What kind of kidney injury does Busulfan cause?

Thrombotic Microangiopathy — Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF.

Is kidney injury from Busulfan reversible?

Variable. Typical onset: Weeks after conditioning/transplant..

How should kidney function be monitored during Busulfan therapy?

Busulfan plasma levels/AUC (therapeutic drug monitoring) during conditioning; Schistocytes, LDH, haptoglobin, platelets and creatinine post-transplant (TA-TMA panel); Bilirubin/weight/liver exam for sinusoidal obstruction syndrome.

How can kidney injury from Busulfan be prevented?

Therapeutic busulfan dosing with PK/AUC level monitoring to limit excess exposure Minimize additive endothelial insults where possible

Who is at higher risk of kidney injury from Busulfan?

High-dose / high-AUC busulfan conditioning; Calcineurin inhibitors (tacrolimus/cyclosporine); Acute graft-versus-host disease; Concurrent infection / total body irradiation / sinusoidal obstruction syndrome.

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Printable monograph

Alkylator

Busulfan

Myleran · Bu

Alkylator · approved 1954 · 8 citations · FAERS AKI reporting ROR 2.64 (95% CI 2.35–2.96, 296 AKI reports)

Dated evidence· through 2019

Fairly sourced6/9 · 5 signals

Met: 8 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 18y)
Met: Beyond single case reports
Not met: Peer-reviewed sources
Met: Landmark reference
Not met: Current through 2019
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 conditioning alkylator that can injure the transplant endothelium and trigger microangiopathy.

ModerateAlkylator

Hematopoietic stem cell transplant conditioningChronic myeloid leukemia (historical)

§01

Signature kidney injury

Signature lesion

Thrombotic Microangiopathy

Transplant-associated thrombotic microangiopathy (TA-TMA) with renal involvement complicates a subset of conditioning regimens; high-dose busulfan (e.g., 16 mg/kg) has been identified as an independent risk factor for post-transplant TMA, and high busulfan exposure also drives sinusoidal obstruction syndrome/VOD.Source: Nakamae et al., Am J Hematol 2006

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Weeks after conditioning/transplant.

Distilled from: “Weeks after conditioning/transplant.”

§02

Renal toxicities, ranked

This agent's defining kidney lesion — its #1 signature. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Thrombotic Microangiopathy#1 · Signaturequalitative — no citable incidence
Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF.

§03

Kidney injury

Mechanism of kidney injury

Conditioning-related endothelial injury - amplified by high busulfan AUC, calcineurin inhibitors, GVHD, infection and complement dysregulation - drives a thrombotic microangiopathy with platelet/fibrin microthrombi in the renal microvasculature, microangiopathic hemolysis and renal ischemia. The same endothelial toxicity at high exposure produces hepatic sinusoidal obstruction syndrome (VOD), which can cause hepatorenal-type renal hypoperfusion. TA-TMA is multifactorial; busulfan intensity is one contributing factor.

Clinical presentation

Microangiopathic hemolytic anemia (schistocytes, elevated LDH, low haptoglobin), thrombocytopenia, hypertension, proteinuria and rising creatinine after transplant; if VOD coexists, weight gain, hepatomegaly and hyperbilirubinemia with secondary renal hypoperfusion.

Management

Identify and treat triggers (reduce/adjust calcineurin inhibitor, treat GVHD/infection), supportive care, and consider complement-directed therapy (eculizumab) in severe TA-TMA. Renal outcomes range from recovery to chronic kidney disease.Lesion-level management framework

Risk factors

High-dose / high-AUC busulfan conditioning
Calcineurin inhibitors (tacrolimus/cyclosporine)
Acute graft-versus-host disease
Concurrent infection / total body irradiation / sinusoidal obstruction syndrome

Prevention

Therapeutic busulfan dosing with PK/AUC level monitoring to limit excess exposure
Minimize additive endothelial insults where possible

Anticancer mechanism· how it treats cancer

Bifunctional alkylsulfonate that cross-links DNA, intensely myelosuppressive with a narrow therapeutic window. Used historically for chronic myeloid leukemia and, principally, as a high-dose conditioning agent (with cyclophosphamide or fludarabine) before hematopoietic stem cell transplant.

§04

Clinical depth

Renal dose adjustment

Busulfan clearance is largely hepatic (GST-mediated); no formal renal CrCl dose banding, but AUC-targeted (therapeutic-drug-monitoring) dosing is standard to avoid the high exposures linked to TMA and VOD. Reduced clearance at high doses warrants level monitoring.

Dialyzability & ESKD dosing

Busulfan is moderately dialyzable in principle, but TDM-guided dosing (not dialysis) is the control strategy; dialysis is reserved for managing TA-TMA-related renal failure rather than for drug removal.

Differential diagnosis

TA-TMA (schistocytes, elevated LDH, low haptoglobin, thrombocytopenia, hypertension, proteinuria) vs calcineurin-inhibitor nephrotoxicity (often without hemolysis), vs VOD-related hepatorenal hypoperfusion (weight gain, hyperbilirubinemia), vs sepsis/ATN. ADAMTS13 is typically not severely deficient, distinguishing TA-TMA from TTP.

