The Injury Atlas See it on the nephron Does the kidney recover? Cross-drug outcomes
ATN
Acute Tubular Necrosis
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.
26signature agents
Deep diveCisplatin ATN & hypomagnesemiaDeep diveIfosfamide FanconiDeep divePemetrexed tubulopathyDeep diveICI nephritisDeep diveHD-MTX nephropathyDeep diveBRAF/MEK tubularDeep diveBisphosphonate injuryDeep diveCAR-T AKI
Where it strikes
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Distal Tubule / Collecting Duct
Fine-tuning of Na, K, Mg, acid & water
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· 1Moderate· 16Mild· 9
Agents’ overall reversibility
Partially reversible· 7Variable· 8Reversible· 11
Agents’ onset window
How soon each agent’s kidney toxicity typically appears — a whole-drug tempo, not specific to this lesion.
Acute (days)· 7Subacute (weeks)· 11Delayed (weeks–months)· 2Variable· 6
Real-world reporting for this lesion
FAERS across all lesions →Agents with a disproportionate FAERS reporting signal for acute tubular necrosis (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.
14Corroborated
Documented in the atlas profile and carrying a FAERS signal — the strongest claim the atlas makes.
42Documented, 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.
0Not 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.
30Reported 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.
ATN is systematically undercounted in FAERS — most true cases are filed under the generic “acute kidney injury” term rather than a distinct acute tubular necrosis code, so the literature-only column is expected to run large here.
5-FluorouracilAbemaciclibAmivantamabBendamustineBleomycinBortezomibBusulfanCarboplatinCarmustine (BCNU)CetuximabCisplatinClofarabineCobimetinibCyclophosphamideCytarabineDasatinibDecitabineDostarlimabDoxorubicinEtoposideEverolimusFludarabineGemcitabineHydroxyureaIfosfamideImatinibIpilimumabMelphalanMethotrexate (high-dose)NivolumabOxaliplatinPaclitaxelPamidronatePembrolizumabPemetrexedRituximabSirolimusTemsirolimusTisotumab vedotinTopotecanTrabectedinVinblastineZoledronic acidZongertinib
44 agents with a significant ATN reporting signal.
Management approach
Full framework →Prevention is the mainstay; once established, supportive care while the tubule recovers.
Drug-level levers
- Hold the agent for a significant creatinine rise; resume only after recovery.
- Dose-reduce or extend the dosing interval for lower-grade or recurrent injury.
- Switch within class to a less nephrotoxic platinum (carboplatin or nedaplatin) when a platinum must continue.
- Switch out of class to a non-nephrotoxic regimen if re-exposure risk is unacceptable.
Pharmacologic toolkit
- Volume expansion — Isotonic saline before and after dosing is the best-evidenced preventive measure for cisplatin ATN.
- Magnesium repletion — Replace urinary magnesium and potassium losses; magnesium supplementation may be renoprotective.
- Avoid co-nephrotoxins — Hold NSAIDs, aminoglycosides, and iodinated contrast where possible.
When to biopsy
Rarely needed — the diagnosis is usually clinical (timing, muddy-brown granular casts). Reserve biopsy for atypical features or when an alternative lesion (AIN, TMA) is suspected.
Monitoring
- · Creatinine / eGFR before each cycle
- · Serum magnesium and potassium
- · Urine output and sediment
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 acute tubular necrosis.
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.
