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Willem Weimar

Publications and source records attributed to Willem Weimar.

At least 55 records · Page 3Linked to original sources
PubMed2005

Contrast-enhanced MR angiography and digital subtraction angiography in living renal donors: diagnostic agreement, impact on decision making, and costs.

OBJECTIVE: The objective of our study was to evaluate the diagnostic agreement, the impact on decision making, and the costs of contrast-enhanced MR angiography and digital subtraction angiography in the workup of living renal donors. CONCLUSION: Contrast-enhanced MR angiography for the preoperative evaluation of renal donors is superior to digital subtraction angiography in revealing vascular anomalies and depicting parenchymal abnormalities and is less costly; furthermore, it does not lead to preoperative decisions that differ from those based on digital subtraction angiography. If contrast-enhanced MR angiography does not provide sufficient information to make a confident decision, an additional digital subtraction angiography examination should be performed.

Adult↗
PubMed2004

Everolimus (Certican) 12-month safety and efficacy versus mycophenolate mofetil in de novo renal transplant recipients.

BACKGROUND: Everolimus is a proliferation inhibitor designed to target chronic rejection, including prevention of acute rejection. Everolimus blocks growth factor-mediated transduction signals, preventing organ rejection by a mechanism different than that of calcineurin inhibitors and of mycophenolate mofetil (MMF). METHODS.: Everolimus (1.5 mg or 3 mg daily) was compared with MMF (2 g daily) in a randomized, multicenter, multinational, 12-month double-blind, double-dummy and 2-year open-label, phase 3 trial in de novo renal allograft recipients (n = 588) who also received cyclosporine and corticosteroids as part of a triple immunosuppressive regimen. RESULTS: At 12 months, there were no statistically significant differences between doses of 1.5 and 3 mg/day everolimus and MMF (2 g/day) in incidence of biopsy-proven acute rejection (23.2%, 19.7%, and 24.0%, respectively), graft loss (4.6%, 10.6%, and 9.2%), or death (5.2%, 4.0%, and 2.6%), respectively. Everolimus 1.5 mg/day and MMF were generally equally well tolerated. Both were better tolerated than everolimus 3 mg/day. The incidence of cytomegalovirus infection was significantly lower in patients receiving either 1.5 or 3 mg/day everolimus than in those receiving MMF (5.2% and 7.6% vs. 19.4%, respectively) (P = .001). CONCLUSIONS: Everolimus is effective in preventing acute rejection and graft loss in de novo renal allograft recipients receiving a triple immunosuppressive regimen. Prevention of acute rejection, along with reduction in cytomegalovirus infection, addresses two factors known to contribute to chronic rejection in such patients.

Adolescent↗
PubMed2004

Increase in serum ionized calcium during diffusive dialysis does not affect left ventricular diastolic function.

An increase in serum Ca2+ during hemodialysis (HD) may lead to impaired left ventricular (LV) relaxation. Since LV diastolic function assessment in dialysis patients is hampered by preload dependence of Doppler measurements, we tested the effect of HD without ultrafiltration (UF) on these measurements. Transmitral E and A velocities, and mitral annulus e and a velocities were measured in 10 patients before and after 1 h of HD without UF. Dialysate Ca2+ was 1.75 mmol/l. Serum Ca2+ after 1 h (1.31 mmol/l; 1.28-1.46 mmol/l) was higher (p = 0.002) than before HD (1.24 mmol/l; 1.09-1.32 mmol/l). E/A (0.8; 0.4-2.8) and e/a (0.7; 0.4-1.3) after 1 h were not different than E/A (0.8; 0.6-5.1) and e/a (0.7; 0.4-1.8) before HD. The increase in serum Ca2+ does not lead to a change in Doppler parameters of LV diastolic function. Changes in these parameters after combined HD-UF are related to preload, not to serum Ca2+.

Adult↗
PubMed2004

Starting a crossover kidney transplantation program in the Netherlands: ethical and psychological considerations.

