunction and CKD early.

Immune checkpoint inhibitors are a cornerstone in the management of many oncological disorders, and their indications continue to grow. However, as with any therapy we must remain vigilant of the possible adverse effects. Although interstitial nephritis is a reported cause of immune checkpoint inhibitor–related kidney injury, immune-mediated glomerular disease has rarely been described. Here, we present three patients being treated with checkpoint inhibitors for colon cancer, metastatic squamous cell carcinoma of the lung, and melanoma, who developed biopsy-proven amyloid A amyloidosis. In all three cases, the malignancies were in remission, yet continued inflammation and amyloid deposition occurred, pointing toward a primary role of the immune checkpoint inhibitor. Treatment generally remains a challenge due to a paucity of reported cases, thus further study of cytokine profile is prudent. In one case, the patient was given tocilizumab in the setting of elevated interleukin-6 levels; unfortunately no appreciable renal benefit was noted and the patient became dialysis dependent. In the other two cases, the patients were treated with colchicine and steroids. One patient had a substantial decrease in proteinuria and inflammatory markers while no significant response was noted in the other. Knowledge of immune checkpoint inhibitor–associated amyloid A amyloidosis is important for the oncologist and the nephrologists.

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