Mitotane
Lysodren · Adrenolytic
Indirect: hypoadrenalism drives hyponatremia/prerenal; cisplatin nephrotoxicity in EDP-M.
LYTEPRE
Moderate#1 · 87% phenotype match
Bone-seeking radiopharmaceutical
Strontium-89 chloride
Metastron · Sr-89
Bone-seeking radiopharmaceutical · approved 1993 · 4 citations
Aging evidence· through 2021
Fairly sourced5/9 · 4 signals
- Not met: 4 citations
- Not met: 12+ references
- Met: Accrued over 10+ years (span: 18y)
- Met: Beyond single case reports
- Met: High-impact journal
- Met: Landmark reference
- Not met: Current through 2021
- 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.
Bone-seeking beta-emitting radiopharmaceutical for painful bone metastases; partly renally excreted with caution in renal impairment, but myelosuppression — not nephrotoxicity — dominates.
Moderateestablished
Palliation of pain from multifocal osteoblastic (sclerotic) bone metastases, classically from prostate and breast cancer
§01
Signature kidney injury
Signature lesion
Intrinsic nephrotoxicity is not a defining or well-quantified effect; the prominent toxicity is transient myelosuppression (e.g., reversible hematologic toxicity reported in roughly half of treated patients in small series). Renal events are uncommon and not reliably enumerated.Source: Zorga & Birkenfeld, Ortop Traumatol Rehabil 2003 (myelosuppression-dominant)
Onset & rechallenge
Time to injuryAcute (~1–7 days)
The hematologic nadir develops over several weeks (roughly weeks 4-8) due to the long half-life, while any renal/excretion concern is tied to the early post-injection days of peak urinary excretion.
Distilled from: “Hematologic nadir typically develops over several weeks (e.g., weeks 4-8) given the long physical half-life; any renal/excretion-related concern relates to the early post-injection days when urinary excretion is highest.”
§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.
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
§03
Kidney injury
Mechanism of kidney injury
Strontium-89 is not a classic tubular toxin; its dominant toxicity is hematologic (myelosuppression, especially thrombocytopenia) from marrow irradiation. The renal relevance is twofold and indirect: a substantial fraction of an injected dose is renally excreted (urinary elimination, greatest in the early days after administration), so impaired renal function reduces clearance and can increase retained radioactivity and marrow exposure — hence caution or relative contraindication in significant renal impairment. Any direct radiation effect on the kidney/urinary tract would be an exposure phenomenon rather than a frequent clinical event. Mild electrolyte effects are possible but not characteristic.
Clinical presentation
Predominantly a transient pain flare and myelosuppression (notably thrombocytopenia/leukopenia) over weeks. There is no characteristic renal syndrome; renal concern is theoretical/PK — reduced clearance in renal impairment increasing systemic and marrow radiation exposure. Mild electrolyte changes are uncommon.
Management
Management is largely hematologic — monitor and support blood counts, with transfusion or treatment delay as needed for cytopenias. There is no specific renal antidote; in renal impairment, weigh the increased retained-dose risk against palliative benefit and consider avoiding the agent. Supportive care for any electrolyte changes.Lesion-level management framework
Risk factors
- Renal impairment (reduced excretion, increased retained dose/marrow exposure)
- Pre-existing marrow compromise or low platelet/WBC counts
- Urinary incontinence (radiation-safety/handling consideration)
- Extensive marrow involvement by tumor
Prevention
- Use caution or avoid in significant renal impairment, gated by renal function assessed before administration
- Verify adequate baseline blood counts before administration
- Encourage hydration and normal voiding to facilitate urinary clearance in the early days; observe radiation-safety urinary precautions
- Patient selection limited to osteoblastic metastases with adequate marrow reserve
Anticancer mechanism· how it treats cancer
A calcium-analog beta-emitting radionuclide (physical half-life ~50.5 days) that, after intravenous injection, is preferentially taken up into the mineral matrix of osteoblastic bone metastases, delivering localized internal radiotherapy that palliates metastatic bone pain; it is not curative and is used for symptom control rather than tumor eradication.
Note · Strontium-89 is renally excreted, so renal impairment is a caution/relative contraindication — but the clinically dominant toxicity is myelosuppression, not nephrotoxicity. Newer bone-targeted radiopharmaceuticals (e.g., radium-223) have largely superseded it in many settings.
