**5.2 Plasmapheresis**

*Perioperative Care for Organ Transplant Recipient*

**4.3 Subclinical antibody mediated rejection**

**4.4 Hyperacute antibody mediated rejection**

**5. Treatment**

**5.1 IVIG**

transplantation [40].

treatment of ABMR [47, 48].

standard T and B lymphocyte crossmatch techniques [39].

antigen-binding) and traces of IgM and IgA [41].

tions as a scavenger of activated complement [43, 44].

A certain amount of kidney transplant recipients present with stable kidney graft function, but histological evidence of smoldering active ABMR on protocol biopsies [35]. These patients often have low-level DSAs (de novo or persistent/recurrent). Evidence suggests that untreated subclinical ABMR is an important predictor of poor renal allograft outcomes [36]. However, the lack of long-term follow-up data has prevented the development of strong guidelines for effective therapeutic interventions.

Nowadays, hyperacute rejection is a rare event in kidney transplantation affecting mostly presensitized patients (previous transplantation, blood transfusions, or pregnancy) [37]. It occurs due to preformed DSA present in high titers and presents as graft failure that can occur within minutes (but sometimes may be delayed for a few days) after transplantation [38]. The occurrence of this type of rejection is extremely rare, as preformed antibodies can usually be excluded by CDC crossmatch. However, there is growing evidence that there may exist hyperacute rejections mediated by endothelial, non-HLA antibodies that cannot be detected in

Treatment for ABMR is not standardized, and there is still no evidence-based treatment guidelines. A recent therapy of ABMR in renal allografts is systematically reviewed by Wan et al. [2]. In addition to plasma exchange and intravenous immunoglobulin, which still present a backbone of treatment, a number of other therapies have been tried in small studies without consistent benefit, including anti-CD20, proteasome inhibitors, complement inhibitors, anti-interleukin-6 receptor blockers,

Intravenous immunoglobulin (IVIG) is used for treatment of ABMR, and it is used as an element of desensitizing protocols for ABO- and HLA-incompatible renal

IVIG is prepared by human plasma from approximately 50,000–100,000 of healthy donors, composed of 90% intact IgG, a few dimers, Fabs (fragment

IVIG. Investigations in the early 1990s suggested the therapeutic potential of IVIG was due primarily to anti-idiotypic interactions with HLA antibodies [42]. Apart from its effects on B cells and phagocytes via Fc-gamma receptors, IVIG also func-

Two general treatment protocols have been developed utilizing IVIG. The first is the use of high dose IVIG (2 g/kg) alone and the second is to combine lower dose IVIG with other modalities, usually plasmapheresis [45]. After the first successful report of Jordan et al. in 1998 [46] who treated acute ABMR in kidney and heart allografts by high-dose IVIG and methylprednisolone, there were more studies with usage of IVIG alone or in combination with plasmapheresis to show effectiveness in

There are many postulated immunomodulatory mechanisms of

and immunoglobulin G-degrading enzyme of *Streptococcus pyogenes* (IdeS).

**82**

Both immunoabsorption (IA) and plasmapheresis (PP) are known to lower HLA-specific antibody levels in a variety of clinical settings [49]. Despite the substantial reductions in the titer of donor-specific anti-HLA antibodies achieved by IA and PP, the graft survival in these patients is significantly reduced, due to rebound synthesis of de novo alloantibodies.

PP is the most frequent modality applied and generally involves 1.0–1.5 volume exchange, using albumin as replacement. It is usually performed daily or every other day for an average of six sessions (up to 14 days). The initial treatment is typically a one-and-one-half-volume exchange with albumin, and subsequent treatments are a one-volume exchange with albumin. To avoid fresh frozen plasma administration, most clinicians prefer an every-other-day PP schedule as albumin alone can often be administered for replacement with interval recovery of the prothrombin time, partial thromboplastin time, and fibrinogen to acceptable levels. This avoids the risk of antigen sensitization. IA is a more selective modality that uses adsorbent membranes for antibody elimination [49, 50].

Few studies have been published where PP modalities are the sole or primary form of antibody reducing therapy [51–54]. However, PP alone has limited success in the treatment of ABMR, and this finding has led to the addition of therapies to prevent immunoglobulin resynthesis and B-cell proliferation. Therefore, PP is often used in combination with other antibody blocking (IVIG), suppression (rituximab, mycophenolate, calcineurin inhibitors), or depleting (bortezomib) modalities [2].
