What kind of kidney injury does Relacorilant cause?

Electrolyte Disturbance — Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia). Other reported patterns: Hypertension.

How should kidney function be monitored during Relacorilant therapy?

Serum potassium at baseline and periodically during treatment (the key renal-relevant lab); Magnesium and bicarbonate/CO2 (alkalosis) alongside potassium; Blood pressure and volume status (mineralocorticoid-excess physiology); ECG/QT when potassium is low or QT-prolonging co-medications are used; Creatinine to exclude an alternative cause if it rises (relacorilant itself is not a tubular toxin).

How can kidney injury from Relacorilant be prevented?

Check baseline potassium and correct it before starting Anticipate mineralocorticoid-excess physiology and consider mineralocorticoid-receptor blockade (e.g., spironolactone) if hypokalemia emerges, as in the mifepristone experience Review co-medications for additive potassium loss or QT prolongation Maintain hydration and nutrition through the nab-paclitaxel cycles

Who is at higher risk of kidney injury from Relacorilant?

Baseline hypokalemia or concurrent potassium-wasting drugs (loop/thiazide diuretics, amphotericin); High endogenous cortisol states or conditions that raise cortisol; Poor oral intake, vomiting, or diarrhea compounding potassium loss; Pre-existing metabolic alkalosis; Concurrent QT-prolonging drugs (hypokalemia amplifies arrhythmia risk).

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Printable monograph

Selective glucocorticoid-receptor antagonist

Relacorilant

Q: Is kidney injury from Relacorilant reversible?

Reversible. Typical onset: Electrolyte shifts, if they develop, track cumulative cortisol/MR activation over the treatment course rather than a single dose, and are typically detected on routine chemistry monitoring during cycles rather than as an acute event..

Lifyorli · REL

Selective glucocorticoid-receptor antagonist · approved 2026 · 3 citations

Up to date· through 2025

Fairly sourced6/9 · 5 signals

Not met: 3 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 24y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2025
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.

A selective glucocorticoid-receptor antagonist whose kidney-relevant hazard is not tubular injury but electrolytes: blocking cortisol's own receptor can push cortisol onto the mineralocorticoid receptor and drive hypokalemia — the effect its selectivity is engineered to minimize.

MildSelective glucocorticoid-receptor antagonist

Platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, in combination with nab-paclitaxelInvestigated across other cortisol-driven and hormone-sensitive tumors (the selective GR-modulation strategy)

§01

Signature kidney injury

Signature lesion

Electrolyte Disturbance

No discrete drug-specific incidence of relacorilant acute kidney injury is published; in the registrational phase 3 ROSELLA trial (Olawaiye, Lancet 2025; n=381) the adverse-event profile with relacorilant plus nab-paclitaxel was similar to nab-paclitaxel alone after adjusting for exposure, and no new safety signals were reported. The renal-relevant concern is electrolyte, specifically hypokalemia, inferred from the pharmacology of GR antagonism rather than from a large observed AKI signal. The precedent is mifepristone, a non-selective GR/PR antagonist, where blocking cortisol's own receptor allowed cortisol to activate the mineralocorticoid receptor and produce clinically significant, spironolactone-responsive hypokalemia (Chu, J Clin Endocrinol Metab 2001). Relacorilant is a selective GR antagonist designed to reduce this and other off-target effects, so the hypokalemia risk is expected to be milder — a monitoring point, not a dominant toxicity.Source: No drug-specific AKI incidence; electrolyte (hypokalemia) risk inferred from GR-antagonist pharmacology (mifepristone precedent — Chu 2001); ROSELLA reported no new safety signals (Olawaiye 2025)

Onset & rechallenge

Time to injuryDelayed (>6 weeks / cumulative)

Electrolyte shifts (hypokalemia), if they develop, track cumulative cortisol/mineralocorticoid-receptor activation over the treatment course and are detected on routine chemistry rather than as an acute event.

Distilled from: “Electrolyte shifts, if they develop, track cumulative cortisol/MR activation over the treatment course rather than a single dose, and are typically detected on routine chemistry monitoring during cycles rather than as an acute event.” · PMID 11502780 (opens PubMed in a new tab)

§02

Renal toxicities, ranked

This agent's kidney lesions ordered by prominence — the #1 signature lesion first, then secondary and rare patterns. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Electrolyte Disturbance#1 · Signaturequalitative — no citable incidence
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).
HypertensionSecondaryqualitative — no citable incidence
On-target loss of endothelial nitric oxide from VEGF-pathway blockade — so characteristic it has been studied as a pharmacodynamic marker of drug exposure.

§03

Kidney injury

Mechanism of kidney injury

The kidney-relevant effect is on distal electrolyte handling, not on tubular structure. Cortisol binds the mineralocorticoid receptor (MR) with affinity similar to aldosterone; normally the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 protects the MR by inactivating cortisol in the distal nephron. When the glucocorticoid receptor is antagonized, negative feedback is lost and circulating cortisol can rise; if cortisol overwhelms the protective enzyme, it activates the distal-tubule MR like a mineralocorticoid, driving sodium retention and renal potassium and hydrogen-ion wasting — hypokalemia and metabolic alkalosis, sometimes with volume/blood-pressure effects (Chu, J Clin Endocrinol Metab 2001, documents exactly this with mifepristone and its reversal by MR blockade). Because relacorilant is selective for GR and is given intermittently around chemotherapy, the magnitude of cortisol-driven MR activation is expected to be smaller than with high-dose mifepristone. There is no evidence of direct tubular, interstitial, or glomerular toxicity from relacorilant itself.

