Search PubMed⌕ Search

Biomedical subjects

D W Gjertson

Publications and source records attributed to D W Gjertson.

14 recordsLinked to original sources
PubMed1992

Survival of nationally shared, HLA-matched kidney transplants from cadaveric donors. The UNOS Scientific Renal Transplant Registry.

BACKGROUND: The importance of HLA histocompatibility typing to the outcome of transplantation of cadaveric kidneys has been controversial. Four years ago, a prospective trial began in all U.S. transplantation centers to determine whether the results of transplantation would improve with the nationwide shipment of kidneys from cadaveric donors to waiting patients undergoing dialysis when there was a match at the HLA-A, B, and DR loci. METHODS: A total of 1386 cadaveric kidneys were shipped from 108 organ centers to 198 transplantation centers and distributed among HLA-matched recipients, 1004 of whom were receiving a first transplant and 382 of whom were receiving a subsequent transplant. Graft survival in these recipients was compared with that in 22,188 recipients of first transplants and 3950 recipients of subsequent transplants whose HLA antigens differed from those of the donor. RESULTS: The rate of graft survival at one year in recipients of HLA-matched first transplants was 88 percent, as compared with 79 percent in the recipients of mismatched grafts (P less than 0.001). The estimated half-life of the kidney after the first year was 17.3 years for matched grafts, as compared with 7.8 years for mismatched grafts (P = 0.003). Among paired kidneys from 470 donors, one-year graft survival was 87 percent in the recipients of matched first grafts, as compared with 80 percent in the recipients of the contralateral kidneys, who did not have HLA matches with the donors. In donors and recipients matched for the more highly defined split Class I and Class II HLA antigens, the rate of graft survival after one year was as high as 90 percent. CONCLUSIONS: The collaborative renal-transplantation program for HLA matching of donors and recipients yielded an increased rate of one-year graft survival and an estimated half-life for matched grafts twice that for mismatched grafts. An increased role for HLA matching in kidney allocation is therefore indicated.

Adolescent↗
PubMed1992

The large center variation in half-lives of kidney transplants.

Based on a log-linear model for analyzing multiple effects, center variation in the UCLA Transplant Registry is the most influential factor in early renal graft survival. Among 68 active centers accounting for 70% of all transplants between 1985 and 1989, the 1-year graft survival (adjusted for 15 covariates) varied from 60 to 90%. The long-term graft survival, as measured by the half-lives of the first cadaver donor transplants at these centers, based on a minimum of 4 years of follow-up data, varied from 3 to 26 years. Although there was some correlation (r = 0.24) of half-life with the 1-year graft survival rate at each center, in many instances, excellent centers had poor half-lives and average centers had excellent half-lives. From a Cox regression analysis on data from 6752 first cadaver-donor renal transplants surviving beyond 1 year (submitted to the UNOS data base), white female recipients of 0 HLA-AB-mismatched kidneys not requiring dialysis in the first week posttransplant had projected half-lives of 14.1 years, whereas black male recipients of 4 HLA-AB-mismatched kidneys requiring therapeutic dialysis had half-lives of 2.3 years. However, adjustment for these factors could only remove 17% of the total variability in the centers' half-lives. Consequently, any algorithm intended to judge a center's renal transplant capabilities should include, even after adjustment for covariates, some function of both 1-year graft survival and half-life beyond 1 year.

Cadaver↗
PubMed1992

HLA matching: a comparison of conventional and molecular approaches.

1. The UNOS national sharing program has produced a 5-fold increase in the number of compatible transplants since 1987. 2. Transplants with 0 broad HLA-antigen mismatches had 87% 1-year graft survival and an 18-year half-life, essentially the same result as with conventional matching. 3. Equally impressive results were obtained with public determinant matching: 1-year graft survival ranging from 84 to 88% and a half-life of 12-15 years. 4. Increasing the number of matched determinants improved the results but reduced the number of compatible recipients identified. 5. Less than 10% of the current transplants have 0 public determinants mismatched. This fraction could be increased to 66% with local sharing and to over 90% with national sharing. 6. The results for cadaver transplants would approach those of related kidneys if compatible grafts were transplanted at the 90% rate obtainable with molecular matching.

Cadaver↗
PubMed1992

Multifactorial analysis of renal transplants reported to the United Network for Organ Sharing Registry.

