Transplantation Immunology.pdf - E-Lib FK UWKS

4 Callaghan and Bradley
1.2. Determinants of Long-Term Outcome
Improvements in long-term graft survival are mainly a result of better outcomes
in the first year posttransplantation (8,9). It is disappointing to note that
the rate of graft loss after 1 yr has remained relatively unchanged since the
1980s, at 3–5% per year. Long-term graft loss is primarily the result of chronic
allograft nephropathy (CAN) (40%) or death with a functioning graft (40%).
Recurrence of the initial renal disease in the renal transplant is also an important
cause of graft failure (10% of late graft loss). CAN is characterized histologically
by intimal hyperplasia in small- and medium-sized arteries, interstitial
fibrosis, glomerulosclerosis, and tubular atrophy. Both immunological (chronic
rejection) and nonimmunological factors contribute to the development of CAN
(10). The clinical manifestations of CAN are a progressive decline in renal
function with proteinuria and hypertension. The precise mechanisms are poorly
understood, but a number of risk factors have been identified.
Immunological risk factors for CAN include previous episodes of acute rejection
(8) and suboptimal immunosuppression (11). Mismatches between the donor
and recipient at the human leukocyte antigen (HLA)-DR, HLA-A, and HLA-B
loci also reduce long-term graft survival in renal transplantation (12). Mismatching
is expressed as a mismatch (MM) grade, and the MM grade may vary between
0-0-0 (full house match) and 2-2-2 (complete mismatch), with each integer signifying
the HLA-A, -B, and -DR locus, respectively. In the United Kingdom, the
number of donor–recipient HLA mismatches has been reduced through the introduction
of HLA matching into the National Kidney Allocation Scheme.
Nonimmunological factors leading to CAN are numerous and include increased
recipient age, male gender, hypertension, and increased donor age (12). Because
there is no effective treatment for CAN other than retransplantation, it is important
to try wherever possible to minimize associated risk factors (11).
The rates of recurrent renal disease in the transplanted kidney and its clinical
impact vary depending on the underlying disease (13). Histological changes
suggestive of diabetic nephropathy can be identified in most grafts in diabetic
recipients, but clinically overt diabetic nephropathy is uncommon. In contrast,
up to 50% of patients with focal segmental glomerulosclerosis experience disease
recurrence, and there is a 50% chance of graft loss within 2 yr.
Death with a functioning graft is most commonly the result of cardiovascular
disease (CVD) in the recipient (14). This is discussed in more detail later.
2. Recipient Evaluation
Evaluation of a prospective recipient for renal transplantation should be performed
as soon as it becomes apparent that therapy for ESRD will be required.
Early transplantation is desirable in patients with ESRD, and there is evidence
that pre-emptive transplantation (i.e., transplantation in the months preceding