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R J Hené

Publications and source records attributed to R J Hené.

At least 19 recordsLinked to original sources
PubMed2004

['New pathways to organ donation'; a recommendation of the Dutch Health Council].

Despite recent efforts at improvement, the current status of postmortem organ donation in the Netherlands is a reason for serious concern. The waiting lists for all organ transplantations are increasing in length. The Dutch Health Council was asked by the Minister of Health to report on any available alternative sources of donor organs, focusing especially on donation from living donors and postmortem donors in whom the heart is no longer beating. Kidney donation by living relatives is a well-known procedure that has been performed since 1950. Since HLA-matching is now less important due to new immunosuppressive regimens, transplants from unrelated living volunteers are also possible with good results. Live donation from emotionally involved persons should be encouraged. In case of ABO incompatibility, donors could be exchanged via the organ exchange institution. Live donation of liver segments by an adult to benefit a child recipient is justified. In case of an adult recipient this should be performed only under exceptional circumstances. Live donation of lung lobes and segments of intestine is still in a developmental phase. Postmortem donation of kidneys and livers from donors in whom the heart is no longer beating should also be encouraged. Donation of the lungs and pancreas from these donors is still an experimental procedure.

ABO Blood-Group System↗
PubMed2001

Quantitative baseline renography 48 hours after renal transplantation predicts long-term graft survival.

Technetium-99m mercaptoacetylglycine (99mTc-MAG3) renography is a successful non-invasive method for the evaluation of renal transplants. In this study we prospectively studied 256 patients after renal transplantation, using the MAG3 uptake capacity in the first 10 min (MUC10), which is an index of renal function representing kidney activity as a fraction of the injected dose. Renal scintigraphy was performed in all patients within 48 h of transplantation. Renograms were obtained over 20 min, after bolus injection of +/-100 MBq 99mTc-MAG3. MUC10 ranged between 0.0 and 94.9. The patients were divided into five groups: group 1, MUC10 <1; group 2, 1< or =MUC10 < 5; group 3, 5 < or = MUC10 <10; group 4, 10 < or = MUC10 < 30; group 5, MUC10 > or =30. In 235 patients, follow-up for 5 years was completed. Considering all the renal transplants, 30% of the grafts ceased functioning within the first 5 years. Six grafts showed a MUC10 of < 1, and none survived the first year. After 5 years, 43% of the grafts with a MUC10 of 1-5 still functioned, as compared with 63% of those with a MUC10 of 5-10, 72% of those with a MUC10 of 10-30 and 83% of those with a MUC10 of > or =30. Kaplan-Meier survival analysis showed significant differences between the five different patient groups based on MUC10 in terms of the percentage of kidneys that ceased to function within 5 years. The period of cold ischaemia and the donor age were known in 178 patients. In contrast to cold ischaemia time, the MUC10 and the donor age showed a significant effect (P<0.05) on graft survival. This study indicates that the MUC10 early after renal transplantation is useful as a prognostic factor in the evaluation of kidney transplants and that a MUC10 of <1 indicates a dismal prognosis for the renal transplant.

Adult↗
PubMed2001

Cyclosporine is associated with endothelial dysfunction but not with platelet activation in renal transplantation.

BACKGROUND: Cyclosporine (CsA) is associated with thrombotic micro-angiopathy and endothelial dysfunction. Markers of endothelial dysfunction may serve to identify patients at risk for development of vascular injury. In this study we measured von Willebrand Factor (vWF) and sP-selectin as possible markers for endothelial dysfunction in renal transplant recipients at different concentrations of CsA. Because sP-selectin can also be derived from platelets an additional in vitro study was performed to study the potential effect of CsA on the expression of P-selectin on platelet surface, while the effects of CsA on the interaction of platelets with Endothelial Cell Matrix (ECM) were studied under flow conditions in a perfusion chamber model. METHODS: CsA was stepwisely replaced by mycophenolate mofetil (MMF) in 15 renal transplant recipients (more than 6 months after transplantation). VWF and sP-selectin were measured at normal CsA (median trough level 130 microg/l), low CsA (trough level 45 microg/l) and after stopping CsA. MMF 2 g daily was added while lowering and stopping CsA. Platelet activation was investigated by measurement of P-selectin on platelet surface by flow-cytometry (FACS), after incubation with CsA (0, 2, 20 and 200 mg/l) in vitro and after perfusion of whole blood over ECM with CsA (0 or 2 mg/l, peak levels). RESULTS: Stepwise withdrawal of CsA gave a dose-related decrease of both vWF and sP-selectin, suggesting reversible endothelial dysfunction. FACS showed no expression of P-selectin on platelets by CsA. Also perfusion studies over ECM demonstrated no platelet activation by CsA but even inhibition of platelet adhesion and aggregation. CONCLUSIONS: The use of CsA is not accompanied by platelet activation. However endothelial dysfunction induced by CsA does occur as reflected by increased vWF and sP-selectin. (See Editorial p. 1).

