What kind of kidney injury does Selinexor cause?

SIADH / Hyponatremia — Inappropriate water retention at the collecting duct — high-dose cyclophosphamide. Other reported patterns: Electrolyte Disturbance, Prerenal / Hemodynamic AKI.

Is kidney injury from Selinexor reversible?

Reversible. Typical onset: Early — within the first cycle/few weeks; front-loaded..

How should kidney function be monitored during Selinexor therapy?

Serum sodium and a full metabolic panel at baseline and each cycle (more often early or with symptoms); CBC weekly initially (thrombocytopenia, neutropenia); Weight, fluid status and nutrition; Symptom/antiemetic-response review; Serum sodium and a full metabolic panel at baseline and each cycle (at least weekly early in treatment, or with symptoms).

How can kidney injury from Selinexor be prevented?

Mandatory prophylactic antiemetics (5-HT3 antagonist with or without olanzapine and an NK1 antagonist) Hydration and nutritional support

Who is at higher risk of kidney injury from Selinexor?

Baseline hyponatremia or poor oral intake; Advanced age/frailty and poor performance status; Concurrent diuretics or other SIADH-inducing drugs; Inadequate antiemetic prophylaxis and dehydration.

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Printable monograph

XPO1 (nuclear export) inhibitor

Selinexor

Xpovio · SELI

XPO1 (nuclear export) inhibitor · approved 2019 · 10 citations · FAERS AKI reporting ROR 1.59 (95% CI 1.30–1.94, 99 AKI reports)

Recent· through 2024

Fairly sourced6/9 · 6 signals

Met: 10 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 2024
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.

A first-in-class nuclear-export inhibitor whose dose-limiting toxicity is hyponatremia — usually grade >=3 and front-loaded.

ModerateXPO1 (nuclear export) inhibitor

Multiple myeloma (with bortezomib/dexamethasone after >=1 prior therapy; with dexamethasone in penta-refractory disease)Relapsed or refractory diffuse large B-cell lymphoma after >=2 lines

§01

Signature kidney injury

Signature lesion

SIADH / Hyponatremia

Representative incidence39%

Hyponatremia is common and dose-limiting. All-grade hyponatremia affected 39% of the selinexor-dexamethasone patients tabulated in the FDA label's STORM adverse-reaction table, reaching grade 3-4 in 22% — making it the leading grade >=3 non-hematologic toxicity, and one of the six grade 3-4 laboratory abnormalities the label lists at >=10%. Both rates come from the trial's safety tables rather than its abstract, which does not mention hyponatremia; a separate phase 1 dose-escalation cohort reported grade >=3 hyponatremia at a concordant 23%. Combination regimens run lower: in BOSTON grade 3-4 hyponatremia was ~8-9%, and in SADAL ~8%.Source: XPOVIO FDA label, STORM adverse-reaction table (openFDA); Chari et al., NEJM 2019 (PMID 31433920); Ho et al., Ther Adv Med Oncol 2022 (PMID 35432603)

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Early — within the first cycle or few weeks; front-loaded.

Distilled from: “Early — within the first cycle/few weeks; front-loaded.”

Long-term outlook & thresholds

Early-detection biomarkers

Serum sodium, measured on a schedule through the first cycles — The drug's dose-limiting electrolyte toxicity — hyponatraemia, which is silent even when severe. Scheduled measurement is the only thing that finds this: the toxicity is characteristically asymptomatic at the grades that force dose changes, so symptoms are not a trigger to test. The integrated safety review of 437 myeloma patients puts the window early — adverse effects mainly occur within the first 8 weeks, are reversible, and respond to supportive care — and reports that hyponatraemia was highly responsive to sodium replacement. That last detail cuts against reading this as pure SIADH, and matches the profile's own framing of an SIADH-like physiology compounded by gastrointestinal sodium and volume losses. A sodium row, not an AKI test: the renal risk here is prerenal, downstream of volume and sodium depletion. No published source establishes an SIADH mechanism for this agent, so no confirmatory osmolality/urine-sodium row is offered.PMID 32094461 (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.

