Introduction:
Membranous nephropathy (MN) is considered a rare manifestation of chronic graft versus host disease (cGvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). MN results from antibody generation to glomerular antigens, such as Phospholipase A2 receptor (PLA2R) or the recently described protocadherin FAT1, an antigen exclusively identified in post-HSCT patients. Although anti-PLA2R antibodies are quite common in non HSCT-MN patients, they have not been described in a patient post-HSCT. The identification of antibodies in HSCT-MN might eventually help inform clinical outcomes and treatment strategies.
Here we present an unusual case of biopsy-proven MN with positive serum and tissue anti-PLA2R antibodies occurring in a patient with active cGvHD post allogeneic HSCT.
Methods:
Case Report
Results:
A 68-year-old male with a history of IPSS intermediate risk RAEB2 myelodysplastic syndrome who underwent myeloablative allogenic HSCT using a 10/10 HLA matched related donor. Initial post HSCT GvHD prophylaxis consisted of methotrexate and tacrolimus. His post-transplant course was complicated by both acute and chronic GvHD for which he required systemic steroids and remained on tacrolimus post-transplantation. Due to ongoing skin and ocular symptoms as well as worsening proteinuria, he was transitioned to a combination of sirolimus and belumosudil.
He was referred to nephrology clinic for a six-month history of leg swelling, shortness of breath, and mild lower abdominal distension that occurred 3 years following his HSCT. He was found to have 4+ proteinuria and 2-3+ blood on urinalysis. Serum creatinine rose from 0.7 mg/dL to 1 mg/dL. 24-hour urine collection was notable for 6183 mg of protein and urine protein to creatinine ratio rose to 16.3 gram/gram the following month. Serum albumin dropped from the prior normal baseline to 2.7 mg/dL. Serologic workup notable for negative or normal Myeloperoxidase and Proteinase 3 antibodies, ANA, HIV, hepatitis B/C, C3, and C4. Serum anti-PLA2R antibody was positive.
Kidney biopsy revealed thickened glomerular capillary walls with silver positive spikes, and focal subendothelial changes suggesting healing focal thrombosis or a non-diffuse thrombotic microangiopathic process. Immunofluorescence shows IgG-positive, PLA2R-positive granular capillary wall deposits. Electron microscopy of one glomerulus demonstrated subepithelial electron-dense deposits with intervening spikes. Paramesangial and subendothelial deposits were rare. The overall diagnosis was consistent with anti-PLA2R-associated MN.
The patient was started on rituximab 1 g every 2 weeks for 2 doses, monthly IVIG, and Losartan 25mg daily.
Conclusions:
While MN is the most common nephrotic lesion detected post-HSCT, it is typically anti-PLA2R negative and a manifestation of chronic GvHD. FAT1-associated MN has thus far been the most commonly linked antibody target in HSCT-MN. We report a novel case of anti-PLA2R positive MN in a patient post-HSCT. Further research is needed to understand these unique processes and develop targeted treatments, potentially improving outcomes for patients with this rare post-HSCT complication.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.