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G G Persijn

Publications and source records attributed to G G Persijn.

At least 37 records · Page 2Linked to original sources
PubMed2000

The relevance of proficiency testing for laboratories involved in cadaveric organ transplantation and its consequences for graft survival.

Organ exchange organizations such as Eurotransplant allocate organs on the basis of histocompatibility testing results. For this reason it is essential that all data reported by the affiliated laboratories are accurate and reliable. The Eurotransplant Reference Laboratory (ETRL) organizes proficiency testing schemes for the tissue-typing centers of the respective renal transplantation units participating in Eurotransplant. Each year, the ETRL sends out 8 peripheral blood samples of healthy blood donors for serological typing and crossmatching, 16 sera to screen for the presence and definition of HLA alloantibodies and 20 DNA samples for molecular typing to the 49 participating centers. The results are collected centrally and reported back to the participants in an open way. These exercises show that the quality of HLA typing, screening and crossmatching improved significantly over the years. In particular, the introduction of molecular typing for HLA-DR resulted in an increase of reliability. The clinical relevance of a reliable HLA typing was demonstrated in a selected group of transplants, the zero HLA-A,-B,-DR- mismatched group. After retyping the donors, 146 of the 3,458 matched transplants appeared to have a mismatch and those transplants had a significantly lower graft survival rate. A continuing problem, however, is the result of screening for panel reactive antibodies (PRA), where the percentage PRA reported for each serum varies significantly from center to center. The results indicate that the use of a PRA value for classification of patients and allocation of organs should be revisited.

Cadaver↗
PubMed1999

Eurotransplant randomized multicenter kidney graft preservation study comparing HTK with UW and Euro-Collins.

The aim was to evaluate the effect of HTK compared to UW and Euro-Collins (EC) on the initial graft function and long term graft survival in two prospective randomized studies. Only kidneys from heart-beating, kidney-only or kidney + heart donors were eligible for entry. Initial non-function (INF) was defined as the absence of life-sustaining renal function, requiring dialysis treatment on two or more occasions, during the first week after transplantation. To evaluate the contribution of the preservation solutions on INF in relation to other factors, a multivariate, 2-step logistic regression model was used. Randomization was performed between July 1990 and September 1992. The UW-HTK study comprised 342 donors and 611 transplants (UW: 168 donors and 297 transplants, HTK: 174 donors and 314 transplants). In the EC-HTK study 317 donors and 569 transplants were included (EC: 155 donors and 277 transplants, HTK: 162 donors and 292 transplants). INF occurred in 33% of either HTK-(n = 105) or UW-(n = 99) preserved kidneys (P = NS), and in 29% of the HTK-(n = 85) and in 43% of the EC-(n = 119) preserved kidneys (P = 0.001). Multivariate analysis showed no significant influence of the preservation solution on the incidence of INF in the UW-HTK study, but factors contributing to INF were donor age, cause of death, retransplantation, and cold ischemic period. The EC-HTK study showed a significantly higher risk of INF, using EC as preservation, in addition to cold ischemic period and donor quality. The 3-year graft survival of HTK-preserved kidneys was 73%, compared to 68% for UW-preserved kidneys in the UW-HTK study (P = NS); while the 3-year graft survival of HTK preserved kidneys was 70% compared to 67% for EC-preserved kidneys in the EC-HTK study (P = NS). We can conclude that HTK is comparable to UW in its preservative abilities, using kidneys from heart-beating kidney-only donors, whereas EC as renal preservation solution should be avoided.

Adenosine↗
PubMed1999

Lung transplant waiting list: differential outcome of type of end-stage lung disease, one year after registration.

BACKGROUND: Donor lung scarcity, distinct natural courses of the different types of end-stage lung diseases, and lung allocation schemes demand appropriate candidate acceptance for a lung transplant and time of listing. This study was undertaken to investigate the association between type of end-stage lung disease and outcome, 1 year after a lung transplant candidate was put on the waiting list. METHODS: From 1990 to 1995, 1376 adult patients were registered for a first lung (n = 1006) or heart-lung (n = 370) transplantation in Eurotransplant. All patients were followed for at least 1 year. For each type of end-stage lung disease (cystic fibrosis, pulmonary fibrosis, emphysema, pulmonary hypertension, congenital heart disease, and other), chances of transplantation, of death on the waiting list, and of removal for other reasons, 1 year after listing, were calculated with the competing risks method. A multivariate Cox regression model was used to assess the influence of the type of end-stage lung disease on the waiting list outflow among other prognostic variables. RESULTS: Lung transplant candidates with emphysema and with pulmonary fibrosis had the highest chance of a transplant; however, patients with pulmonary fibrosis had also the highest probability of dying while waiting, while the emphysema patients and those with the type "other" had the lowest probability. In the multivariate analysis, the type of end-stage lung disease appeared as an independent prognostic factor for both outcomes. Compared to the patients with cystic fibrosis (reference group), only patients with pulmonary fibrosis had a significantly higher chance of a transplant (RR = 1.50); the lowest chance of death for the emphysema and the "other" patients was confirmed (RR = 0.53 and RR = 0.51, respectively). Recipient size, ABO blood group, country and epoch of listing also had a significant impact on the transplant chance, while country of listing and recipient age were the other factors independently influencing the chance of dying on the waiting list. On the heart-lung waiting list, the type of end-stage lung disease solely affected the chance of death prior to transplant. Compared with cystic fibrosis, pulmonary fibrosis had a significantly higher risk (RR = 2.93), closely followed by pulmonary hypertension (RR = 2.57). Factors crucial for the chance of a heart-lung transplant were recipient size, ABO blood group and country of listing. CONCLUSIONS: The type of end-stage lung disease is a distinctive factor for predicting survival on the lung and heart-lung transplant waiting list, and should be taken into account whenever assessing waiting list outcomes. When developing lung allocation schemes, it is medically justified to incorporate the type of end-stage lung disease.

