Radioligand therapy (PSMA)
Lutetium-177 PSMA-617 (vipivotide)
Pluvicto · LUPS
Radioligand therapy (PSMA) · approved 2022 · 11 references
A PSMA-targeted beta-emitter for prostate cancer whose kidney is the highest-dose internal organ — though the salivary glands usually steal the spotlight.
- Signature injury
- Chronic Interstitial Nephropathy
- Severity
- Moderate
- Reversibility
- Partially reversible
- Onset
- Renal changes are delayed/gradual; xerostomia can appear early during treatment.
Signature kidney injury & incidence
Chronic Interstitial Nephropathy — representative grade ≥3 incidence ~9.4%.
Clinically significant nephrotoxicity is uncommon in trial populations and is not well quantified; in VISION renal adverse events were infrequent. Dosimetry consistently shows the kidney is the highest-dose internal organ, but the dose-limiting clinical toxicities are usually xerostomia (salivary/lacrimal uptake) and myelosuppression rather than renal failure. Reported rate: grade >=3 ctcae nephrotoxicity worsening to grade 3 in 9.4% — 32 consecutive heavily pre-treated mCRPC patients selected by 68Ga-PSMA-11 PET/CT and given 177Lu-PSMA-617 monotherapy… (Maffey-Steffan 2020, PMID 31776632).
Source: Maffey-Steffan et al., Eur J Nucl Med Mol Imaging 2020
Reported injury signatures: Chronic Interstitial Nephropathy, Electrolyte Disturbance.
Renal toxicity profile
- Chronic Interstitial NephropathyPrimary
- Electrolyte DisturbanceSecondary
Onset timing & rechallenge
Delayed (>6 weeks / cumulative) — Renal changes are delayed/gradual; xerostomia can appear early.
Mechanism of kidney injury
Clinical presentation
Management
Risk factors
- Baseline CKD or single functioning kidney
- Hydronephrosis/obstructive uropathy from pelvic disease
- High cumulative administered activity
- Prior nephrotoxins (platinum, taxanes)
- Dehydration
Prevention
- Hydration and diuresis to reduce tubular residence time
- Exclude and relieve obstructive uropathy before and during therapy
- Dosimetry awareness of renal absorbed dose (~23 Gy renal tolerance principle)
- Salivary protection measures are investigational; routine amino-acid renoprotection is NOT required (renal dose is lower than PRRT and salivary glands are usually dose-limiting)
Renal dose adjustment
Dialyzability & ESKD dosing
Differential diagnosis
Monitoring
- Review for obstructive uropathy (imaging) if creatinine rises
- Salivary/ocular symptom assessment each cycle
Key trials & series
- VISION (Sartor, NEJM 2021) — registrational phase 3 RCT defining the renal/xerostomia safety profile
- TheraP (vs cabazitaxel) — supportive comparative context
Clinical pearls
- The salivary and lacrimal glands — not the kidneys — are usually the dose-limiting organ, but the kidney is the highest-dose internal organ on dosimetry.
- Unlike PRRT, routine amino-acid renoprotection is not required.
- Always exclude obstructive uropathy from pelvic disease before blaming the drug for a rising creatinine.
- A hemodialysis patient is treatable: reported courses schedule dialysis after each dose to strip the renally-excreted radioligand and handle the dialysate as radioactive waste — the already-failed kidney is no longer the limiting organ, though dialysis only takes off the circulating fraction and marrow dose still runs roughly double.
Anticancer mechanism
Note
Guidelines & consensus
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.
- 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 (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate 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.Kidney Int · PMID 38519239
- 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
References
11 peer-reviewed references. Citation metadata via PubMed / NLM.
- 1.Impact of extended [177Lu]Lu-PSMA-617 therapy on absorbed kidney dose and CKD-EPI values: how long can therapy be safely continued?Topal E et al · Eur J Nucl Med Mol Imaging · 2025 · PMID 40063298
- 2.Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer.Sartor O et al. · N Engl J Med · 2021 · PMID 34161051
- 3.Correlation analyses of radiographic progression-free survival with clinical and health-related quality of life outcomes in metastatic castration-resistant prostate cancer: Analysis of the phase 3 VISION trial.Morris MJ et al. · Cancer · 2024 · PMID 39031642
- 4.Pre-therapeutic dosimetry of normal organs and tissues of 177Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer.Kabasakal L et al. · Eur J Nucl Med Mol Imaging · 2015 · PMID 26227531
- 5.Prediction of Normal Organ Absorbed Doses for [177Lu]Lu-PSMA-617 Using [44Sc]Sc-PSMA-617 Pharmacokinetics in Patients With Metastatic Castration Resistant Prostate Carcinoma.Khawar A et al. · Clin Nucl Med · 2018 · PMID 29688951
- 6.Dosimetry in Lu-177-PSMA-617 prostate-specific membrane antigen targeted radioligand therapy: a systematic review.Nautiyal A et al. · Nucl Med Commun · 2022 · PMID 35045551
- 7.[177Lu]Lu-PSMA-617 Therapy in a Patient with Chronic Kidney Disease.Mercolli L et al. · J Nucl Med · 2023 · PMID 37620052
- 8.Radiation safety and dialysate analysis in hemodialysis following Lu-177-PSMA-617 therapy: A case report.Huang YY et al. · Radiol Case Rep · 2025 · PMID 39624699
- 9.Dosimetry of [(177)Lu]Lu-PSMA therapy in a hemodialysis patient: a case study.Hendriks AD et al. · EJNMMI Res · 2026 · PMID 42020659
- 10.Use of approved Lu-177 radiopharmaceuticals in patients with end-stage renal disease: A review of the literature and proposed treatment algorithm.Trikalinos NA et al. · J Neuroendocrinol · 2024 · PMID 38622851
- 11.The 68Ga/177Lu-theragnostic concept in PSMA-targeting of metastatic castration-resistant prostate cancer: impact of post-therapeutic whole-body scintigraphy in the follow-up.Maffey-Steffan J et al. · Eur J Nucl Med Mol Imaging · 2020 · PMID 31776632
Case reports & series (1)
The weakest rung of clinical evidence — single-patient and small-series reports, strongest first. Each carries a heuristic strength grade (A Strong / B Moderate / C Limited) inferred from its abstract and journal, not a formal appraisal. Weigh well below the primary references above.
- C1.[B · Moderate]Extensive (177)Lu-PSMA Radioligand Therapy Can Lead to Radiation Nephropathy with a Renal Thrombotic Microangiopathy-like Picture.Schäfer H et al. · Eur Urol · 2023 · PMID 35688660
Conference abstracts (1) — non-PubMed, no PMID
- A1.New Therapies and New Challenges: Radioligand Therapy-Related Thrombotic Microangiopathy in the KidneysASN Kidney Week 2024 · SA-PO216Biopsy-proven subacute renal TMA with interstitial fibrosis and glomerulosclerosis after monthly 177Lu-PSMA and 225Ac-PSMA, progressing to dialysis and unresponsive to eculizumab — illustrating cumulative radioligand endothelial injury beyond the expected radiation-nephropathy timeline.