Is kidney injury from Enzalutamide reversible?

Reversible. Typical onset: Hypertension emerges over weeks to months of therapy..

How should kidney function be monitored during Enzalutamide therapy?

Blood pressure at each visit and at home early in therapy; Serum sodium if combination therapy or symptoms; Cardiovascular risk reassessment periodically.

How can kidney injury from Enzalutamide be prevented?

Optimize antihypertensive therapy proactively

Who is at higher risk of kidney injury from Enzalutamide?

Baseline hypertension; Established cardiovascular disease; Older age; Concurrent ADT and/or combination regimens.

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Printable monograph

Androgen-receptor inhibitor

Enzalutamide

Xtandi · Enza

Androgen-receptor inhibitor · approved 2012 · 9 citations

Recent· through 2024

Deeply sourced7/9 · 6 signals

Met: 9 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 10y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2024
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.

Androgen-receptor blockade with a real hypertension signal but minimal direct nephrotoxicity.

MildAndrogen-receptor signaling inhibitor

Castration-resistant prostate cancerCastration-sensitive prostate cancerNon-metastatic CRPC

§01

Signature kidney injury

Signature lesion

Hypertension

Representative incidence11.9%

Hypertension is the dominant renovascular signal. A 2024 JAMA Oncology meta-analysis of androgen-receptor signaling inhibitors found a markedly increased risk of grade ≥3 hypertension (relative risk ~2.25); an earlier meta-analysis showed the same for enzalutamide specifically. Direct intrinsic kidney injury is uncommon; rare hyponatremia appears mainly in combination regimens. Reported rate: hypertension in 11.9% — Pooled analysis of 7 randomized clinical trials of enzalutamide in prostate cancer, 7347 patients (Zhu 2019, PMID 31557062).Source: Zhu et al., Cancer Invest 2019

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Hypertension emerges over weeks to months of therapy.

Distilled from: “Hypertension emerges over weeks to months of therapy.”

§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.

Hypertension#1 · Signatureno population incidence denominator
One of the two most common clinically relevant adverse events (PREVAIL) PMID 24881730 (opens PubMed in a new tab)
Electrolyte DisturbanceRarequalitative — no citable incidence
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

11.9%incidence

SeverityMild

ReversibilityReversible

Evidence9 citations

Nephron map

GlomerulusFiltration barrier (podocytes + endothelium)

Vasculature / EndotheliumGlomerular & peritubular capillaries

Distal Tubule / Collecting Duct

Hypertension

Raised blood pressure — archetypally on-target loss of endothelial nitric oxide from VEGF-pathway blockade, studied as a pharmacodynamic marker of drug exposure. Other agents raise it too: vascular effects of BCR-ABL, BTK and RET inhibitors and of copanlisib; abiraterone's mineralocorticoid excess; androgen suppression or blockade.

§03

Kidney injury

Mechanism of kidney injury

Androgen-receptor signaling inhibition exerts a class effect on the vasculature — reduced endothelial nitric-oxide-mediated vasodilation, plus sympathetic/RAAS contributions — raising systemic blood pressure. Unlike abiraterone, enzalutamide does not redirect steroidogenesis, so it lacks a strong mineralocorticoid-excess electrolyte syndrome; sustained uncontrolled hypertension is how renovascular/cardiovascular injury can accrue over time. Hyponatremia is occasionally reported, largely in combination settings.

Clinical presentation

New or worsened hypertension is the usual finding; serum creatinine is generally stable. Occasional electrolyte abnormalities (including hyponatremia) chiefly in combination therapy. Seizure risk (CNS penetration) is a separate non-renal concern.

Management

Standard antihypertensive treatment to target; intensify rather than interrupt for most hypertension. Rarely requires dose change for renal reasons. Manage combination-related hyponatremia by addressing the contributing agent.Lesion-level management framework

Risk factors

Baseline hypertension
Established cardiovascular disease
Older age
Concurrent ADT and/or combination regimens

Prevention

Optimize antihypertensive therapy proactively

Anticancer mechanism· how it treats cancer

Potent second-generation androgen-receptor inhibitor that blocks androgen binding to the receptor, nuclear translocation of the receptor, and receptor–DNA binding/coactivator recruitment. Used across castration-sensitive, non-metastatic and metastatic castration-resistant prostate cancer.

