Recurrence of Anti-nephrin Antibodies Associated Nephrotic Syndrome after Kidney Transplantation

Introduction: Minimal change disease (MCD) and focal segmental glomerulosclerosis are podocytopathies characterized by damage to the glomerular basement membrane, leading to nephrotic syndrome. Anti-podocyte antibodies have been proposed as potential circulating factors damaging nephrin, a component of the slit diaphragm. We report a case of recurrent MCD after kidney transplantation associated with anti-nephrin antibodies. Case Description: A man in his 50s with end stage kidney disease (ESKD) secondary to biopsy proven minimal change disease, treated with steroids, received a deceased donor kidney transplant. He presented eight weeks post-transplant with complaints of shortness of breath and decreased urine output. Labs at presentation were significant for BUN 56 mg/dL, creatinine 1.97 mg/dL (baseline 1.3–1.5 mg/dL), total protein 3.9 g/dL, serum albumin 1.8 g/dL, and urine protein to creatinine ratio (UPCR) of 8.65 mg/mg. Secondary work up for nephrotic range proteinuria was done and was negative. His hospital course was complicated by hemorrhagic shock due to gastrointestinal bleed from an ulcer. He tested positive for H. pylori and was treated. He clinically improved with bleed resolution however nephrotic syndrome persisted prompting a transplant kidney biopsy. Biopsy showed diffuse podocyte foot process effacement with finely granular podocyte staining for IgG. IgG/nephrin immunofluorescence showed overlap of clustered nephrin with punctate IgG, indicative of anti-nephrin antibodies. He received two doses of rituximab 1000 mg with significant reduction in UPCR to 0.95 and serum albumin increase to 3.3 g/dL. Kidney function improved to baseline. Discussion: In kidney transplant patients, with recurrence of nephrotic syndrome, anti-nephrin antibodies should be considered as a possible contributing etiology. Response to rituximab in this case suggests that B cell targeted therapy may be a reasonable approach of treatment for patients with anti-nephrin associated MCD post-transplant. Interestingly, MCD has been associated with chronic infections. Our patient had H. Pylori infection which was treated prior to B cell therapy. It is unclear how significant that may have been. The role of underlying cause of MCD and anti-nephrin antibodies still needs further exploration.