Lutetium-177 Dotatate
Lutathera · Radioligand therapy (PRRT)
Peptide receptor radionuclide therapy; proximal tubular radiation nephropathy is dose-limiting — amino-acid co-infusion is renoprotective.
CINTMA
Moderate49% phenotype match
Radiopharmaceutical (¹³¹I-MIBG)
Iobenguane I-131
Azedra · MIBG
Radiopharmaceutical (¹³¹I-MIBG) · approved 2018 · 7 citations
Recent· through 2023
Well-established evidence7/9 · 7 signals▾
- 7 citations
- Deep literature (12+ refs)
- Accrued over 14+ years
- Beyond single case reports
- High-impact journal
- Landmark reference
- Registrational / key trials
- Current through 2023
- Real-world FAERS signal
Grades the strength of the evidence base (volume, journal quality, landmark trials, recency, real-world corroboration) — not the drug's severity. A rule-based summary, not a formal certainty appraisal.
A beta-emitting norepinephrine-transporter radioligand cleared through the kidney — where the non-target absorbed dose makes renal function dose-limiting in CKD.
MildTargeted radioligand (radiopharmaceutical) therapy era (2018)
Iobenguane-scan-positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma requiring systemic anticancer therapy (age >=12 years) — FDA-approved indication for AzedraHigh-risk / relapsed neuroblastoma (conventional 131I-MIBG, investigational and off-label)Other MIBG-avid neuroendocrine tumors (investigational)
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Signature kidney injury
Signature lesion
Representative incidence21%
Reported renal toxicity is uncommon and usually low-grade. In a dosimetry-guided high-activity 131I-MIBG cohort, 3 of 14 patients (21%) had transient grade 1 renal toxicity (Maric 2023, small single-center series using conventional 131I-MIBG). In the registrational high-specific-activity trial (Azedra, n=68 dosed), renal failure was not among the most common treatment-emergent events — nausea, myelosuppression and fatigue dominated — and clinically significant (grade >=3) nephrotoxicity was rare. The kidney concern is driven less by acute events than by the delayed, cumulative absorbed radiation dose, so headline incidence figures come from small cohorts and should be read as low-grade signal rather than a robust rate.Source: PMID 36732054
Onset & rechallenge
Time to injuryDelayed (>6 weeks / cumulative)
Biphasic: modest transient creatinine changes within weeks; the characteristic radiation nephropathy is delayed, typically appearing 6-12 months or later, sometimes years out.
Distilled from: “Biphasic — modest, often transient creatinine changes within weeks of a therapeutic dose; the characteristic radiation nephropathy is delayed, typically appearing 6-12 months or later after cumulative renal irradiation, sometimes years out.” · PMID 30291194
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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.
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.
Slow, cumulative tubulointerstitial scarring — fibrosis, tubular atrophy and glomerulosclerosis with no discrete acute phase. The nitrosourea (carmustine/lomustine) lesion and delayed radioligand (radiation) nephropathy; often irreversible and detected only as a creeping creatinine months to years later.
On-target loss of endothelial nitric oxide from VEGF-pathway blockade — so characteristic it has been studied as a pharmacodynamic marker of drug exposure.
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
0%incidence
SeverityMild
ReversibilityVariable
Evidence0 refs
Nephron map
Glomerulus
Vasculature / Endothelium
Proximal TubuleBulk reabsorption + drug uptake (OCT2, OATs)
Distal Tubule / Collecting DuctFine-tuning of Na, K, Mg, acid & water
Interstitium
Tubular Lumen
Acute Tubular Necrosis
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.
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Kidney injury
Mechanism of kidney injury
131I-MIBG is renally excreted — roughly 80% of an administered dose appears in the urine over ~5 days (Coleman 2009) — so the kidney behaves as a high-absorbed-dose, non-target "critical organ" typical of renally-cleared beta-emitting radioligands. Phase 1 dosimetry projected a kidney absorbed dose of about 10.4 Gy for a 500 mCi (18.5 GBq) therapeutic administration, several-fold higher than the ~1.4 Gy delivered to marrow. During filtration, tubular transit and any parenchymal/interstitial retention, beta radiation drives DNA double-strand breaks and reactive-oxygen injury in the proximal tubular epithelium and in glomerular/peritubular capillary endothelium. The result is the classic radiation-nephropathy picture: acute low-grade tubular dysfunction early, then a slow, delayed tubulointerstitial-plus-microvascular (thrombotic-microangiopathy-like) injury with fibrosis, rising creatinine, proteinuria and hypertension over months to years. In renal impairment, slower clearance prolongs the residence time and raises the cumulative renal (and marrow) absorbed dose, which is why the kidney becomes the dose-limiting non-target organ in CKD.
