What kind of kidney injury does Mitotane 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 Mitotane therapy?

Serum sodium and other electrolytes; Volume/blood pressure status and signs of adrenal insufficiency; Renal function (especially during cisplatin-containing cycles); Mitotane plasma concentrations (therapeutic monitoring); Cortisol/ACTH and adequacy of steroid replacement.

How can kidney injury from Mitotane be prevented?

Mandatory glucocorticoid (and mineralocorticoid as needed) replacement to prevent adrenal crisis and resultant prerenal/electrolyte derangement Aggressive antiemesis and maintenance of hydration For patients with mild renal impairment receiving EDP-M, consider 24-hour continuous-infusion cisplatin to reduce nephrotoxicity risk Replace sodium to correct depletion, guided by regular volume-status assessment

Who is at higher risk of kidney injury from Mitotane?

Inadequate glucocorticoid/mineralocorticoid replacement; Concurrent cisplatin (EDP-M regimen); Pre-existing mild renal impairment; Poor performance status with poor oral intake; Persistent vomiting causing volume depletion.

Back to explorer

Printable monograph

Adrenolytic

Mitotane

Lysodren · MTT

Adrenolytic · approved 1970 · 6 citations

Up to date· through 2025

Fairly sourced5/9 · 5 signals

Met: 6 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 8y)
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.

Adrenolytic for adrenocortical carcinoma; renal risk is indirect — adrenal insufficiency drives hyponatremia and prerenal azotemia, compounded by cisplatin in EDP-M.

Moderateestablished

Advanced/metastatic adrenocortical carcinomaAdjuvant therapy after resection of adrenocortical carcinoma (high recurrence risk)Component of the EDP-M regimen (etoposide, doxorubicin, cisplatin + mitotane) for advanced diseaseControl of cortisol hypersecretion in Cushing syndrome (off-label)

§01

Signature kidney injury

Signature lesion

Electrolyte Disturbance

Intrinsic mitotane nephrotoxicity is not characteristically quantified. Clinically important renal events are indirect (adrenal insufficiency-related electrolyte/volume disturbance) or attributable to co-administered cisplatin in EDP-M; incidence not reliably enumerated for mitotane alone.Source: Turla et al., Endocrine 2022 (indirect: hypoadrenalism + cisplatin in EDP-M)

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Adrenal insufficiency and its electrolyte/volume consequences accrue over weeks of adrenolytic therapy (with any cisplatin-associated AKI in EDP-M occurring acutely within days of cycles).

Distilled from: “Adrenal insufficiency and its electrolyte/volume consequences develop over weeks of therapy as adrenolytic effect accrues; cisplatin-associated AKI in EDP-M is acute, within days of chemotherapy cycles.”

Long-term outlook & thresholds

Renal recoveryUsually reversible

Renal events with mitotane are indirect and correctable rather than a fixed lesion: adrenal-insufficiency-driven hyponatremia, volume depletion and prerenal azotemia resolve with adequate glucocorticoid/mineralocorticoid replacement and restoration of volume and electrolytes, and any AKI during EDP-M is managed as cisplatin-associated injury. There is no established direct mitotane tubular toxicity to leave permanent damage.PMID 35567656 (opens PubMed in a new tab)

Early-detection biomarkers

Serum sodium (hyponatremia) — electrolyte / prerenal signature from mitotane-induced hypoadrenalism (cortisol and, importantly, aldosterone deficiency). Mitotane's renal risk is indirect and endocrine: it induces adrenal insufficiency with mineralocorticoid (aldosterone) deficit, so a falling serum sodium is the earliest bedside marker of the volume/electrolyte derangement and prerenal azotemia that follows under-replacement. A systematic review documented aldosterone insufficiency in 36.8% of mitotane-treated patients, grounding sodium as the drug-specific early signal.PMID 34638485 (opens PubMed in a new tab)
Plasma renin activity / serum aldosterone — onset of mitotane-induced mineralocorticoid deficiency that precedes hyponatremia, volume depletion and prerenal azotemia. Because roughly a third of mitotane-treated patients require mineralocorticoid replacement, rising plasma renin activity with an inadequate aldosterone response flags evolving mineralocorticoid deficiency before frank electrolyte/volume-driven renal compromise, prompting fludrocortisone repletion. Drug-specific endocrine marker, not a tubular-injury assay.PMID 32937772 (opens PubMed in a new tab)

Long-term outcome and threshold data distilled from the agent's cited literature — educational, not a substitute for the primary sources.

