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Jérôme Rossert

Publications and source records attributed to Jérôme Rossert.

At least 19 recordsLinked to original sources
PubMed2007

Prevalence and predictors of epoetin hyporesponsiveness in chronic kidney disease patients.

BACKGROUND: The required erythropoiesis-stimulating agent (ESA) dose varies when correcting anaemia in chronic kidney disease (CKD) patients. This analysis was performed to identify the prevalence of and factors associated with ESA hyporesponsiveness. METHODS: This analysis was a post hoc evaluation of epoetin alfa dosage requirements in a subgroup of patients from the Effect of early Correction of Anemia on the Progression of CKD study. The patients in this subgroup were randomly assigned to the high haemoglobin target group (14-15 g/dl for men and 13-14 g/dl for women) and completed a 4-month haemoglobin stabilization phase with complete epoetin dosage data. The relationship of demographics, disease characteristics and laboratory measures with epoetin dosage were evaluated using Pearson's correlation, association measures and analysis of covariance (ANCOVA) models. RESULTS: Of the 93 patients evaluated in this subgroup analysis, 14 (15%) were hyporesponsive to epoetin (maximum dosage >100 IU/kg/week during stabilization). An ANCOVA analysis showed that 52% of the observed variability in epoetin dosage at completion of the stabilization phase could be accounted for by diabetes as the primary cause of kidney disease, angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) use, proteinuria, transferrin saturation, age, pre-treatment haemoglobin, geographical region, serum iron and body mass index (BMI). Unidentified patient characteristics accounted for an additional 16% of the dosage variance. CONCLUSIONS: Older age, higher BMI, anaemia, ACE inhibitor/ARB use and diabetes as the primary cause of kidney disease are associated with increased epoetin requirements when normalizing haemoglobin in anaemic CKD patients.

Adolescent↗
PubMed2006

Effect of organic solvent exposure on chronic kidney disease progression: the GN-PROGRESS cohort study.

It has been suggested that solvent exposure may have a role in the progression of glomerulonephritis (GN) to ESRD, but this has never been tested with an appropriate cohort study design. A total of 338 non-ESRD patients with a first biopsy for primary GN between 1994 and 2001 were included: 194 IgA nephropathies (IgAN), 75 membranous nephropathies (MN), and 69 FSGS. ESRD, defined as an estimated GFR <15 ml/min per 1.73 m2 or dialysis, was registered during a mean follow-up period of 5 yr. Patients' lifelong solvent exposures before and after diagnosis were recorded by interview and assessed by industrial hygienist experts. Cox models were used to estimate adjusted hazard ratios (HR) of ESRD related to exposures. Overall, 15 and 14% of the patients had been exposed at a low and a high level before diagnosis, respectively. Forty-two with IgAN, 12 with MN, and 22 with FSGS reached ESRD. A graded relationship was observed for MN (age- and gender-adjusted HR [95% confidence interval] for low exposure versus none was 3.1 [0.5 to 18.2] and for high exposure versus none was 8.2 [1.9 to 34.7]) and for IgAN (1.6 [0.7 to 3.9] and 2.2 [1.0 to 4.8]) but not for FSGS. Solvent risk was mediated only partly by baseline proteinuria: Adjusted HR for high exposure versus none was 5.5 (1.3 to 23.9) for MN and 1.8 (0.8 to 3.9) for IgAN. In patients with IgAN, there was a trend in increasing HR with exposure duration before and its persistence after diagnosis. These findings support the hypothesized association of solvent exposure with the progression of GN to ESRD. They should prompt clinicians to give greater attention to patients' occupational exposures and possibly to consider professional reclassification.

Adult↗
PubMed2006

Effect of early correction of anemia on the progression of CKD.

BACKGROUND: This study is designed to assess the effect of early and complete correction of anemia by using recombinant human erythropoietin (epoetin) alfa on the progression of chronic kidney disease (CKD). METHODS: Patients were randomly assigned to achieve high (13 to 15 g/dL [130 to 150 g/L]) or low (11 to 12 g/dL [110 to 120 g/L]) hemoglobin-level targets during 4 months of stabilization, followed by 36 months of maintenance. Glomerular filtration rate (GFR) decrease was measured by using iohexol clearance. Quality of life, nutrition, and safety also were monitored. RESULTS: Because of labeling changes for subcutaneous administration of epoetin alfa (Eprex; Johnson and Johnson, Schaffhausen, Switzerland), the study was terminated prematurely. There were 195 patients enrolled in each group; 108 high-hemoglobin and 133 low-hemoglobin patients entered the maintenance phase. Mean maintenance duration was 7.4 months for the high-hemoglobin group and 8.3 months for the low-hemoglobin group. GFR decrease was numerically, but not statistically significantly, lower with the high-hemoglobin group (0.058 versus 0.081 mL/min/1.73 m2/mo [< 0.01 mL/s/1.73 m2/mo]). Physical quality-of-life measures showed trends (Role-Physical, P = 0.055; Physical Function, P = 0.083) or statistically significant improvement (Vitality, P = 0.042) with high hemoglobin levels at the end of the stabilization phase. Adverse events were similar between groups. Cardiovascular adverse events occurred in 25% of the high-hemoglobin and 18% of the low-hemoglobin patients (P = 0.137). Neither epoetin dosage nor hemoglobin level was associated with cardiovascular adverse events or death. CONCLUSION: These data suggest that normalization of hemoglobin levels in patients with CKD is safe. Longer duration studies are needed to clarify efficacy benefits with high hemoglobin levels.

