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F Berthoux

Publications and source records attributed to F Berthoux.

At least 19 recordsLinked to original sources

TNFA2 and d2 alleles of the tumor necrosis factor alpha gene polymorphism are associated with onset/occurrence of idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN) has a strong association with the major histocompatibility complex HLA B8DR3(17)DQ2 haplotype. The tumor necrosis factor (TNF)A gene is located within the major histocompatibility complex region on chromosome 6. We have studied the influence of two functional polymorphisms; the -308 (promoter region) and the TNFd microsatellites on initiation and/or progression of IMN. This was a case-control study comparing data from 100 Caucasians patients (67 male subjects; 67%) with IMN to 232 Caucasians local controls (171 male subjects; 74%). We have analyzed genotypes and alleles distributions and the role of these polymorphisms in disease progression towards end-stage renal failure or patient death. For -308 TNFA polymorphism, distribution of genotypes was significantly different between IMN and controls (chi(2)=16.25; P=0.0003): the A2 allele frequency was 28.0% in IMN vs 15.3% in controls (chi(2)=14.57; P=0.0001). For TNFd polymorphism, alleles distribution (from d1 to d7) was also significantly different between IMN and controls (chi(2)=56.74; P<0.0001) with both diminished d3 allele frequency (chi(2)=27.30; P<0.0001; Pc=0.001) and increased d2 allele frequency (chi(2)=29.95; P<0.0001; Pc=0.001) in IMN. We could not isolate any significant and independent influence of these different genotypes on IMN disease progression. The TNFA2 and TNFd2 alleles were strongly associated with occurrence/initiation of IMN and should be considered as susceptibility genes for this disease.

Adult↗

Tolerability of enteric-coated mycophenolate sodium to 1 year in combination with cyclosporine and corticosteroids in renal transplant recipients.

Enteric-coated mycophenolate sodium (EC-MPS) is therapeutically equivalent to mycophenolate mofetil, but delays release of mycophenolic acid until it reaches the small intestine. De novo renal transplant patients taking part in a 12-month, multicenter, randomized study received cyclosporine microemulsion (CsA-ME, early or delayed to day 6), EC-MPS, steroids, and interleukin-2 antagonist induction. Tolerability data relating to EC-MPS are reported. Ninety-seven patients were randomized to early CsA-ME and 100 patients to delayed CsA-ME. Median daily dose of EC-MPS was 1440 mg at all time points throughout the 12-month period. The most frequently reported adverse events were constipation, anemia, urinary tract infection, abdominal pain, leukopenia, and cytomegalovirus infection; there were four malignancies. Fifty patients (24.6%) discontinued EC-MPS prematurely by 12 months, including 42 patients (84%) who discontinued owing to adverse events. No patient discontinued treatment because of gastrointestinal adverse events. Two-thirds of patients (137 [67.5%]) maintained full EC-MPS dose throughout the 12-month study and did not require any dose reduction or dose interruption. EC-MPS is well tolerated in de novo renal transplant recipients when administered in combination with CsA-ME and steroids, with low rates of dose reductions or interruptions. Gastrointestinal adverse events were responsible for dose reduction or interruption in only 5% of patients.

Adrenal Cortex Hormones↗

Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression.

BACKGROUND: The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. METHODS: This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day. RESULTS: At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P<0.001), fever (25.2% vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and thrombocytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction). CONCLUSION: Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.

Adult↗

[Antibodies and immunomodulation].

CURRENT SITUATION: When examining immunosuppressor induction one important question is to determine the efficacy of anti-CD25 antibodies or the new compound efalizumab compared with anti-lymphocyte globulins and anti-OKT3 agents known to be very effective but with important side effects. DACLIZUMAB: Recent work has shown that 2 injections at 1 mg/kg (one on day 1 the other between day 10 and day 14) completely block interleukin-2 receptor for more than 10 weeks in 98% of the recipients. Instead of the 5 injections every 15 days as indicated by the recommendations, this new protocol is easier to institute and less costly. The efficacy remains to be demonstrated. BASILIXIMAB: This chimeric monoclonal antibody has affinity for the IL-2 receptor. Balisiximab is administered in 2 doses at 20 mg, one on day 0 and the other one on day 4. A unique 40 mg dose on day 1 has a comparable efficacy. OTHER PROTOCOLS: Among the different induction molecules with promising properties, particular attention should be given to efalizumab. The antisense oligonucleotide (ICAM-1; ISIS 2302) appears to show relatively poor tolerance and no therapeutic efficacy. In association with plasmapheresis and intravenous immunoglobulins, it has been shown to be very effective when given to graft candidates with a positive cross match or after transplantation in case of acute rejection.

Antibodies, Monoclonal↗

Excessive body weight as a new independent risk factor for clinical and pathological progression in primary IgA nephritis.

Experimental evidence suggests a role for obesity in the formation and progression of some glomerular lesions, but data for human glomerulonephritis are lacking. In a cohort of 162 incident patients with biopsy-proven immunoglobulin A (IgA) nephropathy, we assessed whether the presence of an elevated body mass index (BMI >/= 25 kg/m(2)) at the time of the first renal biopsy (RB1) correlated with clinical data at RB1 (24-hour proteinuria, arterial hypertension, and renal function), pathological data (global optical score [GOS] with detailed pathological indices), and clinical progression to both arterial hypertension and chronic renal failure (CRF). In both univariate and multivariate analyses, the presence of an elevated BMI at RB1 was significantly associated with the severity of pathological renal lesions (GOS and vascular, tubular, and interstitial indices). Hypertension-free survival was significantly less in overweight patients (P: < 0.0001) compared with those with normal weight. In a Cox regression analysis for hypertension-free survival including 24-hour proteinuria greater than 1 g, GOS, and metabolic parameters, only elevated BMI and GOS were independent factors for the development of arterial hypertension. CRF-free survival was also significantly less in patients with an excessive BMI. In a multivariate Cox regression analysis for CRF-free survival, hypertension, GOS, and BMI at RB1 were independent risk factors for CRF. In IgA nephropathy, excessive body weight and/or BMI are underestimated predictive factors for the development of arterial hypertension and, ultimately, CRF.