Recovery across agents

§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

Mitotane has no well-established direct tubular nephrotoxicity; its renal relevance is indirect and endocrine. By inducing adrenal insufficiency (hypoadrenalism) and accelerating cortisol/aldosterone metabolism, it can produce hyponatremia, volume depletion, and prerenal azotemia, particularly when glucocorticoid/mineralocorticoid replacement is inadequate. Persistent nausea, vomiting, and asthenia signal hypoadrenalism and worsen prerenal physiology. Mitotane is given within the EDP-M regimen alongside cisplatin, a directly nephrotoxic agent — so AKI in these patients is frequently attributable to cisplatin and to the volume/electrolyte derangements of adrenal insufficiency rather than to mitotane itself.

Clinical presentation

Hyponatremia, hypotension, fatigue, nausea/vomiting and prerenal azotemia in the setting of under-replaced adrenal insufficiency; superimposed cisplatin-type AKI when EDP-M is used. Frank intrinsic kidney injury directly from mitotane is not a typical presentation.

Management

Treat the underlying adrenal insufficiency with adequate steroid replacement and restore volume/electrolytes; correct hyponatremia per cause and rate-safe guidelines. For AKI during EDP-M, manage as cisplatin-associated injury (hydration, nephrotoxin avoidance, dose/schedule modification). Mitotane itself is rarely the direct culprit for kidney injury.Lesion-level management framework

Risk factors

Inadequate glucocorticoid/mineralocorticoid replacement
Concurrent cisplatin (EDP-M regimen)
Pre-existing mild renal impairment
Poor performance status with poor oral intake
Persistent vomiting causing volume depletion

Prevention

Mandatory glucocorticoid (and mineralocorticoid as needed) replacement to prevent adrenal crisis and resultant prerenal/electrolyte derangement
Aggressive antiemesis and maintenance of hydration
For patients with mild renal impairment receiving EDP-M, consider 24-hour continuous-infusion cisplatin to reduce nephrotoxicity risk
Replace sodium to correct depletion, guided by regular volume-status assessment

Anticancer mechanism· how it treats cancer

Adrenolytic agent (an o,p'-DDD isomer related to the insecticide DDT) that is selectively cytotoxic to adrenocortical cells, causing focal degeneration of the zona fasciculata and reticularis; it suppresses cortisol production and exerts direct antitumor activity against adrenocortical carcinoma, while also accelerating peripheral steroid metabolism.

Note · The kidney threat with mitotane is endocrine and regimen-driven (hypoadrenalism + cisplatin), not direct tubular toxicity. Mitotane plasma level monitoring (target therapeutic window) is also standard for efficacy/toxicity balance.

§04

Clinical depth

Renal dose adjustment

Mitotane has no standardized CrCl-band renal dose reduction; dosing is guided by plasma-level monitoring and tolerability. Per the FDA label, mitotane is not recommended in severe renal impairment; in mild-to-moderate impairment, monitor plasma levels frequently and modify the dose as needed. In EDP-M with mild renal impairment, cisplatin scheduling (e.g., continuous infusion) is also modified to mitigate nephrotoxicity.

Dialyzability & ESKD dosing

Dialyzability not characterized/clinically relevant; mitotane is highly lipophilic and tissue-distributed, making dialysis removal unlikely to be useful.

Differential diagnosis

In a mitotane-treated patient with AKI/hyponatremia, distinguish (1) adrenal insufficiency with prerenal azotemia/volume depletion, (2) cisplatin-induced tubular injury from EDP-M, and (3) SIADH or other causes — rather than attributing injury to direct mitotane tubular toxicity.