Clinical presentation

When it occurs, the picture is biochemical rather than a rising creatinine: hypokalemia (fatigue, cramps, arrhythmia risk) with possible metabolic alkalosis, occasionally with mild sodium retention and blood-pressure elevation — the mineralocorticoid-excess pattern. Overt acute kidney injury is not a characteristic feature; a significant creatinine rise in a patient on relacorilant plus nab-paclitaxel should prompt a search for another cause (volume depletion, the taxane, contrast, obstruction, or disease progression).

Management

Management is electrolyte repletion and, when needed, mineralocorticoid-receptor blockade — the lesson carried over from mifepristone, where hypokalemia responded to spironolactone (Chu, J Clin Endocrinol Metab 2001). Replace potassium (and magnesium, which facilitates potassium correction), treat any metabolic alkalosis by addressing the driver, and add an MR antagonist for persistent or recurrent hypokalemia attributable to cortisol-MR activation. Hold or adjust per protocol for severe electrolyte derangement. Because relacorilant does not injure the tubule directly, standard supportive care and correction of the electrolyte abnormality — not drug-specific renal rescue — are the mainstays.Lesion-level management framework

Risk factors

Baseline hypokalemia or concurrent potassium-wasting drugs (loop/thiazide diuretics, amphotericin)
High endogenous cortisol states or conditions that raise cortisol
Poor oral intake, vomiting, or diarrhea compounding potassium loss
Pre-existing metabolic alkalosis
Concurrent QT-prolonging drugs (hypokalemia amplifies arrhythmia risk)

Prevention

Check baseline potassium and correct it before starting
Anticipate mineralocorticoid-excess physiology and consider mineralocorticoid-receptor blockade (e.g., spironolactone) if hypokalemia emerges, as in the mifepristone experience
Review co-medications for additive potassium loss or QT prolongation
Maintain hydration and nutrition through the nab-paclitaxel cycles

Anticancer mechanism· how it treats cancer

Oral, first-in-class selective glucocorticoid receptor (GR) antagonist that blocks cortisol signaling at the GR without meaningful antagonism of the progesterone receptor (distinguishing it from mifepristone). In cancer, tumor GR activation by cortisol transcriptionally upregulates anti-apoptotic proteins and blunts chemotherapy-induced tumor-cell death; antagonizing GR restores chemosensitivity. It is given in combination with nab-paclitaxel (dosed around the chemotherapy infusion) in platinum-resistant ovarian cancer.

§04

Clinical depth

Renal dose adjustment

No established pharmacokinetic renal dose adjustment. Relacorilant is a hepatically metabolized small molecule and eligibility in ROSELLA required adequate organ function; dedicated data in severe renal impairment or dialysis are limited. The clinically important levers are electrolyte monitoring and MR blockade rather than a GFR-based milligram change. As a strong CYP3A substrate/inhibitor it carries drug-interaction considerations that matter more to dosing than renal function does.

Dialyzability & ESKD dosing

Not characterized as dialyzable and not clinically relevant: relacorilant is a protein-bound, hepatically cleared small molecule, and its principal renal-relevant effect (hypokalemia) is managed by repletion and mineralocorticoid-receptor blockade, not by dialysis. There is no role for dialysis in removing the drug.

Differential diagnosis

The task is to attribute an electrolyte or creatinine abnormality correctly. Cortisol-MR-driven hypokalemia is favored by concurrent metabolic alkalosis, sodium retention, and sometimes mild hypertension, and it responds to potassium repletion and MR blockade. Distinguish it from GI potassium loss (diarrhea/vomiting), diuretic effect, and amphotericin or platinum-related magnesium/potassium wasting. A genuine rise in creatinine is not expected from relacorilant and should redirect the workup to the nab-paclitaxel partner, volume depletion, contrast, obstruction, or disease — this is an electrolyte story, not a tubular-injury story.

Monitoring

Serum potassium at baseline and periodically during treatment (the key renal-relevant lab)
Magnesium and bicarbonate/CO2 (alkalosis) alongside potassium
Blood pressure and volume status (mineralocorticoid-excess physiology)
ECG/QT when potassium is low or QT-prolonging co-medications are used
Creatinine to exclude an alternative cause if it rises (relacorilant itself is not a tubular toxin)

Key trials & series

ROSELLA / GOG-3073 / ENGOT-ov72 (Olawaiye, Lancet 2025) — randomized phase 3 in platinum-resistant ovarian cancer (n=381); relacorilant plus nab-paclitaxel improved progression-free and interim overall survival versus nab-paclitaxel alone, with a similar adverse-event profile after adjusting for exposure and no new safety signals — the registrational trial and the basis for the 'no dominant renal toxicity' framing.
Selective GR modulation in ovarian cancer models (Taya, J Gynecol Oncol 2024) — preclinical/translational work on the GR-antagonism-restores-chemosensitivity rationale, referencing the randomized phase 2 that showed a progression-free-survival benefit for a selective GR modulator plus chemotherapy.
Mifepristone in refractory Cushing's disease (Chu, J Clin Endocrinol Metab 2001) — the mechanistic anchor for the electrolyte hazard: GR antagonism raised cortisol, which activated the mineralocorticoid receptor to cause severe hypokalemia that responded to spironolactone — the effect relacorilant's GR-selectivity is designed to minimize.

