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CD19 CAR-T cell therapy

Lisocabtagene maraleucel

Breyanzi · LISO

CD19 CAR-T cell therapy · approved 2021 · 8 references

The CD19 CAR-T with the lowest severe-CRS rate of its class — so its kidney story is the same cytokine-and-volume prerenal hit, just dialed down.

Signature injury
Prerenal / Hemodynamic AKI
Severity
Moderate
Reversibility
Reversible
Onset
Early — within the first days to about two weeks after the single infusion, tracking the CRS window. In a 155-patient cohort the median time to peak creatinine was 9.5 days (range 3-30); pediatric CD19 CAR-T AKI all occurred within 14 days; TLS-associated injury clusters around days 3-9.

Signature kidney injury & incidence

Prerenal / Hemodynamic AKI — representative incidence ~22%.

No liso-cel-specific AKI rate is established — the renal literature pools across CD19 and BCMA CAR-T products. In a meta-analysis of 15 studies (694 patients), 22% developed AKI, most KDIGO stage 1 and reversible (Yang, Clin Immunol 2024). Single-center CAR-T cohorts report roughly 18-34% (Sharp, Br J Haematol 2025 — 18%; Gupta, Am J Kidney Dis 2020 — 19%; Ahmed, Clin Lymphoma Myeloma Leuk 2022 — 29%; Vincendeau/Zafrani ICU cohort, Clin Kidney J 2024 — 34%), with focused reviews quoting ~30% (Khan, Clin Hematol Int 2023). Because liso-cel carries the lowest grade ≥3 CRS of the CD19 CAR-Ts (2% in TRANSCEND NHL 001) and CRS severity is the dominant AKI driver, its CRS-related renal burden is expected to track at the lower end — but this is inference, not a measured liso-cel figure.

Source: Yang et al., Clin Immunol 2024 (pooled cross-CAR-T meta-analysis; not liso-cel-specific)

Reported injury signatures: Prerenal / Hemodynamic AKI, Acute Tubular Necrosis, Crystal / Obstructive Nephropathy, Electrolyte Disturbance.

Renal toxicity profile

  1. Prerenal / Hemodynamic AKIPrimary
  2. Acute Tubular NecrosisSecondary
  3. Crystal / Obstructive NephropathySecondary
  4. Electrolyte DisturbanceSecondary

Onset timing & rechallenge

Subacute (~1–6 weeks) — AKI tracks the CRS window in the first days to ~2 weeks after the single infusion; in a 155-patient cohort median time to peak creatinine was ~9.5 days (range 3-30).

Mechanism of kidney injury

The signature injury is hemodynamic and cytokine-mediated rather than a direct tubular toxin. Cytokine release syndrome (CRS) — an IL-6/IFN-γ-driven inflammatory surge as the CAR-T cells engage CD19+ targets — produces vasodilation, capillary leak, fever and hypotension, causing intravascular volume depletion and prerenal AKI that can progress to ischemic acute tubular necrosis if hypoperfusion persists; grade ≥3 CRS is the most consistently identified risk factor across cohorts. Rapid tumor cytolysis can precipitate tumor lysis syndrome (TLS) with uric-acid and calcium-phosphate crystal deposition/obstruction in the tubular lumen. The fludarabine/cyclophosphamide lymphodepletion adds prerenal and tubular stress (fludarabine is renally cleared), high peak inflammatory cytokines correlate with AKI, and neutropenic sepsis contributes ischemic injury; direct CAR-T renal infiltration is described but rare. Electrolyte wasting (hypophosphatemia, hypokalemia, hyponatremia) accompanies the systemic inflammatory/hemodynamic state and is more common than frank AKI.

Clinical presentation

A creatinine rise in the first days-to-weeks after infusion, typically coinciding with fever, tachycardia and hypotension of CRS. Early physiology is prerenal (oliguria, low fractional excretion of sodium, brisk response to fluids); persistent hypoperfusion evolves to ATN with muddy-brown granular casts. Electrolyte derangements are near-universal — hypophosphatemia (~75%), hypokalemia (~56%) and hyponatremia (~51%) in the DLBCL CAR-T series (Gupta, Am J Kidney Dis 2020). When TLS is present, hyperuricemia, hyperphosphatemia, hyperkalemia and a rising LDH appear.

Management

Largely supportive and directed at the underlying CRS. Treat CRS promptly with tocilizumab (and corticosteroids for higher grades), which relieves the capillary-leak hypotension that drives most AKI; give judicious IV fluids and, if needed, vasopressors for prerenal/distributive hypotension; support ischemic ATN. Apply standard TLS measures (aggressive hydration, rasburicase/allopurinol, electrolyte correction) when tumor lysis is present. Hold nephrotoxins and treat neutropenic sepsis. Most AKI is stage 1 and recovers; across pooled cohorts only ~10% required renal replacement therapy and renal recovery is the rule (e.g., 25/28 recovered by a median of 14 days in one series). AKI nonetheless marks a sicker, higher-inflammation course and is associated with worse survival.