Adult↗
PubMed2000

[Epidemiologic increase of various genotypes of vancomycin-resistant Enterococcus faecium in a university hospital].

After a report of a possible relationship between an outbreak of vancomycin-resistant enterococci (VRE) in a nearby hospital and earlier admission of two of the patients with this VRE in the University Medical Centre of Utrecht (UMCU), the Netherlands, an extensive search for VRE carriers was started in the UMCU. In the study period of two months, VRE carriership was diagnosed in 51 patients in nine of the 11 wards investigated. Twenty-six patients in eight wards were colonized with the same VRE genotype as in the nearby hospital; spread was demonstrated in three wards. In addition, six patients of one ward were colonized with a second genotype and seven other patients with a third genotype, while 12 patients were carriers of a unique genotype. Most carriers were found in the internal medicine/nephrology and dialysis ward. Far-reaching measures (such as cohort nursing, admission stops, use of gowns and gloves, disinfection and restriction of use of vancomycin) taken in the four wards where spread was demonstrated, appeared effective but in three wards, spread was again demonstrated later. Frequent readmissions and transfers of patients appear to play an important part in this matter. None of the 51 colonized patients developed a serious VRE infection.

Carrier State↗
PubMed2000

[Daclizumab and basiliximab: monoclonal mouse-man antibodies with effective immunosuppression without side effects].

Four major double-blind randomized trials in kidney transplant patients have shown that the interleukin-2 receptor (IL-2R alpha) antagonists declizumab or basiliximab, when added to an immunosuppressive regimen consisting of cyclosporin and prednisone, reduce the incidence of acute rejections after kidney transplantation by 30-40%, during the first 6 months. Daclizumab and basiliximab are monoclonal antibodies of which the variable parts are of mouse origin and the other components of human origin. The addition of the interleukin-2 receptor antagonists was not accompanied by extra side effects. Ongoing clinical trials aim at answering the question whether the addition of daclizumab and basiliximab will allow to avoid or decrease the use of more toxic immunosuppressive drugs.

Antibodies, Monoclonal↗
PubMed2000

Conversion to mycophenolate mofetil in conjunction with stepwise withdrawal of cyclosporine in stable renal transplant recipients.

BACKGROUND: Mycophenolate mofetil (MMF) is now part of standard immunosuppression in the first phase after renal transplantation. A relevant question is if it can replace drugs such as cyclosporine (CsA) in the maintenance treatment, improving cardiovascular risk profile. METHODS: In 17 patients with a stable renal function (at least 6 months) posttransplantation, we studied the effect of CsA replacement by MMF. After starting MMF (1 g b.i.d.), CsA dosage was reduced from regular to low (median trough level 130 microg/L, respectively, 45 microg/L), followed by complete withdrawal, while prednisone (7.5 mg daily) was continued. We measured ambulatory blood pressure, glomerular filtration rate, renal plasma flow, renal vascular resistance, and metabolic factors at start and after 8 weeks on regular, low-dose CsA, respectively, no CsA with MMF and prednisone. RESULTS: Two patients dropped out after the switch to low-dose CsA/MMF, due to diarrhea in one and a steroid responsive rejection in the other. The complete switch from CsA to MMF was successful in all 15 patients and accompanied by a decrease in 24 hr systolic blood pressure (from 152+/-13 to 145+/-13 mmHg; P<0.01), diastolic blood pressure (93+/-9 to 89+/-12 mmHg; P<0.05), RVR (0.29+/-0.06 to 0.25+/-0.09 mmHg.ml/min; P<0.05), and an increase in glomerular filtration rate (46.6+/-8.8 to 58.0+/-10.5 ml/min; P<0.01) and renal plasma flow. Intermediate low density lipoprotein-cholesterol decreased (0.79+/-0.37 to 0.41+/-0.16 mmol/L; P<0.01). High density lipoprotein-cholesterol decreased, but remained in the safe range. After 1 year two patients stopped the MMF; one because of Kaposi's sarcoma and one because of recurrent infections CONCLUSIONS: The stepwise switch from CsA to MMF was safe and mostly successful, and had beneficial effects on blood pressure, glomerular hemodynamics, and lipid profile. Beneficial trends were already present after partial withdrawal of CsA.

