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T van Gelder

Publications and source records attributed to T van Gelder.

At least 19 recordsLinked to original sources
PubMed2005

Successful vaccination against varicella zoster virus prior to kidney transplantation.

BACKGROUND: In recent years we have observed a number of severe complications of primary varicella-zoster virus (VZV) infections after adult kidney transplantation. We questioned how many patients on the waiting list for kidney transplantation had not been protected against VZV and whether patients with renal insufficiency would be able to develop a specific immune response upon VZV vaccination. METHODS: We examined the VZV antibody titer of 280 patients on the kidney transplant waiting list. Seronegative kidney transplant candidates were vaccinated twice with a live attenuated varicella vaccine at an interval of 6 weeks. CONCLUSIONS: Approximately 3% of patients on the waiting list were seronegative for VZV. Vaccination induced no side effects and resulted in a positive serologic response in most patients.

Adult↗
PubMed2004

The relative importance of cyclosporine exposure in heart, kidney or liver transplant recipients on maintenance therapy.

We investigated the relationship between cyclosporine exposure and the presence of cyclosporine-related side effects and assessed the advantage of the cyclosporine concentration 2 h post-dose (C(2)) over pre-dose concentration (C(0)) monitoring. Cyclosporine area-under-the-concentration-time curves were measured during the absorption phase (AUC(0-4 h)) in 49 liver, 28 heart and 26 kidney transplant recipients (time since transplantation >6 years) with or without cyclosporine-related side effects on maintenance therapy. The cyclosporine C(0) correlated well with AUC(0-4) (r=0.77), whereas C(2) levels correlated strongly with AUC(0-4) (r=0.92). Although we observed a trend towards higher CsA concentrations in transplant recipients with side effects than in patients without CsA toxicity, the large majority of those differences were not statistically significant. Thus, as cyclosporine exposure was not clearly related to the presence of side effects, and C(0) correlated fairly with AUC(0-4), the advantage of monitoring cyclosporine treatment using C(2) rather than C(0), may be limited for patients on cyclosporine maintenance therapy.

Adult↗
PubMed2004

The Cox proportional hazards analysis in words: examples in the renal transplantation field.

When renal transplantation was still in its infancy, failures were more prevalent and successes could be directly derived from facts and events. Because results have improved dramatically over the last decades and many factors have seemed to be involved in these continuously improving results, it is difficult to ascertain the individual contribution of each factor. Survival analysis is the appropriate method for evaluation of factors influencing results of renal transplantation. In this overview, two different methods for survival analysis are compared and described. The Kaplan-Meier analysis is the oldest and most frequently used in renal transplantation epidemiology. Important shortcomings of this method are described and substantiated with examples. The Cox proportional hazards (PH) analysis was developed in 1972 by Sir David Cox. With this multivariable analysis it is possible to identify those variables that influence the rate of failure. With this method, the influences of all other variables in the model are taken into consideration, and adjustment for interaction with other variables or with time can be made. In this article, the Cox analysis and the statistical terms that go with it are described in words and examples are given. In a complex, observational study concerning a multifactor-influenced population such as the renal transplant population, the use of the Cox model is mandatory to unravel the influences of the different variables on the failure rate.

Humans↗
PubMed2003

The superior results of living-donor renal transplantation are not completely caused by selection or short cold ischemia time: a single-center, multivariate analysis.

BACKGROUND: The results of living-donor (LD) renal transplantations are better than those of postmortem-donor (PMD) transplantations. To investigate whether this can be explained by a more favorable patient selection procedure in the LD population, we performed a Cox proportional hazards analysis including variables with a known influence on graft survival. METHODS: All patients who underwent transplantations between January 1981 and July 2000 were included in the analysis (n=1,124, 2.6% missing values). There were 243 LD transplantations (including 30 unrelated) and 881 PMD transplantations. The other variables included were the following: donor and recipient age and gender, recipient original disease, race, current smoking habit, cardiovascular disease, body weight, peak and current panel reactive antibody, number of preceding transplants and type and duration of renal replacement therapy, and time since failure of native kidneys. In addition, the number of human leukocyte antigen identical combinations, first and second warm and cold ischemia periods, left or right kidney and fossa, donor kidney anatomy, donor serum creatinine and proteinuria, and transplantation year were included. RESULTS: In a multivariate model, donor origin (PMD vs. LD) significantly influenced the graft failure risk censored for death independently of any of the other risk factors (P=0.0303, relative risk=1.75). There was no time interaction. When the variable cold ischemia time was excluded in the same model, the significance of the influence of donor origin on the graft failure risk increased considerably, whereas the magnitude of the influence was comparable (P=0.0004, relative risk=1.92). The influence of all other variables on the graft failure risk was unaffected when the cold ischemia period was excluded. The exclusion of none of the other variables resulted in a comparable effect. Donor origin did not influence the death risk. CONCLUSION: The superior results of LD versus PMD transplantations can be partly explained by the dichotomy in the cold ischemia period in these populations (selection). However, after adjustment for cold ischemia periods, the influence of donor origin still remained significant, independent of any of the variables introduced. This superiority is possibly caused by factors inherent to the transplanted organ itself, for example, the absence of brain death and cardiovascular instability of the donor before nephrectomy.

