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P Vereerstraeten

Publications and source records attributed to P Vereerstraeten.

At least 19 recordsLinked to original sources

[Update on the outcome of kidney transplantation at the Free University of Brussels].

The present analysis shows that the results of renal transplantation at the "Université libre de Bruxelles" still have improved in recent years: patient and graft survival at 5 years has risen to 99% and 86% respectively during the 1995-1999 period. This progress is primarily related to the use of less deleterious and more potent immunosuppressants. However, graft failures due to causes other than rejection or patient's death remained unchanged. Among transplantations from living related donors, those from parents yield poorer results than those from children or from one-haploidentical brothers and sisters. Four factors influence cadaveric graft survival: immunosuppression, quality of the graft, donor's age and HLA compatibility, in decreasing order of statistical significance. The immunosuppressive protocols used since 1996 appear particularly promising: thanks to them, 3-year graft survival rate presently reaches 97%.

Belgium↗

Hypercholesterolemia is associated with increased kidney graft loss caused by chronic rejection in male patients with previous acute rejection.

BACKGROUND: Whereas acute rejection is the main risk factor for the occurrence of chronic rejection, mechanisms in addition to the donor-specific immune response probably contribute to late allograft failure. In this study, we investigated the possible role of hypercholesterolemia in the incidence of chronic kidney graft loss. METHODS: By using the actuarial method, we retrospectively analyzed the long-term loss of cadaveric kidney grafts in patients who had a functioning graft at 1 year and had received a transplant and undergone cyclosporin A therapy in our center between 1983 and 1997. RESULTS: As observed previously, patients with acute rejection during the 1st posttransplant year (n=198) had significantly higher actuarial graft loss at 10 years compared with those free of acute rejection (n=244). In patients free of acute rejection at 1 year, hypercholesterolemia (> or =250 mg/dl) had no impact on graft loss at 10 years. On the contrary, in patients with previous acute rejection, those with hypercholesterolemia (n=59) had a higher immunological (36.0% vs. 19.2%; P<0.01) and overall (50.0% vs. 25.3%; P<0.01) graft loss at 10 years compared with patients with serum cholesterol <250 mg/dl (n=139). Among patients with 1st year acute rejection, hypercholesterolemia was associated with a significant increase in graft loss in male but not in female recipients. Multivariate analysis confirmed that hypercholesterolemia was an independent risk factor for chronic graft loss in male patients (P<0.05). CONCLUSION: Hypercholesterolemia is an independent risk factor for kidney graft loss from chronic rejection in male patients with previous acute rejection. Correction of hypercholesterolemia could help to reduce kidney graft loss caused by chronic rejection in this category of patients.

Acute Disease↗

Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi)

BACKGROUND: Chinese-herb nephropathy is a progressive form of renal fibrosis that develops in some patients who take weight-reducing pills containing Chinese herbs. Because of a manufacturing error, one of the herbs in these pills (Stephania tetrandra) was inadvertently replaced by Aristolochia fangchi, which is nephrotoxic and carcinogenic. METHODS: The diagnosis of a neoplastic lesion in the native urinary tract of a renal-transplant recipient who had Chinese-herb nephropathy prompted us to propose regular cystoscopic examinations and the prophylactic removal of the native kidneys and ureters in all our patients with end-stage Chinese-herb nephropathy who were being treated with either transplantation or dialysis. Surgical specimens were examined histologically and analyzed for the presence of DNA adducts formed by aristolochic acid. All prescriptions written for Chinese-herb weight-reducing compounds during the period of exposure (1990 to 1992) in these patients were obtained, and the cumulative doses were calculated. RESULTS: Among 39 patients who agreed to undergo prophylactic surgery, there were 18 cases of urothelial carcinoma (prevalence, 46 percent; 95 percent confidence interval, 29 to 62 percent): 17 cases of carcinoma of the ureter, renal pelvis, or both and 1 papillary bladder tumor. Nineteen of the remaining patients had mild-to-moderate urothelial dysplasia, and two had normal urothelium. All tissue samples analyzed contained aristolochic acid-related DNA adducts. The cumulative dose of aristolochia was a significant risk factor for urothelial carcinoma, with total doses of more than 200 g associated with a higher risk of urothelial carcinoma. CONCLUSIONS: The prevalence of urothelial carcinoma among patients with end-stage Chinese-herb nephropathy (caused by aristolochia species) is a high.

Anti-Obesity Agents↗

Persistent hyperparathyroidism requiring surgical treatment after kidney transplantation.