1. From a multivariate log-linear analysis of 35,625 renal transplants between 1988 and 1991, center effects accounted for 28%, 45%, and 27% of all assignable variation in 3-month, 1-year, and 2-year outcomes, respectively. Although center variation dominated 22 other variables, most factors were relatively independent of transplant center (ie, a percent of factor variation due center less than 10%). Recipient race and health status were notable exceptions; both highly influenced by center affiliation. Centers also differed in the age mix of recipients and racial mix of donors in some epochs. Again, we found only extremely weak correlations among a center's 3-month, 1-year, and 2-year graft survival rates. 2. In order of 3-month accountability, the other important factors were PRA, donor age, recipient working status, year of transplant, HLA-A,B mismatching, previous transplant, donor's death, donor relationship, recipient race, body mass, recipient age, cold ischemia time, donor race, donor kidney mode (ie, left/right kidney), original disease, and HLA-DR mismatching. Regarding 1-year outcome, the important factors were recipient race, donor age, donor's death, donor relationship, HLA-A,B mismatching, previous transplant, and recipient sex. Finally at 2 years, the important factors were recipient race, donor age, year of transplant, donor relationship, recipient sex, working status, donor's death, recipient age, CMV status, body mass, and donor sex. 3. Body mass, donor kidney mode, and CMV status were novel factors in our own multifactorial analyses of the UNOS Registry file. An elevated body-mass index (> 30 kg/m2) had a negative impact on short- and long-term graft survival. Recipients receiving left kidneys had nominal improvement in 3-month graft survival, but no impact thereafter. Survival rates over the 4 combinations of donor/recipient CMV statuses, suggest that this covariate was principally long-term and donor related. 4. It is noteworthy that graft failures in the 2 most recent transplant years, 1990 and 1991, have shown both short- and long-term declines, breaking stationary patterns previously reported in this series on clinical transplants. 5. The transitory nature of most transplantation factors was confirmed in this study, implying that future multifactorial studies in renal transplantation must include some mechanism for varying risks.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1991

National allocation of cadaveric kidneys by HLA matching. Projected effect on outcome and costs.

BACKGROUND: Although receiving a cadaveric kidney matched at the HLA-A, B, and DR loci enhances graft survival in cyclosporine-treated patients, the value of a national system of kidney allocation based on HLA matching, with the attendant increased likelihood of better matching, is still questioned. Some fear that the costs of a national system are unjustified when only a small fraction of donors would exactly match any of the 16,000 potential recipients anyway. We estimated the effect on graft survival of the use of HLA matching for all allocations of cadaveric kidneys in the United States. METHODS: The graft-survival rates in five mutually exclusive groups of transplants with increasing numbers of HLA mismatches were estimated by partitioning the data for 22,190 first-time recipients of cadaveric kidneys. Overall graft survival was projected as a weighted average with use of the percentages of transplants in the hierarchical groups in recipient waiting pools of various sizes. We compared the benefits and costs of HLA matching in a national system with those of introducing cyclosporine, which was projected to enhance graft survival by 7 percentage points at 10 years. RESULTS: Sharing kidneys nationally on the basis of hierarchical HLA matching was estimated to enhance graft survival by an additional 5 percentage points at 10 years. The anticipated five-year cost of national allocation of kidneys by HLA matching for 7000 recipients, including consideration of the costs of graft removal and dialysis after transplant rejection, would be +4F6.5 million less than the cost of using cyclosporine alone. CONCLUSIONS: The use of an HLA allocation system will not add to the cost of renal transplantation, but it will improve the long-term results to the same extent as cyclosporine. We propose the initiation of a national kidney-sharing system based on hierarchical levels of HLA matches.

Cadaver↗
PubMed1991

Survival trends in long-term first cadaver-donor kidney transplants.

