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Oral selective estrogen-receptor degrader (SERD)

Elacestrant

Orserdu · Elac

Oral selective estrogen-receptor degrader (SERD) · approved 2023 · 4 references

An oral SERD with a nausea-dominant profile and minimal intrinsic nephrotoxicity.

Signature injury
Prerenal / Hemodynamic AKI
Severity
Mild
Reversibility
Reversible
Onset
Not characterized for renal events; any prerenal AKI would track GI toxicity.

Signature kidney injury & incidence

Prerenal / Hemodynamic AKI.

Direct nephrotoxicity is not a recognized feature. In the pivotal phase 3 EMERALD trial the dominant toxicities were nausea, fatigue, vomiting and decreased appetite; a discrete renal-injury rate was not reported. Any renal involvement is best understood as indirect/case-level (e.g., volume depletion from GI toxicity).

Source: Bidard et al., J Clin Oncol 2022 (EMERALD)

Reported injury signatures: Prerenal / Hemodynamic AKI.

Onset timing & rechallenge

Variable / unpredictable — Renal events are uncharacterized; any prerenal AKI would track GI toxicity.

Mechanism of kidney injury

No characteristic intrinsic renal lesion is established. Elacestrant is hepatically metabolized (predominantly CYP3A4) and not primarily renally cleared, so direct tubular toxicity is not expected. The plausible, indirect pathway is prerenal/hemodynamic AKI from nausea, vomiting or decreased intake causing volume depletion. Any creatinine change is more likely hemodynamic than a drug-specific tubular effect.

Clinical presentation

If renal injury occurs, a prerenal creatinine rise during GI toxicity with clinical volume depletion; there is no signature proteinuric or tubular syndrome. Nausea, vomiting, fatigue and decreased appetite are the dominant non-renal findings.

Management

Supportive: antiemetics, hydration and dose modification per label for GI toxicity; volume resuscitation for prerenal AKI. There is no drug-specific renal therapy; injury is generally reversible with volume repletion.

Risk factors

  • Volume depletion from nausea/vomiting/poor intake
  • Pre-existing CKD
  • Concurrent nephrotoxins
  • Strong CYP3A4 interactions affecting exposure (pharmacologic, not directly renal)

Prevention

  • Antiemetic prophylaxis and adequate hydration/intake
  • Review CYP3A4 drug interactions

Renal dose adjustment

No renal dose adjustment is established for mild–moderate impairment; severe impairment/ESKD are not well studied. Dose reductions per label are driven by hepatic impairment and CYP3A4 interactions, not renal function.

Dialyzability & ESKD dosing

Highly protein-bound and hepatically metabolized; not expected to be dialyzable. No ESKD dosing guidance exists.

Differential diagnosis

Prerenal AKI from GI volume loss (fluid-responsive) vs unrelated intrinsic renal disease; elacestrant has no characteristic tubular or glomerular lesion, so significant AKI warrants a search for an alternative cause.

Monitoring

  • Nausea/vomiting severity and volume/intake status
  • Liver function and CYP3A4-interacting comedications

Key trials & series

  • EMERALD (Bidard JCO 2022) — pivotal phase 3
  • EMERALD ESR1-mutant subgroup analyses (Bardia Clin Cancer Res 2024)

Clinical pearls

  • GI, not renal: elacestrant's defining toxicity is nausea — any AKI is most likely prerenal from volume loss.
  • Renal literature is absent; keep claims qualitative and conservative.

Anticancer mechanism

Oral selective estrogen-receptor degrader (SERD) that binds the estrogen receptor and promotes its degradation, antagonizing ER signaling including in ESR1-mutant tumors. Approved for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer after progression on endocrine therapy.

Note

Renal literature is genuinely thin/absent — no elacestrant nephrotoxicity or creatinine-specific publication exists. Direct nephrotoxicity is minimal; nausea is the dominant adverse event. Any creatinine mention should be framed conservatively from PK and trial-safety data, not a dedicated renal study.

Guidelines & consensus

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.

  • ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides 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.Nat Rev Nephrol · PMID 41361704
  • SIRM (2022) — SIRM-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)Recommends 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.Radiol Med · PMID 35303246
  • KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies 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.Kidney Int · PMID 33126977
  • KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses 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.Kidney Int · PMID 33276867
  • ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides 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.EClinicalMedicine · PMID 40290844
  • ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree 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.EClinicalMedicine · PMID 40290845
  • ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes 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.EClinicalMedicine · PMID 40290846
  • KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/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.Crit Care · PMID 23394211
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate 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.Kidney Int · PMID 38519239
  • KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides 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.Kidney Int · PMID 34556300
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates 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.Kidney Int · PMID 38388147
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates 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.Kidney Int · PMID 38182299
  • KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages 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.Kidney Int · PMID 40975525

References

4 peer-reviewed references. Citation metadata via PubMed / NLM.

  1. 1.Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial.Bidard FC et al. · J Clin Oncol · 2022 · PMID 35584336
  2. 2.Elacestrant in ER+, HER2- Metastatic Breast Cancer with ESR1-Mutated Tumors: Subgroup Analyses from the Phase III EMERALD Trial by Prior Duration of Endocrine Therapy plus CDK4/6 Inhibitor and in Clinical Subgroups.Bardia A et al. · Clin Cancer Res · 2024 · PMID 39087959
  3. 3.Pharmacology and pharmacokinetics of elacestrant.Beumer JH et al. · Cancer Chemother Pharmacol · 2023 · PMID 37314500
  4. 4.Conventional Chemotherapy Nephrotoxicity.Gupta S et al. · Adv Chronic Kidney Dis · 2021 · PMID 35190107
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.