There are not many publications describing long-term follow-up of persistent hyperparathyroidism requiring surgical treatment after kidney transplantation (PHSKT). In some patients adenomas, rather than multiglandular disease, have been incriminated as the cause of PHSKT. We reviewed the charts of 45 patients followed for 12 to 146 months (median 45 months) after parathyroidectomy for PHSKT. We compared them with (1) those of 951 patients receiving a kidney graft during the same period but not submitted to parathyroidectomy or (2) 90 matched controls selected from this cohort to determine the characteristics of PHSKT patients. The duration of pretransplant dialysis was significantly longer in PHSKT patients than in controls (5.78 +/- 0.41 vs. 3.41 +/- 0.24 years; p < 0.0001). A total of 166 glands were removed or biopsied. Except for one questionable case, no true adenoma was observed even when only one gland was enlarged. The outcome of surgery was not influenced by the technique (subtotal parathyroidectomy versus total parathyroidectomy and autografting) but depended on the amount of resected parathyroid tissue: no failures and 4 cases of hypoparathyroidism in 34 cases with no missing gland at cervical exploration; 3 failures and no permanent hypoparathyroidism in 11 cases with one or two missing glands. Excision of the enlarged glands only was sufficient to cure the patient. No recurrence was observed. Our results suggest that single gland enlargement in PHSKT results in most cases from different rates of involution of the parathyroids after successful kidney transplantation. When fewer than four glands are discovered, resection of all visible glands with or without grafting corrects hypercalcemia in more than 70% of the cases.

Adult↗

Male recipients of kidneys from female donors are at increased risk of graft loss from both rejection and technical failure.

The aim of the present retrospective study was to uncover the factor(s) responsible for the poor outcome of cadaver kidney grafts from female donors in male recipients. The 741 transplantations performed at our center from August 1983 to September 1997 were distributed into four groups according to recipient and donor gender: female donor to female recipient (F to F: n = 117), male donor to female recipient (M to F: n = 172), female donor to male recipient (F to M: n = 170), and male donor to male recipient (M to M: n = 282). All the patients received immunosuppressive therapy based on corticosteroids and cyclosporine, associated or not with either azathioprine or prophylactic anti-lymphocyte globulin. Overall graft survival was lower in the F to M group than in the three other groups (p = 0.009). Failures due to rejection were more frequent during the 1st post-transplant trimester in female than in male donor grafts, irrespective of recipient gender (p = 0.025). All failures due to technical problems occurred during the first 3 months post-transplantation: they were more frequent in the F to M group than in the three other groups (p = 0.040): this could be related to the older age of the donors in the former group. After the first post-transplant year, failures due to causes other than rejection remained low in the F to F group but increased steadily in the three other groups (p = 0.007). Specific survival rates were not correlated with the time-evolution of mean serum creatinine values, daily doses and trough levels of cyclosporine in the four groups of grafts. In conclusion, the poor outcome of F to M grafts results from combined immunologic and technical factors exerting their effects early in the course of transplantation.

Adult↗

Reactivation of hepatitis B after transplantation in patients with pre-existing anti-hepatitis B surface antigen antibodies: report on three cases and review of the literature.

BACKGROUND: Patients who have been exposed to the hepatitis B virus (HBV) and who were able to clear the hepatitis B surface antigen from the serum and to develop anti-hepatitis B surface antigen (anti-HBs) antibodies are not considered at risk for HBV reactivation after solid organ transplantation. METHODS AND RESULTS: We, however, observed three solid organ transplant recipients who demonstrated clinically significant HBV reactivation after transplantation. All patients presented normal liver enzymes and serological stigmates of healed HBV infection at the time of transplantation, as indicated by the absence of hepatitis B surface antigen and the presence of anti-HBs and anti-hepatitis B core antibodies in the serum. Patient 1, a renal transplant recipient, presented HBV reactivation 3 years after transplantation and developed chronic HBV hepatitis. Patient 2 developed HBV reactivation 7 months after a second cadaveric renal graft and died of cirrhosis four and a half years after transplantation. Patient 3, a heart-lung transplant recipient, developed HBV reactivation within months after transplantation, but died of unrelated causes. HBV reactivation in the presence of anti-HBs antibodies has been previously reported in other settings of immunosuppression, mainly in patients with acquired immunodeficiency syndrome and after bone marrow transplantation, and may lead to fatal liver disease. Data from our renal transplant recipients suggest that the incidence of HBV reactivation among patients with anti-HBs and anti-hepatitis B core antibodies is about 5%. CONCLUSIONS: Transplant physicians should be aware of the risk of HBV reactivation in patients presenting with healed HBV infection before transplantation.

