**Abstract**

Kidney transplantation (KT) is the best renal replacement therapy in patients with chronic kidney disease (CKD). However, its success is limited due to insufficient number of donors worldwide and graft or patient loss. A major cause for poorer graft survival is donor-specific antibodies (DSAs). Therapeutic apheresis (TA) is a well-recognized option for increasing the donor pool by treating HLAsensitized patients and making AB0-incompatible KT possible. In addition, its use in patients with DSA has beneficial effect on graft survival. The aim of our review is to demonstrate the current knowledge on the use of TA (plasma exchange and immunoadsorption) in KT. In addition to the current guidelines, new trends in TA use prior to and after KT will be reviewed.

**Keywords:** therapeutic apheresis, kidney transplantation, desensitization, AB0 incompatible transplantation, plasma exchange, immunoadsorption

#### **1. Introduction**

Kidney transplantation is a type of renal replacement therapy (RRT) in patients with end-stage renal disease (ESRD), which is associated with the best patient outcomes. A major breakthrough was detected with the introduction of cyclosporine A in the immunosuppressive regimen. One-year survival improved further more with the use of novel immunosuppression (tacrolimus and mycophenolate), with graft survival rates for the first year after KT surpassing 95%. Despite the amazing results over the years, several problems are still unsolved.

A major obstacle to the success of KT is the shortage of donors worldwide [1]. An additional cause for donor insufficiency is the presence of donor-specific HLA antibodies (DSAs) in ESRD patients. HLA sensitization is caused mainly by blood transfusions, pregnancy, and previous organ transplantation. DSAs are associated with increased risk for acute rejection and poorer graft survival [2].

Another option to increase donor options could be AB0-incompatible transplantation. However, in these cases the innate blood group barrier should be overcome in order to avoid hyperacute rejection.

Finally, long-term graft survival (at the fifth and tenth year after KT) is significantly lower, compared to short-term one. One of explanations for this finding is the development of de novo DSA, which in turn are related to antibody-mediated rejection and poorer graft survival [3].

Therapeutic apheresis (TA) is a method by which pathological elements of the immune system (cells, antibodies, and immune complexes) are being removed via extracorporeal system, thus influencing disease activity. Different TA techniques have been developed over the years. The most important ones in organ transplantation are plasma exchange (PEX) and immunoadsorption (IA).

#### **1.1 Types of TA in kidney transplantation**

#### *1.1.1 Plasma exchange (PEX)*

PEX is an invasive therapeutic method, separating plasma from blood cells. Thus pathogenic antibodies or other large molecules are removed and plasma is replaced by human albumin and/or fresh frozen plasma (FFP). The blood is pumped out of patient's circulation, and is transferred to a separator (centrifugal bowl or hollow fiber membrane), separating plasma from blood cells. Afterward blood cells are pumped into patient's vein and patient's plasma is substituted by protein solution (human albumin and/or FFP). Generally, central venous catheter is used as vascular access, though arteriovenous fistulas and large peripheral veins can also be used. The mechanism of action of PEX is removal of pathogenic antibodies, substitution of plasma proteins, and modification of cell response. However, the procedure is associated with albumin and fibrinogen loss, the latter being linked to increased bleeding risk. Therefore, more selective techniques for antibody removal were developed. A subset of PEX is the selective PEX, in which a special membrane plasma separator with smaller pores is used. Its use in renal transplantation currently is limited.

#### *1.1.2 Double filtration plasmapheresis (DFPP)*

DFPP is a semi-selective separation technique, based on membrane PEX. After initial separation of plasma from blood cells, additional filtration of plasma is performed with different diameter of fiber pores, so that target protein fractions are filtered and the rest are returned into the circulation. This technique showed up to 70% reduction in albumin loss after the procedure lower risk for infections and allergic reactions. The method was used initially for ABo-incompatible transplantation [4].

#### *1.1.3 Cryofiltration*

The technique was designed to remove cryoglobulins in several immune diseases. After plasma is initially filtrated, it is cooled to 4°C. This causes precipitation of cryoglobulins and they do not pass the second membrane. Afterward, the cooled plasma is warmed to body temperature again and is returned to the patient. The method was used in AB0-incompatible transplantation and HLA-sensitized patients. However, further studies are needed to incorporate cryofiltration in transplantation practice [5, 6].

#### *1.1.4 Selective adsorption, immunoadsorption*

In selective adsorption the plasma is filtered at the first step of the procedure, and at the second stage the initial filtrate runs through pre-arranged immunosorbents. Thus specific antibodies can be selectively removed, whereas albumin and clotting factors are returned to the patient. There are two types of selective adsorption—*immunoadsorbtion (IA)* and *selective plasma adsorption*. In IA either the plasma runs through column bearing antigens directed against certain antibody,

#### *Therapeutic Apheresis in Renal Transplantation: Indications and Strategies DOI: http://dx.doi.org/10.5772/intechopen.92843*

or antibodies against certain plasma constituents. In selective plasma adsorption plasma components are removed by binding to ligands other than antibodies and antigens (e.g., heparin and dextransulfate in LDL adsorption).

Practically only IA is used in transplantology. There are different IA techniques according to IA devices [7]:

