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Biomedical subjects

Pierre Merville

Publications and source records attributed to Pierre Merville.

13 recordsLinked to original sources
PubMed2006

Long-term evolution of body composition after renal transplantation: 5-year survey.

BACKGROUND: Thanks to advancements in immunosuppression, patients are living longer with kidney transplants, and nonimmunologic factors (particularly nutritional) have become a major source of morbidity and mortality after successful kidney transplantation (KTx). In this current study, we have prospectively assessed, in a cohort of kidney transplant recipients (KTR), the course of some nonimmunologic factors liable to hinder the long-term outcome of KTR. METHODS: Forty-four consecutive KTR with stable functioning grafts received dietary recommendations and were on the lowest effective dose of steroids. Biochemical nutritional markers, C-reactive protein, lipid profile, and body composition determined by dual-energy X-ray absorptiometry were studied over the first year, 2 years, and 5 years after KTx. RESULTS: No patients died during the follow-up. All patients but 2 were considered normotensive. Clinical diabetes developed in 3 patients. Visceral proteins stabilized at a normal range after the first year. Most of the patients normalized their inflammatory status. A significant improvement in lipid profile was observed. Female patients had a significant increase of weight (13.5%), mainly because of an increase in fat mass: 3.4 kg (19.4%) at 1 year and 5.6 kg (29.7%) at 2 years. In male patients, body composition remained stable and close to baseline values. The evolution of bone mass varied according to gender, total corticoid doses, and calcineurin inhibitors. Patients on low doses of steroids normalized their Z-score over the 5-year period. The increase in bone mass (paired t-test, P = .006) was only significant in patients treated with tacrolimus (analysis of variance for repeated measures, P < .001). CONCLUSIONS: Simple measures and dietary intervention to prevent or correct nonimmunologic disorders should permit improvement of long-term morbidity and mortality of KTR without compromising the functional outcome of their transplant.

Absorptiometry, Photon↗
PubMed2005

[Antopol-Goldman lesion: a rare cause of hematuria].

An Antopol-Goldman lesion or subepithelial pelvic hematoma of the kidney is a rare cause of hematuria. We described a 26 year-old man hospitalized for macroscopic hematuria associated with a subepithelial hematoma whose development might have been favored by arterial hypertension secondary to a renal artery stenosis.

Adult↗
PubMed2005

Shared reactivity of V{delta}2(neg) {gamma}{delta} T cells against cytomegalovirus-infected cells and tumor intestinal epithelial cells.

Long-lasting expansion of Vdelta2(neg) gammadelta T cells is a hallmark of cytomegalovirus (CMV) infection in kidney transplant recipients. The ligands of these cells and their role remain elusive. To better understand their immune function, we generated gammadelta T cell clones from several transplanted patients. Numerous patient Vdelta1(+), Vdelta3(+), and Vdelta5(+) gammadelta T cell clones expressing diverse Vgamma chains, but not control Vgamma9Vdelta2(+) T clones, displayed strong reactivity against CMV-infected cells, as shown by their production of tumor necrosis factor-alpha. Vdelta2(neg) gammadelta T lymphocytes could also kill CMV-infected targets and limit CMV propagation in vitro. Their anti-CMV reactivity was specific for this virus among herpesviridae and required T cell receptor engagement, but did not involve major histocompatibility complex class I molecules or NKG2D. Vdelta2(neg) gammadelta T lymphocytes expressed receptors essential for intestinal homing and were strongly activated by intestinal tumor, but not normal, epithelial cell lines. High frequencies of CMV- and tumor-specific Vdelta2(neg) gammadelta T lymphocytes were found among patients' gammadelta T cells. In conclusion, Vdelta2(neg) gammadelta T cells may play a role in protecting against CMV and tumors, probably through mucosal surveillance of cellular stress, and represent a population that is largely functionally distinct from Vgamma9Vdelta2(+) T cells.

Antigens, Neoplasm↗
PubMed2005

Activation of mesangial cells by platelets in systemic lupus erythematosus via a CD154-dependent induction of CD40.