Adult↗

Experience with the Wujciak-Opelz allocation system in a single center: an increase in HLA-DR mismatching and in early occurring acute rejection episodes.

The present single-center, retrospective study was undertaken to assess the impact of the Wujciak-Opelz allocation system (XCOMB), currently used within Eurotransplant for renal allografts, on the incidence of early occurring rejection episodes (RE). Implementation of the system resulted in an increase of HLA-DR mismatches (MM), while the incidence of HLA-A + B + DR MM remained unchanged. During the 1st post-transplant month, the total number of RE, expressed per patient-months, increased by 64% (0.326 vs 0.199, P = 0.007); when considering only severe and irreversible RE, the increase was 76% (0.158 vs 0.090, P = 0.011). In contrast, from the 2nd to the 12th post-transplant month, the incidence of RE, regardless of severity, was similar before and after implementation of XCOMB. As early occurring RE have detrimental effects on long-term graft outcome, these observations, if confirmed on a larger scale, would justify changes in the allocation algorithm.

Acute Disease↗

Mycophenolate mofetil, together with cyclosporin A, prevents anti-OKT3 antibody response in kidney transplant recipients.

OKT3 monoclonal antibody, a murine IgG2a monoclonal antibody targeting the T cell CD3 antigen, elicits a neutralizing humoral response in 20 to 50% of kidney transplant recipients when the concomitant immunosuppression consists of CsA-Sandimmun (SAND) and azathioprine (AZA). In the present study, we investigated the impact of the newer agents, CsA-Neoral (NEO) and mycophenolate mofetil (MMF) on OKT3 sensitization. Sixty-two consecutive kidney transplant recipients received prophylactic OKT3 (5 mg/d) from days 0 to 13, together with steroids. Concomitant immunosuppression consisted of either AZA + SAND (n=20), AZA + NEO (n=31), or MMF + NEO (n=11). The following doses were used: AZA, 2 mg/kg per d from days 0 to 13, then 1 mg/kg per d; MMF, 2 g/d starting on day 1; and CsA, either SAND or NEO, 6 mg/kg per d from day 6. At least two serum samples per month were available during the initial 3 mo for each patient. IgG anti-OKT3 antibodies were first evaluated by enzyme-linked immunosorbent assay. Patients were considered sensitized if their serum scored positive at a dilution > or = 1/1000. Peak titers of IgG anti-OKT3 antibodies and the incidence of patients harboring neutralizing anti-idiotypic antibodies were also determined. A first reduction in OKT3 sensitization was seen in patients receiving Neoral instead of Sandimmun (AZA + SAND: 10 of 20 [50%] patients sensitized versus 6 of 31 [19%] in the AZA + NEO group; P=0.03). This was probably related to the achievement of higher mean CsA trough blood levels in the NEO group during the first month (253+/-44 versus 186+/-49 ng/ml in SAND patients). Peak antibody titers and the proportion of patients with anti-idiotypic antibodies were similar in the AZA + SAND and AZA + NEO groups. A further reduction in the sensitization rate was observed with the replacement of AZA by MMF (MMF + NEO: 0% sensitized patients; P=0.0013). It is concluded that the combination of CsA-Neoral and MMF efficiently prevents sensitization against OKT3.

Adult↗

A pilot trial of recombinant human interleukin-10 in kidney transplant recipients receiving OKT3 induction therapy.

