What kind of kidney injury does Radium-223 dichloride cause?

Prerenal / Hemodynamic AKI — Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

How should kidney function be monitored during Radium-223 dichloride therapy?

CBC (hemoglobin, ANC, platelets) before each injection; Volume status/weight if diarrhea occurs; Renal monitoring is not specifically mandated for drug toxicity.

How can kidney injury from Radium-223 dichloride be prevented?

Supportive hydration and management of diarrhea/GI losses Avoid combination with abiraterone plus prednisone (ERA-223 fracture/death safety signal)

Who is at higher risk of kidney injury from Radium-223 dichloride?

Extensive marrow involvement / superscan and low marrow reserve; GI fluid losses (diarrhea) causing volume depletion; Concurrent nephrotoxins or obstructive pelvic disease; Baseline CKD.

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Printable monograph

Radiopharmaceutical (alpha-emitter)

Radium-223 dichloride

Xofigo · RA223

Radiopharmaceutical (alpha-emitter) · approved 2013 · 8 citations

Aging evidence· through 2022

Fairly sourced4/9 · 4 signals

Met: 8 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 9y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2022
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.

A calcium-mimetic alpha-emitter that homes to bone metastases — the cleanest kidney of the radiopharmaceutical group.

MildBone-targeted alpha-emitter radiopharmaceutical

Castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastatic disease

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Direct renal toxicity is minimal and not a recognized feature; renal labs are typically unaffected. The dominant toxicities are gastrointestinal (diarrhea, nausea) and myelosuppression. Any AKI is essentially always attributable to other causes (obstruction, dehydration, concomitant nephrotoxins).Source: Parker et al., NEJM 2013

Onset & rechallenge

Time to injuryVariable / unpredictable

GI effects appear early and hematologic nadir develops over weeks, but there is no characteristic renal onset.

Distilled from: “GI effects early; hematologic nadir over weeks. No characteristic renal onset.”

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Renal toxicities, ranked

This agent's defining kidney lesion — its #1 signature. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Prerenal / Hemodynamic AKI#1 · Signaturequalitative — 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

Minimal direct renal handling: excretion is predominantly fecal/intestinal, with only a minor renal/urinary component, and biodistribution studies show small, transient renal remnant activity that clears rapidly. There is no targeted renal irradiation. When AKI occurs it is hemodynamic/prerenal — typically GI fluid losses from treatment-related diarrhea — rather than a drug-specific tubular lesion.

Clinical presentation

GI symptoms (diarrhea, nausea, vomiting) and myelosuppression (anemia, thrombocytopenia, neutropenia) dominate. If a creatinine rise occurs it tracks volume status (diarrhea, poor intake) rather than a primary tubulopathy.

Management

Supportive: rehydrate for volume-mediated prerenal AKI, manage GI symptoms, and support cytopenias. Hold injections for hematologic toxicity per label. No renal-specific antidote or renal dose modification is needed.Lesion-level management framework

Risk factors

Extensive marrow involvement / superscan and low marrow reserve
GI fluid losses (diarrhea) causing volume depletion
Concurrent nephrotoxins or obstructive pelvic disease
Baseline CKD

Prevention

Supportive hydration and management of diarrhea/GI losses
Avoid combination with abiraterone plus prednisone (ERA-223 fracture/death safety signal)

Anticancer mechanism· how it treats cancer

Calcium-mimetic alpha-emitter that incorporates into bone mineral at sites of high osteoblastic turnover (bone metastases), delivering short-range (<100 micron), high-linear-energy-transfer alpha radiation to adjacent tumor with minimal penetration into marrow or soft tissue.

Note · Established (2013) alpha-emitter with a well-characterized non-renal toxicity profile; renal claims are deliberately framed as minimal/indirect, supported by biodistribution and registrational safety data.

§04

Clinical depth

Renal dose adjustment

Standard 55 kBq/kg IV every 4 weeks for 6 injections. No renal dose adjustment is required given negligible renal clearance and exposure; holds are driven by hematologic parameters (ANC, platelets), not CrCl.

Dialyzability & ESKD dosing

Not a clinical consideration for toxicity, and — unlike the renally-excreted radioligands — end-stage renal disease causes no drug accumulation because clearance is predominantly fecal. Dialysis patients have been treated safely and need no renal dose adjustment: in reported hemodialysis and peritoneal-dialysis cases only a small fraction of the administered activity reached the dialysate (~1-2% across a peritoneal-dialysis course), so dialysate contamination and staff radiation exposure stay low. Standard hematologic holds still apply.