Adolescent↗
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

The new Eurotransplant Kidney Allocation System: report one year after implementation. Eurotransplant International Foundation.

BACKGROUND: Upon the availability of a cadaveric donor kidney, a delicate allocation process precedes every transplantation. A remodeled Eurotransplant Kidney Allocation System (ETKAS)-derived from simulation studies-was installed in March 1996. The purpose was to adjust long waiting times and international exchange balances, while aiming at an optimal HLA-mismatch distribution. The new ETKAS consisted of a point-score system that was 100% patient oriented. METHODS: The impact of the new ETKAS on the composition of the waiting list, and the outcome of the allocation procedures during its first year, were evaluated and compared with the results obtained in 1995. RESULTS: The percentage of long-waiting patients and of patients with poorly matchable HLA phenotype increased significantly, from 9% to 19% and from 19% to 29%, respectively. Zero HLA-A-, HLA-B-, HLA-DR-mismatched patients still comprised 23% of the kidney transplant activity. The kidney exchange of the different Eurotransplant countries became balanced within 4 months; this persisted during the rest of the year. Pediatric patients had a high transplantation rate due to an assignment of extra points. The composition of the waiting list showed, after 1 year, fewer long-waiting patients and fewer patients with rare HLA phenotypes. CONCLUSIONS: The new ETKAS was able in its first year to meet the goals set at its introduction. In comparison with the old ETKAS, there was a better trade-off between HLA matching and waiting time. The value of computer simulation studies has been demonstrated impressively in the context of organ allocation.

Cadaver↗
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

Long-term graft survival after liver transplantation in the UW era: late effects of cold ischemia and primary dysfunction. European Multicentre Study Group.

The use of University of Wisconsin (UW) solution in liver transplantation (LTX) has significantly prolonged preservation times and facilitated semielective transplant procedures. Despite this advantage potential risk factors related to the donor, recipient, or cold storage method will persist in the UW era and detrimental effects will be reflected by primary dysfunction (PDF) after LTX. Concern has been voiced about the maximum period of UW preservation in LTX and various cold ischemia times (CIT) are mentioned. To evaluate the effect of UW solution in LTX, a prospective European multicenter study was initiated in 1988 and short-term results have been reported previously. This report focuses on the long-term effects and survival of prolonged preservation with UW solution and primary function after LTX. Three hundred and fifteen LTXs were performed in 288 patients in participating European centers. Complete follow up of at least 6 years was available for 296 grafts in 277 patients. Effects of donor, preservation, and recipient risk factors on PDF including primary non-function (PNF) and initial poor function (IPF) were evaluated. Next, the effect of risk factors on graft survival (GS) was analyzed including the long-term impact of PNF and IPF using multivariate analyses and the Kaplan-Meyer method. PDF occurred in 15.2% (45/296) with PNF in 7.8% and IPF in 7.4%. Patients with IPF had a 34% lower GS at 3 months those with immediate function (IF; 58% vs 91%; P < 0.001). This difference persisted up to 6 years for patients with IPF with a 39% GS vs 72% after IF (P < 0.001). Median CIT was significantly longer in grafts with PNF compared to IPF or IF (P = 0.03). Long-term GS, however, was significantly influenced at a lower CIT threshold with a 6-year GS for CIT < or = 16 h of 67%, compared to a CIT > 16 h of 51% (P = 0.02). Other independent risk factors for the 6-year survival rate were re-LTX, ABO incompatibility, and recipient diagnosis of acute hepatic failure. In conclusion, liver patients with PNF, but not with IPF, have a significantly lower CIT. IPF is associated with a significantly lower 3 month GS compared to IF, but this difference of 34% does not further increase during a 6-year follow up. Although a short term follow up (3 months) shows that with UW solution CIT up to 18 h has no adverse effect on GS, the 6-year data clearyl suggest that CIT should be kept to less than < 16 h to avoid tetrimental effects on lang-term GS after LTX.

Adenosine↗
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↗
PubMed1998

Trends in organ donation.

