Is kidney injury from Nelarabine reversible?

Reversible. Typical onset: Early after treatment initiation (days)..

How should kidney function be monitored during Nelarabine therapy?

Uric acid, phosphate, potassium, calcium and creatinine at initiation and during early cycles; Frequent neurologic examinations (the dose-limiting toxicity); CBC for myelosuppression.

How can kidney injury from Nelarabine be prevented?

IV hydration during cytoreduction Allopurinol or rasburicase prophylaxis in at-risk patients

Who is at higher risk of kidney injury from Nelarabine?

High tumor burden T-ALL / lymphoblastic lymphoma; Baseline hyperuricemia or renal impairment; Volume depletion.

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Printable monograph

Purine analog

Nelarabine

Arranon · Nelar

Purine analog · approved 2005 · 6 citations · FAERS AKI reporting ROR 2.33 (95% CI 1.42–3.81, 16 AKI reports)

Aging evidence· through 2020

Deeply sourced7/9 · 6 signals

Met: 6 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 10y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2020
Met: Real-world FAERS signal

Describes how this page is sourced, not how dangerous the drug is. Thinly sourced means fewer of the sourcing signals are met — not that the agent is kidney-safe. A rule-based summary, not a formal certainty appraisal.

A T-cell-selective purine analog whose rapid leukemic kill can trigger tumor lysis and prerenal AKI.

MildPurine nucleoside analog

Relapsed/refractory T-cell acute lymphoblastic leukemiaT-cell lymphoblastic lymphoma

§01

Signature kidney injury

Signature lesion

Crystal / Obstructive Nephropathy

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.Source: Izzedine & Perazella, Kidney Int Rep 2017 (review)

Onset & rechallenge

Time to injuryAcute (~1–7 days)

Early after treatment initiation (days).

Distilled from: “Early after treatment initiation (days).”

§02

Renal toxicities, ranked

This agent's kidney lesions ordered by prominence — the #1 signature lesion first, then secondary and rare patterns. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Crystal / Obstructive Nephropathy#1 · Signaturequalitative — no citable incidence
Intratubular precipitation of drug or metabolite — high-dose methotrexate and tumor lysis crystals.
Prerenal / Hemodynamic AKISecondaryqualitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Electrolyte DisturbanceSecondaryqualitative — no citable incidence
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

Incidence not quantified

SeverityMild

ReversibilityReversible

Evidence6 citations

Nephron map

Vasculature / Endothelium

Distal Tubule / Collecting Duct

Tubular LumenThe urine flow path

Crystal / Obstructive Nephropathy

Intratubular precipitation of drug or metabolite — high-dose methotrexate and tumor lysis crystals.

§03

Kidney injury

Mechanism of kidney injury

Rapid lysis of T lymphoblasts releases uric acid, phosphate and potassium; intratubular crystal/cast deposition combined with volume depletion drives prerenal and ischemic AKI (tumor lysis nephropathy). Direct tubular nephrotoxicity from nelarabine itself is not a prominent feature.

Clinical presentation

Hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia and a rising creatinine after treatment; the dominant non-renal toxicity is severe neurotoxicity (somnolence, peripheral neuropathy, seizures), which can confound the clinical picture.

Management

Treat tumor lysis with hydration, urate-lowering therapy and electrolyte correction; supportive care and renal replacement therapy for severe AKI. Discontinue for grade >=2 neurologic events (which are not reversed by drug-level reduction). Adequate hydration also limits intratubular crystal deposition.Lesion-level management framework

Risk factors

High tumor burden T-ALL / lymphoblastic lymphoma
Baseline hyperuricemia or renal impairment
Volume depletion

Prevention

IV hydration during cytoreduction
Allopurinol or rasburicase prophylaxis in at-risk patients

Anticancer mechanism· how it treats cancer

Water-soluble prodrug of ara-G (9-beta-D-arabinofuranosylguanine), demethylated by adenosine deaminase, that accumulates preferentially in T lymphoblasts where it is phosphorylated to ara-GTP, incorporated into DNA and halts DNA synthesis, causing apoptosis. Used for relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma, and now incorporated into frontline pediatric T-ALL therapy.

Note · The black-box warning is for neurotoxicity, not nephrotoxicity.

§04

Clinical depth

Renal dose adjustment

No specific renal dose adjustment is defined in the label, but exposure is higher and clearance lower in renal impairment, so the FDA label advises monitoring patients with CrCl < 50 mL/min closely for increased toxicity. Ara-G is renally cleared.

Dialyzability & ESKD dosing

Not formally established; ara-G is a small renally excreted molecule with theoretical dialytic removal, but no validated supplemental dosing exists and HD is used only to manage AKI complications.

