The Injury Atlas Does the kidney recover? Cross-drug outcomesRepresentative per-agent crystal / obstructive nephropathy incidence where a published figure is citable — open an agent's name for its profile and cited source, or hover its dot for the source inline. Agents without a citable figure are omitted; a tier without a number is not the same as a low number.
XTAL
Crystal / Obstructive Nephropathy
Intratubular precipitation of drug or metabolite — high-dose methotrexate and tumor lysis crystals.
18signature agents
Agents’ overall severity
Each agent’s whole-drug severity grade, not the severity of this lesion specifically — an agent whose signature injury is elsewhere can still be graded severe here.
Severe· 2Moderate· 8Mild· 8
Agents’ overall reversibility
Partially reversible· 4Variable· 2Reversible· 12
Agents’ onset window
How soon each agent’s kidney toxicity typically appears — a whole-drug tempo, not specific to this lesion.
Hyperacute (<24 h)· 1Acute (days)· 15Variable· 2
Real-world reporting for this lesion
FAERS across all lesions →Agents with a disproportionate FAERS reporting signal for crystal / obstructive nephropathy (reporting odds ratio with a 95% CI lower bound above 1) — a spontaneous-reporting signal, not incidence or proven causation. FAERS carries reporting and indication biases and has no denominator.
7Corroborated
Documented in the atlas profile and carrying a FAERS signal — the strongest claim the atlas makes.
31Documented, FAERS-silent
Documented in a profile with no reporting signal. Mostly expected: naming this lesion on a report can require a biopsy, and silence is not evidence against the literature.
42Not attributable
A real reporting signal that is not evidence for this drug-lesion pair: no MedDRA term names it, the naming subset asked alone came back flat, or the 2026-08 review attributed the reporting to the population, co-therapy, or class-level literature.
0Reported by name
The terms that name this lesion are disproportionate, but no profile documents it for that agent. Most are echoed by a sibling agent in the same class. Leads for review, never lesions the atlas claims.
AbirateroneAcalabrutinibBendamustineBevacizumabBicalutamideCabazitaxelCapecitabineCarboplatinCisplatinCladribineDarolutamideDenosumabEnfortumab vedotinEnzalutamideEverolimusGemcitabineHydroxyureaIbandronateIbrutinibImatinibIrinotecanLanreotideLeuprolideMethotrexate (high-dose)Mitomycin CNaxitamabNilotinibNintedanibNiraparibOctreotidePacritinibPamidronatePexidartinibPolatuzumab vedotinRadium-223 dichlorideRegorafenibRelacorilantRibociclibRituximabRuxolitinibSelumetinibSonidegibTamoxifenTisotumab vedotinTopotecanTretinoin (ATRA)Trifluridine/tipiracilVandetanibZoledronic acid
49 agents with a significant XTAL reporting signal.
Management approach
Full framework →Prevent precipitation; for established high-dose methotrexate toxicity, glucarpidase rapidly cleaves circulating drug.
Drug-level levers
- Hold further methotrexate until clearance and renal recovery.
- For tumor-lysis urate nephropathy, prophylaxis is the key lever.
Pharmacologic toolkit
- Hydration + urinary alkalinization — Vigorous IV hydration and urine alkalinization keep methotrexate soluble.
- Leucovorin rescue — High-dose leucovorin guided by serial methotrexate levels.
- Glucarpidase — For delayed methotrexate clearance / AKI: recombinant carboxypeptidase-G2 cleaves plasma methotrexate, usually allowing recovery without dialysis.
- Rasburicase (tumor lysis) — For urate crystal nephropathy from tumor lysis, with hydration; also manage hyperphosphatemia.
When to biopsy
Not indicated — the diagnosis is clinical and biochemical (drug levels, uric acid, urine crystals).
Monitoring
- · Serial methotrexate levels, creatinine, urine pH
- · Uric acid, phosphate, potassium (tumor lysis)
Educational use only. Educational synthesis of the published literature — not a treatment protocol, dosing guide, or medical advice. Regimens and agents shown are illustrative of what the literature describes; verify against current guidelines (ASON / KDIGO / ASCO / NCCN) and individualize to the patient. Using this site creates no clinician–patient relationship.
What the guidelines say
All guidelines →Society and consensus recommendations that speak to crystal / obstructive nephropathy.
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.
ADQIConventional cytotoxic chemotherapy-associated nephrotoxicity: consensus report of the 34th Acute Disease Quality Initiative (ADQI) WorkgroupKidney Int 2026 · PMID 41881107Cisplatin is identified as a leading cytotoxic nephrotoxin; the workgroup details preventive measures (adequate isotonic hydration, correction of volume depletion, avoidance of concurrent nephrotoxins, attention to electrolyte/magnesium wasting) and management of cisplatin-associated AKI, with a research agenda for knowledge gaps.Intl. Expert PanelConsensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate ClearanceOncologist 2018 · PMID 29079637For HDMTX infusions <=24 h, glucarpidase may be indicated when the methotrexate concentration is >30 uM at 36 h, >10 uM at 42 h, or >5 uM at 48 h together with a significantly elevated serum creatinine (indicating HDMTX-induced AKI); administer optimally within 48-60 h of infusion start, as it is far less effective beyond 60 h.
Cited incidence across agents
Where the literature gives a representative crystal / obstructive nephropathy figure, the agents ranked highest first. Hover a dot for its cited note.