Renal and extrarenal transplant data were collected for seven geographical regions for the period 1989-1996. In Western Europe and North America the number of kidney donors increased by 926 and 2743, respectively. The total number of transplants also increased in both regions by 3756 and 6936, respectively. Renal transplants accounted for approximately 60% of the total number of transplants and, although the number of renal transplants did not alter in Western Europe, the number rose by 3055 in North America. Outside of these regions the number of extrarenal transplants was 3-18% of the total. The number of living kidney donors in North America increased each year and was higher than the number recruited in Western Europe (3389 vs 943 in 1996). With the exception of Eastern Europe, where virtually no renal transplants were carried out using organs from living donors, the number of living kidney donors rose in other regions: for example, in Latin America, the proportion of living kidney donors rose from 29% in 1970-88 to 51% in 1995, and, in Asia, 90% of kidneys were donated by living donors. As the quality of cadaveric donor organs is often sub-optimal, the use of living donors is likely to increase in both Western Europe and North America, but is unlikely to become the most important source of organs in these regions.

Humans↗
PubMed1997

Risk factors for delayed graft function in cadaveric kidney transplantation: a prospective study of renal function and graft survival after preservation with University of Wisconsin solution in multi-organ donors. European Multicenter Study Group.

BACKGROUND: Delayed graft function (DGF) remains an important complication in renal transplantation. In this multicenter study, we investigated the influence of donor and recipient factors on the occurrence of DGF and DGF's effect on long-term graft survival. METHODS: A total of 547 transplanted kidney allografts, retrieved from multi-organ donors, were analyzed, and results were compared with literature on kidney-only donors. RESULTS: Median follow-up of patients without graft failure was 3.4 years. Twenty-four percent of the recipients developed DGF. In univariate analysis, the following factors significantly increased the incidence of DGF: (a) among the donor factors, mean creatinine level >120 micromol/L and prolonged cold ischemia time (CIT); and (b) among the recipient factors, previous transplant(s), no intraoperative use of mannitol, poor quality of reperfusion, absence of intraoperative diuresis, and pretransplant anuria or oliguria. After stepwise logistic regression, donor age, CIT, recipient's number of previous transplants, and intraoperative diuresis proved to be of independent prognostic value for the occurrence of DGF. Overall graft survival was 91%, 87%, and 72% at 3 months, 1 year, and 4 years after transplantation, respectively. In case of DGF, graft survival was approximately 10% lower when compared with cases with immediate graft function (P<0.001). No difference in incidence of DGF was found between grafts of multi-organ donors and kidney-only donors. CONCLUSIONS: DGF results in an approximately 10% higher rate of graft failure. DGF incidence can be reduced by the administration of mannitol during transplantation, which minimizes CIT and optimizes donor management. Grafts from multi-organ donors and kidney-only donors appear to be of equal quality.

Cadaver↗
PubMed1997

Trends in organ donation.

Presumed consent legislation produces more donors and in particular more organs per donor. In cadaveric donation, the number of elderly donors is increasing, so the quality of organs available is getting poorer. There will be no substantial rise in transplantation unless there is a major breakthrough in the current programs. There will be an increase in the proportion of living (un)related donors and debate about ethics of transplantation. Adverse publicity and debate may affect cadaveric donation and refusal rates.

Australia↗
PubMed1997

Transplant rejection associated with the presence of human leucocyte antigen antibodies detected by the Fc gamma R inhibition test but not by the lymphocytotoxicity test.

The unselected sera from 869 human leucocyte antigen (HLA) immunized patients awaiting a kidney transplant were analysed using the complement-dependent lymphocytotoxicity test (LCT) with peripheral mononuclear blood cells and the complement-independent immune phagocytosis inhibition test (IPI) with monocytes derived from between five and 10 donors. Sera from 659 patients were LCT and IPI negative when tested against this small panel. Seventy-nine patients had HLA immunoglobulin-G (IgG) antibodies, detectable by the IPI only. Sera from 117 patients had concordantly positive IPI and LCT reactivity with cells from certain donors and concordantly negative IPI and LCT reactivity with cells from other donors (no isolated IPI and no isolated LCT reactions). Fourteen patients had a mixed type of reactivity. Laboratory findings were interpreted along with the transplantation history of the respective patients. Group 1 comprised patients for whom negative results were obtained in both the LCT and the IPI; group 2 patients who were also LCT negative but IPI positive. These two groups showed a significantly different history with respect to the number of irreversible immunological transplant rejections. In group 1, 25.3% of the transplanted kidneys had been rejected whereas in group 2, 56.0% of the kidneys had been rejected (p = 5 x 10(-5)). The high incidence of rejections in the group showing only IPI reactions was comparable with that of group 4 comprising patients with concordant IPI and LCT reactions (59.4%). It is inferred from this retrospective study that renal allograft rejection is associated with the development of IPI reactive antibodies which are not detectable by the LCT. The presence of these antibodies prior to transplantation could be detrimental to the transplanted organ. This being the case, the incidence of transplant failures could be reduced by pretransplant screening using the IPI and by avoiding crossmatch positive donors identified by IPI, especially in patients waiting for a retransplantation.

Antibody Specificity↗