On April 15th, 2003, the first crossover kidney transplantation took place in The Netherlands. In September of the same year, a national database was established to facilitate kidney exchange between two donor-recipient couples. During 2004, kidneys from living donors will be exchanged between the seven university medical centers in The Netherlands. One of the conditions for successfully implementing this program was the need to address the ethical and psychologic implications involved. In this article we will discuss the ethical and psychologic considerations that are accompanying the practical preparations for the first Dutch crossover transplantation program. We identified five topics of interest: the influence of "donation by strangers" on the motivation and willingness of donor-patient couples, the issue of anonymity, the loss of the possibility of "medical excuses" for unwilling donors, the view that crossover is a first step to commercial organ trade, and the interference with existing organ donation programs. We concluded that whether viewed separately or in combination, these issues do not impede the efficient organization of a crossover program or raise worrying ethical issues.

Anonyms and Pseudonyms↗
PubMed2004

No important influence of limited steroid exposure on bone mass during the first year after renal transplantation: a prospective, randomized, multicenter study.

BACKGROUND: Steroid-related bone loss is a recognized complication after renal transplantation. In a prospective, randomized, multicenter study we compared the influence of a steroid-free immunosuppressive regimen with a regimen with limited steroid exposure on the changes in bone mass after renal transplantation. METHODS: A total of 364 recipients of a renal transplant were randomized to receive either daclizumab (1 mg/kg on days 0 and 10 after transplantation; steroid-free group n=186) or prednisone (0.3 mg/kg per day tapered to 0 mg at week 16 after transplantation; steroids group n=178). All patients received tacrolimus, mycophenolate mofetil, and, during the first 3 days, 100 mg prednisolone intravenously. Changes in bone mineral density (BMD) were evaluated in 135 and 126 patients in the steroid-free and steroids group, respectively. RESULTS: The mean (+/- SD) BMD of the lumbar spine decreased slightly in both groups during the first 3 months after transplantation (steroid-free -1.3 +/- 4.0% [P<0.01]; steroids -2.3 +/-4.2% [P<0.01]). In the following months, lumbar BMD recovered in both groups (P<0.01), resulting in a lumbar BMD at 12 months after transplantation comparable with the baseline value. No difference between the groups was found at 3 months (steroid-free versus steroids +1.0%; 95% confidence interval -0.0%-+2.0%, P=0.060) and at 12 months after transplantation (steroid-free versus steroids +0.9%; 95% confidence interval -0.8%-+2.6%, NS). CONCLUSION: The use of a moderate dose of steroids during 4 months after transplantation has no important influence on bone mass during the first year after renal transplantation. On average, both regimens prevented accelerated bone loss.

Acute Disease↗
PubMed2004

FTY720, a novel immunomodulator: efficacy and safety results from the first phase 2A study in de novo renal transplantation.

BACKGROUND: FTY720 is the first of a new drug class: sphingosine-1-phosphate receptor agonist. Its effect relates to the modulation of lymphocytes trafficking from blood and peripheral tissues to lymph nodes. This is the first study to evaluate the efficacy and safety of FTY720 in de novo renal transplantation. METHODS: This phase 2a, multicenter, open-label, dose-finding study compared FTY720 (0.25, 0.5, 1.0, or 2.5 mg) with mycophenolate mofetil (MMF), in combination with cyclosporine and corticosteroids. Patients (n=208) received FTY720 (n=167) or MMF (n=41) for 3 months followed by a 3-month follow-up. RESULTS: The incidence of biopsy-confirmed acute rejection at month 3 was 23.3%, 34.9%, 17.5%, and 9.8%, respectively, with FTY720 at doses of 0.25, 0.5, 1.0, and 2.5 mg, versus 17.1% with MMF. The incidence for the composite endpoint (biopsy-confirmed acute rejection, graft loss, or death) was lowest with FTY720 at a dose of 2.5 mg at month 3 (14.6%) compared with FTY720 at doses of 0.25 mg (25.6%), 0.5 mg (34.9%), and 1.0 mg (17.5%), and MMF (19.5%). Safety was comparable between FTY720 and MMF group. The main difference in tolerability was a mild and transient reduction in heart rate. A decrease in peripheral lymphocytes occurred in patients receiving FTY720, as expected from the mode of action, and this was reversible after treatment cessation. CONCLUSIONS: FTY720 at 2.5 mg was found to be as effective as MMF in combination with cyclosporine for the prevention of acute rejection after renal transplantation. FTY720 was well tolerated and not associated with the side effects commonly observed with immunosuppressant therapies.

