Proteinuria in a Renal transplant Recipient Dr. Krishna Prasad First Yr DM Resident NIMS

Pre Transplant history 30 yr female Resident of Anantapur Persistent pedal edema for 3-4 months after an uneventful NVD in 2012 Evaluated at a private hospital in HYD in Nov 2012, diagnosed as nephrotic syndrome with 24 hr U. protein-6g/day and S.creat-1.2mg/dl Started on steroids and ARB Renal biopsy done in Jan 2013 in view of persisting symptoms and increase in S.creat-1.9mg/dl and suggestive of FSGS-NOS

Native kidney biopsy- FSGS

On regular follow up at same hospital Her S.creat gradually increased to 7mg/dl by May 2014 Declared as ESRD and HD initiated via Rt.DLJC in May 2014 at some other hospital Registered for JEEVANDAN On MHD via Lt. RC Avf for 31 months prior to transplant

Post transplant course Underwent Deceased Donor Renal Transplant on 20/12/16 at NIMS Cold ischemia time-1hr No induction On Triple Immunosuppression(Tac+MMF+steroid) Immediate graft function In view of persistent anasarca with hypoalbuminemia and proteinuria and spontaneous thrombosis of AVF - suspected Recurrence of FSGS HIV, HBsAg, Anti HCV-Negative

Graft biopsy

C4D Staining PLAR2 staining

Graft biopsy done on 31/12/16 - s/o Denovo membranous nephropathy with secondary FSGS She received 3 sessions plasmapheresis on 31/12/16, 01/1/17 and 2/1/17 Anti PLA2R Ab staining was brightly positive on graft biopsy Serum Anti- PLA2R was negative In v/o Denovo membranous nephropathy she was treated with 200mg Rituximab on 10/1/17 She was stable at discharge with good urine output, Sr. Cr - 0.7 mg/dl and urine spot PCR 0.94  

Change in Lab parameters with Plasmapheresis and Rituximab

Clinical Course in a nut shell…, NS - FSGS ESRD - MHD DDTx NS - FSGS with MN PLAR2 stain positive, anti PLAR abd Negative EM: Membrane not thickened, Mesangial and paramesangial deposits Recurrene FSGS ?? Recurrenceof MN ? Both??? Recurrence of FSGS with denovo MN ??

Review of literature

Denovo MN Develops in around 2% of adults receiving renal allografts Associated with new-onset hepatitis C virus (HCV) infection, Alport syndrome, ureteral obstruction or even recurrent IgA nephritis (IgAN) Occasionally associated with antibody mediated rejection Usually occurs months or years after transplantation, but rarely it can develop soon after transplantation Clinical presentation is variable from asymptomatic to nephrotic- range proteinuria Indolent course or may have an accelerated course leading to allograft loss

Denovo MN vs Recurrent MN 2% of renal allografts mild-to-moderate mesangial cell proliferation focal segmental distribution of subepithelial deposits IgG1 PLA2R antibodies -neg 25 to 40% No mesangial proliferation Diffuse distribution IgG4 positive

Pathogenesis Peculiar form of immune response triggered by exposure of hidden antigens, probably different from those antigens observed in idiopathic MN In post-transplant de novo MN, phospholipase A2 receptor staining was almost always negative Because MN may also be associated with malignancy or infection, the workup for post-transplant MN should include a careful search for underlying cancer or viral infection

Whether de novo MN has a deleterious impact on the outcome of transplant is still controversial In adult series, some investigators found a high rate of allograft failure with signs of chronic allograft rejection in graft biopsies, and others reported that the allograft survival was not affected by the development of de novo MN There is no formal contraindication to retransplantation

THANK U