Clinical presentation
Most patients are asymptomatic, with the only sign being a mild rise in serum creatinine / fall in eGFR, sometimes with low-grade proteinuria. With high cumulative activity, repeat therapeutic cycles, or preexisting CKD, a delayed chronic radiation nephropathy can emerge months to years later as progressive CKD, proteinuria and new or worsening hypertension. Acute peri-infusion blood-pressure spikes are usually catecholamine-driven (tumor stimulation), not a direct renal event, and should not be misread as acute kidney injury.
Management
Management is largely supportive and preventive. Space out or hold subsequent therapeutic doses if renal function declines; maintain hydration; monitor eGFR, urine protein and blood pressure. Treat hypertension aggressively, with renin-angiotensin blockade (ACE inhibitor / ARB) a reasonable choice given its role in mitigating radiation nephropathy in other settings (extrapolated). There is no specific antidote and no established chelation/rescue for the delivered radiation dose. Refer to nephrology for progressive CKD or significant proteinuria, and ensure peri-treatment catecholamine surges are controlled with adequate alpha-blockade so hypertensive effects are not mistaken for acute renal injury.Lesion-level management framework
Risk factors
- Preexisting CKD / reduced eGFR (slower clearance raises the renal absorbed dose)
- High cumulative administered activity and repeat therapeutic cycles
- High per-cycle renal absorbed dose
- Older age
- Pre-existing hypertension
- Diabetes mellitus
- Prior nephrotoxic chemotherapy (e.g., cisplatin, ifosfamide)
- Solitary functioning kidney or tumor abutting renal parenchyma
- Dehydration / reduced urine output that slows urinary clearance
Prevention
- Assess renal function before therapy — prefer a measured or estimated GFR — and use dosimetry-guided activity planning to keep the cumulative kidney absorbed dose within tolerance (radionuclide-therapy thresholds adopted from EBRT/PRRT are roughly <40 Gy BED without risk factors and <28 Gy with risk factors; extrapolated, not MIBG-validated)
- Ensure adequate hydration and encourage frequent voiding / bladder emptying to speed urinary clearance and lower renal and bladder-wall radiation exposure
- Reduce or individualize administered activity in renal impairment; the CKD evidence base for radiopharmaceutical dosing is limited and sometimes contradictory (Schreuder 2021)
- Give standard thyroid blockade (potassium iodide) — this protects the thyroid, not the kidney, but is part of proper preparation
- Note that amino-acid (lysine/arginine) coinfusion used to protect the kidney in peptide-receptor radionuclide therapy is NOT established for MIBG and should not be assumed to be renoprotective here
Anticancer mechanism· how it treats cancer
High-specific-activity iodine-131 meta-iodobenzylguanidine (131I-MIBG) is a norepinephrine analog taken up via the norepinephrine transporter (NET/SLC6A2) and stored in the neurosecretory granules of catecholamine-secreting neuroendocrine tumor cells; the I-131 label then delivers targeted beta-particle radiation that produces lethal DNA double-strand breaks in the tumor, with a smaller gamma component used for imaging/dosimetry.
Note · Signature injury mapped to 'atn' to capture the scout's read of radiation-mediated tubular injury; 'interstitial' represents the delayed chronic radiation-nephropathy tubulointerstitial/fibrotic component and 'hypertension' its hallmark clinical accompaniment. The dominant clinically observed renal toxicity is low-grade and often transient, but the kidney is the dose-limiting non-target organ in renal impairment because of the high renal absorbed dose from urinary clearance. Radiation-nephropathy pathophysiology also has a thrombotic-microangiopathy (endothelial) component discussed in prose; it is left out of injuryTypes because there is no drug-specific biopsy evidence for Azedra and the aim is to hedge to the evidence. classId 'radiopharm' matches the existing codebase convention for radiopharmaceuticals (e.g., batch-16, batch-17).
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Clinical depth
Renal dose adjustment
The therapeutic activity is weight-based (~18.5 GBq / 500 mCi, capped) preceded by an imaging/dosimetric dose. Because clearance is renal and the kidney is a dose-limiting non-target organ, the prescribing information recommends a reduced therapeutic activity in patients with moderate renal impairment (eGFR ~30 to <60 mL/min/1.73m2). Iobenguane I-131 has not been studied in severe renal impairment (eGFR <30) or in dialysis-dependent patients, so activity should be individualized by measured GFR and/or dosimetry with expert nuclear-medicine input; the broader radiopharmaceutical CKD-dosing evidence remains limited (Schreuder 2021).
