1. Interactive Case Discussion Case 6 Dr Megha S Uppin Asst Prof Dept of Pathology Nizam’s Institute of Medical Sciences Hyderabad

2. Case History 30/M Renal allograft recipient (DOT: 18.8.2009) Live related transplant, Donor: Mother Immediate graft function on triple immunosupression (Tac+MMF+Prednisolone)s No history of post operative complications, CMV, UTIs or any other complication.

3. November 2011, Serum Creatinine: 1.5mg%)

4. Borderline Rejection Treated with methyprednisolone Serum Creatinine improved Lost to follow up for six months and omitted the medicine for 15 days. June 2012, presented with raised serum creatinine: 10mg/dl No uremic symptoms No oliguria, dysuria, fever O/E: No pallor, oedema, BP: 130/80mm Hg Per abdomen: Non tender Clinical diagnosis: Acute rejection

5. Investigations CUE: pH: 5, Albumin: 3+, Pus cells: 10-15, Hb 12.6 g%, TLC: 5600, Plt 70000/cmm Urine Culture: sterile Anti CMV: Negative Serum Albumin: 3.2 Urea: 86, Na: 113, K: 3.4, Chloride: 91, Urine for decoy cells : Negative Color Doppler of transplant kidney: Normal

9. CD 138

12. PLASMA CELL RICH ACUTE CELLULAR REJECTION Provisional Diagnosis

13. C4d

14. ACUTE HUMORAL REJECTION (LATE)WITH PLASMA CELL INFILTRATE Final Diagnosis

15. Follow Up Treated with IV pulse Methyprednisolone Plasmapheresis Rituximab However S Creatinine did not improve Patient is dialysis dependent

16. Plasma Cells In Renal Allograft Viral infection BK and EBV PTLD Drug toxicity Acute rejection(PCAR) – 1 month to many years post transplant – 1.8–2.5% of allograft biopsies – Plasma cells >10% of interstitial infiltrate – Poor response to antirejection therapy HARNEY C. TRANSPLANTATION 1999;68:791–797 R. Gupta Indian J Nephrol. 2012 May;22(3):184-8 Chronic Allograft Damage – Xu et al 40 explanted grafts – 32.5% had both CD138+ plasma cells and diffuse C4d deposits Martin et al – Plasma cells, DSA and C4d are associated in renal transplants developing chronic rejection – plasma cells can be present in absence of acute rejection and associated with chronic allograft damage. – Intra-graft plasma cells might be a source of Abs Martin L. Transplant Immunology (2010)

17. Summary :Issues in this Case C4d is found in 24–43% of type I rejection episodes Concurrent acute T cell rejection with C4d positive AHR is an independent risk factor for graft survival Volker N, Mihatsch MJ. Nephrol Dial Transplant (2003) 18: 2232–2239

18. Late AHR – AMR that occurs more than 6 months after transplantation – Mostly associated with the withdrawal or reduction of immunosuppressants than positive pretransplant PRA – Associated with IFTA – Poor outcome Plasma cells: – Indicator of a more adverse outcome – Accompanied by the appearance or subsequent development of VR PCAR should therefore encourage the clinician to intensify the immunosuppressive schedule Treatment – IVIG