Adult↗

Comparison of ELISA method versus MEIA method for daily practice in the therapeutic monitoring of tacrolimus.

BACKGROUND: For the adequate management of transplant patients on tacrolimus therapy, it is important to obtain optimal blood concentrations. The purpose of this study was to determine the most appropriate method for daily practice of tacrolimus determination in whole blood. We compared enzyme-linked immunosorbent assay (ELISA) with microparticle enzyme immunoassay (MEIA), using European controls and blood samples from organ graft recipients treated with tacrolimus. Time, practicability and cost were considered also. METHODS: The assays were performed according to the procedures detailed in the product inserts. In five European controls and 40 blood samples from kidney and liver transplant patients, we determined the blood levels of tacrolimus by both MEIA and ELISA tests. RESULTS: MEIA gave more reliable results with the European controls (y=1.078x+0.092; r=0.996) than ELISA (y=0.956x+1.307; r=0.946). For the patient samples, the correlation between the two tests was 0.85 and the extreme range of values was +65% and -56% for ELISA vs MEIA. Although the manufacturer of the ELISA test used claims the best sensitivity and precision, in our experience the MEIA test was quicker and cheaper. CONCLUSIONS: MEIA provides a quick, reliable and easy-to-handle method for routine monitoring of tacrolimus blood levels.

Enzyme-Linked Immunosorbent Assay↗

[Update on hepatitis G virus].

HEPATITIS G VIRUS: The hepatitis G virus is an RNA virus with a genomic organization and variability similar to the hepatitis C virus but with a much different pathogenic power which remains to be elucidated. HEPATITIS G: No cases of chronic hepatitis have been observed. Coinfections with HCV and HIV do occur but do not aggravate the prognosis. Anti E2 antibodies are found in the serum and correspond to elimination and neutralization of the HVG genome. There is a high prevalence in transplant recipients (31%), but no modification in liver or kidney grafts has been reported.

Flaviviridae↗

Epidemiological data of treated end-stage renal failure in the European Union (EU) during the year 1995: report of the European Renal Association Registry and the National Registries.

BACKGROUND: The new Centre Questionnaire, mainly based on the collection of epidemiological data, was launched in 1996 and the overall response rate of centres for the 15 countries constituting the European Union (EU) reached 82.2% (66-100%) for 1995. RESULTS: We could derive the following information for a general population of 372.6 million. In 1995, the incidence of new end-stage renal failure (ESRF) patients (Ni/P) was 120 p.m.p. (per million population) with a clear north to south/west gradient (69 in Ireland, 131 in Italy and 163 in Germany). The incidence of ESRF deaths (No/P) was 67 p.m.p. (from 35 in Ireland to 89 in Germany). The net increase of patients was therefore 53 p.m.p. (from 13 in Greece to 74 in Germany). The point prevalence of treated ESRF patients (Ns/P) alive on 31 December 1995 was 644 p.m.p. (from 444 in Finland to 773 in Italy). The mean increase in the stock of ESRF patients was +8.2% (4.6 to 13.0) as a linear rate and +0.085 as a fractional rate (exponential). The first treatment of new patients (Ni) was haemodialysis (HD; 81%), peritoneal dialysis (PD; 18%) and pre-emptive renal transplantation (Tx; 1%). The latest treatment for patients still alive was HD (58.5%), PD (9%) or functional Tx (32.5%). The number of Tx was 30 p.m.p. (from 14 in Greece to 45 in Spain). The death rate was 10.4% for all those with ESRF, with 14.4% for those dialysed and 2.2% for transplanted patients. In 1995, 6.5% of dialysed patients received a graft and 4.0% of transplant patients returned to dialysis. The linear expansion rate of the dialysis pool and the transplant pool was respectively 8.3% and 7.9%. CONCLUSIONS: This data shows considerable disparities among countries of the EU which merit further evaluation. Also this analysis by the ERA Registry provides data of value for health and economic purposes.

Europe↗

Membranoproliferative glomerulonephritis with subendothelial deposits (type 1) associated with hepatitis G virus infection in a renal transplant recipient.

BACKGROUND: Infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is a well-known etiology for membranoproliferative glomerulonephritis (MPGN) with subendothelial deposits (MPGN type 1). MATERIAL AND METHODS: The newly discovered hepatitis G virus (HGV) is currently under active investigation. We report the first case of de novo MPGN type 1 associated with HGV infection in a young male renal transplant recipient who manifested glomerulonephritis (GN) with proteinuria 7 years after transplant, and whose original disease was chronic obstructive pyelonephritis secondary to nephrolithiasis. RESULTS: Serum markers for HBV and HCV infections were negative. HGV infection was detected by specific double-nested reverse transcriptase-polymerase chain reaction (RT-PCR) in sera (positive HGV viremia) 2.5 years after renal transplantation. By specific in situ RT-PCR, the presence of the HGV genome was detected in peripheral blood mononuclear cells and in the kidney biopsy (glomeruli and tubules), but not in the liver. CONCLUSION: This report adds new information on the role of HGV infection in the occurrence of de novo GN (MPGN type 1) in renal transplantation.

Adult↗