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Biomedical subjects

L De Pauw

Publications and source records attributed to L De Pauw.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

Propofol infusion for induction and maintenance of anaesthesia in patients with end-stage renal disease.

We have investigated the pharmacokinetics and pharmacodynamics of propofol in 11 patients with end-stage renal disease (ESRD) compared with nine healthy patients during and after a manually controlled three-stage infusion of propofol 21, 12 and 6 mg kg-1 h-1 lasting a minimum of 2 h. Mean total body clearance was not reduced significantly in the ESRD group (30.66 (SD 8.47) ml kg-1 min-1) compared with the control group (33.75 (7.8) ml kg-1 min-1). ESRD patients exhibited a greater, but not statistically significant, volume of distribution at steady state compared with patients in the control group (11.25 (8.86) vs 5.79 (2.14) litre kg-1, respectively). Elimination half-life values were unchanged by renal failure. Mean times to induction of anaesthesia were similar in both groups: 177 (SD 57) and 167 (58) s for the ESRD and control groups, respectively. Waking time after cessation of propofol infusion was significantly shorter in the ESRD group (474 (156) s) compared with the control group (714 (240) s) (P < 0.05). Mean plasma concentrations on waking were similar. We conclude that the pharmacokinetic and pharmacodynamic profiles of propofol after infusion were not markedly affected by renal failure.

Adult↗
PubMed1998

Isolation and infusion of donor CD34+ bone marrow cells in cadaver kidney transplantation.

BACKGROUND: Infusion of donor bone marrow cells induces tolerance in allograft models. CD34+ stem cells present in human bone marrow could be endowed with tolerogenic properties. METHODS: CD34+ stem cells were isolated from bone marrow extracted from vertebral bodies of cadaveric donors. Donor CD34+ cells (0.6-3.7 x 10(6)/kg) were infused during surgery in 10 kidney transplant recipients receiving OKT3 as induction therapy. Chimerism was investigated using nested PCR for donor-specific HLA alleles. RESULTS: The infusion of CD34+ stem cells was perfectly tolerated. Five patients remained free of acute rejection at follow-up, 47-325 days post-operatively. The five other patients underwent a single episode of corticosensitive acute rejection. Long-term chimerism was not induced in the seven patients investigated for the persistence of donor DNA. CONCLUSIONS: Infusion of donor CD34+ stem cells in kidney transplantation is safe. The clinical usefulness of the procedure remains to be established.

Adult↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

[Primary hyperoxaluria].

Primary hyperoxaluria is a rare hereditary disease. Two types have been identified. Type 1 is due to the deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase/serine: pyruvate amino-transferase whereas, in type 2, the deficiency concerns the glyoxylate reductase/D-glycerate dehydrogenase, a cytosolic enzyme present in the leucocytes and hepatocytes. In the elapsed decade, important progress in molecular biology led to the introduction of new strategies in the diagnosis and treatment of type 1 primary hyperoxaluria. However, the greater rarity of type 2 has so far prevented similar development. The present review recalls the normal metabolism of oxalic acid, details its deviations and their clinical consequences, and describes the methods of diagnosis and treatment to be presently recommended in primary hyperoxaluria.

Biopsy↗
PubMed1996

Prevention of OKT3 nephrotoxicity after kidney transplantation.

