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Anti-PD-L1 antibody

Atezolizumab

Tecentriq · ATEZO

Anti-PD-L1 antibody · approved 2016 · 13 references

An anti-PD-L1 antibody that triggers immune-mediated acute interstitial nephritis, occasionally glomerular disease.

Signature injury
Acute Interstitial Nephritis
Severity
Moderate
Reversibility
Partially reversible
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).

Signature kidney injury & incidence

Acute Interstitial Nephritis — representative incidence ~3.6%.

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. A separate real-world cohort of 1,037 ICI-treated patients supplies the drug-attributable denominator this class otherwise lacks: 18.2% developed AKI of any cause, but only 3.6% (37 patients) had AKI attributed to the checkpoint inhibitor itself — a class figure, not an atezolizumab-specific one.

Source: Lumlertgul et al., Eur J Cancer 2023 (class-level ICI-attributed AKI 3.6%; agent-specific AIN rate not separately quantified)

Reported injury signatures: Acute Interstitial Nephritis, Glomerular Injury / Proteinuria, Hemorrhagic Cystitis, SIADH / Hyponatremia.

Renal toxicity profile

  1. Acute Interstitial NephritisPrimaryAcute tubulointerstitial nephritis is the dominant renal lesion in immune checkpoint inhibitor-associated AKI, seen in 82.7% (125/151) of biopsied cases in the largest multicenter cohort; anti-PD-L1 agents such as atezolizumab carry a lower AKI risk than anti-PD-1 agents
  2. Glomerular Injury / ProteinuriaRareCheckpoint inhibitor-associated glomerular disease (FSGS, minimal-change/podocytopathy, membranous, pauci-immune GN) is case-level and far less common than AIN
  3. Hemorrhagic CystitisRareCase-level immune-related (irAE) cystitis - immune-mediated, not acrolein toxicity.
  4. SIADH / HyponatremiaRareA monotherapy case with endocrinopathies excluded; the SCLC indication drives much of the reporting.

Onset timing & rechallenge

Delayed (>6 weeks / cumulative) — Typically weeks to a few months out (median ~3–4 months), later than classic drug AIN.

Rechallenge: Case-by-case — In the multicenter ICI-AKI cohort ~22% were rechallenged and ~23% of those developed recurrent AKI — feasible but an individualized, co-managed decision.

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).

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

  • Review and minimize concomitant AIN-associated medications (especially PPIs)

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

  • 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.
  • Immune-related non-bacterial cystitis is reported with biopsy support and steroid response — an irAE rather than acrolein-type hemorrhagic cystitis; the bladder-cancer indication adds tumor hematuria to the FAERS term.
  • A monotherapy case attributes SIADH to atezolizumab with endocrinopathies excluded; the extensive-stage SCLC indication — the archetypal paraneoplastic-SIADH tumor — drives much of the reporting.

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.

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.

Guidelines & consensus

Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.