Adult↗
PubMed1999

Effect of cyclosporine on mycophenolic acid trough levels in kidney transplant recipients.

BACKGROUND: Triple drug treatment consisting of mycophenolate mofetil (MMF), in a standard dose of 2 g daily, combined with cyclosporine (CsA) and prednisone, has become the standard immunosuppressive regimen after kidney transplantation in many centers. The need for therapeutic drug monitoring of mycophenolic acid (MPA) has not yet been established. Several drug interactions with MMF are known. We investigated the influence of CsA withdrawal on MPA trough levels in renal transplant patients. METHODS: Fifty-two patients were treated with 1 g of MMF twice daily, and prednisone and CsA targeted between 125 and 175 ng/ml for 6 months after transplantation. At 6 months after transplantation, 19 patients were randomized for continuation of triple therapy (group A), 19 patients discontinued CsA (group B), and 14 patients discontinued prednisone (group C). We compared 12-hr fasted MPA trough levels at 6 and 9 months after transplantation within and between these groups. RESULTS: MPA trough levels during treatment with CsA, MMF, and prednisone were significantly lower than those during treatment with MMF and prednisone only (group B); median levels were 1.87 mg/L (range: 0.56-5.27) vs. 3.16 mg/L (range: 0.32-7.78), respectively (P=0.002). MPA trough levels in groups A and C did not change between 6 and 9 months after transplantation; group A median levels were 1.87 (range: 0.31-4.32) vs. 1.53 mg/L (range: 0.36-3.70), and group C median levels were 1.62 (range: 0.69-10.34) vs. 1.79 mg/L (range: 0.54-6.00), respectively. At 9 months after transplantation, patients in whom CsA was discontinued had higher MPA trough levels as compared with patients who continued the use of triple therapy (P=0.001) or patients in whom steroids were withdrawn (P=0.014). CONCLUSION: A significant increase of MPA trough levels was found after discontinuation of CsA (6 months after transplantation), resulting in almost a doubling of MPA trough levels at 9 months after transplantation. This resulted in increased MPA levels in patients without CsA as compared to MPA levels in patients continuing triple therapy or discontinuing prednisone.

Cyclosporine↗
PubMed1999

A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation.

