Abstract: FR-PO1266
Unmasking a Silent Risk: Renal-Limited Thrombotic Microangiopathy After Lutetium-177 Prostate-Specific Membrane Antigen Radioligand Therapy
Session Information
- Onconephrology: Diagnostic Dilemmas, Therapy-Related Toxicities, and Clinical Cases
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1600 Onconephrology
Authors
- Mehta, Kartik, Maulana Azad Medical College, New Delhi, DL, India
- Ali, Mohammed Omer Khalil, Yale University, New Haven, Connecticut, United States
- Moss, Emily, Yale University, New Haven, Connecticut, United States
- Foster, Yevgeniya G., Yale University, New Haven, Connecticut, United States
- Guevara-Pineda, Daniel, Yale University, New Haven, Connecticut, United States
Introduction
Renal-limited thrombotic microangiopathy (TMA) is an underrecognized cause of kidney injury, which presents without systemic hemolysis, making the diagnosis challenging. Recent reports have identified Lutetium-177 prostate-specific membrane antigen (Lu-177 PSMA) radioligand therapy as a potential trigger for TMA. However, the mechanism of injury remains unclear, with uncertainty regarding the role of complement dysregulation versus radiation-induced endothelial injury.
Case Description
A 69-year-old male presented with progressive acute kidney injury (baseline creatinine 0.9-1 mg/dL to 4.5 mg/dL at presentation), metabolic acidosis and hyperkalemia. Labs showed anemia and thrombocytopenia with mildly elevated LDH, normal haptoglobin, and no schistocytes on peripheral smear. Coagulation profile and renal ultrasound were normal. He received three cycles of Lu-177 PSMA-617, starting five months prior to presentation for prostate cancer. Kidney biopsy showed acute on chronic TMA. His renal function continued to deteriorate, requiring hemodialysis. Autoimmune and infectious workup was negative. Further workup showed normal ADAMTS13 activity, normal C3, C4, and CH50 complement levels, and negative Factor H, I, and B antibodies. A 15-gene complement panel was negative. He progressed to end-stage renal disease and received eculizumab, initiated inpatient and continued outpatient, for possible complement-mediated TMA, which did not precipitate renal recovery.
Discussion
Review of literature identified seven reported cases of Lu-177 PSMA-associated TMA, with two phenotypes: renal-limited TMA and systemic TMA with hemolysis. Biopsy findings and subacute onset after months of initiating Lu-177 PSMA therapy were consistent across cases, suggesting a shared pathophysiology, which may be due to high renal cortical uptake of Lu-PSMA, likely resulting in localized radiation-induced endothelial injury. Notably, renal injury has been reported across a wide dosing range, including standard dosing and limited exposure. Given that many cases of complement-mediated TMA lack identifiable genetic abnormalities, the possibility of complement-mediated TMA cannot be ruled out. Lack of improvement with complement inhibition with eculizumab may possibly be due to a delay in initiation. Vigilant renal monitoring is warranted during Lu-177 PSMA therapy, and early recognition and discontinuation may prevent further renal injury.