The kidney caught in the cytokine storm
CAR-T cytokine-release acute kidney injury
CAR-T cells cure by inflammation, and the same cytokine-release syndrome that fevers and drops the blood pressure starves the kidney of perfusion — so the acute kidney injury after CAR-T is mostly pre-renal and mostly reversible, yet the patients who develop it are the sicker ones, and they do worse.
- 10%
- AKI after CD19 CAR-TAny-grade AKI (5% grade ≥2) among 399 non-Hodgkin-lymphoma patients after CD19 CAR-T at a single center — evolution to CKD was rare and only 3 needed dialysis
- 72%
- of AKI was pre-renalPre-renal causes were the dominant mechanism in that cohort — hemodynamic injury from the cytokine-release syndrome, not a direct tubular poison
- 18%
- AKI in a second cohortAKI in 155 large-B-cell-lymphoma patients (median 9.5 days to peak creatinine); volume depletion was the leading cause (71%) and 25 of 28 recovered kidney function
- 34%
- AKI in ICU patientsAKI among 119 CAR-T patients admitted to intensive care — grade ≥3 CRS and elevated LDH independently predicted it, and KDIGO ≥2 AKI predicted hospital mortality
- reversible
- but marks a sicker patientRenal recovery is the rule and dialysis is uncommon, yet developing AKI after CAR-T is associated with inferior progression-free and overall survival
Teaching case · illustrative composite, not a real patient
A 64-year-old woman with relapsed large B-cell lymphoma receives axicabtagene ciloleucel. On day 4 she develops grade 2 cytokine-release syndrome — fever to 39.5°C, blood pressure 88/50, and tachycardia. Her creatinine, normal at infusion, has risen to 1.8 mg/dL; urine output has fallen and she has not been drinking well. There is no significant proteinuria and the sediment is bland.
The rising creatinine with hypotension and reduced intake during active CRS is read as a pre-renal acute kidney injury driven by the cytokine-release syndrome rather than a direct tubular toxin. The CRS is treated — tocilizumab plus supportive care — and perfusion is restored with careful fluids and hemodynamic support; tumor lysis is checked for and covered. As the CRS resolves over the next several days, urine output and creatinine improve back toward baseline. Because AKI here flags a sicker course, her renal function and survival are watched closely rather than considered incidental.
Teaching point — Acute kidney injury after CAR-T is, above all, a hemodynamic problem: the cytokine-release syndrome causes fever, vasodilation, capillary leak, and hypotension, and the resulting renal hypoperfusion is the leading cause — pre-renal / volume-depletion mechanisms account for roughly 70% of cases across cohorts. Tumor lysis from the rapid tumor kill can add a second hit. The injury is usually mild and reversible and rarely needs dialysis, so the management is treating the CRS and protecting perfusion — but developing AKI identifies a patient with more inflammation and worse survival, so it is a marker to act on, not to wave off. Higher CRS grade, high LDH/ferritin, low albumin, and baseline CKD mark the highest-risk patients.
How it happens
The pathophysiology as a cascade — select a step to follow the mechanism.
How we learned it
- 2019
The ASTCT publishes consensus grading for cytokine-release syndrome and immune-effector-cell neurotoxicity, standardizing how the CAR-T toxicity that drives the kidney injury is defined and graded.
Gave the field a shared language for CRS severity — the exposure variable that later cohorts would tie to AKI.
PMID 30592986 - 2021
Kanduri and colleagues publish a systematic review of the incidence and risk factors of AKI across CAR-T cohorts, establishing kidney injury as a recognized — and largely reversible — complication of cellular therapy.
Consolidated scattered reports into the first systematic view of CAR-T-associated AKI.
PMID 34013119 - 2024
Vincendeau et al. study 119 CAR-T patients admitted to intensive care: 34% developed AKI, grade ≥3 CRS and elevated LDH independently predicted it, and KDIGO ≥2 AKI was an independent risk factor for hospital mortality.
Tied AKI to CRS severity and to death in the sickest CAR-T patients, and flagged persistent CKD in survivors.
PMID 38915438 - 2025
Boardman et al. combine an FDA adverse-event signal across ~6,000 CAR-T reports with a 399-patient CD19 cohort: 10% developed AKI (5% grade ≥2), pre-renal causes predominated (72%), and inflammatory markers (IL-6, TNF-α) tracked with risk.
The largest single-center characterization — pre-renal predominance, an inflammatory signature, and a link between AKI and worse survival.