Clinical pearls

Think electrolytes, not creatinine: relacorilant's kidney-relevant hazard is hypokalemia from cortisol activating the mineralocorticoid receptor, not tubular injury.
It is the selective successor to mifepristone's problem — GR-selectivity is meant to blunt the cortisol-MR hypokalemia that dogged the non-selective antagonist.
If hypokalemia appears, reach for a mineralocorticoid-receptor antagonist (spironolactone) as well as repletion — the same fix that worked with mifepristone.
A rising creatinine on relacorilant plus nab-paclitaxel is usually the taxane, volume, or disease — look past the GR antagonist.
Watch the QT when potassium runs low, especially with other QT-prolonging drugs.

Where it strikes· nephron segments & injury signatures

Nephron segments

Distal Tubule / Collecting Duct

Fine-tuning of Na, K, Mg, acid & water

Vasculature / Endothelium

Glomerular & peritubular capillaries

Injury signatures

Electrolyte Disturbance Hypertension

§05

References

3 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

3 references · 2001–2025 · 2 since 2023

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.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 24 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.

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 reported phenotypes

24 total FAERS reports is below the 50 this atlas requires before quoting an odds ratio, so report counts are shown instead of RORs and none of these counts as a signal. A phenotype missing below was queried and never cleared even the nominal CI bar, 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 2026-08-23.

What reporting says about this profile's documented lesions

Electrolyte Disturbancecorroborated · ROR 15.53 — but the naming terms alone are not disproportionate, so this rests on terms merely consistent with the lesion
HypertensionToo few reports — This agent has too few total FAERS reports for a ratio to mean anything; the atlas shows counts, not shares, below that floor.

SIADH / Hyponatremia

3 reports

Crystal / Obstructive Nephropathy

2 reports

Electrolyte Disturbance

3 reports

Hemorrhagic Cystitis

1 report

FAERS outcomes & reporting trend· 2 of 24 reports w/ death · 17 w/ hospitalization

24 reports is below the 50 this atlas requires before quoting a percentage, so the counts are shown instead of shares.

2 of 24

Reported with a death outcome

too few reports to express as a share

17 of 24

Reported with hospitalization

too few reports to express as a share

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 9 systems · 24 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 2026-08-08.

Renal & urinary

Cystitis Escherichia1Cystitis Haemorrhagic1

Gastrointestinal

Nausea4Diarrhoea2Stomatitis2Vomiting2Abdominal Discomfort1

General / constitutional

Angioedema2Asthenia1Chest Pain1

Metabolic & electrolyte

Dehydration2Hyponatraemia2

Immune / infection

Pneumonia2Clostridium Difficile Infection1

Cardiac

Atrial Fibrillation2

Blood & lymphatic

Febrile Neutropenia2

Nervous system

Aphasia1Cognitive Disorder1

Psychiatric

Confusional State1

Guidelines & consensus· 12

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.

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 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 Relacorilant 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

Enzalutamide

Xtandi · Androgen-receptor inhibitor

Profile

Hypertension; rare electrolyte effects.

HTNLYTE

Mild#1 · 74% phenotype match

Abiraterone

Zytiga · CYP17 inhibitor

Profile

Mineralocorticoid excess: hypokalemia, hypertension, edema.

LYTEHTN

Moderate#2 · 69% phenotype match

Glasdegib

Daurismo · Hedgehog (SMO) inhibitor

Profile

QT prolongation and muscle spasms; AML.

PRELYTE

Mild#3 · 67% phenotype match

Selinexor

Xpovio · XPO1 (nuclear export) inhibitor

Profile

Hyponatremia is common and dose-limiting.

SIADHLYTEPRE

Moderate#4 · 58% phenotype match

Gedatolisib

Revtorpyk · Pan-PI3K inhibitor

Profile

2026 IV pan-PI3K + mTORC1/2 (breast); on-target hyperglycemia and low-grade Na/K/Mg drift — creatinine up 14% vs 8% control, grade 3-4 rare.

LYTEPRE

Mild#5 · 57% phenotype match

Sevabertinib

Hyrnuo · HER2/EGFR TKI

Profile

2025 reversible HER2/EGFR TKI; profuse diarrhea (84-91%) → prerenal AKI, plus EGFR-pathway renal magnesium wasting.

PRELYTE

Mild#6 · 57% phenotype match

Compare Relacorilant 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 Other targeted 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.