Adolescent↗
PubMed2004

Population pharmacokinetics of cyclosporine in kidney and heart transplant recipients and the influence of ethnicity and genetic polymorphisms in the MDR-1, CYP3A4, and CYP3A5 genes.

OBJECTIVE: Our objective was to determine the relationship between single nucleotide polymorphisms (SNPs) in the multidrug resistance 1 (MDR-1) gene and the cytochrome P450 (CYP) genes CYP3A4 and CYP3A5 and the pharmacokinetics of cyclosporine (INN, ciclosporin). METHODS: Cyclosporine pharmacokinetics of 151 kidney and heart transplant recipients undergoing maintenance therapy was described by use of nonlinear mixed-effects modeling (NONMEM) according to a 2-compartment pharmacokinetic model with first-order absorption and elimination. All patients were genotyped for the CYP3A4*1B and *3 , CYP3A5*3 and *6 , and MDR-1 3435C-->T SNPs. RESULTS: For a typical 70-kg white patient, the following parameters were estimated: absorption rate constant, 1.27 h -1; absorption time lag, 0.47 hour; oral volume of distribution of the central and peripheral compartment, 56.3 and 185.0 L, respectively; oral clearance (Cl/F), 30.7 L/h; and oral intercompartmental clearance, 31.7 L/h. Estimated interpatient variability of Cl/F was 28%. Cl/F was significantly correlated with weight and ethnicity; Cl/F was 13% higher (95% confidence interval, 8%-18%; P < .005) in white patients than in black and Asian patients. In carriers of a CYP3A4*1B variant allele, Cl/F was 9% (95% confidence interval, 1%-17%; P < .05) higher compared with CYP3A4*1 homozygotes, and this effect was independent of ethnicity or weight. Incorporation of these covariates into the NONMEM model did not markedly reduce interpatient variability of Cl/F. None of the other SNPs studied significantly influenced any of the pharmacokinetic parameters. CONCLUSION: Patients carrying a CYP3A4*1B variant allele have a significantly higher oral cyclosporine clearance compared with patients homozygous for CYP3A4*1 . However, this genetic effect on cyclosporine disposition was small, and genotyping of transplant recipients for CYP3A4 is thus unlikely to assist in planning initial cyclosporine dosing.

Adult↗
PubMed2004

Peripheral blood dendritic cells in human end-stage heart failure and the early post-transplant period: evidence for systemic Th1 immune responses.

OBJECTIVES: Dendritic cells (DCs) are antigen presenting cells that play a central role in inflammation, allograft rejection and immune tolerance. Myeloid (mDC) and plasmacytoid (pDC) subsets regulate immune reactions by polarising naive T-helper cells into a Th1 or Th2 response, respectively. In this study we examined total peripheral blood DCs, mDC and pDC subsets in chronic heart failure (CHF) and clinical heart transplantation (HTx). METHODS: We compared 16 heart transplant patients before and after HTx to 14 healthy controls. Whole blood was collected pre-HTx and 1-week post-HTx from patients and at corresponding time-points from controls. All patients received induction and maintenance immunosuppression post-HTx. mDCs and pDCs were measured by flow cytometry and were further characterised for maturation and homing potential to the secondary lymphoid organs with CD83 and CCR7, respectively. Data were expressed as absolute numbers/microl whole blood, percentage (%) mDC or pDC of total blood DCs and % positive DCs for CD83 and CCR7. RESULTS: CHF patients had more peripheral blood DCs compared to controls (P<0.01) while only the mDC fraction was increased compared to controls (P=0.01). Percentage CD83(+) and CCR7(+) mDCs was also higher than control levels (P<0.05). One week post-HTx, total DCs, mDCs and pDCs decreased below controls (P<0.001). At the same time % mDCs in peripheral blood increased markedly compared to CHF and control levels (P<0.001). The %CD83(+) mDC, %CD83(+) pDC and %CCR7(+) mDC also returned to control levels and only %CCR7(+) pDC decreased below control levels (P=0.005). CONCLUSIONS: Total peripheral blood DCs are elevated during CHF due to an increase in the mature fraction of the mDC subset suggesting a possible Th1 response in end-stage heart failure. The decrease in total DCs and mature mDCs and pDCs seen post-HTx, probably reflects immunological quiescence through adequate immunosuppression. Peripheral blood DC monitoring may provide a new insight into mechanisms of heart failure and allograft rejection by safe weaning from immunosuppression after clinical HTx.