BACKGROUND: We conducted a randomized, double-blind, placebo-controlled, rising single-dose study to investigate the effects of recombinant human (rh) interleukin (IL) 10 in renal transplant patients who received OKT3 as induction therapy. METHODS: Patients received 0.1 (n=6), 1 (n=6), or 10 microg/kg (n=3) rhIL-10 or placebo (n=6) intravenously 30 min before the first injection of 5 mg of OKT3. We monitored IL-10 serum levels, the effect of rhIL-10 on OKT3-induced cytokine production, clinical toxicity, and the incidence of immunization against OKT3. RESULTS: Serum IL-10 levels in the three experimental groups reached 0.8+/-0.2, 7.9+/-1.3, and 118.6+/-7.3 ng/ml (mean+/-SEM), respectively, 30 min after rhIL-10 injection. Peak plasma levels of tumor necrosis factor-alpha (TNF-alpha) were reduced from 2953+/-1599 pg/ml in patients injected with OKT3 and placebo to 447+/-155, 703+/-246, and 459+/-246 pg/ml in patients injected with 0.1, 1, and 10 microg/kg rhIL-10, respectively. Values for 24-hr TNF-alpha area under the curve decreased from 8988+/-3551 pg x hr/ml in control patients to 2284+/-494, 3950+/-955, and 2420+/-931 pg x hr/ml for the 0.1, 1, and 10 microg/kg rhIL-10 dose groups, respectively (P=0.045). There was also a trend toward reduced plasma levels of IL-2, IL-8, and interferon-gamma in rhIL-10-pretreated patients. Although none of the patients who received placebo or 0.1 or 1 microg/kg rhIL-10 developed an IgM antibody response directed against OKT3 during the first 10 days, this occurred in all three patients who received the highest rhIL-10 dose. In two of these patients, neutralization of OKT3 was associated with a reversible acute rejection episode. CONCLUSIONS: Pretreatment with doses of up to 1 microg/kg rhIL-10 is safe and reduces the release of TNF-alpha induced by OKT3. However, higher doses might promote early sensitization to OKT3.

Adult↗

Absence of deleterious effect on long-term kidney graft survival of rejection episodes with complete functional recovery.

BACKGROUND: Rejection episodes (RE) exert a detrimental influence on long-term kidney graft outcome. However, the impact of the severity of those RE on graft survival and the factors that could predict this impact are ill defined. The present retrospective study was undertaken on adult patients who received 582 cadaver kidney transplants at our center during the last 12 years, to assess the impact on graft survival of RE occurring during the first year after transplantation and to uncover the factors associated with the severity of those RE. METHODS: Three grades of rejection were defined: (1) rejection without loss of graft function (benign rejection); (2) rejection followed by partial loss of graft function (severe rejection); and (3) rejection with return to dialysis (irreversible rejection). The grafts were distributed among four groups: (1) grafts free of rejection; (2) grafts with benign RE (only grade 1 RE); (3) grafts with severe RE (one or more grade 2 RE); and (4) grafts with irreversible (grade 3) RE. RESULTS: Multivariate analyses revealed that (1) the occurrence of RE during the first posttransplant year (group 1 versus groups 2, 3, and 4) was significantly associated with primary immunosuppression with CsA rather than with OKT3 monoclonal antibody, the number of HLA-B + DR mismatches, and the younger recipient's age; (2) in patients with rejection, OKT3 monoclonal antibody prophylaxis was less often used in patients with irreversible RE (group 4) than in those with reversible RE (group 2, benign, and group 3, severe); and (3) no single factor was able to differentiate patients with benign RE (group 2) from those with severe RE (group 3). For grafts still functioning 1 year after transplantation, long-term graft survival was similar in grafts with either no RE or benign RE, but it was significantly lower (P<0.0001) in grafts with severe RE: 8-year survival rates were 89% and 60%, respectively. The decline in graft survival after 1 year was significantly correlated with the serum creatinine value but not with the dose of cyclosporine at 1 year. CONCLUSIONS: Benign RE occurring during the first year after transplantation and resulting in no loss of graft function do not exert a detrimental influence on long-term kidney graft outcome. In contrast, the prognosis of grafts with severe RE during the same period of time is much poorer.

Adult↗

Disseminated angiosarcoma presenting as a hemophagocytic syndrome in a renal allograft recipient.

A case of angiosarcoma arising in the setting of transplantation is reported. This rare and malignant tumor of the endothelial system is seldom observed in allograft recipients, with only seven cases having been previously reported. What is interesting about the present observation is that the tumor is thought to have developed in the vicinity of a Dacron graft and that it showed prominent erythrophagocyte-like activity. This activity was associated with a particular clinical syndrome that shared some attributes with infection-associated hemophagocytic syndrome.

Diagnosis, Differential↗

A case of rapidly fatal systemic capillary leak syndrome in a kidney transplant recipient.

Idiopathic Systemic Capillary Leak Syndrome (SCLS) is a rare entity characterised by idiopathic increasing of capillary permeability associated with recurrent attacks of hypovolaemic shock. We report the case of a 39-year-old man with a SCLS fourteen years after a cadaveric renal transplantation. The clinical evolution was rapidly fatal despite treatment with corticoids, aminophylline and terbutaline which are the most efficient drugs known to prevent attacks.

Adult↗

Renal transplantation exposes patients with previous Kaposi's sarcoma to a high risk of recurrence.