1. In 1966, the half-life (1-year posttransplantation) for first cadaver-donor kidney grafts reported to the UCLA Registry was around 7.5 years (1). Between 1985 and 1990, this half-life was 7.8 +/- 0.02 years. Since 1966, the corresponding 1-year graft survival rates increased by over 30 percentage points. Clearly, improvement in early graft survival has had little bearing on long-term graft outcome. 2. From a stratified multivariate analysis of 40,582 primary cadaveric renal transplants recorded in the UCLA Transplant Registry from 3 consecutive eras (1975-79, 1980-84, 1985-90), the following long-term graft survival trends in covariates have emerged: a) a constant strong negative effect associated with higher numbers of HLA-A,B mismatches, younger and older recipients, diabetics, and longer cold ischemia times in each era; b) an increased beneficial effect on female recipients; c) an increased detrimental effect on Black recipients, despite short-term gains; and d) a positive effect of CsA usage (only in the most recent era). 3. From a multivariate analysis of 15,027 primary cadaveric renal transplants reported to the UNOS Kidney Registry between 1987 and 1990, we analyzed the effects of transplantation factors on survival during 3 consecutive posttransplantation risk periods: 0-1 month; 1-3 months; and beyond 3 months. Few pretransplant factors affected risk of failure within 1-month posttransplantation. However, a good predischarge clinical course (as indicated by CsA usage, no required dialysis during the first postoperative week, and no rejection episodes) was associated with an immediate improvement in graft survival. The effects of most UNOS transplantation factors during the second risk period were comparable to the short-term coefficients estimated from the UCLA file; and the effects of the UNOS factors on "beyond 3-month" risk were comparable to the UCLA long-term coefficients. Conclusively, the dominant pretransplant factor on long-term risk was HLA-A,B tissue matching.

Actuarial Analysis↗
PubMed1991

Assessment of interaction among risk factors in three-month graft survival of first cadaveric renal transplantations: a case-control study.

1. Most multivariate analyses of first cadaver-donor kidney grafts have assumed additivity of covariate effects, ignoring possible interaction terms. Using 21,895 primary cadaveric renal transplants reported to the UNOS Kidney Registry, we attempted to assess whether or not strong interaction effects on graft survival existed among 11 important factors. Due to the small number of cases for many multiway factor combinations, our interaction analyses were limited to studying how stratification by 1 factor affected the graft failure risks of a second factor. Two stratification factors were chosen: recipient race and age. 2. Although there was little evidence of strong factor interaction across 5 racial groupings, differences in risk for several factors (recipient age, donor race, donor age, HLA-B,DR mismatching, and cold ischemia time) between Blacks and non-Blacks appeared to be nonadditive (2 examples listed in Table 3). 3. In a more restricted population of White recipients older than age 16, there was only evidence of interacting effects on 3-month graft survival between donor sex and recipient age. 4. Despite many pairwise factor associations (Figs. 1, 3), it appears that the majority of the transplant covariates are additive with respect to the risk of early graft loss. In future analyses, we suggest inclusion of appropriate interaction terms relating the above-mentioned factors with recipient race and age.

Adolescent↗
PubMed1990

Update: center effects.

1. From a multivariate log-linear analysis of 30,274 renal transplants between 1985 and 1989, center effects accounted for nearly 30% of all assignable variation in 1-year outcome, dominating 15 other factors analyzed. In order of accountability in 1-year graft outcome, the other important factors were donor relationship, CsA usage, donor age, graft number, highest pretransplant antibody, recipient race, HLA-A, B, and DR mismatches, cold ischemia time, donor sex, donor race, and pretransplant transfusions. Original disease, transplant year, recipient sex and age were not significant factors influencing 1-year graft survival. 2. The additive nature of these transplantation factors on the logit scale was confirmed in this analysis, implying that univariate analyses in renal transplantation are not necessarily improper. 3. There was no correlation between center effect and center size as measured by the number of renal transplants per year. Therefore, renal transplantation at small centers will not necessarily produce poorer graft function. 4. Similarly, we found only weak correlation between a center's 1-year graft survival and their patients' graft half-lives beyond 1-year. This suggests that factors determining center success in early graft survival differ from those that influence long-term success. 5. Graft survival rates among patients with and without rejection episodes prior to hospital discharge vary substantially among centers. Centers with poor 1-year graft survival demonstrated a significantly larger variation in graft survival between their patients with and without rejection than did excellent, good, and fair centers. This indicates that posttransplant patient maintenance is another factor influencing center effects on renal graft function.

Female↗
PubMed1990

The UNOS Scientific Renal Transplant Registry: multistep regression models on kidney graft survival.