Monitoring

Serum sodium and other electrolytes
Volume/blood pressure status and signs of adrenal insufficiency
Renal function (especially during cisplatin-containing cycles)
Mitotane plasma concentrations (therapeutic monitoring)
Cortisol/ACTH and adequacy of steroid replacement

Key trials & series

Turla et al. (Endocrine 2022): supportive-care guidance for the EDP-M regimen, explicitly addressing mitotane-induced hypoadrenalism and management of patients with mild renal impairment (cisplatin scheduling)
EDP-M established as standard first-line cytotoxic regimen for advanced adrenocortical carcinoma

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 Prerenal / Hemodynamic AKI

§05

References

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

Evidence accrual

6 references · 2017–2025 · 1 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· boxed warning · renal impairment

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

Boxed warning

WARNING: ADRENAL CRISIS IN THE SETTING OF SHOCK, SEVERE TRAUMA OR INFECTION Patients treated with LYSODREN are at increased risk for developing adrenal crisis in the setting of shock, severe trauma or infection that may lead to death. If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. Monitor patients closely for infections and instruct patients to contact their physician immediately if injury, infection, or any other concomitant illness occurs [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)]. WARNING: ADRENAL CRISIS IN THE SETTING OF SHOCK, SEVERE TRAUMA OR INFECTION See full prescribing information for complete boxed warning. Patients treated with LYSODREN are at increased risk for developing adrenal crisis in the setting of shock, severe trauma or infection that may lead to death. If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. Monitor patients closely for infections and instruct patients to contact their physician immediately if injury, infection, or any other concomitant illness occurs ( 2.3 , 5.1 ).

Renal impairment — from the label

LYSODREN is not recommended for patients with severe renal impairment. In patients with mild or moderate renal impairment, monitor mitotane plasma levels frequently and modify the dosage as needed. (8.7)

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 1,782 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 Disturbancecorroborated · ROR 5.45 — but the naming terms alone are not disproportionate, so this rests on terms merely consistent with the lesion
Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.

SIADH / Hyponatremia

ROR 6.8895% CI 5.13–9.21· 46 reports

Electrolyte Disturbance

ROR 5.4595% CI 4.38–6.78· 85 reports

Hemorrhagic Cystitis

ROR 1.8795% CI 1.04–3.39· 11 reports

FAERS outcomes & reporting trend· 12.9% of reports w/ death · 26.6% w/ hospitalization

12.9%

Reported with a death outcome

230 of 1,782 reports

26.6%

Reported with hospitalization

474 of 1,782 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 1,782 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 1.0895% CI 0.64–1.83· 14 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

Renal & urinary

Adrenal Insufficiency132

Gastrointestinal

Nausea302Diarrhoea167Vomiting151Abdominal Discomfort39Constipation35

General / constitutional

Fatigue277Asthenia104Weight Decreased62Pyrexia46

Nervous system

Dizziness118Headache53Somnolence51

Blood & lymphatic

Anaemia63Neutropenia63Febrile Neutropenia50

Metabolic & electrolyte

Decreased Appetite116Hyponatraemia42

Skin

Rash45

Endocrine

Hypothyroidism35

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 Mitotane 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

Octreotide

Sandostatin · Somatostatin analog

Profile

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

LYTEPRE

Mild#1 · 93% phenotype match

Lanreotide

Somatuline · Somatostatin analog

Profile

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

LYTEPRE

Mild#2 · 91% phenotype match

Darolutamide

Nubeqa · Androgen receptor inhibitor (ARSI)

Profile

Not nephrotoxic; exposure rises in severe renal impairment, so consider dose adaptation.

LYTEPRE

Mild#3 · 90% phenotype match

Strontium-89 chloride

Metastron · Bone-seeking radiopharmaceutical

Profile

Renally excreted, so caution in renal impairment; myelosuppression is the dominant toxicity.

LYTEPRE

Moderate#4 · 87% phenotype match

Neratinib

Nerlynx · HER2 / pan-EGFR TKI

Profile

Severe diarrhea → prerenal AKI; loperamide prophylaxis.

PRELYTE

Moderate#5 · 85% phenotype match

Glasdegib

Daurismo · Hedgehog (SMO) inhibitor

Profile

QT prolongation and muscle spasms; AML.

PRELYTE

Mild#6 · 79% phenotype match

Compare Mitotane 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.