ADQIThe nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupNat Rev Nephrol 2026 · PMID 41361704Provides 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.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.ASONDiagnosis and management of immune checkpoint inhibitor-associated nephrotoxicity: a position statement from the American Society of Onco-nephrologyKidney Int 2025 · PMID 39455026ICI-AKI most commonly presents as acute interstitial nephritis; nephrology consultation and kidney biopsy should be considered for stage 2 or higher AKI or suspected glomerular disease, but where biopsy is not feasible, prompt empiric corticosteroids (prednisone ~1 mg/kg/day) should be started for clinically suspected ICI-AKI since early steroids improve renal recovery, with cautious individualized consideration of ICI rechallenge after recovery.KDIGOKDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerKidney Int 2020 · PMID 33126977Identifies 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.KDIGODiagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Crit Care 2013 · PMID 23394211Defines/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.Expert ConsensusThe Prevention of Cisplatin-Induced Nephrotoxicity: A General Consensus Statement of a Group of Oncologist-Hematologists, Adult and Pediatric Nephrologists, Radiation Oncologists, Clinical Pathologists, Clinical Pharmacologists, and Renal Physiologists on Cisplatin Therapy in Cancer PatientsInt J Prev Med 2022 · PMID 35392316Consensus on modifiable factors for cisplatin nephrotoxicity prevention, addressing hydration methods, magnesium supplementation, dextrose, avoidance of NSAIDs and renin-angiotensin system inhibitors and contrast agents around cisplatin, GFR assessment, antioxidants, and patient factors (age, sex, female hormones).SIRMSIRM-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)Radiol Med 2022 · PMID 35303246Recommends 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.PUMCH Expert PanelClinical recommendations on diagnosis and treatment of immune checkpoint inhibitor-induced renal immune-related adverse eventsThorac Cancer 2020 · PMID 32232975Screen and monitor with serum creatinine, urinalysis/sediment, and 24-hour urine protein; strongly recommend kidney biopsy to confirm ICI-related ATIN and exclude other AKI causes, withdraw nephrotoxins (PPIs, NSAIDs), and initiate corticosteroids when a grade 2 or higher renal irAE is highly suspected, with multidisciplinary decisions on ICI withdrawal and rechallenge.ASCO / CCORole of Bone-Modifying Agents in Metastatic Breast Cancer: An American Society of Clinical Oncology-Cancer Care Ontario Focused Guideline UpdateJ Clin Oncol 2017 · PMID 29035643Endorses denosumab 120 mg SC q4w, pamidronate 90 mg IV q3-4w, or zoledronic acid 4 mg IV q12w or q3-4w; nitrogen bisphosphonates require renal function monitoring and dose/interval adjustment for impaired clearance, whereas denosumab needs no renal dose adjustment (with hypocalcemia risk in CKD).
Offending agents
Signature offenders
26Agents for which acute tubular necrosis is the defining renal lesion.
CisplatinAcute — creatinine peaks ~day 4–7; magnesium wasting can persist for months.AKI in ~20–35% per cycle (classic teaching: ~1 in 3). Hypomagnesemia in 40–100%.SevereZoledronic acidAcute — days to weeks after infusion(s).Nephrotoxicity is the dose-limiting toxicity but largely avoidable; no precise population rate. Reported rate: renal toxicity in 17% — 852 patients with symptomatic newly diagnosed multiple myeloma and at least one lytic bone lesion who received at least… (Raje 2018, PMID 29429912).ModerateNedaplatinDays after dosing; cumulative with repeated cycles.Lower renal cortical platinum accumulation and less frequent nephrotoxicity than equimolar cisplatin; dose-related proximal tubular injury still occurs, but high-grade AKI is uncommon and not robustly quantified in the renal literature. Myelosuppression (notably thrombocytopenia), not nephrotoxicity, is the dose-limiting toxicity. Reported rate: serum creatinine elevation in 9.8% — Patients with gastrointestinal cancer (esophageal, stomach, colon) in a 16-institution Japanese phase II study of… (Taguchi 1992, PMID 1558398).ModeratePlicamycin (mithramycin)With