Offending agents
Signature offenders
18Agents 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, grade 3/4 laboratory TLS fell to 3.1% (MURANO), with clinical TLS rarer still, and structured protocols can drive it near zero.SevereSonrotoclaxEarly and dose-timed. Tumor lysis clusters around the initial ramp-up doses and the first full target dose — the window of maximal, synchronous cytoreduction — typically developing within about 12–72 hours of an effective dose. Kidney injury therefore concentrates in the first days of treatment and at each dose escalation, with risk falling once the bulk of disease has been debulked and full dosing is tolerated. This front-loaded timing is the entire rationale for the stepwise ramp-up.No clean, drug-specific published incidence of sonrotoclax acute kidney injury exists as a discrete endpoint; the renal risk is inferred from the tumor-lysis physiology that defines potent BCL-2 inhibition. The precedent is venetoclax, where laboratory and clinical tumor lysis syndrome were frequent enough — including early fatal cases — that a mandatory ramp-up schedule, risk-stratified prophylaxis, and inpatient monitoring became standard of care (Tambaro & Wierda, Lancet Haematol 2020). Because sonrotoclax is more potent than venetoclax and induces apoptosis faster, its tumor-lysis potential is at least as high, which is precisely why its development and label built in a stepwise dose ramp-up from the outset. Reported drug-specific AKI rates should not be overstated until mature peer-reviewed trial safety data are published. Reported rate: tumor lysis syndrome in 7% — 125 patients with BTK-inhibitor-pretreated relapsed/refractory mantle cell lymphoma enrolled in the global phase I/II… (Eyre 2026, PMID 42385124).SevereMethotrexate (high-dose)Acute — within hours to days of infusion.AKI in ~2–12% of patients and 2–39% of high-dose courses, with severe (AKIN grade ≥2) nephrotoxicity in ~2% of courses.ModerateBendamustineTLS within hours to days of the first cycle; TMA delayed and rare.Direct nephrotoxicity is uncommon; the principal renal risk is acute kidney injury from tumor lysis syndrome in high-burden disease, classically during the first cycle. TLS with renal failure is documented from the first reported case onward; TMA is rare and case-level.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.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.ModerateFludarabineTLS within days of starting therapy; systemic toxicity accrues with impaired clearance.Direct nephrotoxicity is uncommon; the chief renal risks are tumor-lysis-syndrome AKI during cytoreduction and increased systemic toxicity when the renally cleared drug accumulates in renal impairment. About 60% of the active metabolite 2-F-ara-A is renally eliminated, so renal function directly drives exposure. Reported rate: tumor lysis syndrome in 0.33% — 6,137 patients with intermediate- or high-risk advanced chronic lymphocytic leukemia treated with fludarabine 20-40… (Cheson 1998, PMID 9667245).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 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.ModerateOdronextamabEarly and dose-timed. Both CRS and TLS cluster around cycle 1 — the step-up doses and the first full target dose — which is precisely why a graded step-up schedule and admission/monitoring windows are built into administration. CRS usually begins within hours to 1-2 days of a dose; TLS classically develops within about 12-72 hours of initiating effective cytoreduction. Kidney injury therefore concentrates in the first days to first couple of weeks of treatment, with risk falling once the initial tumor burden has been debulked and full dosing is tolerated.There is no clean, drug-specific published incidence of odronextamab acute kidney injury as a discrete endpoint; the renal risk is inferred from its cytokine-release and tumor-lysis complications, which the ELM trials do quantify. In the phase 1 ELM-1 trial (Bannerji, Lancet Haematol 2022; n=145 heavily pretreated relapsed/refractory B-NHL), grade >=3 hypophosphatemia occurred in 27/145 (19%), cytokine release syndrome was the single most common serious adverse event (41/145, 28%), and one of four treatment-related deaths was due to tumor-lysis syndrome. With the optimized 0.7/4/20 mg step-up in the phase 2 ELM-2 cohorts, any-grade CRS was 53.3% (grade >=3 1.7%) in DLBCL (Kim WS, Nat Cancer 2025) and 56% (grade >=3 1.7%) in follicular lymphoma (Kim TM, Ann Oncol 2024) — CRS remained the dominant treatment-emergent adverse event even after mitigation. Kidney injury in this setting rides on these events (CRS hemodynamics, TLS crystal nephropathy, sepsis) rather than on any intrinsic tubular toxicity, so exact AKI rates are not well established and should not be overstated. Reported rate: grade >=3 hypophosphatemia in 19% — 145 heavily pretreated patients with CD20-positive relapsed or refractory B-cell non-Hodgkin lymphoma receiving… (Bannerji 2022, PMID 35366963).ModerateDecitabineEarly after a treatment cycle (days) for tumor lysis; TMA over weeks.Tumor lysis syndrome with AKI is a recognized but uncommon complication when bulky/proliferative disease responds; renal incidence specific to decitabine is not well quantified (case-level). Rare biopsy-proven renal thrombotic microangiopathy has been reported.MildHydroxyureaVery 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.MildNelarabineEarly after treatment initiation (days).Tumor lysis syndrome with attendant AKI is a labeled risk when bulky T-ALL responds rapidly; drug-specific renal incidence is not well quantified (case-level). The dose-limiting and most feared toxicity is neurologic, not renal.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.MildPirtobrutinibEarly after initiation in high-burden disease (first cycle); TLS is usually a single early event.Direct nephrotoxicity is not characteristic. Tumor lysis syndrome is an identified risk when rapidly debulking high-burden lymphoid malignancy; renal-specific incidence is low and not well quantified. BTK inhibitors as a class are also associated with hypertension and bleeding/atrial fibrillation (non-renal).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 114 consecutive adult AML patients receiving induction, fulminant tumor lysis with acute renal failure occurred in 6.1% (95% CI 2.5-12.2), most of whom required hemodialysis; five of those seven patients had inv(16), so risk in that subgroup is substantially higher than the cohort-wide rate. That cohort used cytarabine-daunorubicin induction, so the figure reflects anthracycline-based induction generally — an idarubicin-specific AKI rate is not quantified.Mild