What kind of kidney injury does Clofarabine cause?

Prerenal / Hemodynamic AKI — Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome. Other reported patterns: Acute Tubular Necrosis, Glomerular Injury / Proteinuria, Crystal / Obstructive Nephropathy.

Is kidney injury from Clofarabine reversible?

Partially reversible. Typical onset: Early, typically within the first treatment cycle (days)..

How should kidney function be monitored during Clofarabine therapy?

Vital signs and volume status frequently during each 5-day course (watch for hypotension/capillary leak); Serum creatinine and electrolytes daily during and after each cycle; Uric acid, phosphate, potassium and calcium (tumor lysis) at initiation; Liver enzymes and bilirubin (concurrent hepatotoxicity).

How can kidney injury from Clofarabine be prevented?

Vigorous IV hydration throughout the 5-day infusion course Tumor lysis prophylaxis (allopurinol or rasburicase) in at-risk patients

Who is at higher risk of kidney injury from Clofarabine?

High tumor burden / leukemic hyperleukocytosis; Concurrent sepsis or hypotension; Volume depletion; Concomitant nephrotoxins.

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Printable monograph

Purine analog

Clofarabine

Clolar · Clofar

Purine analog · approved 2004 · 10 citations · FAERS AKI reporting ROR 4.48 (95% CI 3.54–5.66, 72 AKI reports)

Aging evidence· through 2020

Deeply sourced7/9 · 6 signals

Met: 10 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 17y)
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 second-generation purine analog whose systemic inflammatory storm can starve the kidney of perfusion.

ModeratePurine nucleoside analog

Pediatric relapsed/refractory acute lymphoblastic leukemiaAcute myeloid leukemia (off-label)

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Representative incidence6%

A systemic inflammatory response syndrome (SIRS) / capillary-leak syndrome with associated AKI was reported in roughly 4% of treated children in the registration program; hypotension was among the most common grade 3 or greater adverse events in the pivotal phase II trial. Precise renal incidence is not well quantified and most AKI data are case-level. Reported rate: renal insufficiency in 6% — Adults with relapsed and/or refractory non-Hodgkin lymphoma receiving SINGLE-AGENT clofarabine (1-h IV daily x5, q28d)… (Nabhan 2011, PMID 21425150).Source: Nabhan et al., Cancer 2011

Onset & rechallenge

Time to injuryAcute (~1–7 days)

Early — typically within the first treatment cycle (days).

Distilled from: “Early, typically within the first treatment cycle (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.

Prerenal / Hemodynamic AKI#1 · Signaturequalitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Acute Tubular NecrosisSecondaryno population incidence denominator
Severe acute tubular injury described as a dominant AKI mechanism in a clinicopathologic report plus a FAERS review of 29 additional renal adverse-event cases PMID 24081220 (opens PubMed in a new tab)
Glomerular Injury / ProteinuriaRareno population incidence denominator
Collapsing glomerulopathy with heavy proteinuria reported at case level PMID 24081220 (opens PubMed in a new tab)
Crystal / Obstructive NephropathyRarequalitative — no citable incidence
Intratubular precipitation of drug or metabolite — high-dose methotrexate and tumor lysis crystals.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

6%incidence

SeverityModerate

ReversibilityPartially reversible

Evidence10 citations

Nephron map

Glomerulus

Vasculature / Endothelium

Proximal Tubule

Distal Tubule / Collecting Duct

Tubular Lumen

Prerenal / Hemodynamic AKI

Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

§03

Kidney injury

Mechanism of kidney injury

The dominant lesion is hemodynamic. Drug-induced cytokine release (a SIRS / capillary-leak physiology, sometimes overlapping with a cytokine-release-like state during rapid cytoreduction) drives systemic vasodilation, third-spacing and intravascular volume depletion, producing prerenal AKI that can progress to ischemic acute tubular necrosis when hypotension is sustained. Concurrent tumor lysis at treatment initiation adds intratubular urate/phosphate load. Case-level and preclinical data also implicate direct proximal tubular injury and, rarely, a collapsing glomerulopathy-like picture attributable to ribonucleotide reductase inhibition.

Clinical presentation

Rising creatinine with tachycardia, hypotension, edema, hypoxemia and a SIRS picture, often within the first cycle; a concurrent rise in uric acid, phosphate and potassium signals tumor lysis. Proteinuria has been described in severe cases. Hepatotoxicity (transaminitis, hyperbilirubinemia) and skin rash frequently co-occur and help flag the systemic toxicity syndrome.

