Nivolumab

The signature mechanism is loss of T-cell tolerance rather than direct tubular toxicity. PD-1 blockade is thought to reactivate drug-specific or self-reactive T cells, producing a delayed-type hypersensitivity acute tubulointerstitial nephritis (ATIN) with a dense CD4/CD8 T-cell interstitial infiltrate, sometimes granulomatous. A widely cited hypothesis is that checkpoint inhibition abrogates established tolerance to long-used concomitant drugs (proton pump inhibitors, NSAIDs, antibiotics), which then act as the nephritogenic antigen; case reports document AIN with positive drug lymphocyte stimulation tests to a PPI used safely for years before nivolumab. Less commonly, immune dysregulation manifests as glomerular disease (minimal change disease, FSGS, pauci-immune/ANCA-associated GN, immune-complex GN) or thrombotic microangiopathy. Reported tubular findings include karyomegalic, regenerating (Ki-67-positive) epithelium and, rarely, acute tubular injury.

Usually an asymptomatic rise in serum creatinine detected on routine monitoring, often with sterile pyuria and subnephrotic proteinuria; the classic allergic-AIN triad (rash, fever, eosinophilia) is frequently absent. Concurrent extrarenal immune-related adverse events (colitis, hepatitis, dermatitis, thyroiditis) occur in a substantial minority and support an immune etiology. When glomerular disease supervenes, nephrotic-range proteinuria and edema may dominate. Severe cases can require dialysis.

Fully human IgG4 monoclonal antibody against programmed cell death protein 1 (PD-1) on T cells. By blocking PD-1 engagement with its ligands PD-L1/PD-L2, nivolumab releases the inhibitory brake on tumor-reactive T cells, restoring cytotoxic antitumor immunity. The same loss of peripheral T-cell tolerance that drives efficacy underlies its off-target immune-related adverse events.

Hold nivolumab and exclude alternative causes of AKI (volume depletion, obstruction, contrast, other drugs). Discontinue contributing AIN-associated co-medications, especially PPIs. Per oncology/nephrology guidance, treat grade >=2 ICI-AKI with corticosteroids (typically prednisone ~1 mg/kg/day, with IV methylprednisolone pulses for severe disease), tapered over 4-6+ weeks; most patients are steroid-treated and steroids are associated with better renal recovery. Kidney biopsy is advised when the diagnosis is uncertain, to confirm ATIN versus a glomerular lesion or TMA that would change management. In the largest cohort, complete, partial, and no recovery occurred in roughly 40%, 45%, and 15% respectively; rechallenge is feasible in selected patients but recurrent AKI occurs in about a quarter.Lesion-level management framework