1. Two-step Cox regression analyses showed that, for White recipients of first cadaver transplants, pretransplant transfusions, HLA-DR mismatch, donor race, CIT, size mismatch, PRA, old donor, and recipient age were significant prognostic factors during the first 6 months posttransplant, and after that, older donor, CIT, and size mismatch continued to have effects on graft survival in the longer term. 2. For African-American recipients of first cadaver transplants, pediatric donor, cause of donor death, and increasing second warm ischemia time were major risk factors in the early period, but in the late period, the effect of donor age dominated other factors. 3. Multistep linear logistic regression and two-step Cox regression analyses yielded similar results, with donor-related and histocompatibility factors dominating survival outcome in both the short and long terms.

Adult↗
PubMed1989

Short- and long-term effects of HLA matching.

1. Matching shows a positive effect, even in the CsA era. In this report we have seen that in a group of 12,886 patients (90% of whom were given CsA), when a donor and recipient had no A,B,DR mismatches, their overall survival exceeded baseline by 5% at 6 months and by a 2.5-year increase in half-life past 6 months. 2. When loci are combined, their effect on graft survival is greater than when loci are viewed individually. Differences from baseline in Figures 6-13 are greater than those in Figures 2-5. 3. Class II DR antigens show a short-term effect but relatively little long-term differences, whereas Class I antigens (A and B loci) have immaterial short-term effects but significant long-term differences. Comparisons involving DR mismatches (eg, Figures 5, 10, 11, 12) always showed significant differences in short-term survival (an average 9% increase from best to worst mismatch categories), but, when DR was studied alone (Fig. 5), small differences in half-lives between 0, 1, and 2 mismatches were noted (ie, 7.6 years vs 6.0 years). In contrast, when A and B mismatches were studied without DR (eg, Figs. 2, 3, 6-9), 6-month graft survivals were never significantly different from baseline, whereas nearly all comparisons (Figs. 2, 3, 6-12) showed significantly widening half-life differences (approximately 4 years) between best and worst mismatch.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Calculation of probability of paternity using DNA sequences.

This paper formally incorporates allele measurement error into the Essen-Möller version of the probability of paternity. For highly polymorphic genetic systems, an approximate solution to the problem is developed resulting in simple formulas. The DNA sequence of the D14S1 region provided a practical example for testing this approximation. For these sequences, allelic uncertainty arises from determining length of DNA fragments from mobility in gel electrophoresis. D14S1 and standard test results from 35 paternity cases establish the validity of our computational method.

Blotting, Southern↗
PubMed1987

Empirical paternity exclusion rates.

We have developed an empirical method of estimating paternity exclusion rates for any genetic system by counting exclusions among fictitious "nonfather" paternity cases generated from true paternity disputes. Especially for multiallele multiloci systems, this technique has advantages over traditional formulae methods in that it replaces tedious (and, in some cases, impossible) computations with simple data file manipulations, and it avoids introducing quantities such as gametic disequilibrium and recombination fraction that are difficult to measure. Exclusion rates for standard and one-parent paternity cases are given for three racial groups (Caucasians, blacks, and Hispanics) in four genetic systems (HLA, ABO, MNSs, and Rh). Beside the method, of interest are our findings of higher HLA exclusion rates (93.25% for Caucasians, 94.62% for blacks, and 95.82% for Hispanics) compared with rates previously reported and high combined exclusion rates (89.59% for Caucasians, 91.65% for blacks, and 92.54% for Hispanics) in one-parent paternity cases.

ABO Blood-Group System↗
PubMed1986

Empirical validation of the Essen-Möller probability of paternity.

The validity of the Essen-Möller formulation probability of paternity is supported by demonstrating its correctness in a model genetic system--the ABO system. An analysis was made of 1,393 paternity cases typed uniformly for HLA-A and -B, ABO, Rh, and MNSs, in which the mother named one man only as the child's father and in which both mother and putative father identified themselves as Caucasian. For purposes of analysis, putative fathers not excluded from paternity by the four systems tested were regarded as actual fathers. The joint distribution of observed triplets of ABO phenotypes is shown to be statistically consistent with expected values, and the fractions of "true" fathers for a given triplet closely approximated the probability of paternity calculated using a realistic prior probability. Recent allegations of fallaciousness of the method by Li and Chakravarty and Aickin are discussed in terms of the results presented.

ABO Blood-Group System↗