J Korean Soc Transplant.  2011 Jun;25(2):116-122.

A Case of Late Mixed Acute Humoral and Cellular Rejection Successfully Treated with Rituximab, Plasmapheresis and IVIg

• Kim SM
• Oh JS
• Jun JM
• Park YK
• Sin YH
• Kim JK
• Huh K
• Kim YJ

Abstract

Acute antibody-mediated rejection (AMR) developing simultaneously with acute cellular rejection has been rarely reported as a long-term complication of renal transplantation, and it can present on top of another chronic pathology affecting the graft. A 51-year-old female patient with chronic kidney disease of unknown etiology received renal transplantation 12 years ago from a living unrelated donor with 3 HLA mismatches. She received induction therapy with methylprednisolone and was maintained on steroids, mycophenolate mofetil and cyclosporine A (CsA). For a period of twelve years post-transplantation, she was clinically and biochemically stable. She presented with a rise in serum creatinine (SCr.) from 1.3 mg/dL to 2.4 mg/dL but did not have proteinuria. Graft biopsy revealed findings suggestive of acute cellular rejection on top of antibody-mediated rejection (type II) and chronic calcineurin inhibitor toxicity. Panel reactive antibody (PRA) test levels were 3.6%, 91.7% for class I and II respectively. The patient was treated with high-dose methylprednisolone for 3 days but serum creatinine was not fully normalised. After 2 weeks from initial methyl-PDS pulse therapy, she received intravenous immunoglobulin, plasma exchange and anti-CD20 (rituximab). Cyclosporine was changed to tacrolimus. She achieved a complete response, and SCr. was maintained at 1.3 mg/dL without proteinuria. Follow-up PRA test levels were 0%, 75% for class I and II. Current therapies have had considerable success in reversing mixed, acute humoral and cellular rejection since it is being identified quickly and treated aggressively. The best use of rituximab to treat AMR should be evaluated in controlled trials using dosing strategies that include longer courses or retreatment schedules.

Keyword

Transplantation; Graft rejection; Rituximab; Plasmapheresis

MeSH Terms

Antibodies, Monoclonal, Murine-Derived
Appointments and Schedules
Biopsy
Calcineurin
Creatinine
Cyclosporine
Female
Follow-Up Studies
Graft Rejection
Humans
Immunoglobulins
Immunoglobulins, Intravenous
Kidney Transplantation
Methylprednisolone
Middle Aged
Mycophenolic Acid
Plasma Exchange
Plasmapheresis
Proteinuria
Rejection (Psychology)
Renal Insufficiency, Chronic
Retreatment
Rituximab
Steroids
Tacrolimus
Transplants
Unrelated Donors
Antibodies, Monoclonal, Murine-Derived
Calcineurin
Creatinine
Cyclosporine
Immunoglobulins
Immunoglobulins, Intravenous
Methylprednisolone
Mycophenolic Acid
Steroids
Tacrolimus

Figure

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  Fig. 1. Clinical course; MPDS pulse, 250 mg iv bid for 3days; plasmapheresis, 1 plasma volume, 5% albumin replacement solution, COBEⓇ Spectra Apheresis System; Rituximab 200 mg/body single infusion. Abbreviations: CsA, cyclosporine; MMF, mycophenolate mofetil; PDS, prednisone; Bx., biopsy; MPDS, methyl prednisolone; PP/IVIG, plasmapheresis with intravenous immune globulin.

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  Fig. 2. Light microscopically, there was mild to moderate intimal arteritis (PAS stain, original magnification ×400).

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  Fig. 3. Light microscopically, lymphocytes infiltration under-neath the endothelium of large vessels is noted (PAS stain, original magnification ×400).

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  Fig. 4. Immunofluorescent microscopically, there was diffuse staining for C4d in the peritubular capillaries(original magnification ×200).

Reference

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