Acute Tubulointerstitial Nephritis in a Patient on Anti-Programmed Death-Ligand 1 Triggered by COVID-19: A Case Report

Abstract

Rationale: Immune checkpoint inhibitors are monoclonal antibodies used in the treatment of various types of cancers. The downside of using such molecules is the potential risk of developing immune-related adverse events. Factors that trigger these autoimmune side effects are yet to be elucidated. Although any organ can potentially be affected, kidney involvement is usually rare. In this case report, we describe the first known instance of a patient being treated with an inhibitor of programmed death-ligand 1 (anti-PD-L1, a checkpoint inhibitor) who develops acute tubulointerstitial nephritis after contracting the severe acute respiratory syndrome coronavirus 2. Presenting concerns of the patient: A 62-year-old patient, on immunotherapy treatment for stage 4 squamous cell carcinoma, presents to the emergency department with symptoms of lower respiratory tract infection. Severe acute kidney injury is discovered with electrolyte imbalances requiring urgent dialysis initiation. Further testing reveals that the patient has contracted the severe acute respiratory syndrome coronavirus 2. Diagnosis: A kidney biopsy was performed and was compatible with acute tubulointerstitial nephritis. Interventions: The patient was treated with high dose corticosteroid therapy followed by progressive tapering. Outcomes: Rapid and sustained normalization of kidney function was achieved after completion of the steroid course. Novel findings: We hypothesize that the viral infection along with checkpoint inhibitor use has created a proinflammatory environment which led to a loss of self-tolerance to renal parenchyma. Viruses may play a more important role in the pathogenesis of autoimmunity in this patient population than was previously thought.

A case of biopsy‐proven acute interstitial nephritis following atezolizumab‐bevacizumab treatment of advanced unresectable hepatocellular carcinoma

“…9 These findings are consistent with the mechanism underlying irAEs, which is an excessive T-cell response mediated by cytokine activation causing an increased presence of cytotoxic lymphocytes and a diffuse inflammatory infiltrate. 2 Although the patient developed a mild case of COVID-19 during his treatment course, COVID-19-associated kidney injury-rare in itself-tends to demonstrate evidence of tubular damage or necrosis, [16][17][18] which was not observed histologically here. Furthermore, the timeline of the presented patient's AKI appears to precede infection, suggesting ICI therapy as the more likely primary etiology of AIN and further illustrating histology's role in distinguishing etiologies.…”

COVID-19 Outcomes in Patients with Cancer Receiving Immune Checkpoint Inhibitors: A Systematic Review

“…Three case reports[ 12 , 28 , 30 ] and one case series[ 29 ] reported the characteristics of five patients with cancer receiving ICIs who developed an unusual adverse event after having COVID-19, and it was hypothesized that the infection triggered the event in these patients. Reported unusual adverse events after havingCOVID-19 in these patients were (1) acute tubulointerstitial nephritis, (2) hemophagocytic lymphohistiocytosis, (3) digital ischemia, (4) urticarial popular lesions, and (5) erythema multiforme.…”

“…Garassino 2020 [14] 200 24 (12) Chemotherapy, targeted therapy, chemotherapy þ immunotherapy, no treatment…”

Kidney complications following COVID-19 vaccination; a review of the literature

“…Systemic viral infections induce proinflammatory reactions that may increase the disruption of self-tolerance and immunity in patients treated with ICIs resulting in cross-reactivity and, in turn, ATIN. However, this patient was administered cloxacillin a few months before her admission which may have had some involvement in the immune-regulatory imbalance (94). Merino et al reported a case of ATIN following COVID-19 vaccination with Pfizer-BioNTech vaccine.…”