The Injury Atlas
XTAL
Crystal / Obstructive Nephropathy
Intratubular precipitation of drug or metabolite — high-dose methotrexate and tumor lysis crystals.
15agents
Severity mix
Severe· 1Moderate· 8Mild· 6
Reversibility
Partially reversible· 5Reversible· 10
Signature offenders
5Agents for which crystal / obstructive nephropathy is the defining renal lesion.
VenetoclaxAcute — typically within hours to days of each dose-escalation step during the ramp-up.Tumor lysis syndrome is the defining renal risk, concentrated during the weekly dose ramp-up. Early-development unmitigated dosing caused fatal TLS; with the mandated 5-week ramp-up and risk-stratified prophylaxis, clinical TLS fell to ~3% (e.g., grade 3/4 laboratory TLS 3.1% in MURANO), and structured protocols can drive it near zero.SevereMethotrexate (high-dose)Acute — within hours to days of infusion.AKI in ~2–12% of high-dose courses.ModeratePralatrexateDuring treatment cycles; exposure-dependent.Drug-specific renal-injury rates are not well quantified; renal handling resembles methotrexate, and severe renal impairment substantially increases pralatrexate exposure and toxicity (more cytopenias/mucositis). Antifolate crystal-related tubular injury is therefore a class-based, conservative concern rather than a measured rate.ModerateRituximabAcute — typically within hours to a few days of the first infusion.Clinical tumor lysis with the first cycle is uncommon with modern prophylaxis (~1% clinical TLS in a real-world fractionated-rituximab aggressive-B-NHL series), but risk rises sharply with bulky disease, high LDH and Burkitt histology.ModerateObinutuzumabAcute — within hours to days of the first (split) dose.Carries a notably high tumor-lysis risk in CLL — among the highest of the anti-CD20 agents — particularly with the first (split) infusion in high-burden disease (the CLL11 trial enrolled patients with CrCl 30–69 mL/min and saw higher infusion reactions/TLS). Direct nephrotoxicity is case-level.Moderate
Also associated
10Agents that cause crystal / obstructive nephropathy as a secondary pattern alongside a different signature lesion.
CAR-T Cell TherapyAcute — within the CRS window (first days–weeks).AKI ~5–33% across cohorts (commonly ~10–30%), mostly mild and reversible.ModerateCytarabineHours to days after initiating therapy in high-burden disease.Intrinsic tubular nephrotoxicity is uncommon; the major renal risk is AKI from tumor lysis syndrome during leukemia/lymphoma cytoreduction, reported at case and series level including fatal TLS. Direct cytarabine-nephrotoxicity primary literature is genuinely sparse.ModerateInfigratinibEarly (first cycle); reversible and dose-dependent, normalizing during the 7-day off-drug interval of the 21-on/7-off cycle.Hyperphosphatemia is the most common adverse event and the defining FGFR class effect — it occurred in 83 of 108 patients (~77%, any grade) in the pivotal trial. Infigratinib-specific nephrocalcinosis/calciphylaxis rates are not quantified (case reports/series only).ModerateRaltitrexedWithin the first one to two cycles, often heralded by exaggerated systemic toxicity in patients with reduced GFR.Not well quantified as a discrete renal endpoint. Raltitrexed is substantially renally eliminated: in a dedicated pharmacokinetic study, mild-to-moderate renal impairment roughly doubled drug exposure (AUC ratio ~2.0) and nearly doubled terminal half-life, with severe/grade 3-4 toxicity and adverse-event hospitalizations more frequent in the impaired group. The class precedent CB3717, raltitrexed's quinazoline antifolate forerunner, was withdrawn from development specifically because of crystal-related nephrotoxicity.ModerateHydroxyureaVery early (within 12-24 hours of high-dose treatment).Acute tumor lysis syndrome from hydroxyurea is rare and reported at case level, almost exclusively with high-dose cytoreduction of leukemias carrying a high blast burden. Standard-dose hydroxyurea is not characteristically nephrotoxic.MildEtoposideTLS typically within hours to a few days of starting cytotoxic therapy in sensitive tumors; exposure-related myelosuppression accrues over cycles.Etoposide is renally cleared (~30-40% as unchanged drug, so dose-adjust in renal impairment) and is a frequent component of regimens for bulky, rapidly proliferating tumors that can trigger tumor lysis syndrome (TLS). Direct etoposide nephrotoxicity is not a recognized signal; TLS-related AKI risk depends on tumor burden and tumor type rather than a per-drug rate.MildIbritumomab tiuxetanTLS is early (hours to days); cytopenias are delayed (weeks).Direct renal radiation toxicity is essentially negligible — yttrium-90 is a pure beta-emitter and the kidney is not a critical organ on dosimetry; the dose-limiting toxicity is delayed myelosuppression. The renal hazard is indirect tumor lysis syndrome (TLS) in bulky/high-burden disease; a drug-specific TLS rate is not well quantified and is rare.MildCladribineTumor-lysis AKI is acute (24-72 h); high-dose sensorimotor neuropathy is delayed (weeks).At standard hairy-cell-leukemia doses cladribine is renally quiet; clinically significant nephrotoxicity is uncommon and dose-related, worst at historical high investigational doses. The dominant renal hazard is tumor lysis syndrome in bulky/leukocytotic disease, reported at the case level rather than as a population incidence.MildMitoxantroneTumor lysis hours to days post-infusion.Direct nephrotoxicity is low and not quantified; the principal renal risk is tumor lysis syndrome when used in bulky/rapidly proliferating hematologic malignancies. Benign blue-green discoloration of urine/sclera is expected (the anthracenedione chromophore), not injury.MildIdarubicinHours to days after starting induction.Minimal intrinsic nephrotoxicity; the dominant renal threat is tumor lysis syndrome in acute leukemia. In one inv(16) AML induction cohort tumor-lysis AKI occurred in ~6%, with some requiring hemodialysis; a general drug-specific AKI rate is not quantified.Mild