Checkpoint inhibitors (pembrolizumab · nivolumab · ipilimumab)
Immune checkpoint inhibitor
Acute interstitial nephritis with long latency.
AIN
ModerateOpen →
Anti-PD-L1 antibody
Durvalumab
Imfinzi · DURVA
An anti-PD-L1 antibody associated with immune-mediated acute interstitial nephritis and, rarely, glomerular disease.
ModerateImmune checkpoint inhibitor (anti-PD-L1) · approved 2017
Unresectable stage III non-small cell lung cancer (consolidation)Extensive-stage small cell lung cancerBiliary tract cancerHepatocellular carcinoma
Signature kidney injury
Acute Interstitial Nephritis
As with the PD-1/PD-L1 class, any AKI occurs in roughly 15-17% of treated patients, with immune-related AIN representing a smaller, clinically significant fraction (a few percent). Anti-PD-L1 agents trend toward lower AKI risk than anti-PD-1 agents; durvalumab-specific rates are not separately well quantified.
Source: Meraz-Munoz et al., J Immunother Cancer 2020 (class-level any-AKI; agent-specific AIN rate not separately quantified)
Mechanism of kidney injury
PD-L1 blockade breaks tubulointerstitial immune tolerance, producing T-cell-mediated acute (often granulomatous) interstitial nephritis, frequently potentiated by haptenizing co-medications (PPIs, NSAIDs). Less commonly, immune-mediated glomerular lesions occur, including reported de novo membranous nephropathy.
Clinical presentation
Gradual creatinine rise, sterile pyuria, white-cell casts, and modest proteinuria; frequently with other immune-related adverse events. Eosinophilia is inconstant. Nephrotic-range proteinuria suggests a glomerular variant.
Onset
Weeks to several months after starting therapy.
Reversibility
Partially reversible
Anticancer mechanism
Human IgG1 monoclonal antibody blocking PD-L1, restoring T-cell-mediated antitumor activity. Used in lung cancer (including consolidation after chemoradiation in stage III NSCLC), biliary tract, and hepatocellular cancers.
Management
Withhold durvalumab, exclude alternative causes, and treat confirmed/probable immune-related AIN with corticosteroids (prednisone ~0.5-1 mg/kg/day with taper); recovery of at least partial function is common, with additional immunosuppression for steroid-refractory disease. Individualize rechallenge after recovery.
Risk factors
- Concurrent PPIs/NSAIDs and other AIN-associated drugs
- Combination immunotherapy/chemoimmunotherapy
- Reduced baseline GFR
- Coexisting extrarenal immune-related adverse events
Prevention
- Routine creatinine surveillance
- Deprescribing unnecessary AIN-associated medications
- Prompt evaluation (including biopsy where appropriate) for unexplained AKI
Note · Renal toxicity reflects the PD-1/PD-L1 class effect; cited incidence figures are class-level. Durvalumab-specific glomerular toxicity (membranous nephropathy) has been reported, broadening the phenotype beyond AIN.
Clinical depth
Renal dose adjustment
No baseline renal dose adjustment (fixed-dose antibody, not renally cleared). Toxicity-based modification follows irAE grading: withhold for grade 2 nephritis with steroids; permanently discontinue for grade 3-4 or recurrent severe nephritis.
Dialyzability & ESKD dosing
Not dialyzable—IgG1 monoclonal antibody cleared by reticuloendothelial catabolism; not removed by hemodialysis, no supplemental dosing, standard dosing in ESKD.
Differential diagnosis
Distinguish ICI-AIN from prerenal azotemia, obstruction, contrast-associated AKI, and other drug AIN; late onset, sterile pyuria with WBC casts, and concurrent irAEs favor ICI-AIN. Heavy proteinuria/hematuria suggests a glomerular variant (e.g., membranous nephropathy) warranting biopsy. Cystatin C and urine AIN biomarkers help exclude pseudo-AKI.
Monitoring
- Serum creatinine/eGFR before each cycle
- Urinalysis with protein quantification and microscopy if creatinine rises
- Surveillance for concurrent irAEs (LFTs, TSH, glucose)
Key trials & series
- Cortazar Kidney Int 2016 ICI-AKI biopsy series
- Cortazar JASN 2020 multicenter ICI-AKI cohort
- Gupta J Immunother Cancer 2021 multicenter ICI-AKI cohort
Clinical pearls
- Durvalumab AIN behaves like the class—late, steroid-responsive, eosinophil-poor.
- Co-prescribed PPIs are frequent enablers; stop them when investigating AKI.
- Nephrotic-range proteinuria is a red flag for a glomerular variant (membranous nephropathy reported)—biopsy.
- An antibody is never dialyzed off; ESKD patients receive standard dosing.
Where it strikes
Nephron segments
Interstitium
Supporting tissue around the tubules
Glomerulus
Filtration barrier (podocytes + endothelium)
Injury signatures
Acute Interstitial NephritisGlomerular Injury / Proteinuria
Beyond the kidney
Class-level context for the major non-renal toxicities of anti-pd-l1 antibodys.
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
7 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkClinicopathological features of acute kidney injury associated with immune checkpoint inhibitors.Cortazar FB et al. · Kidney Int 2016 · PMID 27282937Biopsy series defining acute interstitial nephritis as the principal checkpoint-inhibitor renal lesion.PMIDClinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study.Cortazar FB et al. · J Am Soc Nephrol 2020 · PMID 31896554Multicenter cohort defining ICI-AKI features, steroid response, and outcomes.PMIDAcute kidney injury in patients treated with immune checkpoint inhibitors.Gupta S et al. · J Immunother Cancer 2021 · PMID 34625513Large multicenter ICI-AKI cohort characterizing risk factors, treatment, and recovery.PMIDNephrotoxicity of Cancer Immunotherapies: Past, Present and Future.Perazella MA et al. · J Am Soc Nephrol 2018 · PMID 29959196Mechanistic review of immunotherapy nephrotoxicity, including ICI-AIN pathophysiology.PMIDAcute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes.Meraz-Munoz A et al. · J Immunother Cancer 2020 · PMID 32601079Cohort quantifying checkpoint-inhibitor AKI incidence and outcomes.PMIDImmune Checkpoint Inhibitors and Kidney Toxicity: Advances in Diagnosis and Management.Seethapathy H et al. · Kidney Med 2021 · PMID 34939017Review covering anti-PD-1 vs anti-PD-L1 differences, diagnosis, biomarkers, and rechallenge.PMIDSociety for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events.Brahmer JR et al. · J Immunother Cancer 2021 · PMID 34172516Consensus management guidance for renal and other immune-related adverse events.