What kind of kidney injury does Estramustine cause?

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

Is kidney injury from Estramustine reversible?

Reversible. Typical onset: Edema/VTE within weeks to the first 2 months..

How should kidney function be monitored during Estramustine therapy?

Serum sodium and fluid balance (estrogenic sodium and fluid retention); Weight, edema and blood pressure; Signs of DVT/PE; LFTs, calcium and glucose; Periodic cardiovascular assessment.

How can kidney injury from Estramustine be prevented?

Cardiovascular risk assessment before starting Consider prophylactic anticoagulation in some regimens (e.g. low-dose warfarin in docetaxel-estramustine protocols) Shortened estramustine exposure schedules

Who is at higher risk of kidney injury from Estramustine?

Prior cardiovascular disease or thromboembolism; Heart failure and edematous states; Longer/higher estramustine exposure (toxicity reduced by shortened dosing schedules).

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Printable monograph

Hormonal–alkylating conjugate

Estramustine

Emcyt · ESTR

Hormonal–alkylating conjugate · approved 1981 · 7 citations

Dated evidence· through 2015Legacy

Largely superseded — displaced in prostate cancer by taxanes and androgen-receptor-pathway agents (abiraterone, enzalutamide, darolutamide); ~5 papers/year over the last five years. Its renal signal is hemodynamic (estrogenic fluid retention, venous thromboembolism), not direct nephrotoxicity.

Fairly sourced6/9 · 5 signals

Met: 7 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 35y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2015
Not 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.

An estradiol-mustard conjugate whose renal signal is hemodynamic — estrogenic fluid retention and thromboembolism, not direct nephrotoxicity.

MildHormonal-alkylating conjugate

Metastatic or progressive (hormone-refractory) prostate carcinoma

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Renal injury is hemodynamic/prerenal rather than a quantified direct rate. The dominant safety liability is venous (and arterial/cardiovascular) thromboembolism with fluid retention/edema; in randomized data the majority of cardiovascular complications occurred within the first year.Source: Petrylak et al., NEJM 2004

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Edema and VTE develop within weeks up to the first 2 months.

Distilled from: “Edema/VTE within weeks to the first 2 months.”

§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.

Prerenal / Hemodynamic AKI#1 · Signaturequalitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

§03

Kidney injury

Mechanism of kidney injury

Largely functional/prerenal via estrogenic activity: sodium and fluid retention with edema, and a markedly increased risk of venous thromboembolism (and arterial/cardiovascular events) from estrogen-mediated procoagulant changes. Fluid shifts, heart failure and thrombotic events can produce prerenal/cardiorenal azotemia; there is no characteristic direct tubulotoxic lesion.

Clinical presentation

Lower-extremity edema, weight gain and dyspnea (fluid overload/heart failure), DVT/PE, and a prerenal rise in creatinine. Cardiovascular/thromboembolic events often occur within the first 1-2 months. Gynecomastia and GI toxicity are common estrogenic/mustard effects.

Management

Diuretics for fluid retention, anticoagulation for venous thromboembolism, and holding the drug for significant cardiovascular/thrombotic events while managing the cardiorenal physiology.Lesion-level management framework

Risk factors

Prior cardiovascular disease or thromboembolism
Heart failure and edematous states
Longer/higher estramustine exposure (toxicity reduced by shortened dosing schedules)

Prevention

Cardiovascular risk assessment before starting
Consider prophylactic anticoagulation in some regimens (e.g. low-dose warfarin in docetaxel-estramustine protocols)
Shortened estramustine exposure schedules

Anticancer mechanism· how it treats cancer

Conjugate of estradiol and a nitrogen mustard (normustine) joined by a carbamate link. It acts mainly as an antimicrotubule agent — binding microtubule-associated proteins and beta-tubulin to disrupt the mitotic spindle (rather than primarily as an alkylator) — while the estradiol moiety suppresses gonadotropins and testosterone; it synergizes with taxanes.

Note · Established (1981) agent; renal injury is prerenal/hemodynamic (fluid retention plus VTE), not direct tubular toxicity, and is not separately quantified.

§04

Clinical depth

Renal dose adjustment

No established CrCl-based dose algorithm; use caution with cardiovascular/cerebrovascular disease and in heart failure. It is contraindicated with active thromboembolic disorders.

Dialyzability & ESKD dosing

Not characterized/not relevant (highly protein-bound and lipophilic).

Differential diagnosis

Estrogenic fluid retention/heart failure versus VTE-related cardiorenal injury versus prerenal volume depletion (GI losses) versus progressive prostate disease/obstruction.

Monitoring

Serum sodium and fluid balance (estrogenic sodium and fluid retention)
Weight, edema and blood pressure
Signs of DVT/PE
LFTs, calcium and glucose
Periodic cardiovascular assessment

Key trials & series

SWOG 9916 (Petrylak, NEJM 2004) — pivotal docetaxel/estramustine survival trial documenting excess cardiovascular events
Randomized estramustine vs conventional estrogen (Hedlund, Scand J Urol Nephrol Suppl 1980) — cardiovascular complication timing

Clinical pearls

The renal signal is hemodynamic/prerenal from estrogenic fluid retention and thromboembolism — not direct nephrotoxicity.
VTE and cardiovascular events are the dominant safety liability and drove estramustine's decline in favor of taxanes.
One-day oral estramustine dosing reduces thromboembolic and GI toxicity.
Adding estramustine to docetaxel improved survival (SWOG 9916) but at the cost of more cardiovascular/embolic events versus mitoxantrone.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Injury signatures

Prerenal / Hemodynamic AKI

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

Class-level context for the major non-renal toxicities of the Hormonal–alkylating conjugate class.

Ophthalmic

Keratopathy, uveitis, retinopathy

Visual disturbance (crizotinib)

Hepatic / Liver

Transaminitis, hepatitis, VOD/SOS

Transaminitis

Neurologic

Neuropathy, encephalopathy, ICANS, PRES

CNS effects (lorlatinib)

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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 · 1980–2015 · 1 since 2013

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· 1

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 · LimitedHemolytic-uremic syndrome during therapy with estramustine phosphate for advanced prostatic cancer.Tassinari D et al. · Oncology 1999 · PMID 9949296Reports acute renal impairment as part of a hemolytic-uremic syndrome arising 3 weeks after starting estramustine phosphate, with renal function improving after drug discontinuation.

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 Estramustine 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

Dacarbazine

DTIC · Alkylator

Profile

Rare hepatic veno-occlusive disease; minimal direct renal injury.

PRE

Mild#1 · 99% phenotype match

Asparaginase

Elspar · Enzyme

Profile

Rare AKI; pancreatitis-mediated.

PRE

Mild#2 · 88% phenotype match

Belzutifan

Welireg · HIF-2α inhibitor

Profile

Anemia/hypoxia; emerging renal profile in VHL/RCC.

PRE

Mild#3 · 88% phenotype match

Eribulin

Halaven · Microtubule inhibitor

Profile

Reduced clearance in renal impairment.

PRE

Mild#4 · 88% phenotype match

Irinotecan

Camptosar · Topoisomerase I inhibitor

Profile

Diarrhea-driven prerenal AKI.

PRE

Mild#5 · 88% phenotype match

Mirvetuximab soravtansine

Elahere · Antibody-drug conjugate (FRα/DM4)

Profile

Ocular toxicity dominates; renal involvement indirect/case-level (GI volume loss).

PRE

Mild#6 · 88% phenotype match

Compare Estramustine 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.