BACKGROUND: Platelets are potential contributors to glomerular injury via the release of chemotactic and/or mitogenic mediators upon activation or through direct CD154/CD40-dependent interaction with cell components of the glomerulus. We examined whether platelets could activate mesangial cells and the potential role of the platelet-associated CD154. METHODS: Thrombin-activated platelets from systemic lupus erythematosus (SLE) patients or from disease or healthy controls were grown with human mesangial cells in the presence or not of a neutralizing anti-CD154 antibody either in contact or in a noncontact setting, the platelets and mesangial cells being separated by a pore size semipermeable membrane. The induction of mesangial cell surface antigens was assayed by flow cytometry. The quantification of mesangial cell proliferation was performed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and the production of transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor (PDGF) and soluble CD40 were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Activated platelets from patients with SLE could induce an up-regulation of the expression of CD40 on mesangial cells with a concomitant release of soluble CD40. This induction required a direct contact between platelets and mesangial cells and was dependent upon the platelet-associated CD154. Pathologic consequences of the up-regulation of CD40 were a CD40-dependent stimulation of the proliferation of mesangial cells and a CD40-dependent increased production of TGF-beta1 by these cells. CONCLUSION: Platelets from patients with SLE can activate mesangial cells through CD40/CD154 interactions, leading to an induction of proliferation of the mesangial cells and an enhanced production of TGF-beta1, a profibrotic cytokine.

Adult↗
PubMed2005

Combating chronic renal allograft dysfunction : optimal immunosuppressive regimens.

Kidney transplantation is the best treatment for patients with end-stage renal disease, both in terms of survival benefit and quality of life. The major limitation is the continuing shortage of kidneys suitable for transplantation, reinforcing the need to maximise graft survival. After the first year of transplantation, chronic renal allograft dysfunction (CRAD) is the first cause of late graft deterioration and failure. CRAD has been defined as a progressive renal dysfunction, independent of acute rejection, drug toxicity and recurrent or de novo nephropathy, with features on biopsy of chronic allograft nephropathy (CAN) characterised by vascular intimal hyperplasia, tubular atrophy, interstitial fibrosis and chronic transplant glomerulopathy. Protocol biopsy-based studies have demonstrated a high and early prevalence of CAN lesions during the first year in patients with normal and stable renal function. Beyond 1 year, the injuries associated with calcineurin inhibitors (CNIs) appear to be very common. The physiopathology of CRAD is complex and multifactorial. Both alloantigen-dependent factors (acute rejection, HLA matching, donor-specific antibodies, inadequate immunosuppression) and alloantigen-independent factors (donor age, brain death, ischaemia/reperfusion injuries, hypertension, hyperlipidaemia, cytomegalovirus, CNI-related nephrotoxicity) are involved. Consequently, CRAD appears as a dynamic process, evolving with time, and immunosuppressive regimens need to be modulated in order to provide the most suitable treatment at the different phases of its natural history. On the basis of this scheme, the new paradigm would be the use of a CNI-based regimen during the period of maximal risk of (subclinical) acute rejection, followed by a conversion to a CNI-free regimen in order to avoid the long-term consequences of nephrotoxicity. Fortunately, new agents are being introduced in clinical practice providing a large range of combinations and allowing individualisation of immunosuppressive regimens. Large, prospective, multicentre trials are warranted, and the challenge is to define new endpoints of CRAD and to determine the best therapeutic strategy.

Chronic Disease↗
PubMed2004

Coordinated expression of Ig-like inhibitory MHC class I receptors and acquisition of cytotoxic function in human CD8+ T cells.