Dialyzability & ESKD dosing
Not characterized; not studied in dialysis-dependent patients. Iobenguane is a small renally-excreted molecule and free radioiodide is in principle dialyzable, but removal of the therapeutic radioligand by hemodialysis has not been quantified, and dialyzing a beta/gamma emitter introduces radiation-safety and radioactive-waste handling concerns. Dialysis is not a recognized method to treat or reverse the delivered renal absorbed dose.
Differential diagnosis
Separate drug-related radiation nephropathy from competing causes common in this population: prerenal azotemia from therapy-related nausea/vomiting and dehydration; acute tubular injury or Fanconi syndrome from prior/concurrent nephrotoxic chemotherapy (cisplatin, ifosfamide); iodinated-contrast-associated AKI from staging CT; tumor-related ureteric obstruction or a mass abutting renal parenchyma; catecholamine-driven hemodynamic/hypertensive kidney effects intrinsic to pheochromocytoma/paraganglioma; and pre-existing diabetic or hypertensive nephrosclerosis. Radiation nephropathy is characteristically delayed and slowly progressive with hypertension and proteinuria, distinct from the abrupt creatinine rise of chemotherapy-associated ATN.
Monitoring
- Baseline and periodic serum creatinine and eGFR — in patients with risk factors, a measured GFR (Tc-99m-DTPA, Cr-51-EDTA, or Tc-99m-MAG3 clearance) detects early change better than creatinine alone (Erbas 2016)
- Urinalysis / urine protein-to-creatinine for emerging proteinuria
- Blood pressure at each visit (radiation nephropathy and the underlying catecholamine excess both raise it)
- CBC — myelosuppression is the principal acute dose-limiting toxicity and is tracked in parallel
- Thyroid function tests (radioiodine exposure)
- Cumulative renal absorbed-dose / dosimetry tracking across cycles
- Long-term renal follow-up, since radiation nephropathy is delayed by months to years
Key trials & series
- Pryma 2018 (NCT00874614) — pivotal open-label single-arm phase 2 registrational trial of high-specific-activity 131I-MIBG (Azedra) in advanced pheochromocytoma/paraganglioma; most common treatment-emergent events were nausea, myelosuppression and fatigue, with renal failure not among them
- Coleman 2009 — first-in-human phase 1 radiation-dosimetry and pharmacokinetic study establishing ~80% urinary excretion at 120 h and a projected kidney absorbed dose of ~10.4 Gy per 500 mCi therapeutic dose
- Maric 2023 — dosimetry-guided high-activity 131I-MIBG series reporting transient grade 1 renal toxicity in 3/14 (21%) patients
- Jimenez 2023 — biomarker-response analysis from the pivotal trial, confirming the ~18.5 GBq therapeutic activity and durable disease control
Clinical pearls
- The kidney is the classic 'critical organ' for a renally-excreted beta emitter: phase 1 dosimetry projected ~10.4 Gy to kidneys versus ~1.4 Gy to marrow per 500 mCi, yet marrow (myelosuppression) is usually the acute dose-limiter — the renal injury is the delayed, cumulative story (Coleman 2009).
- Unlike PRRT (177Lu/90Y-DOTATATE), amino-acid (lysine/arginine) coinfusion is not used for MIBG — renal protection here rests on hydration, frequent voiding, dosimetry and activity reduction in CKD, not on blocking tubular reabsorption.
- In CKD, slower clearance means a higher cumulative renal (and marrow) absorbed dose per unit activity — reduce or individualize the dose; the label reduces it in moderate impairment and provides no data below eGFR 30.
- Radiation nephropathy is delayed: a normal creatinine at discharge does not exclude late injury, so keep monitoring eGFR, proteinuria and blood pressure for months to years.
- Encourage hydration and frequent bladder emptying — it lowers both renal residence time and bladder-wall radiation (a cystitis risk).
- Peri-treatment blood-pressure spikes are usually catecholamine-mediated tumor stimulation, not acute kidney injury — secure adequate alpha-blockade and avoid misattributing them to the kidney.
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References
7 peer-reviewed references. Citation metadata via PubMed / NLM.