In our experience the use of OKT3 as prophylaxis in renal transplantation has been associated with an increased incidence of both delayed graft function and thromboses of graft vessels. OKT3 nephrotoxicity might have been favored by restriction of perioperative fluid infusion to prevent pulmonary edema and by the use of very high dose (30 mg/kg) of methylprednisolone (mPDS) before the first OKT3 injection to reduce the release of cytokines. This led us to modify our perioperative management in three ways: (1) hydration status was optimalized; (2) the calcium-channel blocker diltiazem, considered beneficial for recovery of graft function, was administered on the day of transplantation; and (3) the dose of mPDS given before the first OKT3 injection was fixed at 8 mg/kg. Comparison of two consecutive series of patients (group 1, control patients, N = 172; group 2, managed as described above, N = 173) showed that: (1) the incidence of delayed graft function fell from 52% in group 1 to 22% in group 2 (P < 0.0001): (2) the incidence of pulmonary edema was not significantly increased in group 2 (3.5% vs. 1.7% in group 1, P = 0.5); and (3) the frequency of intragraft thrombosis fell from 7.6% in group 1 to 1.2% in group 2 (P = 0.0034). Multivariate analysis showed that the volemia/diltiazem program and avoidance of high mPDS dose were the most important factors responsible for the reduced occurrence of delayed graft function and graft vessels thrombosis, respectively. We conclude that a combined strategy of appropriate dosage of steroids before the first OKT3 injection, administration of a calcium-channel blocker and optimalization of volemia is safe and efficiently prevents against OKT3 nephrotoxic effects.

Adult↗
PubMed1995

Influence of donor-recipient HLA-DR mismatches and OKT3 prophylaxis on cadaver kidney graft survival.

Previous studies from our center have shown that donor-recipient HLA-DR mismatches (MM), characterized by the presence of the DR antigen in the donor but not in the recipient or vice versa, are associated with differential effects on graft survival (GS): some of them are beneficial (BEN) with results similar to those of HLA-DR identical or compatible pairs (85% 18 months GS) and some are detrimental (DET) (64% 18 months GS), whereas the other MM, neither BEN nor DET (neutral [NEU]) yield intermediate results (78% 18 months GS). The aim of the present study was to update the results at a longer follow-up time and to assess whether they are influenced or not by prophylactic administration of anti-CD3 mAb (OKT3). The analysis of 234 transplantations performed from 1980 to 1994 with only 1 HLA-DR MM confirmed the BEN effects of HLA-DR5 in either the donor or the recipient and the DET effects of HLA-DR1 or -DR2 in the donor and of HLA-DR2 or -DRW6 in the recipient. These effects were independent of those exerted by other, HLA-DR not related, prognostic factors. The transplants with 1 HLA-DR MM were then compared with those with zero HLA-DR MM (n = 378) and 4 groups were formed according to 2 levels of HLA-DR MM (zero or BEN MM vs. NEU or DET MM) and immunosuppression (with vs. without OKT3 prophylaxis). GS at 5 years was 63% in the group with either zero or BEN MM as compared with 41% in the group with either NEU or DET MM in the absence of OKT3 prophylaxis (P < 0.02); in comparison, with OKT3 prophylaxis, GS at 5 years was 73% in the group with either zero or BEN MM as compared with 58% in the group with either NEU or DET MM (P = 0.07). We conclude that the differential effects of HLA-DR MM on GS are still observed under OKT3 prophylaxis, that the effects of HLA-DR and immunosuppression on graft outcome are additive, and that OKT3 induction therapy is superior to therapy without OKT3. These observations could have important implications for the allocation policy and management of renal transplants.

Adult↗
PubMed1995

Combined liver-kidney transplantation in primary hyperoxaluria type 1. Bone histopathology and oxalate body content.

In three patients with end-stage renal failure due to primary hyperoxaluria type 1, successful combined liver-kidney transplantation enabled us to assess the insoluble oxalate pool, which was compared with the histopathological changes observed in iliac crest biopsy specimens. Good correlation was observed between the histopathological grade of bone oxalosis and the estimated oxalate content of the body. In the end-stage of oxalate bone disease, hyperparathyroidism does not play a significant role in bone resorption, which appears to be the consequence of the granulomatous reaction induced by oxalate deposition. Combined liver-kidney transplantation should be performed long before this stage. Early hepatorenal grafting in uremia secondary to primary hyperoxaluria type 1 would avoid the deleterious clinical consequences of systemic oxalosis and shorten the duration of postransplant hyperoxaluria, which may compromise the course of kidney graft.

Adolescent↗