Interactive Case DiscussionCase 6

Dr Megha S UppinAsst Prof

Dept of PathologyNizam’s Institute of Medical Sciences

Hyderabad

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.

November 2011, Serum Creatinine: 1.5mg%)

• 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

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

CD 138

PLASMA CELL RICH ACUTE CELLULAR REJECTION

Provisional Diagnosis

C4d

ACUTE HUMORAL REJECTION (LATE)WITH PLASMA CELL INFILTRATE

Final Diagnosis

Follow Up

• Treated with IV pulse Methyprednisolone• Plasmapheresis• Rituximab

• However S Creatinine did not improve• Patient is dialysis dependent

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)

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

• 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

Thank You