Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Oral selective estrogen-receptor degrader (SERD)
Elacestrant
Orserdu · Elac
An oral SERD with a nausea-dominant profile and minimal intrinsic nephrotoxicity.
MildOral selective estrogen-receptor degrader (SERD) · approved 2023
ER-positive HER2-negative ESR1-mutated advanced/metastatic breast cancer
Signature kidney injury
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)
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. Characterization is conservative given the absence of renal-specific literature; 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.
Onset
Not characterized for renal events; any prerenal AKI would track GI toxicity.
Reversibility
Reversible
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.
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
- Routine creatinine monitoring
- Review CYP3A4 drug interactions
- Avoid concurrent nephrotoxins
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.
Clinical depth
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
- Serum creatinine/eGFR periodically
- 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.
- It is hepatically cleared (CYP3A4) — no renal dose adjustment, but mind CYP3A4 interactions.
- Highly protein-bound and not dialyzable.
- Renal literature is absent; keep claims qualitative and conservative.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKI
Evidence
4 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkElacestrant (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 35584336Pivotal phase 3; nausea is the main adverse event with no meaningful direct nephrotoxicity signal.PMIDElacestrant in ER+, HER2- Metastatic Breast Cancer with ESR1-Mutated Tumors: Subgroup Analyses from the Phase III EMERALD Trial by Prior Duration of Endocrine Therapy and Bone Metastases.Bardia A et al. · Clin Cancer Res 2024 · PMID 39087959EMERALD subgroup analyses reinforcing the manageable, GI-predominant safety profile.PMIDPharmacology and pharmacokinetics of elacestrant.Beumer JH et al. · Cancer Chemother Pharmacol 2023 · PMID 37314500PK/pharmacology review (hepatic clearance) relevant for renal-clearance/creatinine interpretation.PMIDConventional Chemotherapy Nephrotoxicity.Gupta S et al. · Adv Chronic Kidney Dis 2021 · PMID 35190107Onconephrology reference contextualizing the low direct renal risk of oral SERDs.
Related agents
Other agents sharing the same signature kidney injury.