Adult↗
PubMed2003

Anti-CD25 monoclonal antibody therapy affects the death signals of graft-infiltrating cells after clinical heart transplantation.

BACKGROUND: To define whether immunosuppressive agents that block the interleukin (IL)-2 pathway could prevent activation-induced cell death of activated T cells in the graft, we measured expression of IL-2, IL-2 receptor alpha chain (CD25), IL-15, Fas, and Fas ligand by real time reverse transcription-polymerase chain reaction in cardiac allografts. METHODS: We characterized the phenotype of the infiltrating cells (CD3, CD68, CD25) by immunohistochemistry. The proportion of apoptotic graft-infiltrating cells was determined by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining. We analyzed endomyocardial biopsy specimens from cardiac allograft recipients who were treated with anti-CD25 monoclonal antibody (mAb) induction therapy (daclizumab) or with matching placebo in combination with cyclosporine, steroids, and mycophenolate mofetil. RESULTS: Treatment with anti-CD25 mAb affected the number of infiltrating CD3 and CD68 cells and the IL-2-regulated apoptotic pathway. During anti-CD25 mAb treatment, significantly lower intragraft IL-2 and CD25 mRNA transcription levels and decreased numbers of CD25+ T cells were found compared with the levels measured in endomyocardial biopsy specimens from placebo-treated patients (5- to 10-fold, P=0.002 and P<0.0001, respectively). In these samples the intragraft mRNA expression levels of IL-15 were also lower (P=0.02). Inhibition of the IL-2 pathway by anti-CD25 mAb therapy was accompanied by reduced mRNA and protein of Fas ligand and not by reduced Fas expression (P=0.001 and P=0.03). TUNEL staining revealed that the proportion of graft-infiltrating cells was lower in the anti-CD25 mAb patient group than the proportion of apoptotic cells in patients receiving placebo (P=0.06). CONCLUSION: Our data suggest that immunosuppressive agents that affect the IL-2 pathway hinder the mechanism of activation-induced cell death by which the immune system eliminates alloreactive cells.

Antibodies, Monoclonal↗
PubMed2003

[Kidney transplantation: more kidneys from living donors, individualised immunosuppression and better results].

In the period 1996-2001, the number of transplanted postmortal kidneys decreased from 425 to 380, while at the same time the number of kidneys transplanted from living donors increased from 81 in 1996 to 155 per year in 2001. There was a striking increase in the proportion of living non-related donors (59/155). Although the short-term results of kidney transplantation have improved, and kidneys are very rarely lost as a consequence of acute rejection, the average life of a transplanted kidney has scarcely improved. Chronic allograft dysfunction is now the major cause of transplant loss. This process is hardly influenced by the immunosuppressive drugs currently used. To improve the cardiovascular risk profile, several centres discontinue the use of cyclosporin, tacrolimus or prednisone at 6 or 12 months after transplantation or substitute these with other drugs. This is complicated by acute rejection episodes in 10-20% of patients. With the arrival of a number of new immunosuppressive drugs the risk of rejection might be reduced.

Graft Rejection↗
PubMed2003

[Twenty-five years of cyclosporin use in transplantation medicine].