MHC class I-specific inhibitory receptors are expressed by a subset of memory-phenotype CD8(+) T cells. Similar to NK cells, MHC class I-specific inhibitory receptors might subserve on T cells an important negative control that participates to the prevention of autologous damage. We analyzed here human CD8(+) T cells that express the Ig-like MHC class I-specific inhibitory receptors: killer cell Ig-like receptor (KIR) and CD85j. The cell surface expression of Ig-like inhibitory MHC class I receptors was found to correlate with an advanced stage of CD8(+) T cell maturation as evidenced by the reduced proliferative potential of KIR(+) and CD85j(+) T cells associated with their high intracytoplasmic perforin content. This concomitant regulation might represent a safety mechanism to control potentially harmful cytolytic CD8(+) T cells, by raising their activation threshold. Yet, KIR(+) and CD85j(+) T cells present distinct features. KIR(+)CD8(+) T cells are poor IFN-gamma producers upon TCR engagement. In addition, KIR are barely detectable at the surface of virus-specific T cells during the course of CMV or HIV-1 infection. By contrast, CD85j(+)CD8(+) T cells produce IFN-gamma upon TCR triggering, and represent a large fraction of virus-specific T cells. Thus, the cell surface expression of Ig-like inhibitory MHC class I receptors is associated with T cell engagement into various stages of the cytolytic differentiation pathway, and the cell surface expression of CD85j or KIR witnesses to the history of qualitatively and/or quantitatively distinct T cell activation events.

Antigens, CD↗
PubMed2004

Serum leptin, body fat, and nutritional markers during the six months post-kidney transplantation.

Leptin is a 16-kd protein that is thought to be a regulator of food intake and body weight. Many previous studies have reported elevated serum leptin levels in renal failure. In this study, we investigated the outcome of serum leptin and its relationship to body fat (BF), dietary intake, nutritional, and inflammatory markers after kidney transplantation (KTx). A total of 41 kidney transplant recipients were followed-up prospectively during 6 months posttransplantation. Serum leptin, albumin, transferrin, and C-reactive protein (CRP) were measured at KTx, 15 days, 3, and 6 months later. Dietary intake and BF were determined at KTx, 3, and 6 months later. A decrease in serum leptin was observed early at day 15 after KTx; this decrease was significant only in patients with BF >/= 30% of body weight. The decrease was maintained at 3 and 6 months after KTx. In multivariate analysis, an independent impact of higher percentage BF at KTx on the decrease of serum leptin was observed. Serum leptin correlated positively with BF. Conversely, no correlation was found between changes of serum leptin and changes of dietary intake. Leptin correlated positively with CRP at KTx, but not after normalization of renal function. Changes of serum leptin levels were not correlated with those of serum albumin levels. In summary, hyperleptinemia at KTx is manifest in patients with a high percentage of BF. An early and maintained correction follows KTx. Serum leptin levels did not appear to affect alimentary intake at and after KTx.

Adult↗
PubMed2004

Lower incidence of chronic allograft nephropathy at 1 year post-transplantation in patients treated with mycophenolate mofetil.

Chronic allograft nephropathy (CAN) is the main cause of graft failure after the first year of transplantation. This prospective, centrally randomized, open-label study was conducted to examine the possibility that mycophenolate mofetil (MMF) can prevent the emergence of CAN. The incidence of biopsy-proven CAN at 1 year was compared between two cyclosporine-based regimens comprising either mycophenolate mofetil (MMF) or azathioprine (AZA). The AZA group (n = 34) and the MMF group (n = 37) were balanced for all baseline characteristics of donors and recipients, the pre-existence of renal lesions on donor biopsy, the incidence of delayed graft function and acute rejection. Based on an intent-to-treat analysis, the number of patients with CAN at 1 year post-transplantation was significantly reduced in the MMF group (17/37-46%) compared with the AZA group (24/34-71%) (p = 0.03). When observed data were considered, 56/71 (78.8%) patients had a 1-year biopsy, and the number of patients with CAN was significantly lowered in the MMF group (9/29-31%) compared with the AZA group (17/27-63%) (p = 0.01). These results suggest a beneficial effect of MMF on the incidence of CAN at 1 year post-transplantation.

Adolescent↗
PubMed2003

A three-arm study comparing immediate tacrolimus therapy with antithymocyte globulin induction therapy followed by tacrolimus or cyclosporine A in adult renal transplant recipients.

