Abstract: SA-PO216
New Therapies and New Challenges: Radioligand Therapy-Related Thrombotic Microangiopathy in the Kidneys
Session Information
- Onconephrology: Kidney Outcomes during Cancer Treatment and Nephropathies
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Keyser, Michelle Nguyen, UPMC, Pittsburgh, Pennsylvania, United States
- Pantanowitz, Joshua, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
- Amarapurkar, Pooja D., UPMC, Pittsburgh, Pennsylvania, United States
Introduction
Radioligand therapy (RLT) has been increasingly used to treat metastatic castration-resistant prostate cancer. Intravenous (IV) 177Lu-PSMA and 225Ac-PSMA are two effective and well tolerated agents. Data on kidney-related side effects remain limited from initial clinical trials using these treatments. We present a unique biopsy-proven case of renal thrombotic microangiopathy (TMA) in a patient who received IV 177Lu-PSMA and 225Ac-PSMA resulting in rapid decline in kidney function, dialysis initiation and unresponsiveness to eculizumab.
Case Description
A 75-year-old male with stage 3b prostate adenocarcinoma was treated with radical prostatectomy, pelvic radiation, leuprorelin, bicalutamide, abiraterone. Therapy was changed to enzalutamide and darolutamide for new bone lesions. He traveled to Austria to receive IV RLT with 225Ac-PSMA and 177Lu-PSMA monthly for 8 months. 1 month after RLT his serum creatinine rose from 0.9–1.1 mg/dL to 1.3 mg/dL, and to 2.2 mg/dL at 6 months. Lower extremity edema and hypertension were noted at that time. 360 mg 24-hour urine protein, 516 mg/g UACr, normocytic anemia, elevated LDH, schistocytes on peripheral smear, elevated CH50, normal C3, C4, and SC5b-9 level were noted. A kidney biopsy showed subacute TMA, moderate (25%) interstitial fibrosis and tubular atrophy and 20-25% global glomerulosclerosis with double contour and subendothelial edema in the glomerular capillary walls. Losartan was started for hypertension and proteinuria. Eculizumab was added for possible complement-mediated process, but the kidney function declined rapidly. He started hemodialysis 10 months after his last dose of RLT. Eculizumab was trialed for 6 months without renal recovery.
Discussion
RLT such as 177Lu-PSMA and 225Ac-PSMA deliver targeted radiation to cancer cells. Despite being target specific, they may accumulate in the kidneys over time causing endothelial damage, hypertension, TMA and chronic kidney disease. Data on nephrotoxicity from the initial trials is sparse. Additionally, RLT-related kidney damage with use of dual agents 177Lu-PSMA and 225Ac-PSMA remains to be explored. Our case is a distinctive illustration of kidney side effects of RLT. With the expanding use of RLT, it is vital to educate nephrologists to recognize the kidney effects and develop strategies to prevent rapid decline in kidney function.