Abstract: SA-PO531
PLA2R De Novo Membranous Nephropathy and Antibody Mediated Rejection in a Renal Allograft
Session Information
- Immunosuppression, Disease Recurrence, and Malignancy
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Transplantation
- 1702 Transplantation: Clinical and Translational
Authors
- Manolopoulou, Marika, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Jabs, Kathy L., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Lusco, Mark, Vanderbilt University School of Medicine, Nashville, Tennessee, United States
- Paueksakon, Paisit, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background
The pathophysiology of de novo membranous nephropathy (dnMN) is not clearly understood but may be associated with antibody-mediated rejection (AMR) in the allograft. The presence of phospholipase A2 receptor (PLA2R) antibodies usually indicates recurrent MN or dnMN not associated with AMR. We present a case of PLA2R positive dnMN in the presence of AMR and its resolution by histologic evidence upon rejection targeted treatment.
Methods
Our patient is a 19-year old male with end stage renal disease due to obstructive uropathy who received a deceased donor kidney transplant in 6/2015. His immunosuppression included anti-thymocyte globulin (ATG) induction therapy, and maintenance with prednisone, mycophenolate mofetil, and tacrolimus. Post-transplant his serum creatinine (sCr) was stable at 0.99 mg/dl. Fourteen months post-transplant he presented with with a creatinine of 2.2 mg/dl in the setting of likely medication nonadherence. A renal transplant biopsy revealed acute cellular rejection (ACR), AMR (peritubular capillaritis with C4d positivity in >50% of capillaries) and serum donor specific antibody (DSA) positivity. There was also PLA2R positive membranous nephropathy. His infectious workup was negative. He was treated with pulse methylprednisolone, ATG, plasma exchange, intravenous immunoglobulin (IVIG) and rituximab. His sCr decreased to 1.03 mg/dl at hospital discharge.
His interval follow up demonstrated stable renal function. At nineteen months post-transplant his sCr was 1.57 mg/dl, he had negative DSA and undetectable tacrolimus trough level. He was next seen 3 months later with allograft pain and a sCr of 7.0 mg/dl. Renal biopsy was consistent with ACR, microcirculation inflammation suspicious for AMR (negative C4d, positive DSA) and no evidence of membranous nephropathy. He was treated with ATG, methylprednisolone, rituximab, plasma exchange, and IVIG and his sCr decreased to 3.7 mg/dl.
Conclusion
While the pathophysiology of dnMN remains to be elucidated, this disease entity is currently viewed as an alloimmune disease mediated by chronic AMR. In contrast to idiopathic MN, dnMN associated with AMR has not been found to be PLA2R positive. Although rare, the presence of PLA2R positive dnMN should be considered in the setting of AMR. Further study and long term follow up of these patients will help us gain a better understanding.