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J M Smits

Publications and source records attributed to J M Smits.

29 records · Page 2Linked to original sources
PubMed1999

Acceptable HLA mismatches for highly immunized patients.

Highly sensitized patients have developed antibodies against many different HLA antigens due to previous pregnancies, blood transfusions or failed transplants. These antibodies cause a positive crossmatch with almost all potential organ donors. As a positive crossmatch is a contra-indication for transplantation, highly sensitized patients have a low chance of transplantation unless special strategies are introduced. One such strategy is the acceptable mismatch program, which has led to transplantation of more than 300 of these highly sensitized patients within Eurotransplant. Centers are participating in the program on a voluntary basis. Before a patient can be included in this program, extensive antibody screening is necessary to define those HLA-A and -B antigens towards which the patient has never formed antibodies. Organ donor selection is based on complete compatibility with the patients own HLA antigens in combination with the acceptable mismatches. If such a combination is identified, mandatory exchange takes place. Despite the success of the acceptable mismatch program, about 25% of the patients will never receive a donor offer. These are patients with rare HLA antigens or rare combinations of HLA antigens. In the last few years, this group of patients has had the advantage of two additional programs running within Eurotransplant. In the HIT (highly immunized tray) program, sera of highly sensitized patients are sent to the different centers and crossmatched with all ABO compatible donors. In the case of a negative crossmatch, mandatory exchange takes place. Secondly, these patients can benefit from the extra points they receive for their waiting time, high antibody reactivity and rare HLA type in the standard Eurotransplant allocation system. We conclude that the application of these three strategies will lead to a significantly increased transplantation rate of highly sensitized patients.

Cross Reactions↗
PubMed1998

Analysis of the renal transplant waiting list: application of a parametric competing risk method.

BACKGROUND: The strong competition for scarce renal graft resources jeopardizes an individual patient's chances of a transplantation within a reasonable time scale. This study was undertaken to quantify these chances of receiving a transplant. METHODS: All patients registered for their first renal allograft between January 1980 and December 1993 (n=40,636) in Eurotransplant were selected. The influence of patient characteristics, such as age, HLA phenotype frequency, % panel-reactive antibodies, period of registration, and ABO blood group, on the waiting list outflow was studied. The competing risk method was applied, and Poisson models were built to estimate the risk factor effects. RESULTS: The chance of transplantation within 10 years after registration was overestimated by Kaplan-Meier (84%); using the competing risk method it was only 74%. The predicted chance for death on the waiting list was overestimated by 33% (45% Kaplan-Meier vs. 12% competing risk). A time-varying covariate effect on the chances of waiting list outflow was observed. Favorable factors for quick transplantation, such as blood group AB or a common HLA phenotype, were no longer seen to be driving forces for transplantation once 5 to 6 years of waiting time had been accrued. CONCLUSION: When multiple outcomes exist, Kaplan-Meier estimates should not be interpreted as survival rates, while competing risk estimates yield appropriate chances. A significantly decaying effect of the usual allocation parameters is observed with ongoing waiting time. This phenomenon is the statistical basis for redesigning allocation strategies. Organ exchange algorithms should have the potential to adapt to these time-varying effects.

Analysis of Variance↗
PubMed1998

Do noninherited maternal antigens (NIMA) enhance renal graft survival?

To test the hypothesis that noninherited maternal antigens (NIMA) can modulate the alloreactivity of infant cells and provide protection for renal transplant recipients, a study of renal transplantations performed between 1980 and 1991 was undertaken. The survival rate of grafts with a mismatched antigen identical to the NIMA was compared to that of grafts in which the mismatched antigen was not identical to the NIMA. In the case of HLA-A mismatches, graft survival rates were significantly better for NIMA-mismatched transplants: 94% and 83% at 1 and 3 years, respectively, for single NIMA HLA-A mismatched transplants, and 83% and 67% when both HLA-A antigens were mismatched, compared to 76% and 68% (one non NIMA HLA-A mismatch) and 67% and 45% (two non-NIMA HLA-A mismatches). Our results suggest that some class I NIMA-mismatched antigens are not harmful to renal transplant recipients.

Adult↗
PubMed1998

The impact of special programs for kidney transplantation of highly sensitized patients in Eurotransplant.

Highly immunized patients will continue to accumulate on the waiting list of many registries unless special allocation programs are introduced. In Eurotransplant such patients can benefit from 2 programs, the Acceptable Mismatch (AM) and the Highly Immunized Tray (HIT) programs. Kidney exchange is mandatory in these programs. In addition, highly immunized patients who do not participate in these programs profit from additional points in the allocation procedure (ET-HI). In the past 18 months the 3 programs have run in parallel. Here, we show that the AM and HIT programs are highly effective with respect to increasing the patient's chance of finding a crossmatch negative donor in an adequate time course. Furthermore, the transplantation results of AM and HIT are at least comparable to those of the ET-HI. The main gain at present seems to be the significantly shorter waiting time in the AM and HIT programs.

Europe↗
PubMed1996

Association between specific HLA combinations and probability of kidney allograft loss: the taboo concept.