§04

Clinical depth

Renal dose adjustment

No dose adjustment for mild–moderate renal impairment; severe impairment and ESKD have not been formally studied. Reduce dose (to 80 mg once daily) with concomitant strong CYP2C8 inhibitors; no dose adjustment is required for hepatic impairment (Child-Pugh A-C) per label.

Dialyzability & ESKD dosing

Highly protein-bound and hepatically metabolized; not expected to be dialyzable. No established ESKD dosing — use clinical judgment and blood-pressure-directed care.

Differential diagnosis

Hypertension from ARSI vs essential/poorly controlled baseline hypertension vs VEGF-inhibitor hypertension (if on combination antiangiogenics); a rising creatinine should prompt search for a separate prerenal or obstructive cause rather than attribution to the drug.

Monitoring

Blood pressure at each visit and at home early in therapy
Serum sodium if combination therapy or symptoms
Cardiovascular risk reassessment periodically

Key trials & series

PREVAIL and AFFIRM (mCRPC)
PROSPER (nmCRPC)
ARCHES / ENZAMET (castration-sensitive)
El-Taji JAMA Oncol 2024 ARSI cardiovascular meta-analysis

Clinical pearls

Treat the blood pressure, don't stop the drug — enzalutamide hypertension is manageable with standard agents.
No mineralocorticoid syndrome: enzalutamide lacks abiraterone's hypokalemia/alkalosis because it does not shunt steroidogenesis.
It is a potent CYP3A4 inducer — re-check levels of narrow-therapeutic-index co-meds.
An unexplained creatinine rise is rarely the drug itself; look elsewhere.

Beyond the kidney — non-renal toxicities· 3 organ systems

Class-level context for the major non-renal toxicities of the Androgen-receptor inhibitor class.

Cardiac

Cardiomyopathy, QT, ischemia, myocarditis

QT, hypertension, fluid retention

Musculoskeletal

Myalgia, myositis, rhabdomyolysis, ONJ

Bone loss, fatigue, hot flashes

Hepatic / Liver

Transaminitis, hepatitis, VOD/SOS

Transaminitis (abiraterone)

§05

References

7 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

7 references · 2014–2024 · 1 since 2022

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.

Case reports — ranked by strength· 2

Single-patient and small-series reports, graded by evidentiary strength — A Strong (biopsy-proven plus a series and/or positive rechallenge), B Moderate, and C Limited (a single clinically-diagnosed case). Strongest first. Grades are inferred automatically from each report's abstract and journal — a heuristic ranking aid, not a formal quality appraisal.

CaseC · LimitedPosterior reversible encephalopathy syndrome induced by enzalutamide in a patient with castration-resistant prostate cancer.Crona DJ et al. · Invest New Drugs 2015 · PMID 25467090Enzalutamide-induced PRES presenting with hypertension, a blood-pressure-mediated complication aligning with the drug's hypertension signature.CaseC · LimitedA case report of enzalutamide administration in a dialysis-dependent patient with castration-resistant prostate cancer.Tsang ES et al. · J Oncol Pharm Pract 2018 · PMID 28147927First reported enzalutamide use in an end-stage renal disease patient on dialysis, with a sustained rise in systolic blood pressure (hypertension) after drug initiation suggestive of drug accumulation.

FDA label — boxed warning & renal dosing· renal impairment

Quoted verbatim from this agent's current FDA label (Jul 2026) — not paraphrased or interpreted. Full label on DailyMed .

Renal impairment — from the label

No dosage modification is recommended for patients with mild to moderate renal impairment (creatinine clearance [CLcr] ≥ 30 mL/min). XTANDI has not been studied in patients with severe renal impairment (CLcr < 30 mL/min) or end-stage renal disease [see Clinical Pharmacology ( 12.3 )] .

