Biomedical subjects

Jean-Louis Bosmans

Publications and source records attributed to Jean-Louis Bosmans.

6 recordsLinked to original sources

PubMed2005

Use of Neoral C monitoring: a European consensus.

Large-scale clinical trials using C(2) monitoring of cyclosporine (CsA) microemulsion (Neoral) in renal transplant recipients have demonstrated low acute rejection rates and good tolerability with a low adverse event profile in a variety of settings: with or without routine induction therapy; in combination with mycophenolate mofetil; with standard-exposure or low-exposure Neoral; and in patients with immediate or delayed graft function. In liver transplantation, C(2) monitoring significantly reduces the severity and incidence of acute rejection compared with C(0) monitoring, without adverse consequences in terms of renal function or tolerability. Different C(2) targets are appropriate depending on adjunctive immune suppression, level of immunologic risk, CsA tolerability, risk of renal toxicity and time since transplantation. CsA absorption may increase substantially in most patients during the first 1-2 weeks post-transplant, and this should be taken into account to avoid overshooting C(2) target range. A patient with a low C(2) value may be either a low or a delayed absorber of CsA, or be a normal absorber who is receiving too low a dose of Neoral. C(2) monitoring alone is insufficient to differentiate between these types of patients, and measurement of additional timepoints is recommended. Adopting C(2) monitoring in maintenance transplant patients identifies those who are overexposed to CsA. In summary, randomized, prospective, multicenter studies and single-center trials have evaluated Neoral C(2) monitoring within a range of regimens in different organ types, providing a robust evidence base for the benefits of this sensitive monitoring technique.

Absorption↗

PubMed2005

Incidence of C4d stain in protocol biopsies from renal allografts: results from a multicenter trial.

C4d staining of renal allografts is regarded as an in situ marker of active humoral rejection. Few data are available about the incidence of C4d deposition in protocol biopsies compared to indication biopsies. To evaluate whether center-specific factors influence the incidence of C4d detection, we performed a multicenter study. From three European centers, 551 protocol and 377 indication biopsies were reclassified according to the updated Banff criteria and stained for C4d. C4d results were recorded as diffuse or focal positive and statistically correlated to clinical parameters, morphology and graft survival. In the protocol biopsies, a diffuse C4d stain was found in 2.0%, and a focal stain in 2.4%. In indication biopsies, 12.2% were diffusely and 8.5% focally C4d positive (protocol:indication p < 0.0001). The incidence of C4d deposition varied significantly between centers, attributable to variable numbers of presensitized patients with more C4d positive indication and protocol biopsies. Diffuse and focal C4d stain correlated with morphology of humoral rejection in protocol as well as in indication biopsies. Protocol biopsies show a significantly lower incidence of C4d deposition than indication biopsies. Subclinical C4d detection in protocol biopsies had no significant impact on allograft survival in our series.

Biopsy↗

PubMed2003

Long-term renal function after HELLP syndrome.

This study was set up to determine the long-term (5 or more years) renal function after HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome during pregnancy and to answer the question whether long-term renal follow-up is necessary. Women with HELLP syndrome were compared with healthy control subjects who delivered their first child during the same period. There was no difference between groups for body mass index, serum and urinary creatinine levels, creatinine clearance, total urinary protein/creatinine ratio, and urinary microalbumin/creatinine ratio. Women who previously had HELLP syndrome had significantly higher diastolic and systolic blood pressures. Women with HELLP syndrome do not need continued renal follow-up, but have higher systolic and diastolic blood pressures, even 5 years after HELLP syndrome.

Acute Kidney Injury↗

PubMed2003

Protocol biopsy of the stable renal transplant: a multicenter study of methods and complication rates.