BACKGROUND: HLA matching improves the outcome of cadaveric renal transplantation. However, many allografts function well even in the presence of one or more HLA mismatches, which raises the question of whether some mismatches are better recognised by the recipient's immune system than others. We aimed to identify mismatched HLA donor-recipient combinations that were associated with increased graft loss. METHODS: We selected 2877 first, unrelated renal transplants with a single HLA A, B, or DR mismatch, undertaken between 1982 and 1992, from the Eurotransplant database. To enhance statistical power the analysis was restricted to mismatches of an HLA antigen that occurred in 100 or more donors. 1342 transplants met this criterion and were grouped into a definition set (n = 873) and a validation set (n = 469). In the definition set, we studied further only those recipient HLA antigens that occurred in at least 30 cases within each donor antigen mismatch subset. By a Cox proportional hazards model, donor-recipient combinations that led to significantly higher graft loss than in the whole group were defined. Such combinations were classified as taboo; the remaining combinations were classified as indifferent. FINDINGS: 106 individual recipient antigens were found at least 30 times with a corresponding donor mismatch in the definition set; 11 of the 106 had a significant effect on graft survival. Seven combinations were classified as taboo. Taboo combinations, confirmed as such in the validation set, were associated with graft survival of 81% at one year and 50% at 5 years, significantly lower than the rates in the group with indifferent combinations (89% and 69%; p = 0.04) or among 1190 recipients with no mismatches (89% and 72%; p = 0.03). The findings were substantiated by a multivariate analysis that included the effect of patient immunisation, cold ischaemia time, age, and sex. INTERPRETATION: Mismatched donor antigens are differentially recognised depending on the HLA phenotype of the recipient. The findings may have important clinical consequences for graft survival after transplantation.

Cadaver↗
PubMed1996

The outcome of kidney grafts from multiorgan donors and kidney only donors.

From 1988 to 1994, 15356 renal cadaveric transplantations have been performed within the Eurotransplant area (Austria, Belgium, Germany, Luxembourg and The Netherlands); 8746 kidneys were obtained from multiorgan donors and 6610 from kidney only donors. To evaluate the impact of the procurement policy, multiorgan donor (MOD) versus kidney only donor (KOD), on renal graft survival, an observational study has been performed. Multivariate analysis using Cox's proportional hazards model served to quantify the role of the procurement policy on renal graft survival after adjustment for other prognostic factors. The kidneys obtained from MODs had a significantly better graft survival at 1, 3, and 5 years after transplantation than the kidneys obtained from KODs (85%, 75%, and 58% versus 78%, 68%, and 46% (P=0.0001). In the Cox model, patients transplanted with a KOD kidney had a 1.28 times higher risk of losing their graft than patients transplanted with a MOD kidney. This benefit in graft survival for MOD kidneys could not be explained by the fact that the MODs were younger and male, and that UW was used as preservation solution. A plausible explanation is that MODs, on average, because of the nonrenal transplants, are better supervised. We expect that optimal donor management will contribute to a better outcome of all renal grafts.

Adenosine↗
PubMed1996

Long-term results of solid organ transplantation. Report from the Eurotransplant International Foundation.

Graft survival of cadaveric kidney-only, liver-only and heart-only transplants, performed in the Eurotransplant area between 1987-1990, was analysed, up to 5 years after transplantation. 1. HLA-A,-B,-DR mismatches had a statistically significant adverse influence on renal graft survival. 2. Kidney retransplantation was not found to be associated with a higher risk of graft loss, in contrast to liver and heart retransplantation. 3. The use of non-ideal donors (aged under 16 or over 55, non-head trauma donors) in renal transplantation should be re-evaluated, while elderly donors as well as elderly recipients jeopardized liver and heart transplant success rates. 4. A learning phase in liver and heart transplantation was evident from 1987-1990. 5. Time-effect studies can be used to adopt individual monitoring schemes. A persistent risk of graft loss in renal transplantation was observed for transplants from older donors and transplants in older recipients; these grafts constituted a very vulnerable group. For liver and heart retransplants it was noted that once patients had survived the first postoperative month, their relative risk of graft failure was no longer significantly different from patients with a first transplant. A well-considered long-term monitoring scheme for heart allograft recipients who are over age 55 is justified, as these patients had a higher risk of failure compared with younger patients. The same would be advantageous for liver transplants that are performed because of underlying liver malignancies.

Adolescent↗
PubMed1979

Propranolol in conscious spontaneously hypertensive rats. II. Disposition after subcutaneous and intracerebroventricular administration.

The disposition of dl-propranolol was studied in spontaneously hypertensive rats (SHR), both after subcutaneous (s.c.) and intracerebroventricular (i.c.v.) injection of 1 mg/kg. 1. Upon s.c. injection propranolol appeared rapidly in plasma. A maximum concentration of 374 +/- 33 ng/ml (N = 10) was reached 5 min after injection. After a distribution phase with a half-life of t 1/2 alpha = 17 min propranolol was eliminated with a t 1/2 beta = 59 min. 2. Both propranolol and its metabolites were taken up rapidly into all tissues studied. Highest concentrations (10.4 +/- 1.5 micrograms/g, N = 5) were found in lungs 30 min after injection. 3. Neither propranolol nor its metabolites accumulated in any of the tissues examined. 4. Upon i.c.v. injection of propranolol, a maximal concentration of 573 +/- 47 ng/ml (N = 3) was reached in plasma already 2 min after injection. In this case t 1/2 alpha was 13 min and t 1/2 beta was 80 min. 5. Dialysis experiments indicated that propranolol is bound to plasma proteins for 92% in the concentration range of 20--100 ng/ml. With increasing concentrations binding diminishes progressively. At the highest concentration tested (345 ng/ml) only 76% was bound. It is concluded that s.c. and i.c.v. injection of an identical dose of propranolol gives a similar plasma concentration-time profile. Moreover, it is suggested that the pharmacokinetic behaviour of propranolol in SHR does not explain the delayed antihypertensive effect of this drug.

Animals↗