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 58,437 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.

Reporting odds ratio (ROR) — is kidney injury named in this agent's reports more often than in every other drug's? Above 1 means yes, disproportionately.
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· 3 signals

Only significant signals appear (95% CI lower bound above 1) — a phenotype missing here was tested and did not reach significance, 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 2026-10-01.

What reporting says about this profile's documented lesions

Hypertensioncorroborated · ROR 1.47 — on the terms that name the lesion (ROR 1.29)
Electrolyte DisturbanceNo disproportionate reporting — This phenotype IS reportable and this agent has enough reports, yet the reporting is not disproportionate — the one genuinely informative negative of the four.

Hemorrhagic Cystitis

ROR 2.5595% CI 2.33–2.79· 488 reports

Crystal / Obstructive Nephropathy

ROR 1.6895% CI 1.49–1.90· 260 reports

Hypertension

ROR 1.4795% CI 1.40–1.55· 1,568 reports

FAERS outcomes & reporting trend· 19.4% of reports w/ death · 19% w/ hospitalization

19.4%

Reported with a death outcome

11,360 of 58,437 reports

19%

Reported with hospitalization

11,077 of 58,437 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 58,437 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 2026-10-01.

Disproportionality (acute kidney injury):ROR 0.5795% CI 0.50–0.64· 242 AKI reports ·AKI is reported less often than for other drugs (CI entirely below 1) — no disproportionate signal.

General / constitutional

Fatigue10,267Asthenia4,171Back Pain2,298Fall1,834Weight Decreased1,784

Gastrointestinal

Nausea3,259Diarrhoea2,798Constipation1,823Dysphagia1,305Vomiting1,262

Nervous system

Dizziness3,143Headache1,664Somnolence1,017

Vascular

Hot Flush3,882

Metabolic & electrolyte

Decreased Appetite3,408

Musculoskeletal

Arthralgia2,152Pain In Extremity1,223

Respiratory

Dyspnoea1,502

Psychiatric

Insomnia1,362

Guidelines & consensus· 13

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 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsKidney Int 2024 · PMID 38519239Evaluate 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.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 Enzalutamide 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

Leuprolide

Lupron · GnRH agonist

Profile

Metabolic syndrome; indirect renal risk.

HTN

Mild#1 · 76% phenotype match

Relacorilant

Lifyorli · Selective glucocorticoid-receptor antagonist

Profile

2026 GR antagonist (ovarian); hypokalemia via cortisol/mineralocorticoid receptor — the mifepristone effect, blunted by GR-selectivity.

LYTEHTN

Mild#2 · 74% phenotype match

Abiraterone

Zytiga · CYP17 inhibitor

Profile

Mineralocorticoid excess: hypokalemia, hypertension, edema.

LYTEHTN

Moderate#3 · 72% phenotype match

Ripretinib

Qinlock · KIT switch-control inhibitor

Profile

Hypertension and alopecia in GIST.

HTN

Mild#4 · 62% phenotype match

Daratumumab

Darzalex · Anti-CD38 antibody

Profile

Tumor lysis; usable in renal impairment.

PRELYTE

Mild#5 · 57% phenotype match

Isatuximab

Sarclisa · Anti-CD38 antibody

Profile

Tumor lysis in myeloma.

PRELYTE

Mild#6 · 57% phenotype match

Compare Enzalutamide 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 Hormonal / endocrine

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.

Who studies this

The leading contributors to Enzalutamide’s clinical kidney literature on PubMed, ranked by a blend of publication volume and citation impact — filtered toward clinical work via the PubMed Humans heading and clinical publication types (trials, cohorts, case reports, guidelines, reviews). Names link to that author’s work on Enzalutamide; the PMIDs beside each name are up to three of their most recent papers on it, not the full count.

Ranked by a 50/50 blend of publication volume and a position-weighted, capped Relative Citation Ratio (NIH iCite) on this agent’s renal literature; the citation count shown is the raw total, not the ranking score — counted over the 14 clinical records among all 14 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.