BACKGROUND: Clinical trials in renal transplantation must use surrogate markers of long-term graft survival if conclusions are to be drawn at acceptable speed and cost. Morphologic changes in transplant biopsies provide the earliest available evidence of damage, and "protocol" biopsies from stable grafts can be used to reduce the number of patients needed in clinical trials. This approach has been inhibited by concerns over safety, but the risk of biopsy of a stable kidney, with no active inflammation or acute functional impairment, has never been formally estimated. METHODS: In accordance with a predefined set of questions, a retrospective audit of a sequential series of protocol biopsies was performed in four major transplant centers. RESULTS: A total of 2,127 biopsy events were assessed for major complications, and 1,486 were assessed for minor ones. There were no deaths. One graft was lost, under circumstances indicating that the loss should have been prevented. Three episodes of hemorrhage required direct intervention. Three further patients required transfusion. There were two episodes of peritonitis, but one was arguably an unrelated event. All serious complications presented within 4 hr of biopsy. CONCLUSIONS: The incidence of clinically significant complications after protocol biopsy of a stable renal transplant is low. Direct benefits to the patients concerned (irrespective of the benefit that may accrue in clinical trials) were not formally assessed but seem likely to outweigh the risk of the procedure. We believe that it is ethically justifiable to ask renal transplant recipients to undergo protocol biopsies in clinical trials and routine care.

Biopsy↗

PubMed2002

Decreased short-term renal graft survival in Maghrebian recipients.

The influence of race on renal allograft survival is disputed. We studied 16 cadaveric renal transplants in 14 Maghrebian patients, each matched with two controls of local origin. Patient survival at 12 months was 93% in the Maghreb group and 97% in the control group (NS). Graft survivals at 3 months for these two groups were 73% and 97%, respectively (P<0.01). At 6 months, graft survival in the control group remained unchanged at 97%, whereas in the case group it declined further to 59% (P<0.01). Overall graft failure in the Maghreb group amounted to 44% (seven of 16 transplants). In each case, failure was due to biopsy-proven acute rejection. Overall graft failure amongst the controls was only 6% (two of 32 transplants) (P=0.004) (only one case of acute rejection, or 3%) (P=0.01). This study provides evidence for significantly lower short-term renal graft survival in Maghrebian recipients of a Caucasian graft. Acute rejection seems to play a major causative role in graft loss in this group.

Adult↗

PubMedDate not supplied

Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial.

BACKGROUND: Mycophenolate mofetil has replaced azathioprine in immunosuppression regimens worldwide to prevent graft rejection. However, evidence that its antirejection activity is better than that of azathioprine has been provided only by registration trials with an old formulation of ciclosporin and steroid. We aimed to compare the antirejection activity of these two drugs with a new formulation of ciclosporin. METHODS: The mycophenolate steroids sparing multicentre, prospective, randomised, parallel-group trial compared acute rejections and adverse events in recipients of cadaver-kidney transplants over 6-month treatment with mycophenolate mofetil or azathioprine along with ciclosporin microemulsion (Neoral) and steroids (phase A), and over 15 more months without steroids (phase B). The primary endpoint was occurrence of acute rejection episodes. Analysis was by intention to treat. FINDINGS: 168 patients per group entered phase A. 56 (34%) assigned mycophenolate mofetil and 58 (35%) assigned azathioprine had clinical rejections (risk reduction [RR] on mycophenolate mofetil compared with azathioprine 13.7% [95% CI -25.7% to 40.7%], p=0.44). 88 patients in the mycophenolate mofetil group and 89 in the azathioprine group entered phase B. 14 (16%) taking mycophenolate mofetil and 11 (12%) taking azathioprine had clinical rejections (RR -16.2%, [-157.5% to 47.5%], p=0.71). Average per-patient costs of mycophenolate mofetil treatment greatly exceeded those of azathioprine (phase A 2665 Euros [SD 586] vs Euros 184 [62]; phase B 5095 Euros [2658] vs 322 Euros [170], p<0.0001 for both). INTERPRETATION: In recipients of cadaver kidney-transplants given ciclosporin microemulsion, mycophenolate mofetil offers no advantages over azathioprine in preventing acute rejections and is about 15 times more expensive. Standard immunosuppression regimens for transplantation should perhaps include azathioprine rather than mycophenolate mofetil, at least for kidney grafts.

Acute Disease↗