Relacorilant

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)

Reported injury signatures: Electrolyte Disturbance, Prerenal / Hemodynamic AKI.

1. Electrolyte DisturbancePrimary
2. Prerenal / Hemodynamic AKISecondary

Delayed (>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.

• 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)

• Check baseline potassium and correct before starting; monitor potassium during treatment
• 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

• 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)

• 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.

• 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.

• 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 (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