Acute interstitial nephritis (AIN) is a leading cause of acute kidney injury. Drug-induced hypersensitivity remains the most common trigger, but immune-checkpoint-inhibitor (ICI)-associated nephritis is a rapidly growing area, and diagnostics are beginning to move beyond biopsy.
Causes and diagnosis
Common culprits include proton pump inhibitors, NSAIDs, and antibiotics, and ICI-associated AKI (most often interstitial nephritis) occurs in a few percent of patients on checkpoint inhibitors — a risk heightened by concurrent AIN-associated drugs and dual ICI therapy. Kidney biopsy remains the diagnostic gold standard, but the emergence of non-invasive biomarkers — particularly the urinary chemokines CXCL9 and CXCL10, and soluble IL-2 receptor — is promising for diagnosing AIN and distinguishing it from other causes of AKI without biopsy, though these are not yet routine.
Treatment
The cornerstones are prompt withdrawal of the offending drug (and holding the ICI where relevant) plus corticosteroids (typically prednisone 0.5–1 mg/kg/day with a taper), with most patients achieving full or partial recovery when treated early. For steroid-dependent or refractory cases, mycophenolate mofetil, azathioprine, or rituximab (in selected immune-complex or glomerular disease) have been used. Importantly, ICI rechallenge is often feasible after renal recovery, especially when an alternative nephritogenic drug can be eliminated.
| Modality | Role | Note |
|---|---|---|
| Stop offending drug / hold ICI | All AIN | Essential to recovery |
| Corticosteroids | First-line | Recovery in most if early |
| MMF / azathioprine / rituximab | Steroid-refractory | Selected cases |
| Urine CXCL9/CXCL10, sIL-2R | Diagnosis (emerging) | May reduce need for biopsy |
Further reading: ICI-associated nephritis treatment standard (Barbir et al., NDT 2024); urinary CXCL9 as a diagnostic biomarker for AIN (Moledina et al.); reviews of checkpoint-inhibitor nephrotoxicity (2023–2025).