Biomedical subjects

W Weimar

Publications and source records attributed to W Weimar.

At least 19 recordsLinked to original sources

PubMed2006

Living donor kidney exchange for both ABO-incompatible and crossmatch positive donor-recipient combinations.

BACKGROUND: Strategies to decrease the wait time for kidney transplantation include the use of living donor kidneys. However, it is not always possible to donate directly, due to ABO blood type incompatibility or a positive crossmatch. Therefore, other options were explored, including a program for living donor kidney exchange. METHODS: All Dutch kidney transplantation centers agreed on a common donor kidney exchange protocol. The Dutch Transplantation Foundation is responsible for the allocation, crossmatches are centrally performed, and exchanges take place on an anonymous basis. Donors travel to the recipient centers. Surgical procedures are simultaneously scheduled. RESULTS: From January 2004, we registered in total 116 combinations consisting of blood type-incompatible pairs (n = 62) and positive crossmatch pairs (n = 54). In eight match procedures we created 58 new donor-recipient combinations with negative crossmatches, including six triplets and 20 doublets. It proved to be significantly (P = .0014) less difficult to find a solution for the crossmatch-positive combinations than for the blood type-incompatible combinations (67% vs 35%). CONCLUSION: The Dutch national living donor kidney exchange program resulted in a 50% success rate. Combining blood type-incompatible and crossmatch-positive donor-recipient pairs in one program is a realistic option for all blood type combinations.

ABO Blood-Group System↗

PubMed2006

Donor-reactive cytokine production after HLA-identical living related kidney transplantation: a protein-array analysis.

In the present pilot study, we investigated which proteins are produced after donor stimulation of peripheral blood mononuclear cells from recipients of HLA-identical living related kidney transplant. We used a protein-array analysis to determine cytokines, chemokines, and growth factors in supernatant from donor-stimulated mixed lymphocyte reaction cultures. Autologous cultures were considered to be negative controls. In 38 out of 42 proteins (90%), the donor response was higher compared with the autologous response. Therefore, we concluded that even after HLA-identical living related kidney transplantation we could measure a donor-reactive response, which we assumed was directed toward minor histocompatibility or non-HLA antigens.

Chemokines↗

PubMed2006

FoxP3+ T cells can be expanded from rejecting cardiac allografts.

A specific subset of T cells, the FoxP3+ regulatory T cells, control effector T-cell responses to self and foreign antigens. In transplant patients, we and others have shown that high intragraft FOXP3 mRNA levels are associated with acute rejection, suggesting that immune regulation is dependent on immune activation. To study whether transplanted grafts harbor FoxP3+ T cells and to functionally analyze them, graft infiltrating lymphocytes (GILs) must be propagated from the transplanted tissue. In the present study, we analyzed whether FoxP3+ T cells can be grown from endomyocardial biopsies (EMBs; n = 5) from patients after heart transplantation during acute cellular rejection. After 18 to 21 days of culture, 0.5 to 1.0 x 10(6) GILs were cultured from the EMBs. Of these GILs, 10.6% (median; range, 1.6%-17.1%) stained positive for FoxP3. Thus Foxp3+ T cells can be grown from EMBs, providing the tools to functionally characterize these cells in depth in forthcoming studies.

Forkhead Transcription Factors↗

PubMed2006

Varicella zoster virus serostatus before and after kidney transplantation, and vaccination of adult kidney transplant candidates.

In recent years we observed 3 lethal primary varicella infections in adult kidney transplant recipients. Therefore, we wondered how many of our adult renal transplant patients were not protected against varicella zoster virus (VZV), and therefore were at risk for such a primary infection. We also studied the prevalence of VZV seronegativity in the adult patients on our waitlist for kidney transplantation. Finally, we vaccinated these seronegative patients with an attenuated live vaccine. Sera were obtained from 854 transplanted patients, and from 286 candidates on the waitlist for kidney transplantation. We observed that 2.1% of our renal transplant recipients and 3.2% of the patients on the waitlist were seronegative for VZV. We vaccinated 11 seronegative patients on the waitlist twice without side effects. In 7 of 11 patients this resulted in a positive serologic response. In conclusion, the prevalence of VZV seronegativity was low both in renal transplant recipients (2%) and in patients on the waitlist (3%). Vaccination of transplant candidates resulted in a moderate efficiency of 64%.

Adolescent↗

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↗

PubMed2005

The Dutch donor registry: registration rate of hospital personnel, living kidney donors, and patients.