Adult↗
PubMed2004

Intragraft heme oxygenase-1 and coronary artery disease after heart transplantation.

Peri-operative tissue injury triggers the development of Transplant Coronary Artery Disease (TCAD). Animal studies have shown that induction of heme oxygenase (HO)-1 protects the donor organ from the development of TCAD. To investigate the role of HO-1 in TCAD after clinical heart transplantation, we measured intragraft mRNA expression of HO-1, HIF-1alpha, TGF-beta, FLIP, and the Bcl-2/Bax balance. Immunohistochemical staining of HO-1 was performed to determine its origin. Myocardial biopsies taken at the end of the transplantation procedure (time 0), at 1 week and at 10 months after transplantation were studied from recipients with or without angiographic signs of accelerated TCAD, diagnosed after 1 year. At time 0, no differences in mRNA expression for any of the measured parameters were found between TCAD positive and negative patients. At 1 week, mRNA expression of HO-1 and TGF-beta was higher in grafts that developed accelerated TCAD (p=0.001 and p=0.0002). These higher mRNA levels were accompanied by a pro-apoptotic shift in Bcl-2/Bax (p=0.02), suggesting proneness for apoptosis via the mitochondrial pathway. Immunohistochemical staining showed that HO-1 was mainly produced by infiltrating macrophages. At 10 months, again HO-1 and TGF-beta levels were high in TCAD positive patients (p=0.02 and p=0.05), but the expression of apoptotic markers was comparable at this time point. Our results suggest that a higher HO-1 by macrophages in our patient population might be an adaptive response to tissue injury and inflammation, reflecting damage due to the transplantation procedure that finally results in TCAD.

Adult↗
PubMed2004

Tapering immunosuppression in recipients of living donor kidney transplants.

We have previously suggested that the in vitro donor-specific cytotoxic T-lymphocyte precursor (CTLp) assay can guide us to identify patients in which the immunosuppressive load can be tapered. In a clinical trial we had observed that a low (<10/10(6) PBMC) frequency of these CTLp was predictive for an uneventful rejection-free clinical course in patients that were converted from calcineurin inhibitors to mycophenolate mofetil or azathiopine. In the present prospective study in 81 stable kidney transplant recipients, already converted from calcineurin inhibitors, we measured CTLp frequencies and reduced the immunosuppressive load on a routine basis when CTLp were <10/10(6) PBMC. Donor-specific cytotoxicity could not be measured in 50/81 patients, while their reactivity against third-party lymphocytes was not impaired. These 50 patients were tapered in their immunosuppression. Only in one patient, who had stopped all his medication, was a rejection episode diagnosed. We conclude that in patients with a low donor-specific CTLp frequency it is safe to reduce the immunosuppression.

Cells, Cultured↗
PubMed2004

Peripheral blood dendritic cells and GM-CSF as an adjuvant for hepatitis B vaccination in hemodialysis patients.

BACKGROUND: Dysfunctional antigen presentation may underlie the impaired antibody response to hepatitis B vaccination in hemodialysis patients. Dendritic cells are considered to be the most important antigen presenting cells, but their presence and function in hemodialysis patients is unclear. Granulocyte-monocyte-colony stimulating factor (GM-CSF) has been given successfully to hemodialysis patients to increase the proportion of responders to hepatitis B vaccination. Although GM-CSF acts on both monocytes and dendritic cells, the mechanisms underlying its adjuvant quality are largely unknown. METHODS: In this study we analyzed monocytes and dendritic cells in the peripheral blood of hemodialysis patient that had responded to a standard hepatitis B vaccination procedure (responders), patients who had not responded (nonresponders), and healthy controls. The nonresponders were given two additional booster vaccines, both preceded by administration of GM-CSF the day before. RESULTS: After two booster vaccinations with GM-CSF, six out of seven patients developed a protective antibody response to hepatitis B. The memory T-cell response to tetanus toxoid was significantly lower in nonresponders compared to controls. The monocytes of dialysis patients and healthy controls showed a similar expression of relevant cell surface molecules. However, the numbers of circulating dendritic cells were on average 50% reduced compared to healthy controls, with a further reduction after GM-CSF administration. This was accompanied by a decrease of T-cell proliferation in antigen presentation assays. Monocytes showed increased major histocompatibility complex (MHC) class II, CD54, and CD40 expression, while their antigen-presenting capacity remained unchanged. CONCLUSION: GM-CSF is an effective adjuvant for hepatitis B vaccination in primary nonresponding hemodialysis patients, but paradoxically decreases the antigen presenting capacity of peripheral blood mononuclear cells and the number of circulating dendritic cells.

