Lisocabtagene maraleucel

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.

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.

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.Lesion-level management framework

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).

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).

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.