INTRODUCTION: In the Netherlands 13.3 million citizens were contacted by the Dutch donor registry to indicate whether they consented or objected to become an organ/tissue donor after death. Nearly 4.7 million individuals are now registered, which is a 35.1% response rate. We wondered whether kidney patients, living kidney donors, and health personnel would have comparable response rates. METHODS AND RESULTS: A total of 239 individuals were interviewed, of whom 52% indicated to be registered. The highest registration rate was found for hospital personnel (66%) followed by living kidney donors (51%) and patients (38%). In general, more women than men (57% vs 47%) had returned their registration form. CONCLUSION: In the Dutch general public the willingness to make their decision known during life to donate organs/tissue after death is rather low. Presumably motivated individuals (eg, hospital personnel and living kidney donors) scored significantly better, but even in these subgroups 34% and 49%, respectively, were nonresponders.

Humans↗

PubMed2005

Reduction of immunosuppressive load in renal transplant recipients with a low donor-specific cytotoxic T-lymphocyte precursor frequency is safe.

BACKGROUND: Tapering of immunosuppressive medication is indicated to prevent long-term side effects. Recently, we have shown that renal transplant recipients can safely be converted from calcineurin inhibitors to MMF or AZA when their donor-specific cytotoxic T-lymphocyte precursor frequencies (CTLpf) are below 10/10(6) PBMC. We wondered whether a low CTLpf also had predictive value when immunosuppressive medication was reduced in patients only on MMF or AZA and steroid medication. METHODS: Renal transplant recipients with stable renal function at least 2 years after transplantation and with low (<10/10(6) PBMC) CTLpf were included. Their MMF or AZA dose was reduced to 75% and to 50% of the original dose at 4 months and 8 months after inclusion. Endpoint of the study was 12 months after inclusion or developing acute rejection. RESULTS: Forty-five patients have reached the 1-year follow up endpoint. Their median time after transplantation was 4.2 years (range 2.0-15.5 years). Acute rejection was seen in one patient only (who had discontinued all his medication). CONCLUSION: In patients with low CTLpf long after kidney transplantation, a 50% reduction of immunosuppression is safe and further decreasing their immunosuppressive load is the obvious next step.

Azathioprine↗

PubMed2005

Granzyme B ELISPOT assay determines the cytotoxic T lymphocyte precursor frequency after HLA-identical living-related kidney transplantation.

A major goal in organ transplantation is to define the optimal immunosuppressive dose. Recently, we demonstrated that the frequency of cytotoxic T lymphocytes (CTLpf) identifies patients in whom the immunosuppressive load can be safely reduced. However, in peripheral blood mononuclear cells (PBMC) from HLA-identical living-related kidney transplant patients, no donor-specific CTLpf can be measured. The determination of the functional activity of cytotoxic T lymphocytes (CTLs) could be an alternative method for the CTLpf. Granzyme B (GrB) is present in the granules of CTLs and is involved in the direct lethal hit of donor target cells. Therefore, we wondered whether the GrB ELISPOT assay is an alternative method to determine the activity of CTLs after HLA-identical living-related kidney transplantation. We measured the number of GrB producing cells (pc) against donor PBMC and third-party PBMC in PBMC from HLA-identical patients who were reduced in their immunosuppression from 100% to 50% azathioprine with 5 to 10 mg/day prednisone. We found low numbers of GrB pc before reduction of immunosuppression, as only 20% of the patients' PBMC responded to donor cells, whereas 57% of the patients' PBMC responded to donor cells after reduction of immunosuppression. After third-party stimulation, the number of GrB pc increased after tapering the immunosuppressive load (P = .03). Our results demonstrate that the GrB ELISPOT assay might be used as an alternative for the CTLpf after HLA-identical living-related kidney transplantation.

Cell Division↗

PubMed2005

The Dutch algorithm for allocation in living donor kidney exchange.

The shortage of kidneys from brain-dead donors for transplantation has made it necessary to look for alternatives. Living kidney donation is one possibility. However, because of ABO blood group incompatibility or immunological reasons, transplantation of kidneys from a living donor is not always possible. The seven Dutch kidney transplantation centers have developed a joint protocol for crossover, or paired donor exchange, kidney transplantation. To ensure a fair chance for all participating donor-recipient pairs, the Dutch Transplantation Foundation has developed an allocation algorithm to match compatible donor-recipient pairs. A crossover match is performed every 3 months. The computer program developed by the Dutch Transplantation Foundation to match compatible donor-recipient pairs calculates the match probability (MP) of every potential recipient. The MP takes into account the peak panel-reactive antibodies (%PRA) of the recipient, the incidence within the crossover donor population of (compatible) ABO blood group, and HLA unacceptables of the recipient. The potential recipient with the lowest MP, in other words, the recipient with the smallest chance of finding a compatible donor in the pool, is ranked first. Until now, three matches have been performed in the Netherlands. A total of 53 pairs from all seven Dutch transplantation centers have participated. For 22 of the pairs a compatible donor-recipient pair was found.

Algorithms↗

PubMed2005

Nonresident living kidney donors.

