Iobenguane I-131

Acute Tubular Necrosis — representative incidence ~21%.

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

Reported injury signatures: Acute Tubular Necrosis, Chronic Interstitial Nephropathy, Hypertension.

1. Acute Tubular NecrosisPrimary
2. Chronic Interstitial NephropathySecondary
3. HypertensionSecondary

Delayed (>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.

• 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

• 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

• 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

• 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

• 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.

• ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides 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.Nat Rev Nephrol · PMID 41361704
• SIRM (2022) — SIRM-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)Recommends 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.Radiol Med · PMID 35303246
• KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies 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.Kidney Int · PMID 33126977
• KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses 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.Kidney Int · PMID 33276867
• ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides 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.EClinicalMedicine · PMID 40290844
• ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree 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.EClinicalMedicine · PMID 40290845
• ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes 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.EClinicalMedicine · PMID 40290846
• KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/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.Crit Care · PMID 23394211
• KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides 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.Kidney Int · PMID 34556300
• KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates 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.Kidney Int · PMID 38388147
• KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates 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.Kidney Int · PMID 38182299
• KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages 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.Kidney Int · PMID 40975525