BACKGROUND: Adding a fixed dose of 1 g b.i.d. of mycophenolate mofetil (MMF) to an immunosuppressive regimen consisting of cyclosporine and prednisone results in a 50% reduction in the incidence of acute rejection after kidney transplantation. This study was designed to investigate the relationship between pharmacokinetic data (mycophenolic acid area under the curve; MPA AUC) and the prevention of rejection after kidney transplantation. METHODS: A total of 154 adult recipients of a primary or secondary cadaveric kidney graft were randomly allocated, in this double-blind trial, to receive MMF treatment aimed at three predefined target MPA AUC values (16.1, 32.2, and 60.6 microg x hr/ml). During the first 6 months after transplantation, plasma samples for nine AUCs were collected. After analysis of the samples, a coded dose adjustment advice was generated using a Bayesian algorithm, maintaining the double blinding. Immunosuppressive therapy further consisted of cyclosporine and prednisone. The primary end point of this study was the occurrence of biopsy-proven acute rejection within the 6-month study period. RESULTS: A total of 150 patients were eligible for analysis. Although after day 21, the mean MMF dose was reduced, the mean MPA AUC gradually increased and target MPA AUC values were exceeded in all three groups. The incidences of biopsy-proven acute rejection in the low, intermediate, and high target MPA AUC groups were 14 of 51 (27.5%), 7 of 47 (14.9%), and 6 of 52 (11.5%), respectively. The incidences of premature withdrawal from the study due to adverse events in the three groups were 4 of 51 (7.8%), 11 of 47 (23.4%), and 23 of 52 (44.2%), respectively. Logistic regression analysis showed a highly statistically significant relationship between median ln(MPA AUC) and the occurrence of a biopsy-proven rejection (P<0.001). The logistic regression using median ln(Cpredose) was also statistically significant for this relationship (P=0.01), whereas it was not when using mean MMF dose (P=0.082). In contrast, the logistic regression using mean MMF dose for comparison of patients who successfully completed the study versus patients experiencing premature withdrawal due to adverse events was highly significant (P<0.001), whereas this was not significant when using median ln(Cpredose) (P=0.512) or median ln(MPA AUC) (P=0.434). CONCLUSION: MPA Cpredose and MPA AUC are significantly related to the incidence of biopsy-proven rejection after kidney transplantation, whereas MMF dose is significantly related to the occurrence of adverse events.

Acute Disease↗
PubMed1999

von Willebrand factor proteolysis is deficient in classic, but not in bone marrow transplantation-associated, thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) after bone marrow transplantation (BMT) differs from classic TTP in its clinical course and therapy. A characteristic of classic TTP is the inhibition of a plasma protease that specifically cleaves von Willebrand factor (vWF), thus reducing its multimeric size. We investigated whether this protease was also inhibited in BMT-associated TTP. Plasma from patients with classic or BMT-associated TTP was incubated with recombinant vWF R834Q, a vWF mutant with enhanced sensitivity to the protease. The proteolysis of vWF multimers was analyzed and quantified on Western blot. Metalloprotease activity was strongly inhibited in the classic TTP patient group. However, metalloprotease activity was normal in the BMT-associated TTP patient group. The difference in activity between the two patient groups was highly significant (P =.0016). The results indicate that the etiologies of classic and BMT-associated TTP are indeed different and provide an explanation for the lack of success of plasma exchange in BMT-associated TTP.

Adolescent↗
PubMed1999

Preoperative evaluation of living renal donors with gadolinium-enhanced magnetic resonance angiography.

BACKGROUND: Preoperative evaluation of living renal donors includes an intra-arterial digital subtraction angiography (DSA). Inasmuch as this technique is invasive, uses radiation and an iodine-containing contrast medium, an alternative technique would be preferable. The purpose of this study was to determine the accuracy of gadolinium-enhanced magnetic resonance (MR) angiography in the visualization of renovascular anatomy for the preoperative evaluation of renal donors. METHODS: Twenty-four consecutive potential renal donors underwent gadolinium-enhanced MR angiography before the standard of reference, intra-arterial DSA. Both modalities were evaluated in a blinded manner. The results were correlated with the surgical findings. RESULTS: Three MR angiograms were technically unacceptable because of inadequate breath-hold. The remaining 21 donors had 47 renal arteries, including 5 accessory renal arteries, which were all visualized by MR angiography. MR angiography failed to visualize one case of subtle fibromuscular dysplasia in the distal part of a renal artery. In one donor, a small accessory renal artery, which had not been visualized on DSA, was encountered during nephrectomy. CONCLUSION: Gadolinium-enhanced MR angiography is an accurate minimally invasive method for the detection of accessory renal arteries in the preoperative evaluation of potential renal donors. The accuracy for excluding stenosis in general is high; however, the depiction of stenosis that are located far distally, or in the branch vessels, is less accurate. Advantages of gadolinium-enhanced MR angiography over the currently used method, intra-arterial DSA, are the minimal invasive nature, lower costs, and superiority in detecting venous anomalies, renal cysts, and tumors.

