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

2. 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

3. Native kidney biopsy- FSGS

5. 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 at some other hospital
Registered for JEEVANDAN
On MHD via Lt. RC Avf for 31 months prior to transplant

6. 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

7. Graft biopsy

8. C4D Staining
PLAR2 staining

11. 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 mg/dl and urine spot PCR  

12. Change in Lab parameters with Plasmapheresis and Rituximab

13. 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 ??

14. Review of literature

15. 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

16. 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

17. 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

18. 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

19. THANK U