It is currently estimated that about 0.5% of patients will develop Kaposi's sarcoma (KS) after kidney transplantation. Tapering of immunosuppression often leads to KS remission, but also results in graft loss in more than 50% of cases. Whether retransplantation is safe in these patients is unknown. We here report on eight patients who developed KS recurrence after kidney transplantation-(A) Patients with previously treated KS: There were 4 patients who had clinical remission of KS (including three posttransplantation) for periods ranging from 5 months up to 19 years before transplantation. All 4 developed KS recurrence within months after transplantation. In 3 patients, KS regressed only when all immunosuppression was discontinued, at the price of allograft removal. Partial remission occurred in the fourth patient following reduction of immunosuppression and gancyclovir administration; (B) Patients with recurrent KS during a single transplant: 4 patients developed KS after transplantation that regressed following reduction of immunosuppressive therapy. Increased immunosuppression, in the form of steroid pulses in 3 patients was associated with recurrence of KS. Subsequent reduction of immunosuppression caused regression of KS in all 4 patients, but 2 recipients lost their allografts. These data emphasize the high risk of recurrence of KS after renal transplantation. If physicians decide to transplant patients with a history of KS, they should inform the future recipient of the possibility of KS recurrence.

Adult↗

Monocyte procoagulant activity induced by in vivo administration of the OKT3 monoclonal antibody.

The first injection of OKT3 in kidney transplant recipients activates the common pathway of coagulation. This may result in early thrombosis of graft vessels. To this day, the cells involved in this phenomenon have not been identified. The aim of this study was to investigate whether circulating monocytes participated in this OKT3-induced coagulopathy. The procoagulant activity (PCA) of circulating monocytes rose from (mean +/- SEM) 0.15 +/- 0.02 mU/mL to 0.40 +/- 0.05 mU/mL at 3 hours (P = .002) and 0.56 +/- 0.21 at 5 hours (P = .045) after the initial OKT3 injection. These monocytes displayed increased tissue factor expression at the same moments (mean flourescence intensity: 14 +/- 2 before OKT3 injection versus 54 +/- 14 at 3 hours, P = .008 and 34 +/- 7 at 5 hours, P = .01). Tissue factor mRNA was detected in blood by reverse transcriptase-polymerase chain reaction as early as 2 hours after OKT3 administration. The circulating monocytes also displayed a steady increase in membrane expression upregulation of ICAM-1, CD29, CD11b, and CD11c. In vitro experiments showed that OKT3 as well as 2 mitogenic, humanized anti-CD3 antibodies potently induced monocytic PCA whereas the 4 nonmitogenic anti-CD3 antibodies tested were over 1,000-fold less potent than OKT3. We conclude that (1) OKT3 induces in vivo tissue factor gene upregulation and membrane expression resulting in increased PCA of circulating monocytes; and (2) nonmitogenic anti-CD3 antibodies seem devoid of significant procoagulant properties.

Blood Coagulation↗

OKT3 prophylaxis in renal grafts with prolonged cold ischemia times: association with improvement in long-term survival.

The data on patients participating in two randomized, prospective studies with similar immunosuppressive regimens were updated and combined to evaluate the long-term effects of OKT3 according to cold ischemia time (< or = or > 24 hr). Among 159 patients in the OKT3 and 153 in the cyclosporine A (CsA) group, 8 and 12 deaths occurred, respectively (P = NS). In patients with cold ischemia > 24 hours, OKT3 prophylaxis resulted in a lower mean number of rejection episodes per patient than did CsA prophylaxis within one year (mean +/- SEM: 0.87 +/- 0.11 vs. 1.35 +/- 0.14, respectively; P = 0.008) and within five years (1.07 +/- 0.12 vs. 1.49 +/- 0.15, respectively; P = 0.032). In contrast, rejection incidences in patients with cold ischemia < or = 24 hours was not significantly different in the two groups. In all study patients, there was a trend towards higher graft survival rates in the OKT3 group versus the CsA group (at 5 years, 73% vs. 66%, respectively; P = 0.182). Among recipients of kidneys with cold ischemia times > 24 hours, OKT3 patients had significantly higher graft survival than CsA patients at two years (84% vs. 64%, respectively) and at five years (71% vs. 56%, respectively; P = 0.045). Significant differences were not observed in recipients of kidneys with cold ischemia times < or = 24 hours. In conclusion, patients receiving renal grafts with long cold ischemia times strongly benefit from OKT3 prophylaxis.

Adult↗