Evidence accrual
7 references · 2009–2023 · 3 since 2021Citations per year in this profile — 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.LandmarkEfficacy and Safety of High-Specific-Activity 131I-MIBG Therapy in Patients with Advanced Pheochromocytoma or Paraganglioma.Pryma DA, et al. · J Nucl Med · 2018 · PMID 30291194Pivotal open-label single-arm phase 2 registrational trial (NCT00874614) supporting FDA approval of high-specific-activity 131I-MIBG (Azedra); establishes the ~18.5 GBq therapeutic dose and the safety profile in which nausea, myelosuppression and fatigue — not renal failure — were the most common events.
- 2.LandmarkRadiation dosimetry, pharmacokinetics, and safety of ultratrace Iobenguane I-131 in patients with malignant pheochromocytoma/paraganglioma or metastatic carcinoid.Coleman RE, et al. · Cancer Biother Radiopharm · 2009 · PMID 19694582First-in-human phase 1 dosimetry/PK study; documents ~80% urinary excretion by 120 h and a projected kidney absorbed dose of ~10.4 Gy per 500 mCi therapeutic dose — the mechanistic backbone for the kidney as the renally-cleared, dose-limiting non-target organ.
- 3.Efficacy and Safety of 131I-MIBG Dosimetry-Guided High-Activity 131I-MIBG Therapy of Advanced Pheochromocytoma or Neuroblastoma.Maric I, et al. · J Nucl Med · 2023 · PMID 36732054Dosimetry-guided high-activity 131I-MIBG cohort providing the headline renal-toxicity signal — transient grade 1 renal toxicity in 3/14 (21%) patients — used for the incidence estimate.
- 4.Safe use of radiopharmaceuticals in patients with chronic kidney disease: a systematic review.Schreuder N, et al. · EJNMMI Radiopharm Chem · 2021 · PMID 34417933Systematic review of radiopharmaceutical dosing in CKD (iobenguane one of three agents examined); underpins the renal dose-adjustment guidance and the caveat that CKD-specific dosing evidence for therapeutic radiopharmaceuticals is limited and inconsistent.
- 5.Renal Function Assessment During Peptide Receptor Radionuclide Therapy.Erbas B, et al. · Semin Nucl Med · 2016 · PMID 27553471Reviews the radionuclide-therapy 'critical organ' mechanism (glomerular filtration, proximal tubular reabsorption, interstitial retention), renal absorbed-dose thresholds, risk factors, and measured-GFR monitoring — the framework applied to MIBG's radiation nephropathy.
- 6.Nephrotoxicity after PRRT with 177Lu-DOTA-octreotate.Bergsma H, et al. · Eur J Nucl Med Mol Imaging · 2016 · PMID 27160225Radioligand-therapy nephrotoxicity cohort informing the radiation-nephropathy differential and dose-threshold context (mean kidney dose ~20 Gy, low grade 3/4 toxicity), an analogous renally-relevant radionuclide-therapy comparator.
- 7.Biomarker response to high-specific-activity I-131 meta-iodobenzylguanidine in pheochromocytoma/paraganglioma.Jimenez C, et al. · Endocr Relat Cancer · 2023 · PMID 36472300Biomarker-response dataset from the pivotal trial confirming the ~18.5 GBq (~500 mCi) therapeutic activity and durable disease/blood-pressure control, anchoring dose and indication context.
Guidelines & consensus· 12
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 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 Iobenguane I-131 sits in nephrotoxicity space — each dot is an anti-cancer agent, positioned so neighbors share a kidney-injury phenotype.
Phenotype-similar agents· nearest neighbors in nephrotoxicity space
Profile
Samarium-153 lexidronam
Quadramet · Bone-seeking radiopharmaceutical (153Sm-EDTMP)
Renally excreted; dominant toxicity is reversible myelosuppression; caution in renal impairment.
ATNLYTE
Moderate47% phenotype match
Fotemustine
Muphoran · Nitrosourea (alkylating)
Class delayed cumulative tubulointerstitial/ATN; usually mild; acute signal often really cisplatin.
CINATNLYTE
Moderate43% phenotype match
Sonidegib
Odomzo · Hedgehog (SMO) inhibitor
Elevated CK / rhabdomyolysis → pigment nephropathy.
ATN
Mild43% phenotype match
Strontium-89 chloride
Metastron · Bone-seeking radiopharmaceutical
Renally excreted, so caution in renal impairment; myelosuppression is the dominant toxicity.
ATNLYTE
Moderate42% phenotype match
Nimustine (ACNU)
Nidran · Nitrosourea (alkylating)
Water-soluble nitrosourea; renal risk inferred at class level; cumulative delayed tubulointerstitial injury; DLT is myelosuppression.
CINATNLYTE
Moderate42% 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.