Autor:innen:
M. Rußwurm (Marburg an der Lahn, DE)
T. Maier-Giebing (Marburg an der Lahn, DE)
J. Hoyer (Marburg an der Lahn, DE)
Introduction
Acute humoral rejection (AMR) is a major threat to renal allograft survival in the early transplant period, it accounts for up to 40% of graft losses within the first year. Although various immunomodulatory treatments (Tx) are used to treat AMR, there is no golden standard. In every unique clinical situation regarding Mismatch, serological follow-up, severity of AMR, long- and short-term adverse events of immunosuppressive Tx, careful consideration which Tx to choose is imperative. As far as there is still a lack of understanding not only pathomechanisms but also how to integrate the ample histological and immunological data available in the single case, rational for Tx still seems to be somewhat arbitrary and is subject to the treating physicians experience. Nevertheless, there are situations in which one might leave the beaten track.
Here we present a case of severe, sustained early AMR, treated with the various immunosuppressive agents and techniques in the armamentarium, finally AMR being successfully resolved by an extensive plasmapheresis approach.
Case report
At renal transplantation, immunosuppressive Tx has been initiated with Cyclosporin, Methylprednisone (Predni) and Mycophenolate. While the Pt. developed no graft function postoperatively, she underwent the first renal transplant biopsy (Bx) at d6 followed by a pre-emptive Predni pulse for Tx of suspected acute cellular rejection. The first histology report, however, revealed the typical picture of AMR.
We then initiated Tx for AMR with a course of anti-thymocyte immunoglobulin, Plasma Exchange, Rituximab, Immunoadsorption (IA) and intravenous immunoglobulin, the Pt. remaining anuric still.
We decided to serial-connect a high-molecular weight filter device, called double filtration plasmapheresis (DFPP) with an IA system, treating the pt. every other day. After the 2nd Tx the transplant developed excretory function, accompanied by significant decline in serum creatinine. Follow-up Bx at day 50 still showed active AMR but with significantly lesser activity. The pt. was dismissed at d60 with improved and stable renal function. We performed DFPP+IA thrice weekly for 2 months and consecutively weaned the patient over one year. The last SCr was 1,52 mg/dl.
Discussion
The capability of DFPP+IA in clearing main effectors of AMR was the rational to adopt this approach in an experimental Tx intent. Although we cannot rule out the impact of long-term effects of the preliminary treatments, the chronological relationship of DFPP+IA initiation and renal recovery appears convincing. To our knowledge, this is the first report of DFPP+IA for Tx of severe AMR. Thus, we consider the implications of this case to be twofold: First, aggressive treatment of severe AMR could be successful even in long-term graft dysfunction. Second, DFPP+IA should be considered a rescue-treatment option for selected high-risk patients with proven severe acute humoral rejection in which other treatments failed.