CKD After 225Ac-PSMA617 Therapy in Patients with Advanced Metastatic Prostate Cancer: A Report of Two Cases
Bibliographic record
Abstract
Introduction: A promising therapeutic efficacy has been demonstrated with targeted radionuclide therapy (TRNT) using 225Ac-PSMA617 in patients with advanced metastatic castration-resistant prostate cancer (mCRPC). However, these novel agents may be associated with significant toxicity. As seen in animal models, the multiple alpha particles generated in the decay chain of 225Ac may accumulate in the renal tubular cells, resulting in nephropathy. We report our experience with 225Ac-PSMA617 therapy in 2 patients with advanced mCRPC who developed kidney injury. Case Description: Patient 1 is a 68-year-old man with widely metastatic mCRPC despite multiple lines of therapy and secondary chronic hydronephrosis with bilateral nephrostomy tubes. He received 3 rounds of 225Ac-PSMA617 in 2-month intervals. Baseline serum creatinine was 1.6 mg/dL (eGFR 44 mL/min/1.73m2) and it increased up to 3.3 mg/dL (eGFR 18 mL/min/1.73m2) after 225Ac-PSMA617 therapy. A kidney biopsy was obtained and revealed severe interstitial fibrosis with ongoing tubular injury and interstitial inflammation. A trial of corticosteroids therapy was attempted with no improvement in kidney function. 225Ac-PSMA617 therapy was discontinued because of related kidney failure. Patient 2 is a 67-year-old man with mCRPC with progression on multiple prior therapies. He first initiated Lu177-PSMA and one year later this was combined with 225Ac-PSMA617 in 2-month intervals. He received 5 rounds of 225Ac-PSMA617 in total, the last round being complicated with grade 3 cytopenias leading to cessation of treatment. Baseline serum creatinine at initiation of TRNT was 1.0 mg/dL (eGFR 82 mL/min/1.73m2). He subsequently developed progressive CKD and serum creatinine was 1.7 mg/dL (eGFR 40 mL/min/1.73m2) on last follow-up. Discussion: We report 2 cases of progressive kidney disease in the setting of 225Ac-PSMA617 therapy for patients with advanced mCRPC. One underwent kidney biopsy showing tubulointerstitial injury, consistent with 225Ac-PSMA617-related tubular accumulation of toxic nuclides seen in animal models. This kidney injury was not responsive to corticosteroids therapy. Our case studies emphasized the need for careful assessment and monitoring of kidney function in patients receiving these novel agents.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.004 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".