Innovative Strategies in Onconephrology: Managing Checkpoint Inhibitor-Associated Nephritis

Nephrologists are navigating the intricate challenges of managing kidney complications induced by immune checkpoint inhibitors, with acute interstitial nephritis emerging as a pressing concern that demands innovative management strategies.

Managing immune checkpoint inhibitor-associated nephritis remains a central concern as corticosteroid reliance grows. Primarily, the discontinuation of immune checkpoint inhibitors coupled with corticosteroid therapy forms the backbone of initial treatment. Consensus guidance from major societies advises grading toxicity, holding ICIs for significant renal involvement, initiating prednisone at approximately 0.5–1 mg/kg for grade 2–3 with a gradual taper, and involving nephrology to consider kidney biopsy when the diagnosis is uncertain or kidney function declines. While effective, this approach often places undue reliance on steroids, exposing patients to potential side effects.

These clinical realities raise practical questions: who needs a biopsy, how quickly should steroids begin, and when is it safe to reintroduce checkpoint therapy? In daily practice, answers hinge on the tempo of kidney injury, competing oncologic priorities, and patient comorbidities. Thoughtful coordination between oncology and nephrology helps align risk tolerance and timelines.

Advances in biomarkers may enable more tailored management of checkpoint inhibitor–associated nephritis; early candidates include urine chemokines such as CXCL9/CXCL10 and IL-9, as well as biopsy patterns that distinguish drug-induced interstitial nephritis from other causes. Rather than promising a wholesale shift, these tools may help stratify risk and guide therapy in conjunction with clinical judgment.

Emerging observational reports and small cohorts suggest infliximab may be a viable option when steroids fall short. Infliximab is considered as a potential second-line treatment, especially for steroid-refractory cases, and has shown benefit in case series and small cohort reports, with some patients achieving renal recovery.

For patients with immune-related nephritis, decisions are concrete: temporarily holding immune checkpoint therapy to protect kidney function, starting steroids with attention to side effects and tapering schedules, and, in selected refractory cases, discussing second-line options such as infliximab.

Clinicians also face the question of when and how to taper steroids without precipitating a relapse. Slow, deliberate tapers with close monitoring of creatinine and urinalysis are common, and early engagement of nephrology can help balance relapse risk against steroid toxicity.

Taken together, current practice prioritizes guideline-aligned steroid-based management and careful grading, considers infliximab in select refractory cases supported by observational reports, and looks to emerging biomarkers to refine risk stratification. Rechallenge with ICIs may be reasonable after renal recovery and steroid taper in carefully selected patients, ideally within a multidisciplinary discussion that weighs cancer control against the risk of recurrent nephritis.

Key takeaways

• First-line care centers on holding ICIs as indicated, grading toxicity, and initiating corticosteroids with a planned taper; involve nephrology and consider biopsy when diagnosis is uncertain.
• When steroids are inadequate, anti–TNF agents such as infliximab are being explored in select, refractory cases based on case series and small cohorts.
• Candidate biomarkers (for example, urine CXCL9/CXCL10 or IL-9, alongside biopsy patterns) may help stratify risk and guide therapy, but their clinical roles are still evolving.
• Multidisciplinary coordination among oncology, nephrology, and pharmacy is essential for decisions about tapering, second-line therapy, and potential ICI rechallenge after recovery.