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The Issue: Does HLA Matching Matter?
Questions about the significance of HLA (human leukocyte antigen) matching for living or deceased kidney donation appear frequently on the LDO Message Board. The prevailing wisdom these days is that a close antigen match isn't as important as it used to be. More effective anti-rejection drugs have improved acceptance by transplant recipients of kidneys that are not closely matched. Even "zero" matches are considered. As a consequence, transplant teams have been more willing to accept low-match donations, which has expanded the pool of possible donors for a given patient.
But does HLA matching not really matter at all? Are there consequences to the patient of receiving a kidney with a lower antigen match? These questions arise because living donors can find themselves in a position of not matching well with a loved one, yet receive assurances by the medical staff that a low match doesn't matter.
To address this issue, LDO looked at data for three time periods compiled by Organ Procurement and Transplant Network (OPTN)/Scientific Registry of Transplant Recipients (SRTR) that relate graft (donated organ) survival rates to the level of HLA match. The data covered the period 1990-1998 reported in the UNOS Scientific Registry Data as of September 5, 2000, the period 1995 - 2002 reported as of May 6, 2005, and the period 1996 - 2006 reported as of May 1, 2008.
Summary of Findings
Based on the OPTN/SRTR data, we draw the following conclusions:
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A living donor kidney is better than a deceased donor kidney. This finding is true at all levels of HLA matching and over all time frames (three months, one year, five years, and 10 years). That is, even a zero match living donor organ has a better survival rate than a perfectly matched deceased donor organ.
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In general, the better the HLA match, the longer the graft survival. That is, if a choice is available, a closer match is preferred. This result becomes more pronounced over time. Graft survival rates are best with a perfect (six out of six) match, followed by a clustering of results for HLA matching of one to five antigens, with the lowest graft survival rates for a zero match. (Results for HLA mismatch have not been tested to see if the differences are statistically significant.)
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There have been modest improvements in graft survival rates when the 1996 - 2006, 1995 - 2002, and 1990 - 1998 periods are compared. The improvements are most pronounced for deceased donations, but the improvements are not sufficient to overcome the better survival rates of living donor organs.
Therefore, the answer to the question of whether HLA matching matters depends on the context of the question:
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The level of HLA match does not matter when determining whether a person can donate. We have observed that transplant teams often do not consider HLA matching when identifying potential donors. The HLA match may be used as a tie-breaker if there is more than one living donor available.
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The level of HLA match does matter to graft survival: the better the HLA match, the better the kidney survival rate over time. Therefore, given a choice, a potential transplant recipient would prefer the highest HLA match available.
All kidney graft survival results, regardless of HLA mismatch are generally positive. The costs and benefits of a transplant, even of a zero match, must be weighed against alternative treatment such as dialysis.
Note that there may be explanations for the relationship between HLA match and kidney survival rates that require additional investigation. For example, there may be a relationship between "sicker" patients' willingness to take a poorly matched organ because they don't have the luxury of time to wait for a better match. As a consequence, they may show lower graft survival rates simply by having been in poorer health from the start, not necessarily because the organ wasn't a good match.
Use this information with caution.
Details of Survival Rates by Level of HLA Match
To illustrate the effect of HLA matching on graft survival, we created the following graph using the most recent data from OPTN/SRTR. The graph illustrates the unadjusted graft survival rates for living donor and deceased donor kidney transplants.
The graft source and HLA match are denoted as follows: "Living Donor 6:6 match" means six of six HLAs were matched (a perfect match) by a living kidney donor; "Living Donor 0:6 match" means there was a zero HLA match from a living donor; "Deceased Donor 6:6" means a perfect match from a deceased donor; and "Deceased Donor 0:6" means zero of six HLAs were matched (a "zero" match) by a deceased kidney donor.
The lines were generated using survival rates for three months, one year, five years, and 10 years to give a sense of the effect of antigen matching over time. The three month data cover transplants in 2005 - 2006; one year data cover transplants in 2005 - 2006; five year data cover transplants in 2001 - 2006; and 10 year data cover transplants in 1996 - 2006. The data reports can be found here.
To learn more about HLA matching, click here. Questions, comments? Please post them on the LDO! Message Board.