Atezolizumab
Tecentriq · Anti-PD-L1 antibody
Interstitial nephritis; rare glomerular disease.
AINGLOM
ModerateOpen →
Immune checkpoint inhibitor
Immune Checkpoint Inhibitors
Keytruda · Opdivo · Yervoy · ICI
Release the immune brakes and the interstitium pays — weeks to months later.
ModerateImmune checkpoint inhibitor · approved 2014
MelanomaNSCLCRenal cellMany others
Signature kidney injury
Acute Interstitial Nephritis
Representative incidence3%
ICI-associated AKI ~2–5% (higher with combination therapy); ~93% of biopsies show interstitial nephritis.
Source: Cortazar et al., JASN 2020
Mechanism of kidney injury
Loss of self-tolerance lets T cells attack the renal tubulointerstitium — an immune-related adverse event driven by reactivation of drug-specific T cells. The long latency distinguishes it from classic drug-induced AIN.
Clinical presentation
AKI with modest sterile pyuria and sub-nephrotic proteinuria; eosinophilia is frequently ABSENT. Other immune-related adverse events (rash, colitis, thyroiditis) may coexist.
Onset
Delayed — median ~14 weeks after starting therapy.
Reversibility
Reversible
Anticancer mechanism
Pembrolizumab, nivolumab and ipilimumab block PD-1, PD-L1 or CTLA-4, restoring anti-tumor T-cell activity. Melanoma, NSCLC, renal cell and many others.
Management
Hold ICI and give corticosteroids (prednisone 0.5–1 mg/kg, tapered); biopsy if unclear. Rechallenge is possible but recurs in ~23%.
Risk factors
- Combination ICI therapy
- Lower baseline eGFR
- Concurrent PPI / AIN-associated drugs
Prevention
- Review and avoid concurrent AIN-causing drugs
- Monitor creatinine
Note · The most common immunotherapy-related kidney lesion; latency is the diagnostic clue.
Where it strikes
Nephron segments
Interstitium
Supporting tissue around the tubules
Injury signatures
Acute Interstitial Nephritis
Beyond the kidney
Class-level context for the major non-renal toxicities of immune checkpoint inhibitors.
Endocrine
Thyroiditis, hypophysitis, diabetes
- Thyroiditis, hypophysitis, type-1 diabetes
Gastrointestinal
Diarrhea, colitis, mucositis, perforation
- Immune colitis
Hepatic / Liver
Transaminitis, hepatitis, VOD/SOS
- Immune hepatitis
Pulmonary
Pneumonitis, ILD, effusions, hypertension
- Pneumonitis
Dermatologic
Rash, HFS, SJS/TEN, vitiligo
- Rash, vitiligo, rarely SJS/TEN
Evidence
5 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkClinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study.Cortazar FB et al. · J Am Soc Nephrol 2020 · PMID 31896554Landmark 138-case study: risk factors, 93% interstitial nephritis, steroid response.LandmarkClinicopathological features of acute kidney injury associated with immune checkpoint inhibitors.Cortazar FB et al. · Kidney Int 2016 · PMID 27282937Seminal first series defining ICI-AKI as delayed interstitial nephritis.PMIDDiagnosis and management of immune checkpoint inhibitor-associated acute kidney injury.Sprangers B et al. · Nat Rev Nephrol 2022 · PMID 36168055Authoritative review of mechanism, incidence and management.PMIDAcute interstitial nephritis related to immune checkpoint inhibitors.Belliere J et al. · Br J Cancer 2016 · PMID 27832664Shows all three checkpoint classes cause interstitial nephritis.PMIDImmune Checkpoint Inhibitors and Kidney Toxicity: Advances in Diagnosis and Management.Seethapathy H et al. · Kidney Med 2021 · PMID 34939017Practical management review on biopsy, steroids and rechallenge.