§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.

SIADH / Hyponatremia#1 · Signature39%PMID 34925019 (opens PubMed in a new tab)
Hyponatremia ~39% all-grade, 22% grade >=3 with selinexor-dexamethasone (pooled analysis)
Electrolyte DisturbanceSecondaryqualitative — 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.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

39%incidence

SeverityModerate

ReversibilityReversible

Evidence10 citations

Nephron map

Vasculature / Endothelium

Distal Tubule / Collecting DuctFine-tuning of Na, K, Mg, acid & water

SIADH / Hyponatremia

Inappropriate water retention at the collecting duct — high-dose cyclophosphamide.

§03

Kidney injury

Deep diveDrug-induced SIADH: the sodium falls and the tumour takes the blameHyponatremia is the commonest electrolyte disorder in oncology and its commonest explanation is the cancer itself — which is exactly why a drug that impairs free-water excretion can go on being given for months while the sodium is treated as a feature of the disease.

Mechanism of kidney injury

Hyponatremia is the signature electrolyte toxicity — an SIADH-like physiology often compounded by gastrointestinal sodium and volume losses from nausea, vomiting, diarrhea and anorexia. Selinexor is not a direct tubular nephrotoxin; associated AKI is typically prerenal from volume depletion. In myeloma, exclude pseudohyponatremia from a high paraprotein.

Clinical presentation

A falling serum sodium (often asymptomatic; grade 3-4 is Na <125 mmol/L) with prominent nausea, vomiting, diarrhea, anorexia, weight loss and fatigue; cytopenias are also common. The disturbance clusters in cycles 1-2.

Management

Correct sodium per standard protocols (limit correction to ~8-10 mmol/L per 24 h to avoid osmotic demyelination), hydrate, and escalate antiemetics. Interrupt and dose-reduce for grade 3-4 hyponatremia, treating to Na >=130 mmol/L before resuming.Lesion-level management framework

Risk factors

Baseline hyponatremia or poor oral intake
Advanced age/frailty and poor performance status
Concurrent diuretics or other SIADH-inducing drugs
Inadequate antiemetic prophylaxis and dehydration

Prevention

Mandatory prophylactic antiemetics (5-HT3 antagonist with or without olanzapine and an NK1 antagonist)
Hydration and nutritional support

Anticancer mechanism· how it treats cancer

First-in-class oral selective inhibitor of nuclear export (SINE) that covalently binds exportin-1 (XPO1/CRM1), blocking nuclear export of tumor-suppressor proteins (p53, IkB, FOXO, p21) and of oncoprotein mRNAs (c-myc, cyclin D, Bcl-2). The resulting nuclear retention reactivates tumor suppressors and triggers cell-cycle arrest and apoptosis.

Note · Recent (2019) agent with strong, quantified electrolyte data; flagged for the onconephrology audience because hyponatremia is common and dose-limiting.

§04

Clinical depth

Renal dose adjustment

Limited renal data; no dedicated adjustment for mild-moderate renal impairment is established, and severe CKD/dialysis are not well studied — individualize with onconephrology input. Dose is otherwise modified for hyponatremia and cytopenias.

Dialyzability & ESKD dosing

Not established; highly protein-bound and not expected to be meaningfully dialyzable.

Differential diagnosis

Distinguish SINE/SIADH-like hyponatremia from hypovolemic hyponatremia (GI losses), pseudohyponatremia (myeloma paraprotein) and diuretic-induced hyponatremia; and prerenal AKI from myeloma cast nephropathy, hypercalcemia or contrast.

