FAT1-associated membranous nephropathy after hematopoietic stem cell transplantation: a case report and review of the literature

Abstract We report a 55-year-old man who developed nephrotic syndrome 52 months after allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia. He had chronic graft-versus-host disease controlled with low-dose prednisolone and tacrolimus. Asymptomatic proteinuria was detected five months before referral, followed by progressive edema, massive pleural effusion, and ascites. At presentation, laboratory testing showed profound hypoalbuminemia, mildly reduced kidney function, and nephrotic-range proteinuria. Kidney biopsy demonstrated membranous nephropathy, with periodic acid-methenamine silver staining showing spikes and bubbling of the glomerular basement membrane. Immunofluorescence showed granular capillary-wall immunoglobulin G staining with immunoglobulin G1 predominance over immunoglobulin G4, and protocadherin FAT1 immunofluorescence showed granular staining along the glomerular basement membrane. Prednisolone was increased from 5 to 30 milligrams per day while tacrolimus was continued, resulting in improved proteinuria, serum albumin, edema, and kidney function at five months without clinically significant infectious complications. We also reviewed 29 reported cases of protocadherin FAT1-associated membranous nephropathy after hematopoietic stem cell transplantation, including the present case. The review showed variable onset timing, substantial proteinuria at presentation, inconsistent immunoglobulin G4 positivity, and heterogeneous treatment with corticosteroids, rituximab, calcineurin inhibitors, and other regimens. Our case and review indicate that this disease can present late, cannot be excluded by non-immunoglobulin G4-predominant staining, and remains heterogeneous in diagnostic evaluation, treatment, and outcomes. Further accumulation of cases is needed to clarify the clinical spectrum and optimal management of this disease.