Adjuvants, Immunologic↗
PubMed2004

Steroid-withdrawal at 3 days after renal transplantation with anti-IL-2 receptor alpha therapy: a prospective, randomized, multicenter study.

Steroids have been included in most immunosuppressive regimens after renal transplantation, but are feared for their side-effects. We conducted a prospective multicenter study to investigate whether it is feasible to withdraw steroids early after transplantation with the use of anti-IL-2Ralpha induction, tacrolimus and mycophenolate mofetil (MMF). A total of 364 patients were randomized to receive either two doses of daclizumab (1 mg/kg) and, for the first 3 days, 100 mg of prednisolone (daclizumab group n = 186), or steroids (tapered to 0 mg at week 16; controls n = 178). All patients received tacrolimus and MMF. The incidence of biopsy-confirmed acute rejection at 12 months was not different between the daclizumab group (15%) and the controls (14%) (95% confidence interval of difference: -6 to + 8%, NS). Graft survival at 12 months was comparable in the two groups (daclizumab group: 91%; controls: 90%). Mean arterial blood pressure, serum lipids, and incidence of patients with hyperglycemia were temporary lower in the daclizumab group compared with controls. The immunosuppressive regimen of the daclizumab group was associated with increased costs. In conclusion, with the use of anti-IL-2Ra induction and daily therapy with tacrolimus and MMF it is feasible to withdraw steroids at 3 days after renal transplantation.

Adolescent↗
PubMed2004

Fundamental role for HO-1 in the self-protection of renal allografts.

Tissue attenuates to injury by the effects of heme oxygenase (HO)-1. The induction of HO-1 expression is modulated by a (GT)(n) dinucleotide polymorphism in the promoter of the gene, of which increased activity is associated with short (S) ( 27 repeats). Graft survival was associated with donor and not with recipient HO-1 gene polymorphism (log rank p = 0.005; hazard ratio 0.51, 95% CI 0.32-0.83). The beneficial effect of the donor HO-1 genotype was observed in grafts exposed to prolonged cold ischemia time and acute rejection. Patients who received a kidney from L-homozygotes lost their graft significantly more often to chronic allograft nephropathy (CAN) than carriers of S-alleles (p = 0.015). Multivariate analysis showed reduced risk for graft failure in kidneys with S-alleles in comparison to L-homozygotes (odds ratio 0.50, 95% CI 0.27-0.93, p = 0.03). Kidneys that are carriers of HO-1 S-allele are less vulnerable to tissue injury resulting in less CAN and better graft survival.

Graft Survival↗
PubMed2004

Significance of acute versus chronic troponin T elevation in dialysis patients.

INTRODUCTION: Cardiac troponin T (cTnT) is often elevated in hemodialysis (HD) patients without acute coronary syndrome (ACS). The aim was to assess the predictive value for mortality of pre-dialysis cTnT in asymptomatic patients. If patients became symptomatic during follow-up, cTnT was followed to assess its diagnostic value for ACS. METHODS: Forty-nine asymptomatic HD patients were included: 30 patients with a history of cardiovascular disease (CV+) and 19 without (CV-). In 11 patients cTnT, myoglobin and creatine kinase (CK) were measured before and during HD. During ACS, cTnT was followed until recovery. A cTnT of > or =0.03 mug/l was considered elevated. Follow-up was 2 years. RESULTS: cTnT was elevated in 82% (40/49). More CV+ patients had an elevated cTnT (28/30) than CV- patients (12/19; p = 0.02). There was no change in cTnT, myoglobin and CK during HD. During ACS, cTnT increased above baseline, and tended to return to baseline after recovery. Mortality was 33% (16/49). Patients with elevated cTnT had a higher mortality rate (16/40) than patients with negative cTnT (0/9; p = 0.02). CONCLUSIONS: Elevated cTnT levels in asymptomatic HD patients are not caused by acute myocardial injury or by HD itself. They may be related to chronic myocardial damage and decreased clearance, and are of prognostic value. During ACS, however, a cTnT rise above the individual baseline is diagnostic of acute myocardial injury.