BACKGROUND: Induction therapy with antithymocyte globulin (ATG) reduces the incidence of acute rejection after transplantation. A study was undertaken to assess the efficacy and safety of ATG induction on tacrolimus-based and cyclosporine A (CsA)-based therapies compared with immediate tacrolimus triple therapy in kidney transplant recipients. METHODS: In a 6-month, open-label, randomized, prospective study conducted in 30 European centers, 555 renal transplant patients were randomly assigned to tacrolimus triple therapy (Tac triple, n=185), ATG induction with tacrolimus (ATG-Tac, n=186), or ATG induction with CsA microemulsion (ATG-CsA, n=184); all were combined with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection episode confirmed by biopsy. RESULTS: Patient demographics and clinical parameters at baseline were similar. Patient and graft survival rates were similar in all groups. The incidence of clinically apparent acute rejection was significantly higher (P=0.003) for Tac triple (33.0%) compared with ATG-Tac (22.6%) and the incidence for ATG-Tac was significantly lower (P=0.004) than for ATG-CsA (37.0%). The incidences of acute rejection confirmed by biopsy (primary endpoint) were 25.4%, 15.1%, and 21.2% for Tac triple, ATG-Tac, and ATG-CsA, respectively (Tac triple vs. ATG-Tac, P=0.004). The incidences of corticosteroid-resistant acute rejection were 7.0% (Tac triple), 4.8% (ATG-Tac), and 10.9% (ATG-CsA) (ATG-Tac vs. ATG-CsA, P=0.038). In the ATG groups, the incidences of leukopenia, thrombocytopenia, serum sickness, fever, and cytomegalovirus infection were significantly higher (P<0.05). CONCLUSIONS: Acute rejection was significantly lower in the ATG-Tac group compared with the ATG-CsA and Tac triple groups. Significantly more hematologic and infectious adverse events were observed in both ATG induction groups.

Acute Disease↗
PubMed2003

Potential role of soluble CD40 in the humoral immune response impairment of uraemic patients.

CD40/CD154 interaction is essential for both humoral and cellular immune response. We investigated whether this interaction could be altered in patients with kidney failure who are known to present an impaired immune response. To that aim, we measured the levels of the soluble form of CD40 (sCD40), which is known to interfere with CD40/CD154 interaction, in 43 chronic renal failure patients, 162 hemodialysed patients, and 83 healthy donors. Uraemic and haemodialysed patients presented a three- and fivefold increase, respectively, of the antagonist soluble form of CD40 in their serum, when compared to healthy subjects. Serum sCD40 levels correlated with those of creatinine in uraemic non-haemodialysed patients. While sCD40 is widely excreted in urine of healthy individuals, it is not eliminated by dialysis sessions on classic membranes. The return to a normal kidney function in nine haemodialysed patients who received renal transplantation, leads to a rapid decrease of serum sCD40 levels. This natural sCD40 exhibited multimeric forms and was able to inhibit immunoglobulin production by CD154-activated B lymphocytes in vitro. Furthermore, the positive correlation we observed between the serum levels of sCD40 and the deficient response to hepatitis B vaccination in uraemic patients suggests that sCD40 also compromises the humoral response in vivo.

Adolescent↗
PubMed2002

Renal failure after liver transplantation: outcome after calcineurin inhibitor withdrawal.

Chronic nephrotoxicity is one of the most serious side-effects of calcineurin inhibitor treatment and a factor in mortality and morbidity after liver transplantation. In our transplant centre, among patients who underwent a liver transplantation between January 1989 and December 2000, 14 liver graft recipients (6.86%) developed de novo severe renal dysfunction as defined by a serum creatinine concentration above 200 micromol/L. Renal biopsy was performed in nine cases and evidenced histological lesions compatible with chronic nephrotoxicity related to calcineurin inhibitor treatment. For nine patients, we report the results of a prospective non-randomized study consisting of cyclosporine or tacrolimus withdrawal associated with administration of mycophenolate mofetil or azathioprine. Despite this therapeutic modification, we did not observe a significant renal function improvement but on the other hand, there was no graft rejection.

Adolescent↗