Management

Interrupt clofarabine immediately for signs of SIRS or capillary leak; provide aggressive fluid resuscitation and hemodynamic support (vasopressors as needed), and consider corticosteroids for systemic inflammatory features. Treat concurrent tumor lysis with hydration, rasburicase/allopurinol and electrolyte correction. Discontinue the drug for severe or progressive renal injury; renal replacement therapy is reserved for refractory metabolic derangements or volume overload. Most cases improve with drug withdrawal and supportive measures.Lesion-level management framework

Risk factors

High tumor burden / leukemic hyperleukocytosis
Concurrent sepsis or hypotension
Volume depletion
Concomitant nephrotoxins

Prevention

Vigorous IV hydration throughout the 5-day infusion course
Tumor lysis prophylaxis (allopurinol or rasburicase) in at-risk patients

Anticancer mechanism· how it treats cancer

Second-generation deoxyadenosine (purine nucleoside) analog phosphorylated intracellularly to clofarabine triphosphate, which inhibits ribonucleotide reductase (depleting the dNTP pool) and competitively inhibits DNA polymerase, terminating chain elongation. It also disrupts mitochondrial membrane integrity with release of cytochrome c and apoptosis-inducing factor, triggering apoptosis independent of cell division. Used for relapsed or refractory pediatric acute lymphoblastic leukemia and, off-label, refractory acute myeloid leukemia.

Note · Renal injury is largely case-level; the SIRS/capillary-leak signal is the most consistently reported renal mechanism. The label carries a warning for capillary leak syndrome and SIRS.

§04

Clinical depth

Renal dose adjustment

Limited renal pharmacokinetic data; the label advises starting at a reduced dose and monitoring closely when CrCl is 30-60 mL/min, and clofarabine is not recommended (avoid) when CrCl is below 30 mL/min. Renal clearance accounts for a substantial fraction of elimination, so impaired clearance raises systemic exposure.

Dialyzability & ESKD dosing

Not formally characterized; no established supplemental dosing for hemodialysis. Given its small size and renal elimination, removal is theoretical, but it is not used in dialysis-dependent patients and HD is employed only to manage AKI complications, not to dose the drug.

Differential diagnosis

Distinguish drug-induced SIRS/capillary-leak prerenal AKI from sepsis-associated AKI (blood cultures, procalcitonin), from tumor lysis nephropathy (urate/phosphate elevation, uric-acid:creatinine ratio), and from ischemic ATN on the basis of urine microscopy (muddy-brown granular casts favor established ATN) and the temporal link to hypotension during infusion.

Monitoring

Vital signs and volume status frequently during each 5-day course (watch for hypotension/capillary leak)
Serum creatinine and electrolytes daily during and after each cycle
Uric acid, phosphate, potassium and calcium (tumor lysis) at initiation
Liver enzymes and bilirubin (concurrent hepatotoxicity)

Key trials & series

Jeha et al. phase II pediatric refractory/relapsed ALL trial (J Clin Oncol 2006) — basis of FDA approval
Jeha et al. phase I dose-finding study (Blood 2003)

Clinical pearls

Hypotension and capillary leak during the infusion are the key renal hazard — fluids and pressor support, not nephrotoxin avoidance alone, protect the kidney.
Co-occurring transaminitis and rash should raise suspicion for the systemic toxicity syndrome that drives the AKI.
Always layer tumor lysis prophylaxis on top, because rapid leukemic kill compounds the prerenal insult.

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

8 primary references — trials, cohorts, mechanism, and reviews. Single-patient case reports are listed separately below, graded by strength. Citation metadata via PubMed / NLM.

Evidence accrual

8 references · 2003–2020 · 1 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.

Case reports — ranked by strength· 2

Single-patient and small-series reports, graded by evidentiary strength — A Strong (biopsy-proven plus a series and/or positive rechallenge), B Moderate, and C Limited (a single clinically-diagnosed case). Strongest first. Grades are inferred automatically from each report's abstract and journal — a heuristic ranking aid, not a formal quality appraisal.

CaseC · LimitedClofarabine-associated acute kidney injury and proteinuria.Kintzel PE et al. · Pharmacotherapy 2011 · PMID 2192359465-year-old man with relapsed AML who developed severe acute kidney injury and 4.1 g proteinuria temporally related to clofarabine, judged a probable adverse drug reaction.CaseC · LimitedHypertension and Life-Threatening Bleeding in Children with Relapsed Acute Myeloblastic Leukemia Treated with FLT3 Inhibitors.Yılmaz Karapınar D et al. · Turk J Haematol 2015 · PMID 25912283Two children on clofarabine-containing salvage chemotherapy with FLT3 inhibitors developed acute kidney injury and acidosis alongside hypertension and hemorrhage.