PMID 39568416 - 2025
Sharp et al. report 155 large-B-cell-lymphoma patients: 18% developed AKI (median 9.5 days to peak creatinine), volume depletion was the leading cause, baseline CKD and axicabtagene ciloleucel were risk factors, and AKI was associated with inferior survival.
Confirmed the pre-renal-dominant, mostly-reversible pattern and its adverse prognostic weight in a second large cohort.
PMID 40589093
The landmark studies
Predictors and implications of renal injury after CD19 CAR T-cell therapy
Boardman AP, et al. · Haematologica 2025 · PMID 39568416
AKI is a common CAR-T toxicity, predominantly pre-renal, linked to systemic inflammation (IL-6, TNF-α, low albumin) and to inferior overall survival, though progression to CKD is rare.
AKI 10% any grade, 5% grade ≥2; pre-renal 72%; 3 patients needed dialysis; CRS/neurotoxicity and high inflammatory cytokines predicted AKI
AKI after CAR-T therapy is associated with inferior survival in relapsed/refractory large B-cell lymphoma
Sharp J, et al. · Br J Haematol 2025 · PMID 40589093
AKI was common, driven mainly by volume depletion, largely reversible, and independently more likely with baseline CKD and axicabtagene ciloleucel — but it carried worse progression-free and overall survival.
AKI 28/155 (18%); median 9.5 d to peak creatinine; volume depletion 71%, CRS 18%, TLS 4%; RRT 2.6%; 25/28 recovered (median 14 d); CKD aRR 3.5, axi-cel aRR 2.1
Acute kidney injury after CAR-T cell therapy: clinical patterns, management, and outcomes
Vincendeau M, et al. · Clin Kidney J 2024 · PMID 38915438
In critically ill CAR-T patients, AKI was frequent, driven by severe CRS and high LDH, predicted hospital mortality, and left a high burden of CKD in survivors.
AKI 41/119 (34%); grade ≥3 CRS OR 1.20 and LDH OR 1.44 for AKI; KDIGO ≥2 AKI mortality OR 1.50; CKD 75% at 6 mo, 67% at 1 yr
ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells
Lee DW, et al. · Biol Blood Marrow Transplant 2019 · PMID 30592986
Defined a uniform grading of CRS and ICANS by immune-effector-cell therapies — the severity scale that cohorts tie to the risk of acute kidney injury.
CRS graded 1–4 by fever, hypotension, and hypoxia; the higher-grade CRS that drives hemodynamic AKI is grade ≥3
What the data says now
AKI in a large-B-cell-lymphoma cohort
155 patients, median 9.5 days to peak creatinine
PMID 40589093How it's managed
- 1
Treat the CRS and protect perfusion
Because most CAR-T AKI is pre-renal, the kidney's best defense is prompt cytokine-release-syndrome management (tocilizumab and supportive care) together with careful volume resuscitation and hemodynamic support to restore renal perfusion.
Largest cohort — pre-renal predominance (72%), inflammation-linked risk · PMID 39568416
- 2
Anticipate and cover tumor lysis
Risk-stratify for tumor lysis syndrome before and during CAR-T — hydration and urate-lowering — since the rapid tumor kill can precipitate it and add urate/phosphate and electrolyte injury to the hemodynamic insult.
Cohort — TLS among the identified AKI etiologies · PMID 40589093
- 3
Monitor the high-risk patient through the CRS window
Baseline CKD, high tumor burden with elevated LDH/ferritin, low albumin, grade ≥3 CRS, and axicabtagene ciloleucel mark higher-risk patients; check creatinine closely through the CRS window, where the creatinine typically peaks around 9–10 days after infusion.
Cohorts — CKD aRR 3.5 and axi-cel aRR 2.1; CRS grade and LDH predictive · PMID 40589093
- 4
Expect recovery — but treat AKI as a red flag
Most patients recover renal function (e.g. 25 of 28 in one cohort) and dialysis is uncommon, yet AKI is associated with worse survival and, in ICU-level cases, persistent CKD — so it is a prognostic marker to act on, not an incidental lab.
Cohorts — 25/28 recovery yet inferior PFS/OS; high CKD in ICU survivors · PMID 38915438
What the guidelines say
Society and consensus recommendations addressing this syndrome, each with its key recommendation quoted verbatim.
Every citation on this page is a real, PubMed-verified reference. The teaching case is an illustrative composite, not a real patient. Medical-education content — not medical advice.