  • ASON (2025) — Diagnosis and management of immune checkpoint inhibitor-associated nephrotoxicity: a position statement from the American Society of Onco-nephrologyICI-AKI most commonly presents as acute interstitial nephritis; nephrology consultation and kidney biopsy should be considered for stage 2 or higher AKI or suspected glomerular disease, but where biopsy is not feasible, prompt empiric corticosteroids (prednisone ~1 mg/kg/day) should be started for clinically suspected ICI-AKI since early steroids improve renal recovery, with cautious individualized consideration of ICI rechallenge after recovery.Kidney Int · PMID 39455026
  • ASCO (2021) — Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline UpdateFor grade 2 or higher ICI-related nephritis/AKI, hold the ICI, exclude alternative causes, and initiate corticosteroids (prednisone 0.5-1 mg/kg/day for grade 2, 1-2 mg/kg/day for grade 3-4) tapered over 4-6 weeks once creatinine improves; permanently discontinue for grade 4 toxicity.J Clin Oncol · PMID 34724392
  • ESMO (2022) — Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-upFor ICI-related AKI, exclude alternative etiologies and stop concomitant nephrotoxins (PPIs, NSAIDs); ESMO permits continuing the ICI for stage 1 AKI with monitoring, but recommends withholding the ICI and starting corticosteroids for stage 2 or higher nephritis, escalating immunosuppression for steroid-refractory disease.Ann Oncol · PMID 36270461
  • SITC (2021) — Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse eventsGrade ICI-related AKI by CTCAE; for persistent grade 2 or higher renal toxicity, discontinue the ICI, exclude other causes, and treat with corticosteroids with a taper begun once creatinine improves toward grade 1, considering kidney biopsy and additional immunosuppression for refractory cases.J Immunother Cancer · PMID 34172516
  • IC-OS (2026) — Immune Checkpoint Inhibitor-Associated Cardiovascular Toxic Effects: International Cardio-Oncology Society Position StatementConcerns for myocarditis continue to dominate the spectrum of CV toxic effects in patients receiving ICI therapy. Recommendations for management vary according to severity. Multidisciplinary collaborations remain key for managing acute toxic effects and future cancer treatment decisions, including ICI rechallenge.JAMA Oncol · PMID 41231466
  • EULAR (2021) — EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitorsOncologists should be encouraged to consult rheumatologists promptly for assessment when rheumatic musculoskeletal and systemic signs or symptoms are suspected due to immunotherapy, and rheumatologists should provide facilitated access for such patients.Ann Rheum Dis · PMID 32327425
  • ASCO (2018) — Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice GuidelineWithhold the checkpoint inhibitor and start corticosteroids for grade 2 or higher immune-related renal toxicity after excluding other causes of AKI, with steroid taper as renal function recovers and permanent discontinuation for severe (grade 4) events.J Clin Oncol · PMID 29442540
  • PUMCH Expert Panel (2020) — Clinical recommendations on diagnosis and treatment of immune checkpoint inhibitor-induced renal immune-related adverse eventsScreen and monitor with serum creatinine, urinalysis/sediment, and 24-hour urine protein; strongly recommend kidney biopsy to confirm ICI-related ATIN and exclude other AKI causes, withdraw nephrotoxins (PPIs, NSAIDs), and initiate corticosteroids when a grade 2 or higher renal irAE is highly suspected, with multidisciplinary decisions on ICI withdrawal and rechallenge.Thorac Cancer · PMID 32232975
  • ADQI (2026) — Immune Checkpoint Inhibitor-Associated Acute Kidney Injury: A Report from the 34th Acute Disease Quality Initiative (ADQI) Consensus ConferenceAKI occurs in up to 20% of ICI-treated patients with ICI-AKI accounting for roughly 2-5% of cases, and acute tubulointerstitial nephritis dominates (80-90% of biopsies); no clinical feature reliably separates ICI-AKI from other causes, so kidney biopsy remains the diagnostic gold standard and emerging biomarkers are not yet ready for routine use. Early glucocorticoid initiation (within 3 days of diagnosis) is associated with higher rates of kidney recovery, and recurrent ICI-AKI occurs in fewer than 20% of rechallenged patients, supporting cautious rechallenge in selected patients with individualized multidisciplinary decisions for transplant recipients and other high-risk groups.J Am Soc Nephrol · PMID 42536415
  • ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.Nat Rev Nephrol · PMID 41361704
  • SIRM (2022) — SIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.Radiol Med · PMID 35303246
  • KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.Kidney Int · PMID 33126977
  • KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.Kidney Int · PMID 33276867
  • ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.EClinicalMedicine · PMID 40290844
  • ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.EClinicalMedicine · PMID 40290845
  • ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.EClinicalMedicine · PMID 40290846
  • KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.Crit Care · PMID 23394211
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.Kidney Int · PMID 38519239
  • KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.Kidney Int · PMID 34556300
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.Kidney Int · PMID 38388147
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.Kidney Int · PMID 38182299
  • KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.Kidney Int · PMID 40975525

References

13 peer-reviewed references. Citation metadata via PubMed / NLM.

