What kind of kidney injury does Darolutamide 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: Prerenal / Hemodynamic AKI.

How should kidney function be monitored during Darolutamide therapy?

Renal (and hepatic) function to inform starting dose; Blood pressure (class-level monitoring); For exposure-related tolerability in severe renal impairment; Concomitant BCRP-substrate drugs.

How can kidney injury from Darolutamide be prevented?

Recognize that exposure rises in severe renal impairment; start at 300 mg twice daily in severe renal impairment (eGFR 15-29) and in moderate hepatic impairment per labeling Review concomitant medications for interaction potential (e.g., BCRP substrates) Routine renal-specific prophylaxis not otherwise required

Who is at higher risk of kidney injury from Darolutamide?

Severe renal impairment (increased exposure); Concurrent moderate hepatic impairment (also increases exposure); Co-administration affecting BCRP substrates / shared metabolic pathways; General frailty/volume depletion in advanced prostate cancer.

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Printable monograph

Androgen receptor inhibitor (ARSI)

Darolutamide

Nubeqa · DARO

Androgen receptor inhibitor (ARSI) · approved 2019 · 5 citations

Up to date· through 2025

Fairly sourced4/9 · 4 signals

Not met: 5 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 6y)
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.

Next-generation androgen receptor inhibitor for prostate cancer; not intrinsically nephrotoxic, but systemic exposure rises in severe renal impairment, prompting dose consideration.

Mildrecent

Nonmetastatic castration-resistant prostate cancer (nmCRPC)Metastatic hormone-sensitive prostate cancer (mHSPC), in combination with docetaxel and androgen-deprivation therapy

§01

Signature kidney injury

Signature lesion

Electrolyte Disturbance

No characteristic intrinsic nephrotoxicity. In ARAMIS, rates of adverse events including hypertension were similar to placebo. Renal-relevant findings are pharmacokinetic (increased exposure in severe renal impairment); intrinsic renal injury incidence not meaningfully quantified.Source: Fizazi et al., NEJM 2019 (ARAMIS; AE profile similar to placebo)

Onset & rechallenge

Time to injuryVariable / unpredictable

No intrinsic renal injury is described (onset not applicable); the days reflect pharmacokinetics only — exposure differences in renal impairment are present from initiation, with steady state reached in about 2 days.

Distilled from: “Not applicable for intrinsic injury; exposure differences in renal impairment are present from initiation and steady state (reached in ~2 days).”

§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).
Prerenal / Hemodynamic AKISecondaryqualitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

§03

Kidney injury

Mechanism of kidney injury

Darolutamide is not an established direct nephrotoxin. Its renal relevance is pharmacokinetic: it is metabolized (oxidation and glucuronidation) and excreted in urine and feces, and systemic exposure increases in patients with severe renal impairment, so accumulation — not tubular or glomerular injury — is the concern. As an AR-pathway inhibitor (ARSI class), it can be associated with class-level cardiometabolic and, uncommonly, electrolyte/blood-pressure effects, but it showed no excess hypertension versus placebo in its pivotal trial. Any prerenal physiology relates to general illness/volume status rather than a specific drug lesion.

Clinical presentation

Generally no renal-specific presentation. The issue is increased darolutamide exposure (and potential for exposure-related adverse effects) in patients with moderate-to-severe renal impairment, rather than a recognizable nephrotoxic syndrome. Mild electrolyte or blood-pressure changes are uncommon and class-level.

Management

No renal-specific treatment is needed for the drug itself. In severe renal impairment, reduce the starting dose to 300 mg twice daily at treatment initiation given increased exposure, and monitor for exposure-related adverse effects. Manage incidental electrolyte/blood-pressure changes supportively.Lesion-level management framework

Risk factors

Severe renal impairment (increased exposure)
Concurrent moderate hepatic impairment (also increases exposure)
Co-administration affecting BCRP substrates / shared metabolic pathways
General frailty/volume depletion in advanced prostate cancer

Prevention

Recognize that exposure rises in severe renal impairment; start at 300 mg twice daily in severe renal impairment (eGFR 15-29) and in moderate hepatic impairment per labeling
Review concomitant medications for interaction potential (e.g., BCRP substrates)
Routine renal-specific prophylaxis not otherwise required

Anticancer mechanism· how it treats cancer

Structurally distinct second-generation androgen receptor (AR) signaling inhibitor that competitively antagonizes the AR, blocks AR nuclear translocation and AR-mediated transcription, and has low blood-brain barrier penetration (reducing CNS/seizure effects); it suppresses AR-driven prostate cancer growth.

