Checkpoint inhibitors (pembrolizumab · nivolumab · ipilimumab)
Immune checkpoint inhibitor
Acute interstitial nephritis with long latency.
AIN
ModerateOpen →
Anti-PD-L1 antibody
Avelumab
Bavencio · AVEL
An anti-PD-L1 antibody carrying the class risk of immune-mediated acute interstitial nephritis.
ModerateImmune checkpoint inhibitor (anti-PD-L1) · approved 2017
Merkel cell carcinomaUrothelial carcinoma (first-line maintenance)Advanced renal cell carcinoma (with axitinib)
Signature kidney injury
Acute Interstitial Nephritis
Immune-related nephritis follows the PD-1/PD-L1 class pattern: any AKI in roughly 15-17% of patients and clinically significant immune-related AIN in a smaller subset. Anti-PD-L1 agents trend toward lower AKI risk than anti-PD-1 agents; avelumab-specific renal incidence is not separately quantified and rests on class-level pharmacovigilance and meta-analysis data.
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 disrupts peripheral tolerance, driving T-cell-mediated acute interstitial nephritis, often potentiated by haptenizing co-medications; occasional immune-mediated glomerular disease occurs. When combined with the VEGFR-TKI axitinib in RCC, superimposed VEGF-pathway effects (hypertension, proteinuria, and rarely thrombotic microangiopathy) can coexist with or mimic immune nephritis.
Clinical presentation
Subacute creatinine rise with sterile pyuria, white-cell casts, and low-grade proteinuria; often concurrent with other immune-related adverse events. With axitinib co-therapy, new/worsening hypertension and proteinuria may dominate.
Onset
Weeks to months after initiation.
Reversibility
Partially reversible
Anticancer mechanism
Human IgG1 anti-PD-L1 monoclonal antibody that blocks PD-L1 and, by retaining its native Fc, may additionally engage antibody-dependent cellular cytotoxicity, restoring antitumor T-cell responses. Used in Merkel cell carcinoma, urothelial carcinoma (first-line maintenance), and renal cell carcinoma (with axitinib).
Management
Hold avelumab, exclude prerenal/obstructive and VEGFR-TKI-related contributors, and treat immune-related AIN with corticosteroids; many patients recover at least partially. When combined with axitinib, manage hypertension and proteinuria per VEGFR-TKI pathways and distinguish those from immune nephritis (biopsy if unclear).
Risk factors
- Concurrent PPIs/NSAIDs and other AIN-associated drugs
- Combination regimens (e.g., with a VEGFR TKI)
- Lower baseline kidney function
- Other active immune-related adverse events
Prevention
- Serial creatinine and (with axitinib) blood-pressure and proteinuria monitoring
- Minimize concomitant AIN-associated drugs
- Early nephrology evaluation and biopsy when appropriate
Note · Cited incidence figures are class-level; no dedicated single-agent avelumab renal case reports are well established in the literature, so attribution rests on class data. Avelumab is frequently combined with axitinib in RCC, where VEGFR-TKI renal effects may coexist.
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. Avelumab requires premedication to prevent infusion reactions (unrelated to renal dosing).
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
Separate ICI-AIN (late onset, sterile pyuria, WBC casts, concurrent irAEs, steroid-responsive) from axitinib-driven hypertension/proteinuria and TMA, from prerenal azotemia, and from obstruction. Heavy proteinuria points to a glomerular/VEGF-related process; biopsy and timing relative to each agent help attribute. Cystatin C and urine AIN biomarkers help exclude pseudo-AKI.
Monitoring
- Serum creatinine/eGFR before each cycle
- Blood pressure and urine protein when combined with axitinib
- Urinalysis/microscopy and irAE surveillance if creatinine rises
Key trials & series
- Cortazar JASN 2020 multicenter ICI-AKI cohort (class)
- Gupta J Immunother Cancer 2021 multicenter ICI-AKI cohort (class)
- Lima Immunopharmacol Immunotoxicol 2024 anti-PD-1 vs anti-PD-L1 AKI meta-analysis
Clinical pearls
- In RCC, avelumab is partnered with axitinib—decide whether AKI/proteinuria is immune (AIN) or VEGF-pathway driven before steroids.
- Avelumab AIN, like the class, is late and steroid-responsive and often eosinophil-poor.
- No solid single-agent case series exists; manage on class principles and biopsy atypical cases.
- Premedicate for infusion reactions—but that is unrelated to any renal dose adjustment.
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 characterizing checkpoint-inhibitor-associated acute interstitial nephritis.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 and recovery.PMIDImmune Checkpoint Inhibitors and Kidney Toxicity: Advances in Diagnosis and Management.Seethapathy H et al. · Kidney Med 2021 · PMID 34939017Review of diagnosis, class differences, biomarkers, and management of ICI kidney toxicity.PMIDAcute kidney injury associated with anti-PD-1 and anti-PD-L1 drugs: a meta-analysis of randomized clinical trials.Lima IG et al. · Immunopharmacol Immunotoxicol 2024 · PMID 38825890Meta-analysis comparing AKI risk across anti-PD-1 and anti-PD-L1 agents (including avelumab class).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 data on checkpoint-inhibitor AKI incidence and risk factors.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.