Differential diagnosis

If AKI occurs, look beyond the drug: obstructive uropathy from pelvic disease, dehydration from GI losses, concomitant nephrotoxins, and baseline CKD — radium-223 is rarely the cause.

Monitoring

CBC (hemoglobin, ANC, platelets) before each injection
Volume status/weight if diarrhea occurs
Renal monitoring is not specifically mandated for drug toxicity

Key trials & series

ALSYMPCA (Parker, NEJM 2013) — registrational phase 3 RCT showing OS benefit with a favorable, non-renal toxicity profile
Re-treatment phase 1/2 (Sartor, Prostate 2019) — no new renal safety signals over 2 years

Clinical pearls

Excretion is mostly fecal — radium-223 is the 'clean kidney' agent of the radiopharmaceutical group.
The toxicity story is marrow plus GI, not renal; no renal dose adjustment and no amino-acid renoprotection.
Do not combine with abiraterone/prednisone (ERA-223 safety signal) — a key non-renal prescribing pearl.
A rising creatinine on radium-223 should trigger a hunt for obstruction or volume depletion, not radiation nephropathy.
Dialysis is no barrier: because clearance is fecal (not renal), ESKD causes no accumulation — reported HD and PD patients were treated at standard activity with only ~1-2% of the dose recovered in dialysate.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Injury signatures

Prerenal / Hemodynamic AKI

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References

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

Evidence accrual

8 references · 2013–2022 · 2 since 2020

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 (Mar 2026) — not paraphrased or interpreted. Full label on DailyMed .

Renal impairment — from the label

No dedicated renal impairment trial for Xofigo has been conducted. Based on subgroup analyses in the randomized clinical trial, dose adjustment is not needed in patients with existing mild (creatinine clearance [CrCl] 60 to 89 mL/min) or moderate (CrCl 30 to 59 mL/min) renal impairment. No dose adjustment can be recommended for patients with severe renal impairment (CrCl less than 30 mL/min) due to limited data available (n = 2) [see Clinical Pharmacology ( 12.3 )] .

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 5,023 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

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

Hemorrhagic Cystitis

ROR 2.4895% CI 1.83–3.38· 41 reports

Crystal / Obstructive Nephropathy

ROR 2.1895% CI 1.51–3.14· 29 reports

Electrolyte Disturbance

ROR 1.3895% CI 1.08–1.77· 63 reports

FAERS outcomes & reporting trend· 20.4% of reports w/ death · 23.2% w/ hospitalization

20.4%

Reported with a death outcome

1,027 of 5,023 reports

23.2%

Reported with hospitalization

1,165 of 5,023 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 5 systems · 5,023 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 0.7795% CI 0.53–1.11· 28 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

General / constitutional

Fatigue278Pain233Malaise203Asthenia196Back Pain112

Blood & lymphatic

Anaemia283Haemoglobin Decreased243Platelet Count Decreased186Thrombocytopenia131Pancytopenia115

Gastrointestinal

Nausea239Diarrhoea213Vomiting117

Metabolic & electrolyte

Decreased Appetite175

Musculoskeletal

Bone Pain145

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 Radium-223 dichloride 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

Elotuzumab

Empliciti · Anti-SLAMF7 mAb

Profile

Kidney-neutral antibody; unchanged PK in severe impairment and dialysis; no renal dose adjustment.

PRE

Mild#1 · 89% phenotype match

Pexidartinib

Turalio · CSF1R inhibitor

Profile

Boxed hepatotoxicity; secondary renal effects.

PRE

Mild#2 · 89% phenotype match

Tisotumab vedotin

Tivdak · Antibody-drug conjugate (tissue factor/MMAE)

Profile

Ocular/bleeding toxicity dominates; renal involvement essentially unreported.

PRE

Mild#3 · 88% phenotype match

Elacestrant

Orserdu · Oral selective estrogen-receptor degrader (SERD)

Profile

2023 oral SERD; nausea-dominant, minimal intrinsic nephrotoxicity.

PRE

Mild#4 · 88% phenotype match

Tovorafenib

Ojemda · Type II pan-RAF (BRAF) inhibitor

Profile

2024 pediatric glioma RAF inhibitor; creatinine rise.

PRE

Mild#5 · 88% phenotype match

Dordaviprone

Modeyso · Imipridone (ONC201; DRD2/ClpP)

Profile

2025 imipridone for H3 K27M glioma; renally well tolerated — QT prolongation, not nephrotoxicity, is the safety focus.

PRE

Mild#6 · 88% phenotype match

Compare Radium-223 dichloride 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 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 dichloride· this agentPRE — 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 chlorideLYTE — 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.