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J M Cecka

Publications and source records attributed to J M Cecka.

At least 145 records · Page 8Linked to original sources

Improvement of kidney transplant regraft results by using trauma death donors.

Patients who have lost a transplanted kidney are widely recognized as high-risk patients for retransplantation. We have found a profound difference in cadaver kidney regraft survival associated with the age and sex of the donor. Kidneys from male cadaver donors yielded significantly higher graft survival rates than kidneys from female donors. The difference in graft survival at one year was 7% for all first transplants (n = 2974), 14% if the recipient was sensitized, and 18% in 688 patients being regrafted. The difference was even more striking in regraft recipients of kidneys from young male donors (72% one-year graft survival) as compared with recipients of kidneys from older female donors (44% one-year graft survival). The donor age and sex effects correlated well with the cause of donor death. Young male donors accounted for 59% of trauma deaths whereas older female donors made up only 7%. Nontrauma donors, on the other hand, were 38% older female and 14% younger male. The survival of trauma-death donor kidneys in regrafted patients was 69% at one year and 37% for nontrauma donor kidneys, a 32% difference (P less than 0.001). These results indicate that regraft survival could be significantly increased through the use of cadaver kidneys from trauma death donors.

Adolescent↗

The transfusion effect.

1. Pretransplant blood transfusions improved the survival of first cadaver donor renal allografts by 10% at one year in CsA-treated recipients. 2. Pretransplant transfusions improved the survival of living-related donor transplants as well. HLA-identical sibling grafts had a 5% higher graft survival rate in transfused than nontransfused patients. Living-related donor transplants in one haplotype-mismatched combinations had a 10% higher one-year graft survival rate in transfused recipients. One-year graft survival in nontransfused recipients of one haplotype-mismatched sibling transplants was 75%, a result slightly lower than that for CsA-treated first cadaver donor recipients. 3. Transfusions given prior to retransplantation did not improve survival of the second graft. As patients who have previously rejected a transplant are at high risk of sensitization, blood transfusions should be avoided if possible. 4. For black recipients, transfusions improved one-year cadaver graft outcome by 17%. The effect was smaller in white recipients (8%), but significant nevertheless. One-year graft survival was 55% in nontransfused blacks and 68% in nontransfused whites. The impact of recipient race on the transfusion effect may explain some of the discrepancies between the UCLA and European registries on the magnitude of the transfusion effect. 5. Even centers with high overall success rates with cadaver donor transplants had poor graft survival in nontransfused recipients. The transfusion effect cannot be explained simply as a reflection of center performance. 6. The number of transfusions required to see an improvement in graft survival was small. Even a single transfusion significantly improved graft outcome in male and nulliparous female recipients. Since the risk of sensitization increased with multiple transfusions, large numbers of unnecessary transfusions should be avoided. 7. There may be alternatives to transfusion for those patients unwilling or unable to accept blood products and for patients at high risk of sensitization (parous females) as a result of transfusion. HLA matching resulted in high survival rates among nontransfused recipients.

Blood Transfusion↗

Donor factors.

1. Kidneys from female donors between the ages of 31 and 50 had consistently poorer graft survival rates than kidneys from male donors or younger female donors. 2. Sensitized first cadaver kidney recipients of older female donor kidneys had a one-year graft survival rate of 65% as compared with 82% in recipients of young male donor grafts (p less than 0.001). Retransplanted recipients of older female donor grafts had a one-year graft survival rate of 48% as compared with 70% in recipients of young male donor kidneys (p less than 0.001). 3. The effects on graft survival of donor age and sex were considerably greater than the effect of cold ischemia in excess of 36 hours. 4. The cause of donor death was a risk factor for sensitized and regraft recipients. In data from 45 transplant centers, sensitized first transplant recipients of nontrauma donor kidneys had a one-year graft survival rate of 67% versus 78% (p = NS) for recipients of trauma donor kidneys. Regraft recipients of nontrauma donor grafts had a one-year graft survival rate of 55% versus 67% (p less than 0.05) for recipients of trauma donor kidneys. 5. The cause of donor death effect and the effects of donor age and sex may be related as older female donors accounted for 37% of nontrauma donors and only 7% of trauma donors were older females. 6. A surprisingly high percentage of older female (6%) and nontrauma donor kidneys (3%) failed on the first day posttransplant in regrafted patients. A very sensitive crossmatch may help reduce the number of immediate failures. 7. HLA matching improved graft survival of female donor kidneys to a greater extent than male donor kidneys in regrafted patients. With zero or one mismatch at HLA-B,DR there was no difference in one-year graft survival between male and female donor kidneys. In first cadaver transplants, the difference in graft survival between older female and young male donor grafts was minimized by very good matching. Matching also abrogated the donor sex and age effects in living-related donor transplants. 8. Sensitized patients and patients who have previously rejected a kidney should be given priority for young male trauma donor organs when these become available.