Monitoring

Busulfan plasma levels/AUC (therapeutic drug monitoring) during conditioning
Schistocytes, LDH, haptoglobin, platelets and creatinine post-transplant (TA-TMA panel)
Bilirubin/weight/liver exam for sinusoidal obstruction syndrome

Key trials & series

Ho BMT-CTN consensus Biol Blood Marrow Transplant 2005 - defines post-transplant TMA including the renal component
Nakamae Am J Hematol 2006 - high-dose busulfan as an independent TA-TMA risk factor
Tolbert Biol Blood Marrow Transplant 2019 - conditioning regimen as key determinant of TA-TMA with renal injury

Clinical pearls

PK-guided (AUC-targeted) busulfan dosing is the single best lever to reduce both TA-TMA and VOD risk.
TA-TMA is a complement-mediated, multifactorial endothelial injury - busulfan is a contributor, not the sole cause.
Look for the haptoglobin/LDH/schistocyte triad with rising creatinine weeks post-transplant before anchoring on calcineurin-inhibitor toxicity.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Injury signatures

Thrombotic Microangiopathy

Beyond the kidney — non-renal toxicities· 3 organ systems

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

Hematologic

Cytopenias, thrombosis, TMA

Myelosuppression; secondary malignancy risk

Neurologic

Neuropathy, encephalopathy, ICANS, PRES

Ifosfamide encephalopathy (chloroacetaldehyde)

Cardiac

Cardiomyopathy, QT, ischemia, myocarditis

High-dose cyclophosphamide cardiotoxicity

§05

References

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

Evidence accrual

8 references · 2001–2019 · 2 since 2017

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

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

Boxed warning

WARNING: MYELOSUPPRESSION Busulfan Injection causes severe and prolonged myelosuppression at the recommended dosage. Hematopoietic progenitor cell transplantation is required to prevent potentially fatal complications of the prolonged myelosuppression [see Warnings and Precautions ( 5.1 )] . WARNING: MYELOSUPPRESSION See full prescribing information for complete boxed warning. Causes severe and prolonged myelosuppression. ( 5.1 ) Hematopoietic progenitor cell transplantation is required to prevent potentially fatal complications of the prolonged myelosuppression. ( 5.1 )

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 15,641 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· 8 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

Thrombotic Microangiopathycorroborated · ROR 36.93

Thrombotic Microangiopathy

ROR 36.9395% CI 33.41–40.81· 405 reports

Hemorrhagic Cystitis

ROR 10.9595% CI 10.05–11.93· 544 reports

Fanconi Syndrome

ROR 4.7395% CI 2.97–7.51· 18 reports

Glomerular Injury / Proteinuria

ROR 4.1395% CI 3.35–5.09· 89 reports

SIADH / Hyponatremia

ROR 3.0195% CI 2.59–3.48· 179 reports

Acute Interstitial Nephritis

ROR 2.7395% CI 1.98–3.75· 38 reports

Acute Tubular Necrosis

ROR 1.9195% CI 1.13–3.23· 14 reports

Hypertension

ROR 1.2095% CI 1.08–1.34· 345 reports

FAERS outcomes & reporting trend· 29.4% of reports w/ death · 20.7% w/ hospitalization

29.4%

Reported with a death outcome

4,592 of 15,641 reports

20.7%

Reported with hospitalization

3,233 of 15,641 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 15,641 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 2.6495% CI 2.35–2.96· 296 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

Cystitis Haemorrhagic436

Immune / infection

Graft Versus Host Disease915Cytomegalovirus Infection873Acute Graft Versus Host Disease825Chronic Graft Versus Host Disease645Cytomegalovirus Infection Reactivation595

Blood & lymphatic

Febrile Neutropenia863Thrombocytopenia566Pancytopenia450Neutropenia430Thrombotic Microangiopathy377

Gastrointestinal

Mucosal Inflammation1,110Diarrhoea490Graft Versus Host Disease In Gastrointestinal Tract343

Hepatobiliary

Venoocclusive Liver Disease875Venoocclusive Disease525

General / constitutional

Pyrexia816Multiple Organ Dysfunction Syndrome357

Skin

Acute Graft Versus Host Disease In Skin585Graft Versus Host Disease In Skin361

Respiratory

Respiratory Failure476

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 Busulfan 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

Ixazomib

Ninlaro · Proteasome inhibitor

Profile

Rare TMA reports.

TMA

Moderate#1 · 78% phenotype match

Bortezomib

Velcade · Proteasome inhibitor

Profile

Rare TMA; reverses myeloma cast nephropathy.

TMAGLOM

Moderate#2 · 65% phenotype match

Capecitabine

Xeloda · Pyrimidine analog (oral 5-FU)

Profile

Diarrhea-driven prerenal AKI; dose-adjust for CrCl.

PRETMA

Mild#3 · 60% phenotype match

5-Fluorouracil

Adrucil · Pyrimidine analog

Profile

Rare TMA, esp. with mitomycin; mostly renally safe.

TMAPRE

Mild#4 · 60% phenotype match

Ponatinib

Iclusig · BCR-ABL TKI

Profile

Vascular toxicity and hypertension.

HTNPRETMA

Moderate#5 · 57% phenotype match

Trastuzumab emtansine (T-DM1)

Kadcyla · Antibody-drug conjugate (HER2/DM1)

Profile

Rare nodular regenerative TMA-like signals.

TMAGLOMHTN

Moderate#6 · 57% phenotype match

Compare Busulfan 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 Alkylating agents

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 Busulfan’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 Busulfan; 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 25 clinical records among all 55 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.