repeated / cumulative dosing (days to weeks).Cumulative, dose-related nephrotoxicity is a recognized dose-limiting toxicity; when used for hypercalcemia, its antiresorptive potency can overshoot to symptomatic hypocalcemia. Precise modern incidence is not well quantified because the drug is now essentially obsolete. The comparative hypercalcemia-tolerability review cited here pooled trials of at least 10 patients and reported serum creatinine elevation in 5% of plicamycin-treated patients, alongside hepatotoxicity in 26% and nausea/vomiting in 23%. The creatinine figures it gives for etidronate (8%), clodronate (5%) and pamidronate (2%) are bisphosphonate rates from the same review and are not plicamycin's.ModerateEnfortumab vedotinVariable; tubular/prerenal AKI tracks with intercurrent GI toxicity, and hyperglycemic-AKI events are often reported after the second or third dose.Renal injury is not a prominent or well-quantified trial signal, and EV is usable across the spectrum of renal function (including eGFR <30). When AKI occurs it spans prerenal (GI-toxicity dehydration), hyperglycemia/DKA-associated, and case-level tubular (ATN) patterns. In EV-201 cohort 2, three of 89 patients had treatment-related deaths within 30 days (one each from AKI, metabolic acidosis and multi-organ dysfunction), underscoring a real but uncommon acute renal-metabolic risk.ModerateTrastuzumab deruxtecanVariable; reported during ongoing therapy, sometimes resolving over months after discontinuation.Renal data are emerging and under-published. AKI/proteinuria are reported at case level; a reversible proximal-tubule Fanconi syndrome (glucosuria, phosphate/potassium wasting, non-anion-gap acidosis) has been described and attributed to the deruxtecan payload. Renal-specific incidence is not quantified.ModerateLenalidomideVariable; azotemia reported from weeks to several months after initiation.AKI/azotemia is uncommon but recognized, described mainly in case series of plasma-cell dyscrasias with underlying renal insufficiency; not reliably quantified as an incidence. Rare Fanconi syndrome and TMA are reported. Because ~80% of lenalidomide is renally cleared as unchanged drug, accumulation in renal impairment is the dominant driver of toxicity, including myelosuppression.ModerateDatopotamab deruxtecan (Dato-DXd)Not well characterized (recent approval); by class analogy a subacute tubular pattern during cumulative dosing.Renal signal is theoretical and not yet quantified, extrapolated from the ADC class. In TROPION-PanTumor01 and the phase III TROPION-Breast01 the dominant toxicities were mucosal (stomatitis ~50%) and ocular events, nausea, and interstitial lung disease; grade ≥3 treatment-related adverse events were lower than chemotherapy (~21%), and kidney-specific events were not prominent.ModerateTrabectedinRhabdomyolysis often around the 4th cycle; hepatotoxicity/myelosuppression nadir ~days 5-15.The drug is not directly nephrotoxic and shows no cumulative renal toxicity; clinically important AKI is rare and driven by rhabdomyolysis. The per-cycle rhabdomyolysis rate is not quantified (case-level). The dominant organ toxicity is hepatic — grade 3-4 transaminitis fell from ~34% to ~2% with dexamethasone premedication. Reported rate: rhabdomyolysis in 0.7% — 10,841 trabectedin-treated patients pooled from the Yondelis pharmacovigilance and clinical-trials databases, April… (Grosso 2012, PMID 22484722).ModeratePentostatinDuring or after dosing cycles; generally reversible with dose reduction or discontinuation.At modern low doses clinically significant nephrotoxicity is uncommon and a precise contemporary incidence is not quantified; serious dose-related AKI was historically tied to higher-dose regimens. Tumor lysis can add a secondary AKI mechanism in bulky disease.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 PK 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 for crystal-related nephrotoxicity.ModerateMelphalan flufenamide (melflufen)Cytopenias within the first cycles; any renal change is typically subacute and multifactorial.Direct nephrotoxicity is not a prominent trial signal; the renal relevance is pharmacokinetic and disease-context. A dedicated phase II study (BRIDGE) in myeloma patients with moderate or severe renal impairment characterized melphalan exposure across renal function and supported a reduced 30 mg dose for moderate impairment, with no new safety signals but substantial treatment-emergent toxicity (including deaths in a heavily pretreated population). As a melphalan-delivery system, its renal liabilities mirror the alkylator class (myelosuppression, and the alkylator-associated risk of tubular injury at high exposure).ModerateProcarbazineVariable; tumor-lysis-related AKI within days of starting in bulky disease, hypersensitivity-type injury after re-exposure.Not well quantified at the drug-specific level. Procarbazine appears in classic onconephrology reviews of the renal complications of cytotoxic therapy as an agent with recognized renal/urological complications, and it is part of multi-agent lymphoma regimens in which acute renal failure (often multifactorial — tumor lysis, volume depletion, combined nephrotoxins) is described. Discrete procarbazine-attributable nephrotoxicity is largely case-/review-level rather than quantified.ModerateSamarium-153 lexidronamMyelosuppression nadirs within weeks; recovery typically over the following weeks.Clinically meaningful nephrotoxicity is uncommon; the dominant and dose-limiting toxicity is reversible myelosuppression. No reliable drug-specific AKI incidence is established. Renal caution stems from renal/urinary excretion of the unbound radiopharmaceutical.ModerateTelisotuzumab vedotin (Teliso-V)Onset is not well characterized for this agent; with cytotoxic ADC payloads, tubular injury would typically evolve over days to a few weeks of cumulative exposure.Drug-specific renal toxicity data for telisotuzumab vedotin are sparse. In the pivotal LUMINOSITY trial the dominant toxicities were peripheral neuropathy, peripheral edema, hypoalbuminemia, fatigue, and nausea; clinically significant nephrotoxicity was not highlighted as a frequent or signature event. Any renal risk is therefore largely class-extrapolated from MMAE-bearing ADCs rather than measured for this agent. A precise renal incidence rate cannot be stated from existing literature.ModerateVemurafenibEarly — most cases arise within the first weeks to three months of therapy (all AKI events in the Teuma cohort occurred in the first trimester of treatment); later onset is uncommon.Clinically meaningful AKI is a recognized but variably quantified effect, and vemurafenib is the strongest renal offender of the BRAF/MEK class. Small serum-creatinine rises are common and usually low-grade; overt AKI produced the first case series of 8 patients with significant-to-severe renal insufficiency (Launay-Vacher, Cancer 2014) and 132 vemurafenib AKI reports to FDA FAERS over 3 years, far exceeding dabrafenib's 13 (Jhaveri, JAMA Oncol 2015). The monotherapy denominator comes from a retrospective single-center cohort of 74 patients with BRAF-V600-mutant metastatic melanoma, with creatinine measured before treatment, monthly on treatment and 3 months after stopping: 44 of 74 (59.5%) met the KDIGO threshold of a 1.5-fold creatinine rise, and 40 of those 44 (91%) were stage 1. Read that figure with its definition attached — it is creatinine-based, and BRAF/MEK inhibitors also blunt tubular creatinine secretion, so a share of any such cohort is pseudo-AKI rather than tubular injury; the authors biopsied two stage-1 patients to demonstrate real tissue damage. Men were over-represented among the AKI-positive patients (75% versus 40%). Adding a MEK inhibitor lowers it substantially: in the companion cobimetinib cohort 9 of 38 (24%) developed AKI, all within three months and mostly stage 1-2, about a 60% reduction versus monotherapy.ModerateGallium nitrateDuring or within a few days of the 5-day continuous infusion — usually within the first week of a cycle. Creatinine generally trends back toward baseline once the drug is stopped and hydration is maintained.Nephrotoxicity is the dose-limiting toxicity. At the approved antihypercalcemic dose (200 mg/m2/day by continuous IV infusion x 5 days) a rise in serum creatinine is reported in roughly 10% of patients; at higher antineoplastic doses it is far more frequent — e.g., dose-limiting azotemia in 4 of the first 10 patients (40%) at 