Adolescent↗

The changing role of HLA matching.

1. In the precyclosporine era, there was a 12% difference in graft survival at one year between recipients of HLA identical and one-haplotype mismatched transplants from living-related donors. This difference increased to 20% at 5 years. 2. Recipients of cadaver donor transplants which were not mismatched at HLA-A,B antigens had a 10% higher graft survival rate at one year than recipients of kidneys which were completely mismatched at HLA-A,B. The difference increased to 17% at 5 years. 3. Patient survival at 5 years posttransplant was 5% higher in recipients of HLA-A,B matched grafts than in recipients of completely mismatched grafts. 4. The percentage of zero HLA-A,B mismatched grafts which functioned was 7% higher at one day and 10% higher at one month than completely mismatched grafts to sensitized recipients. 5. Sensitization following a rejected transplant occurred two to three times more frequently in recipients who rejected an HLA-A,B mismatched graft and were subsequently retransplanted. 6. Sensitized recipients generally received transplants which were better matched for HLA-A,B antigens as a result of selection against mismatches at the crossmatch. Twenty percent of highly sensitized recipients were transplanted with no mismatches at HLA-A,B. HLA-DR matching was not affected by sensitization. 7. HLA-C locus antigens were typed in 30% of donors and recipients since 1979. Matching for the C locus antigens in addition to HLA-A,B or HLA-DR antigens did not improve graft survival. 8. The number of patients typed for HLA-DR antigens has steadily increased since 1978, with 90% of patients transplanted in 1984 and 1985 typed for DR antigens. 9. Since the introduction of cyclosporine, there has been a significant increase in the number of poorly matched transplants at the expense of well-matched transplants. This trend coincided with a decrease in the number of cadaver donor kidneys shared between distant centers. 10. Matching for HLA-B and -DR locus antigens had a larger effect on cadaver kidney graft survival than matching for HLA-A,B or HLA-DR antigens separately. First cadaver transplants with zero HLA-B,DR antigens mismatched had a 90% one-year graft survival rate when the recipient received cyclosporine. One approach toward increasing the number of such well-matched transplants would involve extensive sharing of kidneys from B locus homozygous donors, since these account for half of the zero HLA-B,DR mismatched transplants.(ABSTRACT TRUNCATED AT 400 WORDS)

Cyclosporins↗

The roles of sex, race, and ABO groups.

1. Recipient sex did not play a significant role in transplant outcome. 2. Donor sex emerged as a surprisingly major factor in recent transplants. Cyclosporine did not increase graft survival of female donor kidneys from donors between the ages of 31 and 50 above survival rates achieved by conventional immunosuppression. Male kidneys had a 7% higher one-year survival rate than female kidneys in first cadaver transplants and a 13% higher one-year survival rate in regraft recipients treated with cyclosporine. 3. Female donor kidneys had poorer early function rates in cyclosporine-treated patients. The first day nonfunction rate was 27% in first cadaver recipients of female donor kidneys and 19% for male donor kidneys. Among recipients whose kidneys did not function in the early posttransplant period, recipients of female donor grafts had higher average serum creatinine levels than recipients of male donor grafts. 4. The poorer survival and early function rates of female cadaver donor kidneys were also affected by the age of the donor in first transplant recipients. Kidneys from females less than 30 years old survived as well as male donor kidneys, suggesting that the effect was not strictly sex-associated. 5. Matching for HLA-A,B antigens abrogated the effect of donor sex. Graft survival was the same for both male and female kidneys when no HLA-A,B antigens were mismatched between the donor and recipient in first cadaver, cadaver regraft, and living-related donor transplants. Mismatches at HLA-A,B reduced survival of female donor grafts in patients who were retransplanted by as much as 25% at one year, while male donor grafts were much less affected. 6. Black recipients had significantly lower graft survival rates than white recipients of first cadaver donor transplants. Although cyclosporine improved graft survival in blacks, there remained a 10% discrepancy between the survival of transplants in black recipients and in white recipients. 7. Although the number of transplants was small, there was no apparent race effect in blacks who were retransplanted with a cadaver donor kidney or who received a transplant from a living related donor when cyclosporine was used. 8. The poor graft survival of black donor kidneys transplanted to white recipients was due in part to very poor HLA matching. 9. The black donor kidney showed a striking similarity to the older female donor kidney in recipients treated with cyclosporine. There may be an association between cyclosporine nephrotoxicity or rejection and kidneys from hypertensive donors. 10. There were no differences in graft survival between recipients of the various blood types in recent transplants.(ABSTRACT TRUNCATED AT 400 WORDS)