INTRODUCTION: The increasing number of immigrant residents has resulted in more foreign patients on the kidney transplant waiting list. While the willingness of their relatives to participate in a living kidney donation program is not different from that of relatives of autochthonous patients, many extra logistic and financial problems have to be solved, when the potential donor has to travel to Rotterdam. The fear of the authorities that the donor might stay in the Netherlands after donation is another hurdle. METHODS AND RESULTS: We analysed 395 living kidney transplantations performed in Rotterdam from 1981 to 2003. In 32 instances the donor came from abroad. Another 14 potential foreign donors came to Rotterdam but did not donate for various reasons. We calculated the costs for visa, travel, insurance, and loss of income. Total financial impact for the 46 (potential) donors, amounted to capital JE, Ukrainian 56,604.09, which is capital JE, Ukrainian 1768.88 per actual performed donation. One kidney donor remained illegally in the Netherlands. CONCLUSION: We conclude that the efforts and support for foreign kidney donors to come to the Netherlands is justified and cost-effective. No evidence was found for a kidney donation immigration route.

Cost-Benefit Analysis↗

PubMed2005

Ultrafiltration improves aortic compliance in haemodialysis patients.

An elevated pulse pressure leads to an increased pulsatile cardiac load, and results from arterial stiffening. The aim of our study was to test whether a reduction in volume overload by ultrafiltration (UF) during haemodialysis (HD) leads to an improvement of aortic compliance. In 18 patients, aortic compliance was estimated noninvasively before and after HD with UF using a pulse pressure method based on the Windkessel model. This technique has not been applied before in a dialysis population, and combines carotid pulse contour analysis by applanation tonometry with aortic outflow measurements by Doppler echocardiography. The median UF volume was 2450 ml (range 1000-4000 ml). The aortic outflow volume after HD (39 ml; 32-53 ml) was lower (P=0.01) than before (46 ml; 29-60 ml). Carotid pulse pressure after HD (42 mmHg; 25-85 mmHg) was lower (P=0.01) than before (46 mmHg; 35-93 mmHg). Carotid augmentation index after HD (22%; 3-30%) was lower (P=0.001) than before (31%; 7-53%). Carotid-femoral pulse wave velocity was not different after HD (8.7 m/s; 5.6-28.9 m/s vs 7.7 m/s; 4.7-36.8 m/s). Aortic compliance after HD (1.10 ml/mmHg; 0.60-2.43 ml/mmHg) was higher (P=0.02) than before (1.05 ml/mmHg; 0.45-1.69 ml/mmHg). The increase in aortic stiffness in HD patients is partly caused by a reversible reduction of aortic compliance due to volume expansion. Volume withdrawal by HD moves the arterial wall characteristics back to a more favourable position on the nonlinear pressure-volume curve, reflected in a concomitant decrease in arterial pressure and improved aortic compliance.

Adult↗

PubMed2005

The effects of renal transplantation on circulating dendritic cells.

The effects of immunosuppressive agents on T cell function have been well characterized but virtually nothing is known about the effects of renal transplantation on human dendritic cells (DCs). With the use of flow cytometry, we studied the kinetics of myeloid and plasmacytoid DCs in peripheral blood of 24 kidney allograft recipients before and after transplantation, and in 23 donors before and after kidney donation. All patients were treated with tacrolimus, mycophenolate mofetil and prednisone. Surgery resulted in a strong decline in the number of myeloid and plasmacytoid DCs, both in kidney donors and in their recipients. However, in donors this effect was transient, as the numbers of both DC subsets had normalized completely by the third postoperative month. In contrast, the recovery of myeloid DC counts in kidney transplant recipients was only incomplete at the end of the 3-month follow-up, despite tapering of immunosuppression. The seven patients who required additional immunosuppressive treatment because of acute rejection experienced an even more marked decrease in DC counts in the early postoperative period compared with patients who remained rejection-free. Surgical procedures markedly affect the numbers of circulating myeloid and plasmacytoid DCs. Immunosuppressive drugs have important additional in vivo effects on this cell type and impair the reconstitution of the myeloid DC subset in peripheral blood after renal transplantation.

Adult↗

PubMed2005

The direct and indirect allogeneic presentation pathway during acute rejection after human cardiac transplantation.

Alloreactive T cells may be activated via a direct or an indirect antigen presentation pathway. We questioned whether the frequency of interferon (IFN)-gamma producing cells determined by enzyme-linked immunospot (ELISPOT) assay is an effective tool to monitor the direct and/or indirect presentation pathway. Secondly, we wondered whether early and late acute rejection (AR) are associated with both pathways. Before (n = 15), during (n = 18) and after (n = 16) a period of AR, peripheral blood mononuclear cell (PBMC) samples were tested from 13 heart transplant recipients. The direct presentation pathway was always present. The number of IFN-gamma producing cells reactive to this pathway increased significantly (P = 0.04) during AR and the number decreased (P = 0.005) after AR therapy. In contrast, the indirect allogeneic presentation pathway was present in only eight of 18 AR samples. When the indirect presentation pathway was detectable, it increased significantly during AR. Five of eight of these AR occurred more than 6 months after transplantation. The ELISPOT assay, enumerating alloreactive IFN-gamma producing cells, is a valuable tool to determine the reactivity via both the direct and the indirect presentation pathway. The direct presentation pathway always plays a role in AR, while the indirect pathway contributes especially to late AR.

