What kind of kidney injury does Thiotepa cause?

Hemorrhagic Cystitis — Bleeding inflammation of the bladder urothelium — classically acrolein injury from the oxazaphosphorines (prevented by mesna), but also reported as immune-related, intravesical-chemical, or radiation-recall injury.

How should kidney function be monitored during Thiotepa therapy?

Urinalysis and gross-hematuria assessment during/after conditioning; BK/JC viruria/viremia when HC is prolonged or late; Renal function (post-renal obstruction from clots; exposure in CKD).

How can kidney injury from Thiotepa be prevented?

Hyperhydration and bladder protection during conditioning Mesna with concurrent oxazaphosphorines (cyclophosphamide/ifosfamide) Manage viral reactivation when detected

Who is at higher risk of kidney injury from Thiotepa?

Multi-alkylator conditioning (thiotepa + busulfan + fludarabine; cyclophosphamide); HLA-mismatched / male recipients; BK/JC viruria in transplant; Renal impairment (increased thiotepa/TEPA exposure).

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Printable monograph

Alkylator

Thiotepa

Tepadina · TT

Alkylator · approved 1959 · 8 citations · FAERS AKI reporting ROR 3.05 (95% CI 2.66–3.50, 207 AKI reports)

Recent· through 2024

Deeply sourced7/9 · 6 signals

Met: 8 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 26y)
Met: Beyond single case reports
Not met: Peer-reviewed sources
Met: Landmark reference
Met: Current through 2024
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 small alkylator whose urothelial bite shows up as hemorrhagic cystitis, not tubular injury.

MildAlkylator

Stem cell transplant conditioning (e.g., thiotepa-busulfan-fludarabine)Breast and ovarian cancerCNS lymphoma/leptomeningeal disease (intrathecal)Superficial bladder cancer (intravesical)

§01

Signature kidney injury

Signature lesion

Hemorrhagic Cystitis

Hemorrhagic cystitis is a recognized complication of alkylator-based conditioning, but no thiotepa-attributable rate exists. Post-transplant HC is reported at roughly 12-37% ACROSS conditioning regimens; in a 134-patient allogeneic cohort on uniform cyclophosphamide-based GVHD prophylaxis, overall HC was 23%, with TBF (thiotepa-busulfan-fludarabine) conditioning an independent risk factor at OR 1.32 alongside HLA mismatch and comorbidity score (Galli 2024). These are cohort-wide incidences confounded by concurrent cyclophosphamide and by BK/JC reactivation — thiotepa's own contribution is quantified as a relative risk, not an incidence.Source: Galli et al., Eur J Haematol 2024

Onset & rechallenge

Time to injuryVariable / unpredictable

Early hemorrhagic cystitis during/after conditioning; later HC with viral (BK/JC) reactivation.

Distilled from: “Early HC during/after conditioning; later HC with viral (BK/JC) reactivation.”

§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.

Hemorrhagic Cystitis#1 · Signaturequalitative — no citable incidence
Bleeding inflammation of the bladder urothelium — classically acrolein injury from the oxazaphosphorines (prevented by mesna), but also reported as immune-related, intravesical-chemical, or radiation-recall injury.

§03

Kidney injury

Mechanism of kidney injury

Thiotepa and its active metabolite TEPA are excreted in urine, where reactive alkylating species injure the bladder urothelium, causing mucosal inflammation, ulceration and hemorrhage (hemorrhagic cystitis). The parent drug is partly renally cleared and renal impairment increases thiotepa/TEPA exposure, but direct tubular nephrotoxicity is not the dominant lesion. BK/JC polyomavirus reactivation frequently co-contributes to HC in the transplant setting.

Clinical presentation

Dysuria, urinary frequency, and hematuria ranging from microscopic to gross with clots; suprapubic/bladder pain. Renal function is usually preserved unless clot obstruction causes post-renal AKI.