FDA label — boxed warning & renal dosing· renal impairment

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

Renal impairment — from the label

Reduce the clofarabine starting dose by 50% in patients with CrCL of 30 to 60 m L/min. There is insufficient information to make a dosage recommendation in patients with CrCL less than 30 m L/min or in patients on dialysis. The pharmacokinetics of clofarabine in patients with renal impairment and normal renal function were obtained from a population pharmacokinetic analysis of three pediatric and two adult studies. In patients with CrCL 60 to less than 90 m L/min (N = 47) and Cr CL 30 to less than 60 m L/min (N = 30), the average AUC of clofarabine increased by 60% and 140%, respectively, compared to patients with normal (N = 66) renal function (CrCL greater than 90 m L/min).

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 2,271 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· 4 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

Acute Tubular Necrosiscorroborated · ROR 5.65
Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.
Glomerular Injury / ProteinuriaNo 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.
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.

Thrombotic Microangiopathy

ROR 6.5995% CI 3.64–11.92· 11 reports

Hemorrhagic Cystitis

ROR 5.8295% CI 4.31–7.88· 43 reports

Acute Tubular Necrosis

ROR 5.6595% CI 2.53–12.59· 6 reports

Electrolyte Disturbance

ROR 1.7095% CI 1.22–2.38· 35 reports

FAERS outcomes & reporting trend· 39.6% of reports w/ death · 31.6% w/ hospitalization

39.6%

Reported with a death outcome

900 of 2,271 reports

31.6%

Reported with hospitalization

717 of 2,271 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 2,271 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 4.4895% CI 3.54–5.66· 72 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Renal & urinary

Acute Kidney Injury72

Blood & lymphatic

Febrile Neutropenia270Neutropenia121Pancytopenia100Bone Marrow Failure83Thrombocytopenia81

Gastrointestinal

Mucosal Inflammation125Nausea111Vomiting101Diarrhoea72

General / constitutional

Pyrexia206Multiple Organ Dysfunction Syndrome89Oedema79

Immune / infection

Sepsis159Pneumonia91Septic Shock73

Hepatobiliary

Blood Bilirubin Increased97Alanine Aminotransferase Increased86Aspartate Aminotransferase Increased81

Respiratory

Respiratory Failure76Dyspnoea70

Vascular

Hypotension86

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 Clofarabine 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

Blinatumomab

Blincyto · BiTE (CD19×CD3)

Profile

CRS and tumor lysis → AKI.

PREATNXTAL

Moderate#1 · 69% phenotype match

Elranatamab

Elrexfio · Bispecific (BCMA×CD3)

Profile

CRS and tumor lysis — emerging.

PREATNXTAL

Moderate#2 · 69% phenotype match

CAR-T cell therapy

Kymriah · Yescarta · CAR-T cell therapy

Profile

CRS-driven prerenal AKI and tumor lysis.

PREATNXTAL

Moderate#3 · 66% phenotype match

Methotrexate (high-dose)

Trexall · Antifolate

Profile

Crystal nephropathy; glucarpidase rescue.

XTALATN

Moderate#4 · 59% phenotype match

Obinutuzumab

Gazyva · Anti-CD20 antibody

Profile

High tumor-lysis risk in CLL.

XTALATNPRE

Moderate#5 · 58% phenotype match

Rituximab

Rituxan · Anti-CD20 antibody

Profile

Tumor lysis with bulky disease; treats some GN.

XTALATNPRE

Moderate#6 · 58% phenotype match

Compare Clofarabine 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.

Who studies this

The leading contributors to Clofarabine’s clinical kidney literature on PubMed, ranked by a blend of publication volume and citation impact — filtered toward clinical work via the PubMed Humans heading and clinical publication types (trials, cohorts, case reports, guidelines, reviews). Names link to that author’s work on Clofarabine; the PMIDs beside each name are up to three of their most recent papers on it, not the full count.

Ranked by a 50/50 blend of publication volume and a position-weighted, capped Relative Citation Ratio (NIH iCite) on this agent’s renal literature; the citation count shown is the raw total, not the ranking score — counted over the 15 clinical records among all 16 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.