Adult↗

PubMed2005

Hypotension during hemodialysis results from an impairment of arteriolar tone and left ventricular function.

AIMS: Hypotensive episodes are a major complication of hemodialysis. Hypotension during dialysis could be directly related to a reduction in blood volume or to a decrease in cardiovascular activation as a response to decreased cardiac filling. A decreased cardiovascular activation could be due to patient-related or to dialysis-related factors. In order to study the isolated effect of a reduction in filling pressure, lower body negative pressure (LBNP) causes activation of the cardiovascular reactivity with a decrease in cardiac filling, but without the influence of the dialysis procedure that could affect cardiovascular reactivity. METHODS: We studied the relationship between relative blood volume (RBV), central venous pressure (CVP), systolic arterial pressure, heart rate, stroke volume index (SI), and total peripheral resistance index (TPRI) during a combined dialysis/ultrafiltration and during LBNP to -40 mmHg in 21 hemodialysis patients with a high incidence of hypotension. Systolic arterial pressure, heart rate, SI and TPRI were measured by Finapres. CVP was measured after cannulation of the jugular vein. During dialysis RBV was measured by a blood volume monitor (BVM). In order to study the conditions in which hypotension occurred after dialysis, we divided the patients into 2 groups: hypotensive (H) and non-hypotensive (NH) during dialysis. RESULTS: Baseline levels did not show any significant differences. During dialysis systolic arterial pressure declined gradually in the H group from 30 minutes before the onset of hypotension. There was a similar decrease of RBV and increase of heart rate in both groups with a large interindividual variation. At hypotension, H patients showed a significantly smaller increase in TPRI as compared to NH patients. The reduction in SI tended to be greater at hypotension, while CVP decreased to a similar extent in both groups. Moreover, during LBNP, a similar reduction in CVP resulted in a much smaller decrease in SI. Systolic arterial pressure was only slightly lowered due to a much greater increase in TPRI. CONCLUSION: We conclude that dialysis-related hypotension in our patient group did not result from an inability to maintain blood volume or from decreased cardiac filling. Hypotension appeared to result from the inability to adequately increase arteriolar tone and a reduction in left ventricular function. Both vascular tone and left ventricular function appeared to be impaired by the dialysis procedure.

Arterioles↗

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

Body image after laparoscopic or open donor nephrectomy.

BACKGROUND: Laparoscopic donor nephrectomy (LDN) is thought to result in a better cosmetic outcome for the altruistic healthy donor than open donor nephrectomy (ODN). To the authors' knowledge, no studies have established the opinion of donors with respect to their bodily appearance. This study investigates the body image of donors after ODN and LDN. METHODS: Donors who underwent surgery between 1994 and 2001 were invited to fill out a body image questionnaire. This questionnaire consists of two subscales: the body image scale (BIS) and the cosmetic scale (CS). A total of 56 LDN subjects and 69 ODN subjects responded to the questionnaire (72% of 174 donors). RESULTS: Both groups were comparable in terms of gender, current age, and body mass index (BMI). The time from donation until the time of this study (follow-up assessment) was significantly longer for the ODN groups. The BIS and CS were found to be comparable between the two groups. No associations were found between BIS or CS and follow-up duration. There also was no association between BIS or CS and gender, age and BMI. CONCLUSIONS: The body image ratings of donors do not significantly differ after ODN or LDN.

Adult↗

PubMed2004

[Cross-over transplantation; a new national program for living kidney donations].

In the Netherlands, cross-over kidney transplantation has been introduced as an extra option in the living kidney donation programme. In cross-over transplantation, patients who cannot be given their own partner's kidney for immunological reasons are given a kidney from the partner of another patient in exchange for a kidney from their own partner. There is no difference in the medical indications and contraindications between direct and indirect living donation. There are no ethical obstacles since the net gain for the two couples is no different from that of direct living kidney donation and because the exchange takes place on the basis of equality. One should be aware that the extra possibilities may result in more psychological pressure on potential donors. It is important that the donation procedures start at the same moment and that the wishes of patients and donors for anonymity be preserved. A successful cross-over kidney transplantation programme requires a large pool of donors and patients. Therefore, this has been organised in a national programme. The Dutch Transplantation Foundation is responsible for the allocation of cross-over kidneys. Organ trade will thus be impossible. The seven Dutch centres for kidney transplantation have developed a protocol.

Female↗

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↗