Transplantation Immunology.pdf - E-Lib FK UWKS

16 Callaghan and Bradley
HLA compatibility at the level of amino acid triplets in antibody-accessible
regions of HLA molecules, may also be valuable in identifying more HLAmatched
donors for this group of patients (94).
Clinical strategies to decrease PRAs, and thus increase the chances of a negative
crossmatch, include administration of intravenous gammaglobulin (95),
induction immunosuppression with antithymocyte globulin (96), plasma exchange/
immunoabsorption (97), or a combination of the above (98).
8. BK-Virus-Associated Nephropathy
Renal transplant recipients are, like all transplant recipients, at increased
risk of infection, particularly viral infections such as cytomegalovirus infection
(99). A review of infectious complications after renal transplantation is
beyond the scope of this chapter. However, since it was first reported in 1995,
BK-virus-associated nephropathy (BKVN) has emerged as an important cause
of renal allograft loss and is therefore highlighted here.
BK virus (also known as polyomavirus hominis 1) is an unenveloped doublestranded
DNA virus that infects 75% of the general population. Primary infection
occurs in childhood, resulting in a vague flu-like illness. The route of transmission
is unclear. BK virus then persists in the urinary tract, from where it may
undergo asymptomatic reactivation in immunocompetent individuals. In the
immunocompromised the disease is more virulent, especially in kidney transplant
patients (100).
In renal transplant recipients, BK viral disease has a wide variety of manifestations,
including ureteric stenosis, transient graft dysfunction, or irreversible
allograft failure secondary to BKVN. BKVN is defined as deterioration of
graft function associated with histologically apparent BK virus allograft infection
(101). It occurs in approx 8% of renal transplant patients (102), and the
incidence appears to be rising. This may be the result of the use of more potent
immunosuppressants, increased awareness, and better diagnostic tools.
Definitive diagnosis of BKVN requires allograft biopsy (103). BKVN is seen
as intranuclear inclusion bodies in tubular epithelial cells with enlarged nuclei.
Ongoing viral replication leads to an accompanying inflammatory response with
fibrosis and eventually atrophic tubules. Infected cells shed into the urine are
known as decoy cells. Quantitative polymerase chain reaction (PCR) of BKV
DNA in serum is the most commonly used noninvasive test, with sensitivity
and specificity of 100% and 88%, respectively (102).
In the absence of rejection, which is often coexistent, management consists
of immunosuppressant reduction. If rejection is present, management is difficult—a
two-step protocol of antirejection treatment followed by lowered immunosuppression
has been advocated (100). Antiviral treatment with cidofivir may
be of use, but it is potentially nephrotoxic and has not yet been evaluated in