Differential diagnosis

Distinguish tumor lysis nephropathy (urate/phosphate surge) from prerenal azotemia and from leukemic infiltration of the kidney. Note that altered mental status in these patients may reflect nelarabine neurotoxicity rather than uremia/metabolic encephalopathy.

Monitoring

Uric acid, phosphate, potassium, calcium and creatinine at initiation and during early cycles
Frequent neurologic examinations (the dose-limiting toxicity)
CBC for myelosuppression

Key trials & series

Children's Oncology Group AALL0434 phase III trial adding nelarabine to frontline T-ALL therapy (Dunsmore, J Clin Oncol 2020)
Phase II relapsed/refractory T-ALL studies underpinning approval

Clinical pearls

Nelarabine's signature toxicity is neurologic; the renal risk is the tumor lysis that accompanies rapid T-ALL kill.
Hydration plus urate-lowering therapy at the start of a responding course is the key renal protection.
A creatinine rise with new confusion should prompt separate evaluation of TLS and CNS toxicity.

Beyond the kidney — non-renal toxicities· 4 organ systems

Class-level context for the major non-renal toxicities of the Purine analog class.

Gastrointestinal

Diarrhea, colitis, mucositis, perforation

Mucositis and diarrhea

Hepatic / Liver

Transaminitis, hepatitis, VOD/SOS

Transaminitis (methotrexate)

Hematologic

Cytopenias, thrombosis, TMA

Myelosuppression

Pulmonary

Pneumonitis, ILD, effusions, hypertension

Methotrexate / gemcitabine pneumonitis

§05

References

6 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.

Evidence accrual

6 references · 2010–2020 · 3 since 2018

Primary (non–case-report) references per year — a proxy for how actively the agent's renal literature is accruing. Recent years are highlighted. Reflects curation depth, not a systematic bibliometric count.

FDA label — boxed warning & renal dosing· boxed warning · renal impairment

Quoted verbatim from this agent's current FDA label (Feb 2026) — not paraphrased or interpreted. Full label on DailyMed .

Boxed warning

WARNING: NEUROLOGIC ADVERSE REACTIONS Severe neurologic adverse reactions have been reported with the use of nelarabine. These adverse reactions have included altered mental states including severe somnolence, central nervous system effects including convulsions, and peripheral neuropathy ranging from numbness and paresthesias to motor weakness and paralysis. There have also been reports of adverse reactions associated with demyelination, and ascending peripheral neuropathies similar in appearance to Guillain-Barré syndrome [see Warnings and Precautions (5.1) ]. Full recovery from these adverse reactions has not always occurred with cessation of therapy with nelarabine. Monitor frequently for signs and symptoms of neurologic toxicity during treatment with nelarabine. Discontinue nelarabine for neurologic adverse reactions of NCI Common Toxicity Criteria for Adverse Events (CTCAE) Grade 2 or greater [see Warnings and Precautions (5.1) ] . WARNING: NEUROLOGIC ADVERSE REACTIONS See full prescribing information for complete boxed warning. Severe neurologic adverse reactions have been reported with the use of nelarabine. These adverse reactions have included altered mental states including severe somnolence, central nervous system effects including convulsions, and peripheral neuropathy ranging from numbness and paresthesias to motor weakness and paralysis. There have also been…

Renal impairment — from the label

Closely monitor patients with moderate or severe renal impairment for toxicities. ( 8.6 )

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 956 of them for this agent. Nobody counts the patients who were fine, so none of these numbers is an incidence, a risk, or a rate: they describe what gets reported, shaped by a drug's fame, its indication, and who was watching. How these numbers work.

Reporting odds ratio (ROR) — is kidney injury named in this agent's reports more often than in every other drug's? Above 1 means yes, disproportionately.
Renal phenotypes — the same question asked separately for each kind of kidney injury, so the ratios differ from the overall one and from each other.
Outcomes — a share of this agent's own reports, not of patients: how many were filed as involving a death or a hospitalization. Not a case-fatality rate.

FAERS reported renal phenotypes· 3 signals

Only significant signals appear (95% CI lower bound above 1) — a phenotype missing here was tested and did not reach significance, except Prerenal / Hemodynamic AKI, Pseudo-AKI, Renal Cysts, Chronic Interstitial Nephropathy — outside the clinician-reviewed MedDRA term map, never queried — and ATN and AIN, queried but biopsy-bound: real cases are filed as generic “acute kidney injury”, so their absence is not a negative. As of 2026-10-01.

What reporting says about this profile's documented lesions

Electrolyte Disturbancecorroborated · ROR 2.2 — but the naming terms alone are not disproportionate, so this rests on terms merely consistent with the lesion
Crystal / Obstructive NephropathyNo disproportionate reporting — This phenotype IS reportable and this agent has enough reports, yet the reporting is not disproportionate — the one genuinely informative negative of the four.
Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.

