Acute rejection and chronic nephropathy: a systematic review of the literature.
BACKGROUND
The risk of graft failure is the pivotal measure of effectiveness when evaluating immunosuppressive regimens for renal transplantation. However, to date most randomized trials of immunosuppressive therapy have had acute rejection as the primary endpoint for treatment comparisons. The objective here was to review the evidence relating acute rejection to renal graft function and graft survival.


METHODS
A systematic review of the published literature was undertaken. Studies were reviewed if they included the following: study populations of adults undergoing renal transplantation, endpoints of graft loss or survival, and quantitative data on the associations between acute rejection and graft function and survival.


RESULTS
Overall, 31 observational studies were included. The definition of acute rejection varied, and there was substantial heterogeneity in study design and methodology. In all but two studies, acute rejection was associated with an increased risk of graft loss-risk ratios ranged from 1.2 (no definition reported) to 10.5 (confirmed by biopsy and grade I Banff criteria). In addition, there was fairly strong evidence linking timing of acute rejection and graft survival and weaker evidence linking the number of episodes and graft survival. The heterogeneity between studies invalidated pooling of quantitative studies.


CONCLUSIONS
The weight of the evidence indicates that occurrence, timing, and number of acute rejection episodes are associated with increased risk of graft loss. Less is known about the severity of rejection, which is important because many immunosuppressive regimens lessen severity. Quantifying these relationships is a priority if acute rejection continues to be a surrogate trial endpoint.
Wu
Olivia
O
Division of Community Based Sciences, Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom. o.wu@clinmed.gla.ac.uk
Levy
Adrian R
AR
Briggs
Andrew
A
Lewis
Gavin
G
Jardine
Alan
A
D006084:Graft Rejection / Q000453:epidemiology*; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007674:Kidney Diseases / Q000453:epidemiology*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000473:pathology*; D011183:Postoperative Complications / Q000453:epidemiology; D012307:Risk Factors