Risk factors

  • High-grade (grade ≥3) cytokine release syndrome — the most consistent driver
  • High tumor burden / elevated LDH and ferritin (inflammatory and TLS risk)
  • Baseline chronic kidney disease or elevated pre-infusion creatinine
  • ICU admission and severe multi-organ CRS
  • Concomitant nephrotoxins and neutropenic sepsis
  • Higher-grade ICANS (neurotoxicity) in some cohorts
  • Prior autologous/allogeneic stem-cell transplant; older age
  • Product choice: axicabtagene ciloleucel carried higher AKI risk than other CD19 products in at least one comparative cohort

Prevention

  • Risk-stratify for TLS (bulky/high-count disease): hydration plus allopurinol or rasburicase before and through infusion
  • Recognize and treat CRS early (tocilizumab ± corticosteroids) to abort the hemodynamic driver of AKI
  • Optimize volume and avoid nephrotoxins (contrast, aminoglycosides, NSAIDs) around infusion
  • Renally dose-reduce fludarabine in impaired kidney function — it accumulates and adds tubular stress
  • Daily kidney-function and electrolyte surveillance through the first 2-4 weeks

Renal dose adjustment

Liso-cel is a one-time, per-kilogram CAR+ T-cell dose with no renal dose adjustment for the cell product itself and no CrCl threshold on the label. The renal-relevant lever is the lymphodepletion regimen: fludarabine is renally cleared and should be dose-reduced in kidney impairment to limit accumulation and tubular toxicity. CAR-T has been delivered feasibly in patients with reduced renal function and even end-stage renal disease with careful lymphodepletion planning, and baseline renal impairment did not worsen renal or efficacy outcomes in a matched cohort (Wood, Transplant Cell Ther 2022).

Dialyzability & ESKD dosing

Not applicable to the living CAR-T cells, which are not removed by dialysis. Circulating cytokines are only partially cleared by extracorporeal modalities and this is not standard therapy. Fludarabine's active metabolite (in the conditioning regimen) is partly dialyzable but timing is not standardized. CAR-T therapy has been administered successfully to dialysis-dependent patients, so ESRD is not an absolute contraindication (Wood, Transplant Cell Ther 2022; Khan, Clin Hematol Int 2023).

Differential diagnosis

Distinguish CRS-driven prerenal AKI / ischemic ATN (hypotension, fever, timed to the CRS window) from TLS crystal nephropathy (hyperuricemia/hyperphosphatemia, rising LDH, days 3-9), from fludarabine/cyclophosphamide tubular effects and hemorrhagic cystitis, from contrast- or antimicrobial-related nephrotoxicity, and from neutropenic-sepsis ATN. Timing relative to CRS and the electrolyte/urate pattern usually identify the dominant mechanism. Across products, axicabtagene ciloleucel (axi-cel) carries a higher CRS and AKI burden than liso-cel or tisagenlecleucel (tisa-cel), whose 4-1BB constructs produce milder cytokine kinetics.

Monitoring

  • Daily serum creatinine, urine output and weight through the first 2-4 weeks post-infusion
  • CRS grade and vital signs (temperature, blood pressure, heart rate) — the leading AKI predictor
  • Electrolytes: phosphate, potassium, sodium and magnesium (derangements are near-universal)
  • TLS panel (uric acid, phosphate, potassium, calcium, LDH) in high-tumor-burden patients
  • Inflammatory markers (ferritin, CRP) as severity/AKI-risk surrogates

Key trials & series

  • TRANSCEND NHL 001 (Abramson, Lancet 2020) — registrational phase 1 in relapsed/refractory large B-cell lymphoma; grade ≥3 CRS in only 2% and grade ≥3 neurological events in 10%, the low-CRS profile that frames liso-cel's comparatively modest CRS-driven AKI risk
  • Gupta, Am J Kidney Dis 2020 — foundational two-center CAR-T (axi-cel/tisa-cel) nephrotoxicity series: AKI 19% (prerenal and ATN) with the electrolyte-abnormality spectrum
  • Sharp, Br J Haematol 2025 — 155-patient DLBCL cohort defining onset, causes (volume depletion 71%, CRS 18%, TLS 4%) and the axi-cel-versus-other-product risk difference; AKI linked to inferior survival
  • Yang, Clin Immunol 2024 — meta-analysis (694 patients) anchoring the ~22% pooled AKI incidence

Clinical pearls

  • Liso-cel's grade ≥3 CRS rate is the lowest of the CD19 CAR-Ts (2% in TRANSCEND), so its CRS-driven AKI should track lower — but the mechanism is identical to axi-cel/tisa-cel, just less intense.
  • Most post-CAR-T AKI is prerenal from CRS capillary-leak hypotension and reverses as CRS is controlled with tocilizumab — treat the cytokine storm, not just the creatinine.
  • Electrolyte derangements (hypophosphatemia, hypokalemia, hyponatremia) are more common than frank AKI and are easy to miss.
  • AKI after CAR-T is a red flag for a severe-inflammation phenotype and is associated with worse progression-free and overall survival — it is prognostic, not merely renal.
  • Dialysis dependence and reduced eGFR are not absolute contraindications: CAR-T has been delivered safely with careful, dose-adjusted lymphodepletion planning.