Adult↗
PubMed2004

Ten-year follow-up of recipients of a kidney or heart transplant who received induction therapy with a monoclonal antibody against the interleukin-2 receptor.

OBJECTIVES: Twelve years ago, we performed two randomized clinical trials to investigate safety and efficacy of induction therapy with BT563, a highly potent murine monoclonal antibody against the interleukin-2 receptor after kidney and heart transplantation. We analyzed the long-term safety and efficacy data from all 120 patients who participated in the two randomized trials after kidney and heart transplantation 10 years ago. MATERIALS AND METHODS: One of these two trials was a randomized, double-blind, placebo-controlled trial, with 60 primary and secondary kidney allograft recipients (cadaveric and living-related donors). The control group was treated with the standard regimen at that time, consisting of cyclosporin and prednisone. In the study group, BT563 was added for 10 days. The second trial was a randomized, double-blind trial, with 60 recipients of a primary heart transplant. In that study, we compared induction therapy with BT563 with the standard regimen at that time, consisting of cyclosporin, prednisone, and OKT3 (both induction agents were given for 7 days). RESULTS: Patient survival in the kidney trial was excellent: in the BT563 group, 24 patients were alive (80%), and in the placebo, group 21 (70%) 10 years after transplantation. Also, graft survival was good: in the BT563 group, 63.3% of the kidneys (19/30) were functioning, in the placebo group, 72.4% (21/29) were functioning (P = 0.455). Also, in the heart study, patient (and graft) survival was excellent: 18 patients were alive in the BT563 group (58%), and in the OKT3 group, 21 (72%) patients were alive (P = ns). No increase in the incidence of malignancies was observed between patients treated with BT563 compared with the control groups. Patients following heart transplantation more often suffered from a malignancy than did patients after kidney transplantation (20/60 vs 10/59). CONCLUSIONS: We report follow-up data on all patients participating in the two randomized trials, and our data reflect a total of 932 years of patient follow-up. Patient and graft survival appear to be excellent in both the BT563-treated patients and the control groups. BT563 treatment was not associated with an increased likelihood of developing infections or malignancies.

Antibodies, Monoclonal↗
PubMed2003

The frequency of interferon-gproducing cells reflects alloreactivity against minor histocompatibility antigens.

BACKGROUND: In human leukocyte antigen (HLA)-identical living-related renal transplant recipients, no donor-specific alloreactivity can be detected in regular tests (mixed lymphocyte culture, helper T-lymphocyte precursor frequencies, cytotoxic T-lymphocyte precursor frequencies) to identify patients responding to minor histocompatibility antigens (mHag). We questioned whether a more sensitive method like the Elispot-assay could be more appropriate. METHODS AND RESULTS: Peripheral blood mononuclear cells (PBMC) from 16 HLA-identical living-related kidney transplant patients 3 months (range, 2 weeks to 5 months) after transplantation were tested for the frequency of interferon (IFN)-gamma producing cells by the Elispot-assay. PBMC from the recipient were stimulated with irradiated donor PBMC and corrected for backward stimulation. Donor-specific IFN-gamma producing cells (pc) in the range of 5 to 115 per million PBMC (median, 30 per million PBMC) were found. To evaluate the frequency of spot forming cells in time, PBMC from six patients who received an HLA-identical renal transplant were stimulated with irradiated donor PBMC before, approximately 3 months after, and 12 months after transplantation. Four patients who received an HLA-mismatched living-related kidney served as positive control. In the HLA-identical group, frequencies in the range of 0 to 10 IFN-gamma pc per million PBMC were found before transplantation, 0 to 30 per million PBMC 3 months after transplantation, and 0 to 45 per million PBMC 12 months after transplantation. In the HLA-mismatched group, significantly higher numbers were found: 10 to 480 IFN-gamma pc per million PBMC before, 20 to 360 per million PBMC at 3 months, and 30 to 590 per million PBMC 12 months after transplantation. CONCLUSION: Under immunosuppressive therapy, IFN-gamma pc specific for donor mHag can be found after HLA-identical living-related renal transplantation.

Blood Group Incompatibility↗