Carmustine (BCNU)
BiCNU · Nitrosourea alkylator
Delayed interstitial fibrosis with high cumulative dose.
CINTMA
ModerateOpen →
Radioligand therapy (PSMA)
Lutetium-177 PSMA-617 (vipivotide)
Pluvicto · LUPS
A PSMA-targeted beta-emitter for prostate cancer whose kidney is the highest-dose internal organ — though the salivary glands usually steal the spotlight.
ModerateTargeted radioligand therapy (PSMA) · approved 2022
PSMA-positive metastatic castration-resistant prostate cancer (mCRPC), after androgen-receptor pathway inhibition and taxane chemotherapy
Signature kidney injury
Chronic Interstitial Nephropathy
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.
Source: Sartor et al., NEJM 2021
Mechanism of kidney injury
PSMA is also expressed on the proximal renal tubular brush border, and filtered ligand is reabsorbed there, so radiation is delivered to the proximal tubule, raising the theoretical risk of chronic radiation nephropathy. Salivary and lacrimal glands likewise concentrate the ligand, producing the prominent xerostomia/dry-eye toxicity. Acute tubular injury can also be hemodynamic if pelvic disease causes obstruction or dehydration.
Clinical presentation
Renal injury is typically a mild, gradual eGFR decline; the clinically prominent toxicities are xerostomia and dry eyes plus hematologic effects (anemia, thrombocytopenia). A rising creatinine should prompt evaluation for obstructive uropathy from pelvic/nodal disease.
Onset
Renal changes are delayed/gradual; xerostomia can appear early during treatment.
Reversibility
Partially reversible
Anticancer mechanism
Beta-emitting lutetium-177 conjugated to a small-molecule ligand (PSMA-617 / vipivotide tetraxetan) that binds prostate-specific membrane antigen (PSMA, glutamate carboxypeptidase II) overexpressed on prostate-cancer cells. After binding and internalization, targeted beta radiation produces lethal DNA damage.
Management
Largely supportive: hydrate, relieve obstruction, and hold/reduce for grade >=3 renal or marrow toxicity. Manage xerostomia symptomatically. Monitor and replace electrolytes as needed.
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)
Note · A 2022 (frontier-era) agent; renal dosimetry is well characterized but clinical nephrotoxicity incidence is thinly quantified. Renal framing rests on dosimetry plus class radiation-nephropathy reasoning.
Clinical depth
Renal dose adjustment
Standard 7.4 GBq IV every 6 weeks for up to 6 cycles. No simple CrCl-based table; the same ~23 Gy renal radiation-tolerance principle applies (renal dose ~0.4-0.55 Gy/GBq in dosimetry series). Hold/reduce for grade >=3 renal or hematologic toxicity; caution with significantly impaired baseline GFR.
Dialyzability & ESKD dosing
Not relevant as management (structural radiation effect rather than a removable drug). No established ESKD dosing; such patients are generally not candidates.
Differential diagnosis
Distinguish drug-related radiation effect from obstructive uropathy (hydronephrosis on imaging — common in pelvic prostate cancer), prior platinum/taxane tubular injury, and dehydration. Exclude obstruction before attributing AKI to the radioligand.
Monitoring
- Serum creatinine/eGFR and CBC before each cycle
- Review for obstructive uropathy (imaging) if creatinine rises
- Salivary/ocular symptom assessment each cycle
- Electrolytes as needed
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.
- Clinically significant nephrotoxicity is low and not well quantified in trial cohorts.
Where it strikes
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Chronic Interstitial NephropathyElectrolyte Wasting
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkLutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer.Sartor O et al. · N Engl J Med 2021 · PMID 34161051VISION registrational phase 3 RCT defining the renal/xerostomia safety profile of PSMA radioligand therapy.PMIDCorrelation 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 39031642VISION post hoc analysis supporting outcome surrogacy and the patient-reported toxicity context.PMIDPre-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 26227531Foundational dosimetry: kidneys and parotid glands receive the highest normal-organ doses.PMIDPrediction 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 29688951Kidneys are the highest absorbed-dose internal organ and limited maximum permissible activity in most patients.PMIDDosimetry in Lu-177-PSMA-617 prostate-specific membrane antigen targeted radioligand therapy: a systematic review.Nautiyal A et al. · Nucl Med Commun 2022 · PMID 35045551Systematic review of organ dosimetry framing kidneys vs salivary/lacrimal organs at risk.PMIDWhole-Body and Microenvironmental Localization of Radium-223 in Naive and Mouse Models of Prostate Cancer Metastasis.Abou DS et al. · J Natl Cancer Inst 2015 · PMID 26683407Radiopharmaceutical biodistribution methodology relevant to renal handling of bone/PSMA-targeted radiotherapeutics.
Related agents
Other agents sharing the same signature kidney injury.
Profile
Lomustine (CCNU)
Gleostine · Nitrosourea alkylator
Cumulative interstitial nephritis and CKD.
CIN
ModerateOpen →
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
ModerateOpen →