Monitoring

Serum sodium and a full metabolic panel at baseline and each cycle (more often early or with symptoms)
CBC weekly initially (thrombocytopenia, neutropenia)
Weight, fluid status and nutrition
Symptom/antiemetic-response review
Serum sodium and a full metabolic panel at baseline and each cycle (at least weekly early in treatment, or with symptoms)

Key trials & series

STORM (Chari, NEJM 2019) — pivotal trial; hyponatremia ~22%, predominantly grade >=3
BOSTON (Grosicki, Lancet 2020) — phase 3 in myeloma after >=1 prior line
SADAL (Kalakonda, Lancet Haematol 2020) — pivotal DLBCL trial

Clinical pearls

STORM hyponatremia was overwhelmingly grade >=3 — check sodium at least weekly early; it is dose-limiting, not a nuisance.
Scheduled multi-agent antiemetic prophylaxis plus hydration is the highest-yield intervention because much of the hyponatremia/AKI is GI-loss-driven.
In myeloma, exclude pseudohyponatremia from paraprotein and correct sodium slowly.
Toxicity is front-loaded (cycles 1-2) and managed with dose interruption/reduction.

§05

References

8 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

8 references · 2018–2024 · 3 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.

CaseB · ModerateSelinexor-associated hyponatremia: single-center, real-world data.Kala J et al. · Kidney Int 2020 · PMID 32828243Single-center real-world series of selinexor-associated hyponatremia, the drug's signature SIADH/hyponatremia kidney signature.CaseC · LimitedFirst case report of tumor lysis syndrome and acute renal failure after selinexor use in multiple myeloma.Castellon C et al. · Leuk Lymphoma 2021 · PMID 34369242Case report of tumor lysis syndrome with acute renal failure following selinexor in a multiple myeloma patient.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 8,606 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· 2 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

SIADH / Hyponatremiacorroborated · ROR 8.59 — but the naming terms alone are not disproportionate, so this rests on terms merely consistent with the lesion
Electrolyte Disturbancecorroborated · ROR 5.14 — on the terms that name the lesion (ROR 2.99)
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 8.5995% CI 7.61–9.69· 275 reports

Electrolyte Disturbance

ROR 5.1495% CI 4.64–5.69· 388 reports

FAERS outcomes & reporting trend· 17% of reports w/ death · 30.7% w/ hospitalization

17%

Reported with a death outcome

1,459 of 8,606 reports

30.7%

Reported with hospitalization

2,642 of 8,606 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 8,606 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 1.5995% CI 1.30–1.94· 99 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Gastrointestinal

Nausea2,622Diarrhoea1,325Vomiting951Constipation452

General / constitutional

Fatigue1,985Asthenia863Weight Decreased648Fall291Pyrexia258

Blood & lymphatic

Thrombocytopenia756Platelet Count Decreased687Anaemia466White Blood Cell Count Decreased325Neutropenia242

Metabolic & electrolyte

Decreased Appetite1,384Dehydration281Hyponatraemia218

Nervous system

Dizziness470Headache239

Immune / infection

Pneumonia472

Respiratory

Dyspnoea306

Psychiatric

Confusional State236

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 Selinexor 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

Vinflunine

Javlor · Vinca alkaloid

Profile

Used because of renal impairment (cisplatin-unfit urothelial); CrCl-based dose bands; watch SIADH/hyponatremia.

LYTEPRESIADH

Mild#1 · 83% phenotype match

Glasdegib

Daurismo · Hedgehog (SMO) inhibitor

Profile

QT prolongation and muscle spasms; AML.

PRELYTE

Mild#2 · 78% phenotype match

Interleukin-2 (high-dose)

Proleukin · Cytokine

Profile

Capillary-leak prerenal AKI.

PRELYTESIADH

Moderate#3 · 75% phenotype match

Neratinib

Nerlynx · HER2 / pan-EGFR TKI

Profile

Severe diarrhea → prerenal AKI; loperamide prophylaxis.

PRELYTE

Moderate#4 · 73% phenotype match

Afamitresgene autoleucel (Afami-cel)

Tecelra · MAGE-A4 TCR-T cell therapy

Profile

First TCR-T cell therapy for a solid tumor; CRS-associated hemodynamic AKI.

PRELYTE

Moderate#5 · 72% phenotype match

Ziftomenib

Komzifti · Menin inhibitor

Profile

2025 NPM1-mutated AML menin inhibitor; differentiation syndrome and tumor lysis.

PRELYTE

Moderate#6 · 72% phenotype match

Compare Selinexor 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 Other targeted agents

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.