Cyclosporin has greatly improved the short and medium-term outcomes for solid organ transplantation. However, the effect on the long-term outcome has been less impressive. This can partly be attributed to the side effects of cyclosporin, and partly to the fact that the use of cyclosporin has not led to a reduced incidence of chronic allograft nephropathy. Efforts to minimise these side effects have led to the development of the microemulsion form of cyclosporin and improved methods for therapeutic drug monitoring (dosage based on blood levels instead of body weight). Finally, the introduction of new immunosuppressive drugs has made it possible to further reduce the dose of cyclosporin; this might eventually lead to cyclosporin-free immunosuppressive regimens.

Cyclosporine↗
PubMed2003

Ischemia times and donor serum creatinine in relation to renal graft failure.

BACKGROUND: The results of renal transplantation are dependent on many variables. To simplify the decision process related to a kidney offer, the authors wondered which variables had the most important influence on the graft failure risk. METHODS: All transplant patients (n=1,124) between January 1981 and July 2000 were included in the analysis (2.6% had missing values). The variables included were donor and recipient age and gender, recipient original disease, race, donor origin, current smoking, cardiovascular disease, body weight, peak and current panel reactive antibody (PRA), number of preceding transplants, type and duration of renal replacement therapy, and time since failure of native kidneys. Also, human leukocyte antigen (HLA) identity or not, first and second warm and cold ischemia times, left or right kidney and fossa, donor kidney anatomy, donor serum creatinine and proteinuria, and transplantation year were included. RESULTS: In a multivariate model, cold ischemia time and its time-dependent variable significantly influenced the graft failure risk censored for death (P<0.0001) independent of any of the other risk factors. The influence primarily affected the risk in the first week after transplantation; thereafter, it gradually disappeared during the first year after transplantation. Donor serum creatinine also significantly influenced the graft failure risk in a time-dependent manner (P<0.0001). The risk of a high donor serum creatinine is already enlarged in the immediate postoperative phase and increases thereafter; the curve is closely related to the degree of the elevation. The other variables with a significant influence on the graft failure rate were, in order of decreasing significance, recipient age, donor gender, donor age, HLA identity, transplantation year, preceding transplantations, donor origin, and peak PRA. CONCLUSIONS: Donor serum creatinine and cold ischemia time are important time-dependent variables independently influencing the risk of graft failure censored for death. The best strategy for improving the results of cadaveric transplantations is to decrease the cold ischemia time and to allocate kidneys from donors with an elevated serum creatinine to low-risk recipients.

Adult↗
PubMed2003

Unusual presentation of herpes virus infections in renal transplant recipients exposed to high mycophenolic acid plasma concentrations.

Viral infections constitute an important problem for transplant recipients and their physicians. Often the balance between adequate and over-immunosuppression is hard to find and therapeutic drug monitoring might be a welcome adjunct in the management of transplant patients. We report four renal transplant recipients with extra-ordinary presentations of viral disease who were all treated with mycophenolate mofetil and in whom high mycophenolic acid (MPA) trough levels were found. High MPA levels may reflect over-immunosuppression resulting in infectious complications.

Adult↗
PubMed2003

Pilot studies: one swallow does not make a summer...

What should we expect from pilot studies, done in small series of patients? In the literature there are many examples of small studies with very promising results, that in subsequent larger or better controlled studies proved to be much less promising, or even disastrous. In some instances the initial favourable outcome was due to selection bias. In others the use of nonvalidated methods of measuring outcome made the reproducibility of promising observations problematic. However, we have to start somewhere. In ths issue The et al. report favourable results of granisetron treatment in four out of five patients with chronic fatigue syndrome. A prospective, randomised, placebo-controlled, double-blind clinical trial with granisetron in patients with chronic fatigue syndrome is now ongoing.

Humans↗
PubMed2002

[Fatal fibrosing cholestatic hepatitis following renal transplantation].

A 65-year-old HBsAg positive man developed progressive cholestatic liver enzyme abnormalities with histopathological portoportal septum formation, cholestasis, limited mixed infiltrate and hepatocellular ballooning with a ground glass aspect after renal transplantation. Both clinical and pathological features were characteristic of fibrosing cholestatic hepatitis (FCH), a histological variant of hepatitis-B-virus (HBV) infection with a high mortality rate which affects immunocompromised patients. The diagnosis was made about 9 months after transplantation, after retrospective analysis had shown a postoperative increase in HBV replication. Discontinuation of prednisone treatment and starting antiviral lamivudine therapy reduced HBV DNA load immediately. However due to renal failure caused by hepatorenal syndrome, lamivudine therapy had to be interrupted. The patient died following subacute liver failure with progressive FCH. This case illustrates the importance of early diagnosis and treatment with reduction of immunosuppression and institution of antiviral therapy to prevent progression of FCH in immunocompromised HBsAg positive patients.