Management

Hydration, continuous bladder irrigation for clots, and treatment of contributing viral infection; severe cases may need cystoscopic clot evacuation or fulguration. Most hemorrhagic cystitis resolves with supportive care.Lesion-level management framework

Risk factors

Multi-alkylator conditioning (thiotepa + busulfan + fludarabine; cyclophosphamide)
HLA-mismatched / male recipients
BK/JC viruria in transplant
Renal impairment (increased thiotepa/TEPA exposure)

Prevention

Hyperhydration and bladder protection during conditioning
Mesna with concurrent oxazaphosphorines (cyclophosphamide/ifosfamide)
Manage viral reactivation when detected

Anticancer mechanism· how it treats cancer

Polyfunctional aziridine alkylating agent that cross-links DNA; small and lipophilic, it penetrates the CNS well. Used in high-dose transplant conditioning regimens (e.g., TBF), for CNS and breast/ovarian malignancies, and intravesically for superficial bladder cancer.

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Clinical depth

Renal dose adjustment

Renal impairment increases thiotepa and TEPA exposure, so use caution and consider dose reduction in moderate-to-severe impairment; no rigidly validated CrCl band exists. Exposure is best managed by clinical PK awareness rather than a fixed formula.

Dialyzability & ESKD dosing

Small, lipophilic, rapidly cleared; specific HD-removal data are limited and dialysis is not used for drug clearance. In ESKD, exposure considerations argue for cautious dosing rather than reliance on dialysis.

Differential diagnosis

Hemorrhagic cystitis (urothelial bleeding, dysuria, bland renal function) vs BK/JC virus-associated HC (later onset, viruria) vs clot-obstruction post-renal AKI vs true tubular injury. Bladder, not nephron, is the lesion; preserved creatinine with hematuria/dysuria is the giveaway.

Monitoring

Urinalysis and gross-hematuria assessment during/after conditioning
BK/JC viruria/viremia when HC is prolonged or late
Renal function (post-renal obstruction from clots; exposure in CKD)

Key trials & series

Galli Eur J Haematol 2024 - large cohort linking TBF (thiotepa-busulfan-fludarabine) conditioning to higher HC risk
TBF and other thiotepa-based conditioning protocols as the principal HC exposure context

Clinical pearls

Thiotepa's renal-tract toxicity is in the bladder (hemorrhagic cystitis), not the tubule - creatinine is usually normal.
In transplant HC, always test for BK/JC reactivation; it co-drives bleeding and changes management.
Renal impairment raises thiotepa/TEPA exposure - dose cautiously even though the kidney is not the target organ.

Where it strikes· nephron segments & injury signatures

Nephron segments

Bladder / Urothelium

Urine storage (outflow, not a nephron segment)

Injury signatures

Hemorrhagic Cystitis

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

6 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

6 references · 2000–2024 · 1 since 2022

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 · LimitedInappropriate antidiuretic hormone secretion after high-dose thiotepa.Sica S et al. · Bone Marrow Transplant 1999 · PMID 10482945Case of SIADH with hyponatremia attributed to high-dose thiotepa in a patient with primary CNS lymphoma, a thiotepa-specific renal water-handling/electrolyte toxicity.CaseC · LimitedRecurrence of SIADH after a high-dose regimen of thiotepa, carboplatin, and etoposide phosphate.Kleta R et al. · Med Pediatr Oncol 1998 · PMID 9680945Pediatric case describing recurrent syndrome of inappropriate antidiuretic hormone secretion (hyponatremia) following a high-dose thiotepa-containing regimen.

