Mismatch Matters for Kids' Kidney Transplants

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Mismatch Matters for Kids' Kidney Transplants

By Crystal Phend, Senior Staff Writer, MedPage Today
Published: July 21, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
   
Action Points 
Explain that a study has found that antigen incompatibility hurts pediatric kidney transplant outcomes, but may often be unavoidable unless changes are made to the organ allocation system.

Point out that the estimated frequency of finding a donor without any HLA-DRB1 mismatch who was also compatible for blood type was less than two per 100 local donors for most patients in the study, and lower for Asian minorities.
Antigen incompatibility hurts pediatric kidney transplant outcomes, but may often be unavoidable unless changes are made to the organ allocation system, researchers suggested.

One or two mismatches for human leukocyte antigen (HLA)-DRB1 between the donor and pediatric recipient boosted risk of rejection by 70% (P=0.006), Peter G. Stock, MD, PhD, of the University of California San Francisco (UCSF), and colleagues found in a retrospective cohort study.

However, the chances of a perfect match were slim under the current local organ-sharing scheme, the group reported in the July issue of the Archives of Surgery.

The estimated frequency of finding a donor without any HLA-DRB1 mismatch who was also compatible for blood type was less than two per 100 local donors for most patients in the study.

For Asian minorities, the chances were even lower.

Longer waiting time on dialysis can mean severe growth retardation and greater risk of dying for children who need a kidney, Stock's group noted.

"Based on the current allocation system, most pediatric recipients would benefit more by minimizing dialysis time and accepting an HLA-DR-mismatched kidney," they wrote in the paper.

The current United Network for Organ Sharing allocation system emphasizes donor organ quality without a priority on HLA-DR mismatch.

Some changes to that system could help pediatric kidney waitlist patients, though, the researchers urged.

They advocated moving beyond local boundaries for organ sharing to a regional donor pool to give kids a better chance of finding their best HLA-DRB1 match.

Another recommendation was to calculate the frequency of a donor without any HLA-DRB1 mismatch for each patient on the waiting list.

Those with a higher probability of a perfect match could benefit from waiting, whereas those with "an exceedingly low probability, such as ethnic minorities, should undergo transplantation regardless of HLA-DRB1 mismatch," the researchers suggested.

Even then, HLA-DRB1-mismatched donors could be selected with less mismatching for closely linked HLA class II antigen loci (HLA-DRB3, DRB4, and DRB5 and HLA-DQ), they added.

"Ultimately, for each patient, the potential benefit of avoiding HLA-DRB1 mismatching should be balanced by the detrimental effects of increased waiting time," Stock and colleagues concluded.

Their study included 178 patients younger than 21 who had a successful kidney transplantation at UCSF with daclizumab (Zenapax) induction therapy from 1997 through 2006.

One- and five-year rates for graft outcomes were 97% and 82% for graft survival and 35% and 55% for rejection.

During the median of 4.1 years of follow-up, HLA-DRB1 mismatching didn't predict graft failure or sensitization.

But history of rejection, which was more likely with HLA-DRB1 mismatch, did independently predict both graft failure (hazard ratio 7.7, P=0.01) and sensitization (odds ratio 9.7, P=0.001).

Sensitization is an important issue for these children, who are likely to need at least one retransplantation later in life, the researchers pointed out.

They acknowledged that the study could not control for potential confounding from unmeasured factors like medication adherence, although restricting the sample to those on daclizumab eliminated confounding from different immunosuppression regimens.

Another limitation was use of medical record review and examination of available blood samples for diagnosis of rejection and sensitization, which may have underestimated outcomes.

The researchers reported having no conflicts of interest to disclose.

Primary source: Archives of Surgery
Source reference:
Vu LT, et al "HLA-DR matching in organ allocation balance between waiting time and rejection in pediatric kidney transplantation" Arch Surg 2011; 146: 824-829.

http://www.medpagetoday.com/Nephrology/KidneyTransplantation/27666