Aged↗
PubMed2002

Down-regulated donor-specific T-cell reactivity during successful tapering of immunosuppression after kidney transplantation.

Stable cadaveric renal transplant patients were routinely converted from cyclosporin A (CsA) to either azathioprine (AZA) or mycophenolate mofetil (MMF) 1 year after transplantation to reduce the side effects of long-term immunosuppressive therapy. Thereafter, the AZA and MMF dose was gradually tapered to 50% at 2 years after transplantation. We questioned whether a reduction of immunosuppressive treatment results in a rise of donor-specific T-cell reactivity. Before transplantation (no immunosuppression), 1 year (high dose immunosuppression) and 2 years (low dose immunosuppression) after transplantation, the T-cell reactivity of peripheral blood mononuclear cells (PBMC) against donor and third-party spleen cells was tested in mixed lymphocyte cultures (MLC) and against tetanus toxoid (TET) to test the general immune response. We also measured the frequency of donor and third-party reactive helper (HTLpf) and cytotoxic (CTLpf) T-lymphocyte precursors in a limiting dilution assay. Donor-specific responses, calculated by relative responses (RR = donor/third-party reactivity), were determined. Comparing responses after transplantation during high dose immunosuppression with responses before transplantation (no immmunosuppression), the donor-specific MLC-RR (P = 0.04), HTLp-RR (P = 0.04) and CTLp-RR (P = 0.09) decreased, while the TET-reactivity did not change. Comparing the responses during low dose with high dose immunosuppression, no donor- specific differences were found in the MLC-RR, HTLp-RR and CTLp-RR, although TET-reactivity increased considerably (P = 0.0005). We observed a reduction in donor-specific T-cell reactivity in stable patients after renal transplantation during in vivo high dose immunosuppression. Tapering of the immunosuppressive load had no rebound effect on the donor-specific reactivity, while it allowed recovery of the response to nominal antigens.

Down-Regulation↗
PubMed2001

Pretransplant donor-specific helper T cell reactivity as a tool for tailoring the individual need for immunosuppression.

BACKGROUND: A reliable immunological assay for quantification of donor-specific alloreactivity to identify patients at risk for future allograft rejection would be a helpful tool in organ transplantation. Therefore, we questioned whether the T cell reactivity in patients measured before transplantation was predictive for the occurrence of acute rejection during the first year after kidney transplantation. METHODS: The pretransplant T cell reactivity of peripheral blood mononuclear cells to donor and third-party antigens was tested in mixed lymphocyte cultures, and to tetanus toxoid. In addition, we measured the frequency of donor and third-party reactive helper T lymphocyte precursor and cytotoxic T lymphocyte precursors using limiting dilution analysis. RESULTS: Patients who experienced acute rejection had significantly higher donor-specific mixed lymphocyte cultures responses (n=38; median stimulation index): 113 vs. 15, P=0.005) and helper T lymphocyte precursor frequency (n=37; median 194/106 vs. 62/106, P=0.009) measured before transplantation compared to patients without acute rejection. All patients with a low mixed lymphocyte culture response (stimulation index</=20; 13/13 vs. 12/25, P=0.001) and an undetectable helper T lymphocyte precursor frequency (<10/106 peripheral blood mononuclear cells; 7/7 vs. 17/30, P=0.04) before transplantation did not experience acute rejection. The donor-specific cytotoxic T lymphocyte precursor frequency (n=34; median 53/106 vs. 28/106, P=0.58) and tetanus toxoid-reactivity (n=38; median stimulation index: 53 vs.16, P=0.56) measured before transplantation did not correlate with acute rejection. No correlation between third-party reactivity and acute rejection was observed. CONCLUSIONS: From these results we conclude that despite the current HLA matching criteria, undetectable helper T lymphocyte precursor frequency and low mixed lymphocyte culture responses against donor antigens measured before transplantation are predictive for a rejection-free first posttransplant year. These in vitro assays can be used to identify patients who require less immunosuppression after transplantation.

Acute Disease↗