ABO Blood-Group System↗

The Los Angeles Transplant Society.

For some 20 years a coordinated arrangement for sharing cadaver organs has been in place in Southern California. It's 11 transplant centers have performed 4,947 kidney transplants from 7,480 referred donors. There were 430 transplants done in 1985. The policy has been to keep one kidney and share the other within the pool. This has resulted in a better than average level of matching for HLA, and an overall better than average graft survival. The graft survival rates at the centers have been increasing yearly. Much of the improvement in graft survival resulted from the introduction of cyclosporine, but a summation of many factors contributed to a steady yearly increase. There are some 600 patients waiting for transplantation. With greater efforts in procurement of cadaver kidneys, especially from minorities, and continued collaboration between the transplant centers, it should become possible to transplant all those who are in need of a kidney.

Adolescent↗

Microsequence analysis of Ia antigens from three strains of rats.

Homologues of Ia antigens of the mouse are identified in three rat strains by partial N-terminal amino acid sequence analysis. Ia antigens of the rat were isolated by indirect immune precipitation using specific rat alloantisera. Rat Ia antigens consist of two components, alpha and beta, which have respective mol. wts. of approximately 35 000 and 28 000. Partial N-terminal sequence analysis of each of the alpha components of the H-1a, H-11 and H-1n haplotypes yields a single, apparently homogeneous sequence which is identical among the three haplotypes and is strikingly homologous to the alpha polypeptides of the I-E subregion of mouse and to the human polypeptide, p34. Partial N-terminal sequence analysis of the beta components shows that a mixture of polypeptides is present for each haplotype. There are differences in the beta sequences among the three haplotypes and potential homologies between the rat beta sequences and the sequences of the beta polypeptides of the I-A and I-E subregions of mouse. These obserations imply that the rat has at least two distinct groups of Ia molecules. The organization of genes encoding the Ia polypeptides in the major histocompatibility complex of the rat is discussed.

Amino Acid Sequence↗

Structure of Ia antigens from the rat. Mouse alloantisera demonstrate at least two distinct molecular species.

Ia antigens isolated from spleen cells of rats and mice are composed of two polypeptide chains, designated alpha and beta. Mouse alloantisera specific for the I-Ak and I-Ek subregions react with two distinct groups of rat Ia antigens, designated A-like and E-like, respectively. Two-dimensional gel electrophoresis and peptide map analysis demonstrate that the A-like antigens of rat are distinct from the E-like antigens. Both rat Ia antigens react with alloantiserum produced in rats congenic for the major histocompatibility complex (MHC). These results demonstrate for the first time that two distinct Ia antigens are present in the rat. Accordingly, the rat, like the mouse, may have Ia antigens encoded by at least two subregions of the rat MHC. The existence of multiple Ia gene products in rats is revealed by chemical techniques even in the absence of formal genetic evidence of more than one I subregion in the rat.

Animals↗

Partial N-terminal amino acid sequence analyses and comparative tryptic peptide maps of murine Ia molecules encoded by the I-A subregion.

The partial N-terminal amino acid sequences and tryptic peptide maps of I-A subregion products from the H-2b, H-2d, H-2k and H-2s haplotypes demonstrate that haplotype-associated differences are present in both alpha and beta polypeptides. The genetic and evolutionary implications of these multiple amino acid substitutions and the homology relationships among Ia molecules from human, guinea pig and the I-E subregion of the mouse are discussed.

Alleles↗