Adult↗
PubMed1999

Management of renal cell carcinoma in von Hippel-Lindau disease.

BACKGROUND: An evaluation of nephron-sparing surgery (NSS) or radical nephrectomy (RN) for treating renal cell carcinoma (RCC) in patients with von Hippel-Lindau disease (VHL) was carried out. METHODS: Between 1976 and 1997, 10 patients with RCC from four VHL families, of whom seven were from one family, were studied by clinical and histopathological examination. Before 1991, three patients were treated using RN, and thereafter five patients were treated using NSS. Two patients were not operated on. RESULTS: RCCs in our patients showed a slow growth rate (on average 0.3 cm year-1), and asymptomatic patients presented with tumours of low-grade malignancy. In all patients, tumours were surrounded by a fibrous pseudocapsule. In 5 out of 17 tumours, pseudocapsular invasion was observed, and three of these five tumours broke through the pseudocapsule. To date, these patients have not shown a less favourable outcome than those without pseudocapsular involvement by tumour growth. Multicentricity of RCC was relatively low (4.6 lesions per kidney). In two of the three RN patients, only a single satellite lesion, in the direct vicinity of a RCC, was found in one kidney. Six tumours (1.8-5.5 cm) were enucleated by NSS. During a mean follow-up of 30 months, renal function in these patients was well preserved. CONCLUSIONS: In our patients, RCCs grew slowly, were of low grade, had a dense fibrous pseudocapsule and were thus good candidates for NSS.

Adult↗
PubMed1998

Efficacy and muscle safety of fluvastatin in cyclosporine-treated cardiac and renal transplant recipients: an exercise provocation test.

BACKGROUND: Dyslipidemia is found in the majority of renal and cardiac transplant recipients. Although 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors significantly lower low-density lipoprotein cholesterol (LDL-C) levels, such treatment has been associated with muscle toxicity, especially when used in combination with cyclosporine (CsA). We investigated the efficacy and muscle safety of fluvastatin, a new 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, in CsA-treated transplant recipients. METHODS: The efficacy was determined by measuring the lipid profile before and after 8 weeks of fluvastatin therapy. As parameter for possible muscle damage, the rise in serum levels of the muscle proteins creatine kinase and myoglobin was measured after an exercise provocation test (30 min on a bicycle ergometer at 60% of their maximal work load) before and during fluvastatin therapy. Nineteen CsA-treated renal and cardiac transplant recipients with hypercholesterolemia were selected. RESULTS: After 8 weeks of treatment with a dose of fluvastatin necessary to reduce LDL-C below 3.5 mmol/L (20 mg for 3 and 40 mg for 16 patients), total cholesterol was lowered by 20% and LDL-C by 30%, and HDL2-C was increased by 35% (all P<0.01). The rise in creatine kinase after exercise before and during fluvastatin therapy was, respectively, 40% and 51%, and the rise in myoglobin was 64% and 50%. These rises were not significantly different. Hence, there was no indication for subclinical muscle pathology by fluvastatin use. Fluvastatin was well tolerated, and no adverse effects on liver or kidney function were found. CONCLUSIONS: Fluvastatin can effectively lower LDL-C in CsA-treated renal and cardiac transplant recipients, without demonstrable adverse effects.

Adult↗
PubMed1998

[Mycophenolic acid: a welcome adjunct immunosuppressant after organ transplants].

Three major double-blind trials in kidney transplantation patients have shown that mycophenolic acid (mycophenolate mofetil), added to an immunosuppressive regimen consisting of cyclosporine and prednisone, reduces the incidence of acute rejection after kidney transplantation by 50%, during the first six months. This statistically significant reduction is achieved equally with daily doses of 2 or of 3 g. In view of the fact that the side effects (diarrhoea, abdominal cramps, leukopenia) are more frequently found in the patients treated with 3 g, it is advised to prescribe 2 g mycophenolic acid. As acute rejection is a risk factor for the development of chronic rejection and because a beneficial effect of mycophenolic acid on chronic rejection in animal models has been observed, there may also be an effect on late graft loss due to chronic rejection after kidney transplantation in man.

Cyclosporine↗