Anticancer mechanism

Autologous CD19-directed chimeric antigen receptor (CAR) T-cell product with 4-1BB costimulation, manufactured and infused at a defined 1:1 CD4:CD8 composition after fludarabine/cyclophosphamide lymphodepletion. The CAR redirects the patient's T cells to CD19 on malignant B cells, driving T-cell activation, proliferation and cytolysis of the tumor. It is a one-time single infusion, not a chronically dosed drug.

Note

Liso-cel-specific renal data are sparse; the incidence figures and mechanisms are drawn from the pooled CD19/BCMA CAR-T nephrotoxicity literature and are hedged accordingly. The signature signal is CRS-driven prerenal/hemodynamic AKI with TLS crystal nephropathy as the second pathway, both concentrated in the first two weeks and usually reversible. Reversibility is coded 'reversible' to reflect the dominant course (most cohorts show renal recovery), though a sicker ICU subgroup showed CKD sequelae at 6-12 months.

Guidelines & consensus

  • TLS Expert Panel (2008) — Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based reviewPrevention is the best management: hydration plus prophylactic rasburicase for high-risk patients, hydration plus allopurinol or rasburicase for intermediate-risk, and monitoring for low-risk; for established TLS add aggressive hydration and diuresis plus allopurinol or rasburicase for hyperuricemia. Urinary alkalinization is NOT recommended.J Clin Oncol · PMID 18509186
  • TLS Consensus Panel (2010) — Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensusStratify each patient as low/intermediate/high TLS risk using tumor type, bulk/stage, proliferation rate, baseline laboratory TLS, and renal impairment/involvement, then match prophylaxis intensity (monitoring vs allopurinol vs rasburicase) to the assigned risk level.Br J Haematol · PMID 20331465
  • BCSH (2015) — Guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies on behalf of the British Committee for Standards in HaematologyRisk-adapted prophylaxis and management of TLS in haematological malignancy: hydration with allopurinol for lower-risk and rasburicase for high-risk patients, with monitoring of electrolytes and renal function to prevent and treat AKI.Br J Haematol · PMID 25876990
  • Cairo-Bishop (2004) — Tumour lysis syndrome: new therapeutic strategies and classificationDefines the Cairo-Bishop criteria distinguishing laboratory TLS (>=2 metabolic abnormalities: hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia within 3 days before to 7 days after therapy) from clinical TLS (laboratory TLS plus AKI, cardiac arrhythmia, or seizure), with a severity grading scheme adopted by subsequent guidelines.Br J Haematol · PMID 15384972
  • ASTCT (2019) — ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector CellsGrade CRS by fever, hypotension and hypoxia (grades 1-4) and grade ICANS using the ICE/encephalopathy score plus level of consciousness, seizures, motor findings and raised intracranial pressure/edema; this is the standard severity framework that triggers tocilizumab and corticosteroid escalation in CAR-T and bispecific antibody toxicity (the Lee 2019 consensus).Biol Blood Marrow Transplant · PMID 30592986
  • 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 (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

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

  1. 1.Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study.Abramson JS et al. · Lancet · 2020 · PMID 32888407
  2. 2.Acute Kidney Injury and Electrolyte Abnormalities After Chimeric Antigen Receptor T-Cell (CAR-T) Therapy for Diffuse Large B-Cell Lymphoma.Gupta S et al. · Am J Kidney Dis · 2020 · PMID 31973908
  3. 3.Acute kidney injury following chimeric antigen receptor T-cell therapy: Epidemiology, mechanism and prognosis.Yang Y et al. · Clin Immunol · 2024 · PMID 38996858
  4. 4.Acute kidney injury after chimeric antigen receptor T-cell therapy is associated with inferior survival in patients with relapsed/refractory large B-cell lymphoma.Sharp J et al. · Br J Haematol · 2025 · PMID 40589093
  5. 5.Acute kidney injury after CAR-T cell therapy: exploring clinical patterns, management, and outcomes.Vincendeau M et al. · Clin Kidney J · 2024 · PMID 38915438
  6. 6.Impact of Chronic Kidney Disease and Acute Kidney Injury on Safety and Outcomes of CAR T-Cell Therapy in Lymphoma Patients.Ahmed G et al. · Clin Lymphoma Myeloma Leuk · 2022 · PMID 35934632
  7. 7.Outcomes of CD19-Targeted Chimeric Antigen Receptor T Cell Therapy for Patients with Reduced Renal Function Including Dialysis.Wood AC et al. · Transplant Cell Ther · 2022 · PMID 36174934
  8. 8.Safety of CAR-T Cell Therapy in Patients With Renal Failure/Acute Kidney Injury: Focused Review.Khan I et al. · Clin Hematol Int · 2023 · PMID 37010812
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.