§04
Clinical depth
Renal dose adjustment
No standardized renal dose-reduction scheme; instead, renal impairment is a caution/relative contraindication because reduced clearance increases retained activity and marrow exposure. Dosing is activity-based (e.g., ~150 MBq) per protocol with attention to baseline counts and renal function.
Dialyzability & ESKD dosing
Not a standard management consideration; once incorporated into bone mineral, strontium-89 is not meaningfully removed by dialysis. Early circulating/urinary fraction is renally handled, but dialysis is not used as antidotal clearance.
Differential diagnosis
Cytopenias after strontium-89 reflect marrow irradiation (expected) rather than renal disease; if azotemia appears, evaluate for dehydration, obstruction from prostate cancer, or other nephrotoxins rather than a primary strontium tubular lesion.
Monitoring
- Complete blood count, particularly platelets and white cells, at baseline and serially for weeks after dosing
- Renal function before administration
- Pain response (efficacy)
- Radiation-safety urinary precautions in the days after injection
Key trials & series
- Zorga & Birkenfeld (Ortop Traumatol Rehabil 2003): palliative Sr-89 series demonstrating effective bone-pain palliation with predominantly mild, transient hematotoxicity
- Liepe et al. (Semin Nucl Med 2021): dosimetry/biodistribution review of bone-seeking beta emitters including strontium-89, detailing excretion and normal-tissue dose
Clinical pearls
- Long physical half-life (~50 days) means a delayed hematologic nadir.
- Largely supplanted by radium-223 in modern bone-metastasis palliation in many centers.
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
§05
References
3 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
3 references · 2003–2021 · 1 since 2019Primary (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.
- 1.Strontium-89 in palliative treatement of painfull bone metastases.Zorga P et al. · Ortop Traumatol Rehabil · 2003 · PMID 18034034Clinical series of palliative Sr-89 showing efficacy for bone pain with predominantly mild, transient hematotoxicity — supports myelosuppression (not nephrotoxicity) as the dominant toxicity.
- 2.Dosimetry of Bone Seeking Beta Emitters for Bone Pain Palliation Metastases.Liepe K et al. · Semin Nucl Med · 2021 · PMID 34895886Dosimetry/biodistribution review covering strontium-89 excretion and normal-tissue (including marrow) radiation doses, underpinning the renal-excretion and marrow-toxicity considerations.
- 3.LandmarkAcute Kidney Injury in Patients with Cancer.Rosner MH et al. · N Engl J Med · 2017 · PMID 28467867Onconephrology context for interpreting indirect/exposure-related renal considerations versus intrinsic nephrotoxicity in cancer therapeutics.
Case reports — ranked by strength· 1
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.
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 Strontium-89 chloride 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.
Phenotype-similar agents· the numbered markers on the map above
Profile
Neratinib
Nerlynx · HER2 / pan-EGFR TKI
Severe diarrhea → prerenal AKI; loperamide prophylaxis.
PRELYTE
Moderate#2 · 87% phenotype match
Octreotide
Sandostatin · Somatostatin analog
Kidney-neutral/possibly renoprotective; renally cleared, caution in severe CKD/dialysis.
LYTEPRE
Mild#3 · 83% phenotype match
Lanreotide
Somatuline · Somatostatin analog
Kidney-neutral (CLARINET: diarrhea dominant); increased exposure in renal impairment.
LYTEPRE
Mild#4 · 82% phenotype match
Glasdegib
Daurismo · Hedgehog (SMO) inhibitor
QT prolongation and muscle spasms; AML.
PRELYTE
Mild#5 · 81% phenotype match
Darolutamide
Nubeqa · Androgen receptor inhibitor (ARSI)
Not nephrotoxic; exposure rises in severe renal impairment, so consider dose adaptation.
LYTEPRE
Mild#6 · 81% phenotype match
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 Radiopharmaceuticals
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.
- 1Radium-223 dichloridePRE — Prerenal / Hemodynamic AKIMild
- 2Ibritumomab tiuxetanPRE — Prerenal / Hemodynamic AKIMild
- 3Iobenguane I-131ATN — Acute Tubular NecrosisMild
- 4Samarium-153 lexidronamATN — Acute Tubular NecrosisModerate
- 5Lutetium-177 DotatateCIN — Chronic Interstitial NephropathyModerate
- 6Lutetium-177 PSMA-617 (vipivotide)CIN — Chronic Interstitial NephropathyModerate
- 7Strontium-89 chloride· this agentLYTE — Electrolyte DisturbanceModerate
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.