Hemorrhagic Cystitis

ROR 2.5595% CI 1.27–5.11· 8 reports

Electrolyte Disturbance

ROR 2.2095% CI 1.40–3.47· 19 reports

SIADH / Hyponatremia

ROR 2.1995% CI 1.09–4.39· 8 reports

FAERS outcomes & reporting trend· 22% of reports w/ death · 33.6% w/ hospitalization

22%

Reported with a death outcome

210 of 956 reports

33.6%

Reported with hospitalization

321 of 956 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 956 reports

Bars rank systems by summed reaction-term mentions (a report counts once per term it names) — an ordinal “more vs less reported” cue, not a tally of distinct reports. Renal & urinary first. As of 2026-10-01.

Disproportionality (acute kidney injury):ROR 2.3395% CI 1.42–3.81· 16 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Nervous system

Neuropathy Peripheral60Neurotoxicity60Peripheral Sensory Neuropathy54Guillain-Barre Syndrome42Peripheral Motor Neuropathy35

Blood & lymphatic

Febrile Neutropenia75Neutropenia49Thrombocytopenia39Platelet Count Decreased35Anaemia33

Immune / infection

Sepsis56Septic Shock30

Musculoskeletal

Muscular Weakness55Rhabdomyolysis28

General / constitutional

Pyrexia36

Respiratory

Respiratory Failure35

Hepatobiliary

Alanine Aminotransferase Increased27

Gastrointestinal

Diarrhoea27

Guidelines & consensus· 14

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.

General onco-nephrology references

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.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.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.KDIGOKDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationKidney Int 2020 · PMID 33276867Addresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.ADDIKDIntegrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceEClinicalMedicine 2025 · PMID 40290844Provides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.ADDIKDAligning kidney function assessment in patients with cancer to global practices in internal medicineEClinicalMedicine 2025 · PMID 40290845Three consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.ADDIKDA methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEClinicalMedicine 2025 · PMID 40290846Establishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.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.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsKidney Int 2024 · PMID 38519239Evaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.KDIGOExecutive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesKidney Int 2021 · PMID 34556300Provides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisKidney Int 2024 · PMID 38388147Updates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisKidney Int 2024 · PMID 38182299Updates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.KDIGOExecutive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Kidney Int 2025 · PMID 40975525Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.

Where Nelarabine sits in nephrotoxicity space — each dot is an anti-cancer agent, positioned so neighbors share a kidney-injury phenotype. Its 6 closest are filled and lead to a numbered marker, matching the numbered cards below.

Position is a 2-D projection (MDS) of each agent's injury signature, nephron target, severity, and class, so two dots can sit close on the page while differing on an axis the projection flattened — the numbered ranking is computed from the full metric, not from the distance you see. Open the full map.

Phenotype-similar agents· the numbered markers on the map above

Hydroxyurea

Hydrea · Ribonucleotide reductase inhibitor

Profile

Tumor lysis in myeloproliferative disease.

XTALPRELYTE

Mild#1 · 100% phenotype match

Cladribine

Leustatin · Purine analog

Profile

Tumor lysis; high-dose nephrotoxicity.

XTALPRELYTE

Mild#2 · 100% phenotype match

Fludarabine

Fludara · Purine analog

Profile

Tumor lysis; accumulates in renal impairment.

XTALPRELYTE

Moderate#3 · 95% phenotype match

Etoposide

Etopophos · Topoisomerase II inhibitor

Profile

Tumor lysis; renally cleared.

XTALPRELYTE

Mild#4 · 89% phenotype match

Pomalidomide

Pomalyst · Immunomodulatory drug (IMiD)

Profile

Tumor lysis; usable in renal impairment.

PRELYTEXTAL

Mild#5 · 89% phenotype match

Thalidomide

Thalomid · Immunomodulatory drug (IMiD)

Profile

Tumor lysis and bradycardia.

PRELYTEXTAL

Mild#6 · 89% phenotype match

Compare Nelarabine with its nearest agents

Nearest agents by kidney-injury phenotype (shared injuries, nephron target, severity, class) — a similarity approximation, not a claim of shared drug identity or mechanism.

Kidney risk across Antimetabolites

Same-class agents ordered by their documented kidney-injury profile — atlas severity, an acute-kidney-injury FAERS signal, and how many injury types each is documented to cause. Agents nearer the top carry the lighter documented renal profile.

A comparison of documented kidney-injury data within one drug class — not a substitution recommendation. Efficacy, indication, and non-renal toxicity differ between these agents and are out of scope here. Educational only, not medical advice.