Checkpoint inhibitors (pembrolizumab · nivolumab · ipilimumab)
Immune checkpoint inhibitor
Acute interstitial nephritis with long latency.
AIN
ModerateOpen →
Anti-PD-L1 antibody
Atezolizumab
Tecentriq · ATEZO
An anti-PD-L1 antibody that triggers immune-mediated acute interstitial nephritis, occasionally glomerular disease.
ModerateImmune checkpoint inhibitor (anti-PD-L1) · approved 2016
Non-small cell lung cancerSmall cell lung cancerUrothelial carcinomaHepatocellular carcinoma (with bevacizumab)Melanoma (combination)
Signature kidney injury
Acute Interstitial Nephritis
Across the checkpoint-inhibitor class, any acute kidney injury occurs in roughly 15-17% of treated patients in cohort studies, while clinically significant immune-related AKI (most often acute interstitial nephritis) affects a smaller subset (commonly a few percent). Meta-analysis suggests anti-PD-L1 agents like atezolizumab carry somewhat lower AKI risk than anti-PD-1 agents; PD-L1-specific rates are not precisely separated.
Source: Meraz-Munoz et al., J Immunother Cancer 2020 (class-level any-AKI; agent-specific AIN rate not separately quantified)
Mechanism of kidney injury
Loss of peripheral immune tolerance from PD-L1 blockade permits activated CD4+/CD8+ T-cell infiltration of the tubulointerstitium, producing acute (often granulomatous) tubulointerstitial nephritis; reactivation of T cells primed against tubulointerstitial self-antigens or haptenizing drugs (PPIs, NSAIDs) is implicated, with a relative paucity of eosinophils compared with classic drug AIN. Glomerular lesions—pauci-immune/crescentic glomerulonephritis, fibrillary GN, and podocytopathies (minimal-change/FSGS)—occur less commonly.
Clinical presentation
Subacute rise in creatinine, sterile pyuria, white-cell casts, and low-grade (sub-nephrotic) proteinuria; eosinophilia/eosinophiluria are variable and often absent. AKI with hematuria and heavier proteinuria suggests a glomerular variant. Frequently accompanied by other immune-related adverse events (rash, colitis, thyroiditis).
Onset
Typically weeks to a few months after initiation (median time to checkpoint-inhibitor AKI is on the order of 3-4 months, characteristically later than classic drug AIN).
Reversibility
Partially reversible
Anticancer mechanism
Humanized IgG1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1), interrupting PD-1/PD-L1 (and PD-L1/B7.1) inhibitory signaling to restore antitumor T-cell activity. Used across lung, urothelial, hepatocellular, and other cancers, often with bevacizumab or chemotherapy.
Management
Hold the checkpoint inhibitor and exclude prerenal, obstructive, and other causes; pursue kidney biopsy when feasible to confirm AIN versus a glomerular lesion. Corticosteroids (e.g., prednisone ~0.5-1 mg/kg/day with taper) are first-line for immune-related AIN, with most patients recovering at least partial function; steroid-refractory cases may need additional immunosuppression. Rechallenge is individualized after recovery, recognizing a meaningful AKI recurrence rate.
Risk factors
- Concurrent proton-pump inhibitors, NSAIDs, or other AIN-associated drugs
- Combination checkpoint-inhibitor or chemoimmunotherapy regimens
- Lower baseline kidney function
- Other concurrent immune-related adverse events
Prevention
- Baseline and serial creatinine monitoring
- Review and minimize concomitant AIN-associated medications (especially PPIs)
- Early nephrology involvement and consideration of biopsy for unexplained AKI
Note · Renal immune-related toxicity is a class effect of PD-1/PD-L1 inhibitors; biopsy-based series predominantly show acute interstitial nephritis. Cited incidence figures are class-level rather than atezolizumab-specific, but biopsy-proven atezolizumab AIN and glomerular cases are documented.
Clinical depth
Renal dose adjustment
No baseline renal dose adjustment (fixed-dose antibody not renally cleared). The relevant 'adjustment' is immune-toxicity grading: per consensus guidance, withhold for grade 2 (creatinine 2-3x baseline) and treat with steroids, and permanently discontinue for grade 3-4 or recurrent severe nephritis.
Dialyzability & ESKD dosing
Not dialyzable—an IgG1 monoclonal antibody cleared by reticuloendothelial catabolism; not removed by hemodialysis and no dose supplementation needed. ESKD patients can receive standard dosing.
Differential diagnosis
Distinguish ICI-AIN from prerenal azotemia (volume/contrast/HCC-related), obstruction, and other drug AIN; the late onset, sterile pyuria with WBC casts, frequent absence of eosinophilia, and concurrent irAEs favor ICI-AIN. Cystatin-C-based eGFR and urine biomarkers (TNF-alpha, IL-9, CXCL9) help separate true AIN from pseudo-AKI and other causes; hematuria with heavier proteinuria points to a glomerular variant requiring biopsy.
Monitoring
- Serum creatinine/eGFR before each cycle
- Urinalysis with urine protein and microscopy if creatinine rises
- Screen for concurrent immune-related adverse events (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
- ICI-AIN is typically late (months in) and steroid-responsive—unlike classic drug AIN it often lacks eosinophilia.
- A concurrent PPI or NSAID is a common co-conspirator; deprescribe it as part of management.
- Biopsy when the picture is atypical—atezolizumab also causes glomerular lesions (pauci-immune/crescentic, fibrillary, podocytopathy).
- Urinary CXCL9/TNF-alpha/IL-9 and cystatin C help separate true AIN from pseudo-AKI before committing to steroids or rechallenge.
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
8 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 establishing acute interstitial nephritis as the dominant lesion of checkpoint-inhibitor AKI.PMIDClinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study.Cortazar FB et al. · J Am Soc Nephrol 2020 · PMID 31896554Landmark 138-patient multicenter cohort defining AIN predominance, steroid response, and rechallenge 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 (429 cases) characterizing risk factors, treatment, and recovery.PMIDImmune checkpoint inhibitor nephrotoxicity: what do we know and what should we do?Perazella MA et al. · Kidney Int 2019 · PMID 31685311Core mechanism/management review of ICI nephrotoxicity (loss of tolerance, AIN, treatment).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 AKI incidence (~16.5%) and risk factors with checkpoint inhibitors.PMIDA case of biopsy-proven acute interstitial nephritis following atezolizumab-bevacizumab treatment of advanced unresectable hepatocellular carcinoma.Patel R et al. · Cancer Rep (Hoboken) 2024 · PMID 39051557Agent-specific biopsy-proven atezolizumab AIN illustrating diagnosis and steroid management.PMIDCrescentic Fibrillary Glomerulonephritis in the Setting of Immune Checkpoint Inhibitor Therapy: A Report of Two Cases.DiFranza LT et al. · Glomerular Dis 2022 · PMID 37113492Two atezolizumab-associated glomerular (crescentic fibrillary GN) cases highlighting the glomerular variant.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 immune-related adverse events including renal toxicity grading and steroids.