700 mg/m2 in the SWOG advanced-bladder-cancer trial, which forced a longer inter-cycle interval. Precise incidence is uncertain because the supporting trials are small and heterogeneous, so the headline figure should be read with caution.ModerateCarboplatinAcute when it occurs (high-dose regimens).Clinically significant nephrotoxicity uncommon at standard doses; emerges mainly at high/myeloablative doses.MildBRAF / MEK InhibitorsAcute–subacute during therapy.Pharmacovigilance shows vemurafenib > dabrafenib. Mild creatinine elevation common, serious AKI uncommon. Reported rate: acute kidney injury in 21% — 199 patients who received dabrafenib/trametinib in a single large US healthcare system between 2010 and 2019… (Seethapathy 2022, PMID 33355659).MildEncorafenibWeeks into therapy when it occurs.Renal injury with BRAF/MEK therapy is uncommon and largely case-level (tubular injury and acute interstitial nephritis reported); usually mild and reversible with drug interruption. In COLUMBUS, grade 3-4 creatine-phosphokinase elevation (7%) and hypertension (6%) were the renally relevant events with encorafenib plus binimetinib.MildCobimetinibWeeks into therapy.AKI with BRAF/MEK therapy is uncommon and mostly mild; a pharmacovigilance analysis found adding a MEK inhibitor to vemurafenib was associated with a ~60% reduction in acute kidney injury versus vemurafenib alone.MildBinimetinibWeeks into therapy.Clinically significant intrinsic nephrotoxicity is uncommon; modest creatinine elevations occur and CK elevation is a recognized MEK-class effect. In COLUMBUS, grade 3-4 blood-CK increase occurred in ~7% with encorafenib plus binimetinib; rare rhabdomyolysis can secondarily threaten the kidney.MildIbandronateAcute when it occurs (days), related to dose and infusion rate; antiresorptive electrolyte effects within the first days.Lower renal risk than zoledronate or pamidronate. In a 2-year phase III breast-cancer trial, adverse renal events with IV ibandronate were ~4% versus ~4.5% with placebo — essentially at background. Bisphosphonates as a class can cause toxic ATN (zoledronate) or collapsing FSGS (pamidronate), but ibandronate is the renal-safety outlier within the class. Reported rate: serum creatinine increase >=44.2 micromol/l in 2% — Women with breast cancer and bone metastases receiving intravenous ibandronate 6 mg every 3-4 weeks for up to 6 months,… (von 2008, PMID 18334511).MildLurbinectedinVariable across cycles (not tightly defined) — monitor with each dose.Not directly tubulotoxic; clinically significant AKI is rare and arises from rhabdomyolysis or tumor lysis. Rhabdomyolysis was formally recognized post-approval (FDA FAERS) and as an isolated phase 1 dose-limiting toxicity; the trial rate is not quantified. The dominant toxicity is hematologic (grade >=3 neutropenia ~41%) with frequent transaminase elevations.MildSonidegibCK elevations during the first weeks-to-months of therapy; rhabdomyolysis-driven AKI would follow a significant muscle-injury event.Asymptomatic creatine-kinase elevation is more common with sonidegib than vismodegib (a class-distinguishing signal), and rhabdomyolysis is a labeled but rare event. Clinically significant pigment nephropathy/ATN is uncommon but is the feared renal consequence.MildIobenguane I-131Biphasic — modest, often transient creatinine changes within weeks of a therapeutic dose; the characteristic radiation nephropathy is delayed, typically appearing 6-12 months or later after cumulative renal irradiation, sometimes years out.Reported renal toxicity is uncommon and usually low-grade. In a dosimetry-guided high-activity 131I-MIBG cohort, 3 of 14 patients (21%) had transient grade 1 renal toxicity (Maric 2023, small single-center series using conventional 131I-MIBG). In the registrational high-specific-activity trial (Azedra, n=68 dosed), renal failure was not among the most common treatment-emergent events — nausea, myelosuppression and fatigue dominated — and clinically significant (grade >=3) nephrotoxicity was rare. The kidney concern is driven less by acute events than by the delayed, cumulative absorbed radiation dose, so headline incidence figures come from small cohorts and should be read as low-grade signal rather than a robust rate.Mild