  1. 1.Acute kidney injury in patients receiving immune checkpoint inhibitors: a retrospective real-world study.Lumlertgul N et al. · Eur J Cancer · 2023 · PMID 37499561
  2. 2.Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors.Cortazar FB et al. · Kidney Int · 2016 · PMID 27282937
  3. 3.Urinary C-X-C-motif ligand 9 (CXCL9) in immune checkpoint inhibitor-associated acute interstitial nephritis.Gupta S et al. · Kidney Int · 2025 · PMID 40578686
  4. 4.Clinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study.Cortazar FB et al. · J Am Soc Nephrol · 2020 · PMID 31896554
  5. 5.Acute kidney injury in patients treated with immune checkpoint inhibitors.Gupta S et al. · J Immunother Cancer · 2021 · PMID 34625513
  6. 6.Immune checkpoint inhibitor nephrotoxicity: what do we know and what should we do?Perazella MA et al. · Kidney Int · 2019 · PMID 31685311
  7. 7.Acute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes.Meraz-Munoz A et al. · J Immunother Cancer · 2020 · PMID 32601079
  8. 8.A 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 39051557
  9. 9.Crescentic Fibrillary Glomerulonephritis in the Setting of Immune Checkpoint Inhibitor Therapy: A Report of Two Cases.DiFranza LT et al. · Glomerular Dis · 2022 · PMID 37113492
  10. 10.Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events.Brahmer JR et al. · J Immunother Cancer · 2021 · PMID 34172516
  11. 11.Non-bacterial Cystitis With Increased Expression of Programmed Cell Death Ligand 1 in the Urothelium: An Unusual Immune-Related Adverse Event After Atezolizumab Administration for Metastatic Breast Cancer.Obayashi A et al. · Cureus · 2022 · PMID 35800819
  12. 12.A Case Report of Non-Bacterial Cystitis Caused by Immune Checkpoint Inhibitors.Zhu S et al. · Front Immunol · 2021 · PMID 35003107
  13. 13.Severe Hyponatremia Triggered by Immune Checkpoint Inhibitor Therapy in a Patient With Mulvihill-Smith Syndrome.Tavdy T et al. · AACE Clin Case Rep · 2024 · PMID 38799049

Case reports & series (2)

The weakest rung of clinical evidence — single-patient and small-series reports, strongest first. Each carries a heuristic strength grade (A Strong / B Moderate / C Limited) inferred from its abstract and journal, not a formal appraisal. Weigh well below the primary references above.

  1. C1.[B · Moderate]Overlap of Thrombotic Microangiopathy and Mesangial Proliferative Glomerulonephritis Caused by Combination Therapy with Atezolizumab and Bevacizumab.Horino T et al. · Intern Med · 2023 · PMID 35705272
  2. C2.[B · Moderate]Acute Tubulointerstitial Nephritis and Secondary Renal Amyloidosis: A Rare Complication of Atezolizumab.Ullah N et al. · Cureus · 2023 · PMID 38156149

Conference abstracts (2) — non-PubMed, no PMID

  1. A1.Rituximab in Atezolizumab-Associated IgA Vasculitis: A Bridge Between Renal Protection and Cancer TreatmentArriola Montenegro JJ, Riaza Ortiz C, Sethi S, Herrmann S · ASN Kidney Week 2025 · SA-PO0905A 75-year-old man on atezolizumab for metastatic small-cell carcinoma developed IgA vasculitis (skin) plus AKI, with kidney biopsy showing IgA nephropathy with focal necrotizing and crescentic glomerulonephritis and acute tubular injury — a glomerular/vasculitic ICI lesion distinct from the usual interstitial nephritis. Stopping atezolizumab with rituximab and a prednisone taper achieved renal recovery while preserving cancer-treatment options.
  2. A2.A case of atezolizumab-associated tubulointerstitial nephritisZakharova E, Makarova T, Vorobyeva O · Journal of Onco-Nephrology · DOI 10.1177/23993693221080479Acute tubulointerstitial nephritis attributed to the PD-L1 inhibitor atezolizumab — the classic checkpoint-inhibitor interstitial lesion. Published in the Journal of Onco-Nephrology (not PubMed-indexed).
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.