Note · This is a pharmacokinetic (exposure) consideration, not nephrotoxicity. Darolutamide's low CNS penetration distinguishes it within the ARSI class; its renal story is about dose adaptation in severe impairment.

§04

Clinical depth

Renal dose adjustment

Reduce the starting dose to 300 mg twice daily in severe renal impairment (eGFR 15-29 mL/min/1.73 m2, not on hemodialysis) and in moderate hepatic impairment, because systemic exposure is increased; standard 600 mg twice daily otherwise.

Dialyzability & ESKD dosing

Dialyzability not formally established; darolutamide is substantially protein-bound and hepatically metabolized, so dialysis is unlikely to be a primary management consideration. Use clinical judgment and labeling in dialysis patients.

Differential diagnosis

AKI or electrolyte disturbance in a darolutamide-treated patient should prompt evaluation for dehydration, obstruction from prostate cancer, contrast/other nephrotoxins, or concomitant therapy — rather than attribution to a direct darolutamide tubular effect.

Monitoring

Renal (and hepatic) function to inform starting dose
Blood pressure (class-level monitoring)
For exposure-related tolerability in severe renal impairment
Concomitant BCRP-substrate drugs

Key trials & series

ARAMIS (Fizazi et al., NEJM 2019): darolutamide prolonged metastasis-free survival in nmCRPC with an adverse-event profile similar to placebo (no excess hypertension, seizures, or falls)
Zurth et al. (Clin Pharmacokinet 2021): dedicated PK study showing increased exposure in severe renal and moderate hepatic impairment, recommending dose-adaptation consideration

Clinical pearls

Low blood-brain-barrier penetration limits CNS/seizure effects, a class-distinguishing feature.
Watch BCRP-substrate interactions; little CYP/P-gp interaction otherwise.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Distal Tubule / Collecting Duct

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

Injury signatures

Electrolyte Disturbance Prerenal / Hemodynamic AKI

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

Class-level context for the major non-renal toxicities of the Androgen receptor inhibitor (ARSI) 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

5 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.

Evidence accrual

5 references · 2019–2025 · 3 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.

FDA label — boxed warning & renal dosing· renal impairment

Quoted verbatim from this agent's current FDA label (Jun 2025) — not paraphrased or interpreted. Full label on DailyMed .

Renal impairment — from the label

(not on hemodialysis): Recommended dose is 300 mg twice daily. ( 8.6 ) Moderate

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 5,501 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

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.
Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.

Crystal / Obstructive Nephropathy

ROR 2.2795% CI 1.61–3.19· 33 reports

SIADH / Hyponatremia

ROR 1.8595% CI 1.35–2.54· 39 reports

Hemorrhagic Cystitis

ROR 1.4995% CI 1.02–2.17· 27 reports

FAERS outcomes & reporting trend· 12.2% of reports w/ death · 21.8% w/ hospitalization

12.2%

Reported with a death outcome

670 of 5,501 reports

21.8%

Reported with hospitalization

1,200 of 5,501 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 9 systems · 5,501 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 0.6595% CI 0.44–0.95· 26 AKI reports ·AKI is reported less often than for other drugs (CI entirely below 1) — no disproportionate signal.

General / constitutional

Fatigue829Asthenia352Pain145Fall126Malaise126

Vascular

Hot Flush622

Gastrointestinal

Diarrhoea234Nausea192Constipation162

Nervous system

Dizziness236Neuropathy Peripheral189Headache118

Musculoskeletal

Arthralgia235Pain In Extremity170Myalgia115

Respiratory

Dyspnoea195

Skin

Rash170

Metabolic & electrolyte

Decreased Appetite150

Psychiatric

Insomnia111

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 Darolutamide 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

Lanreotide

Somatuline · Somatostatin analog

Profile

Kidney-neutral (CLARINET: diarrhea dominant); increased exposure in renal impairment.

LYTEPRE

Mild#1 · 99% phenotype match

Octreotide

Sandostatin · Somatostatin analog

Profile

Kidney-neutral/possibly renoprotective; renally cleared, caution in severe CKD/dialysis.

LYTEPRE

Mild#2 · 97% phenotype match

Mitotane

Lysodren · Adrenolytic

Profile

Indirect: hypoadrenalism drives hyponatremia/prerenal; cisplatin nephrotoxicity in EDP-M.

LYTEPRE

Moderate#3 · 90% phenotype match

Glasdegib

Daurismo · Hedgehog (SMO) inhibitor

Profile

QT prolongation and muscle spasms; AML.

PRELYTE

Mild#4 · 89% 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#5 · 89% 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#6 · 88% phenotype match

Compare Darolutamide 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.