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The Issue

Questions about the significance of HLA (human leukocyte antigen) matching for living or cadaveric 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 organs that are not closely matched. Even "zero" matches are considered in some cases.

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 an organ 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, we looked at data for two time periods compiled by United Network for Organ Sharing (UNOS) that relate graft (donated organ) survival rates to the level of HLA match. The data covered the period 1990-1998, as reported in the UNOS Scientific Registry Data as of September 5, 2000, and data for 1995 - 2002, reported as of May 6, 2005.

Summary of Findings

Based on the UNOS data, we draw the following conclusions:

• Living donation is better than cadaveric donation. This result is true at almost all levels of HLA matching and over all time frames. That is, even a zero match living donor organ has a better survival rate than a perfect match cadaveric organ. The advantage of a living donor organ becomes more pronounced over time.

• 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 also becomes more pronounced over time. Results appear to be 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 worst results for a zero match. Results for HLA mismatch have not been tested to see if the differences are statistically significant.

• There have been modest improvements in graft survival rates when the 1995 - 2002 rates are compared to the 1990 - 1998 rates. The improvements are most pronounced for cadaveric donations, but the improvements are not sufficient to overcome the better survival rates of living donor organs.

Therefore, if given a choice, a recipient favors a living donor organ, and regardless of source would prefer a higher antigen match.

All results, regardless of HLA mismatch are generally positive. Of course, the benefit of a transplant, even of a zero match, must be weighed against alternative treatment such as dialysis.

Finally, there may be other explanations for the relationship between HLA match and survival rates that would 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 and patient 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.

Ranking of Survival Rates by HLA Matching

To illustrate the effect of HLA matching on graft and patient survival, we have ranked the UNOS data results by level of matching. We also combine the results for living and cadaveric donation to compare the relative value of these forms of donation to the patient. Rankings are shown for short-term (after three months) and long-term (after five years) survival rates to give a sense of the effect of antigen matching over time. The results are shown in the table below.

The graft source and HLA match are denoted as follows: "Living 6 of 6" means six of six HLAs were matched (a perfect match) by a living kidney donor; "Cadaver 3 of 6" means three of six HLAs were matched (a "half" match) by a cadaveric donor; and so on. (To learn more about HLA matching, click here.)

The source data for this analysis can be found at the UNOS web site.

Questions, comments? Please post them on the LDO! Message Board.

© 2008 International Association of Living Organ Donors, Inc.