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

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

Boxed warning

WARNING: SEVERE MYELOSUPPRESSION and CARCINOGENICITY TEPADINA may cause severe marrow suppression, and high doses may cause marrow ablation with resulting infection or bleeding. Monitor hematologic laboratory parameters. Hematopoietic progenitor (stem) cell transplantation (HSCT) is required to prevent potentially fatal complications of the prolonged myelosuppression after high doses of TEPADINA [see Warnings and Precautions (5.1) ] TEPADINA should be considered potentially carcinogenic in humans [see Warnings and Precautions (5.7) ] WARNING: SEVERE MYELOSUPPRESSION and CARCINOGENICITY See full prescribing information for complete boxed warning. May cause severe marrow suppression or ablation with resulting infection or bleeding. Monitor hematologic laboratory parameters. (5.1) Potentially carcinogenic in humans. (5.7)

Renal impairment — from the label

In patients with moderate (creatinine clearance (CLcr) of 30 mL/min to 59 mL/min) renal impairment, decreased renal excretion may result in increased plasma levels of thiotepa and TEPA [see Clinical Pharmacology ( 12.3 ) ] . This may result in increased toxicity. Monitor patients with moderate to severe (CLcr < 30 mL/min) renal impairment for signs and symptoms of toxicity following treatment with TEPADINA for an extended period of time.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 9,494 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

Hemorrhagic Cystitiscorroborated · ROR 5.68 — on the terms that name the lesion (ROR 78.45)

Thrombotic Microangiopathy

ROR 42.9895% CI 38.17–48.39· 287 reports

Hemorrhagic Cystitis

ROR 5.6895% CI 4.89–6.59· 175 reports

SIADH / Hyponatremia

ROR 4.1795% CI 3.55–4.90· 150 reports

Glomerular Injury / Proteinuria

ROR 1.6795% CI 1.10–2.54· 22 reports

FAERS outcomes & reporting trend· 28.1% of reports w/ death · 19.1% w/ hospitalization

28.1%

Reported with a death outcome

2,672 of 9,494 reports

19.1%

Reported with hospitalization

1,813 of 9,494 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 7 systems · 9,494 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 3.0595% CI 2.66–3.50· 207 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Immune / infection

Cytomegalovirus Infection533Acute Graft Versus Host Disease458Cytomegalovirus Infection Reactivation424Infection422Sepsis400

Blood & lymphatic

Febrile Neutropenia814Neutropenia412Thrombocytopenia394Thrombotic Microangiopathy268

Gastrointestinal

Mucosal Inflammation807Diarrhoea291Graft Versus Host Disease In Gastrointestinal Tract234

General / constitutional

Pyrexia516Multiple Organ Dysfunction Syndrome272

Skin

Acute Graft Versus Host Disease In Skin448Graft Versus Host Disease In Skin257

Hepatobiliary

Venoocclusive Liver Disease403

Respiratory

Respiratory Failure229

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 Thiotepa 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

Cyclophosphamide

Cytoxan · Oxazaphosphorine alkylator

Profile

Vasopressin-independent hyponatremia; hemorrhagic cystitis.

SIADHCYST

Mild#1 · 65% phenotype match

Cabazitaxel

Jevtana · Taxane

Profile

Rare AKI; mostly GI-mediated.

PRECYST

Mild#2 · 42% phenotype match

Ifosfamide

Ifex · Oxazaphosphorine alkylator

Profile

Chloroacetaldehyde → Fanconi syndrome.

FANCATNLYTE

Severe#3 · 38% phenotype match

Docetaxel

Taxotere · Taxane

Profile

Fluid retention; low direct renal toxicity.

PRECYSTTMA

Mild#4 · 34% phenotype match

Doxorubicin

Adriamycin · Anthracycline

Profile

Experimental podocyte model; clinical proteinuria rare.

GLOMTMACYST

Mild#5 · 34% phenotype match

Gefitinib

Iressa · EGFR TKI

Profile

Rare nephrotic syndrome.

GLOMAINCYST

Mild#6 · 34% phenotype match

Compare Thiotepa 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 Thiotepa’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 Thiotepa; the PMIDs beside each name are up to three of their most recent papers on it, not the full count.

Lehmann, Leslie — their work on Thiotepa, on PubMed (opens in a new tab)2 papers · 3 citesPMID 41238193 (opens PubMed in a new tab)PMID 32372349 (opens PubMed in a new tab)

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 13 clinical records among all 35 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.