CYP17 inhibitor
Abiraterone
Zytiga · Abi
CYP17 inhibitor · approved 2011 · 9 references
CYP17 blockade drives an ACTH-mediated mineralocorticoid excess — hypokalemia, hypertension, edema.
- Signature injury
- Electrolyte Disturbance
- Severity
- Moderate
- Reversibility
- Reversible
- Onset
- Within the first weeks of therapy; recurs if glucocorticoid coverage is inadequate or interrupted.
Signature kidney injury & incidence
Electrolyte Disturbance — representative grade ≥3 incidence ~12%.
Mineralocorticoid-excess effects are common: in COU-AA-301 fluid retention, hypertension and hypokalemia were all more frequent than with placebo-prednisone. Severe (grade 3–4) hypokalemia, occasionally to 1.7–2.1 mEq/L, is reported even with concomitant prednisone. Meta-analysis confirms an increased relative risk of hypertension. A single-center retrospective cohort of 79 patients reported renal events in 63.3% of abiraterone-treated patients — AKI in 30.4%, half of whom progressed to chronic kidney disease (Pujol-Pujol 2025). Reported rate: grade >=3 hypokalemia in 12% — 597 men with newly diagnosed high-risk metastatic castration-sensitive prostate cancer randomized to abiraterone… (Fizazi 2019, PMID 30987939).
Source: Fizazi et al., Lancet Oncol 2019 (LATITUDE)
Reported injury signatures: Electrolyte Disturbance, Hypertension.
Renal toxicity profile
- Electrolyte DisturbancePrimaryMineralocorticoid excess — hypokalemia significantly more frequent than prednisone/placebo (COU-AA-301)
- HypertensionSecondaryMineralocorticoid-driven hypertension, more frequent vs placebo (COU-AA-301)
Onset timing & rechallenge
Subacute (~1–6 weeks) — Within the first weeks of therapy; recurs if glucocorticoid coverage is inadequate or interrupted.
Mechanism of kidney injury
Clinical presentation
Management
Risk factors
- Inadequate or missed glucocorticoid co-therapy
- Baseline hypertension or hypokalemia
- Concurrent loop/thiazide diuretics
- Pre-existing adrenal suppression
Prevention
- Co-administer prednisone/prednisolone exactly as labeled
- Pre-emptive potassium repletion
- Use eplerenone (not spironolactone) for residual mineralocorticoid activity
Renal dose adjustment
Dialyzability & ESKD dosing
Differential diagnosis
Monitoring
- Serum potassium every cycle (more often if abnormal)
- Blood pressure at each visit
- Fluid/edema status
- Liver function tests per label
- Adherence to prednisone
Key trials & series
- COU-AA-301 (de Bono NEJM 2011) and COU-AA-302 mCRPC trials
- LATITUDE / STAMPEDE castration-sensitive trials
- Gill Clin Genitourin Cancer 2017 eplerenone real-world cohort
Clinical pearls
- The syndrome is apparent mineralocorticoid excess: low renin AND low aldosterone with hypokalemic alkalosis — the culprit is deoxycorticosterone, not aldosterone.
- Use eplerenone, NOT spironolactone — spironolactone's androgen-receptor agonism can blunt the anticancer effect.
- Most hypokalemia is preventable by ensuring the patient actually takes the co-prescribed prednisone.
- Eplerenone can permit steroid-sparing in selected patients who must avoid prednisone (Gill 2017).
Anticancer mechanism
Note
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
9 peer-reviewed references. Citation metadata via PubMed / NLM.
- 1.Abiraterone-Associated Renal Damage in Patients with Advanced Prostate Cancer as a Risk Factor for Mortality and Chronic Kidney Disease.Pujol-Pujol M, Rivero-Martínez M, Puente J, et al · J Clin Med · 2025 · PMID 41226956
- 2.Acute Kidney Injury in a Cancer Patient Exposed to Relugolix and Abiraterone.Elleisy M et al · Urol Int · 2025 · PMID 40652931
- 3.Abiraterone and increased survival in metastatic prostate cancer.de Bono JS et al. · N Engl J Med · 2011 · PMID 21612468
- 4.Efficacy of Eplerenone in the Management of Mineralocorticoid Excess in Men With Metastatic Castration-resistant Prostate Cancer Treated With Abiraterone Without Prednisone.Gill D et al. · Clin Genitourin Cancer · 2017 · PMID 28131750
- 5.Abiraterone-Associated Mineralocorticoid Excess: A Case Report.Shaffi SK et al. · Cureus · 2024 · PMID 38318572
- 6.Serious Hypokalemia Associated with Abiraterone Acetate in Patients with Castration-Resistant Prostate Cancer.Yamamoto Y et al. · Case Rep Urol · 2018 · PMID 30305978
- 7.The Cardiovascular Toxicity of Abiraterone and Enzalutamide in Prostate Cancer.Iacovelli R et al. · Clin Genitourin Cancer · 2017 · PMID 29339044
- 8.Cardiovascular Events and Androgen Receptor Signaling Inhibitors in Advanced Prostate Cancer: A Systematic Review and Meta-Analysis.El-Taji O et al. · JAMA Oncol · 2024 · PMID 38842801
- 9.Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial.Fizazi K et al. · Lancet Oncol · 2019 · PMID 30987939
Case reports & series (2)
The weakest rung of clinical evidence — single-patient and small-series reports, strongest first. Each carries a heuristic strength grade (A Strong / B Moderate / C Limited) inferred from its abstract and journal, not a formal appraisal. Weigh well below the primary references above.
- C1.[C · Limited]Severe Late-Onset Abiraterone-Induced Hypokalemia in a Diabetic Patient With Concomitant Adrenal Gland Incidentaloma: A Diagnostic Challenge.Tumminia A et al. · Case Rep Endocrinol · 2025 · PMID 40521126
- C2.[C · Limited]Ascending Flaccid Paralysis Secondary to Hypokalemia in A Cancer Patient using Abiraterone - A Case Report.de Almeida DCB et al. · Curr Drug Saf · 2023 · PMID 35469572