Adolescent↗
PubMed2005

[How to improve estimation of renal function in the elderly].

Kidney function is defined by the glomerular filtration rate (GFR). It has been clearly established that serum creatinine should not be used alone to estimate GFR, and that estimated GFR should be calculated using formulas that take into account various parameters including serum creatinine. In adults, two formulas are mostly used to estimate GFR: the Cockcroft-Gault formula and the MDRD formula. In elderly, GFR should only be estimated using the MDRD formula, since the Cockcroft-Gault formula systematically underestimates GFR. GFR tends to decrease with age, but it should be 60 mL/min/1,73 m2 or higher in all subjects who do not suffer from kidney disease, regardless of age.

Aged↗
PubMed2005

Antibody-mediated pure red cell aplasia (PRCA) treatment and re-treatment: multiple options.

In the vast majority of patients with antibody (Ab)-mediated pure red cell aplasia (PRCA), simple withdrawal of the erythropoiesis-stimulating agent (ESA) does not effectively reverse PRCA. In contrast, immunosuppressive treatments can induce the disappearance of anti-erythropoietin Abs and a reversal of PRCA. Consensus opinion on the optimal therapy has not been established, but individual case reports or case series suggest that kidney transplantation or treatment with corticosteroids plus cyclophosphamide are the most effective therapies. However, treatment with cyclosporine is an interesting alternative, since it appears to be effective in at least two-thirds of patients and with minimal side effects. Due to the key role of ESAs in the management of patients with chronic kidney disease (CKD), some patients have been re-treated with an ESA following resolution of Ab-mediated PRCA. In all reported cases, this treatment increased haemoglobin levels, alleviated the need for transfusions and did not have side effects. However, one should be extremely cautious when deciding to re-treat a patient with ESA, due to the small number of reported cases and the possibility of publication bias.

Antibodies↗
PubMed2005

Erythropoietin-induced, antibody-mediated pure red cell aplasia.

Pure red cell aplasia (PRCA) is a rare haematological condition that is characterized by severe aregenerative anaemia due to an almost complete cessation of red blood cell production. While antibody-mediated PRCA was extremely rare before 1998, the incidence of this disorder increased sharply after 1998 in patients receiving subcutaneous epoetin alfa produced by Ortho-Biotech and marketed outside the USA. The diagnosis of antibody-mediated PRCA relies mostly on the results of bone marrow biopsy or aspirate, which shows an absence of erythroid precursors and/or red cell maturation arrest while counts of white cell and platelet precursors are normal, and on the identification of circulating anti-erythropoietin antibodies. Retrospective analysis of PRCA cases has shown that immunosuppressive therapy can induce a disappearance of anti-erythropoietin antibodies in most patients. Eur J Clin Invest 2005; 35 (Suppl. 3): 95-99.

Antibodies↗
PubMed2005

Epoetin-induced autoimmune pure red cell aplasia.

During the first 10 yr of therapy with recombinant human erythropoietin ([EPO]), only three cases of antibody-associated pure red cell aplasia have been described in patients who were treated with EPO, whereas several millions of patients have received this treatment. Thus, the possibility for epoetin to induce the formation of anti-EPO antibodies was considered extremely low. However, since 1998, a significant increase in the number of cases of EPO-induced pure red cell aplasia has been found in patients with chronic kidney disease with a peak in 2001 and 2002. The incidence rate seems now to be back to the baseline level. The change in formulation of epoetin a sold outside the United States seems to be the cause of these antibodies.

Autoimmune Diseases↗
PubMed2004

Treatment of erythropoietin-induced pure red cell aplasia: a retrospective study.

BACKGROUND: Recombinant human erythropoietin is the standard treatment for anaemia related to chronic kidney disease, and its widespread use has been favoured by a very high therapeutic index. However, since 1998, more than 200 patients worldwide with chronic kidney disease treated in this way have developed neutralising antibodies to erythropoietin, causing pure red cell aplasia. We aimed to collate clinical and pathological features in patients unequivocally shown to have erythropoietin-induced pure red cell aplasia. METHODS: We retrospectively obtained data from the files of 47 patients with pure red cell aplasia. We assessed treatment and outcome of patients and defined recovery from pure red cell aplasia as an increase in reticulocyte counts to more than 20 000 per microL in patients who were no longer transfusion-dependent. FINDINGS: When patients developed pure red cell aplasia, all were receiving erythropoietin subcutaneously, and the product most typically prescribed was epoetin alfa (Eprex, Ortho Biotech). The median delay between start of erythropoietin treatment and occurrence of pure red cell aplasia was 11 months (IQR 7.5-14). Nine patients received no immunosuppressive treatment, and none of these recovered. Of 37 patients who received immunosuppressive therapy, 29 (78%) recovered. All six patients who received a kidney transplant recovered within 1 month, and recovery rates were between 56% and 88% in patients treated with corticosteroids, corticosteroids plus cyclophosphamide, or ciclosporin. No relapse of pure red cell aplasia happened after stopping immunosuppressive treatment, but no patient was rechallenged with erythropoietin. INTERPRETATION: Immunosuppressive treatment accelerates recovery from erythropoietin-induced pure red cell aplasia.

Adrenal Cortex Hormones↗
PubMed2004

Recommendations on haematological criteria for the diagnosis of epoetin-induced pure red cell aplasia.

Pure red cell aplasia (PRCA) is a rare condition characterised by an arrest in red blood cell production, which may be congenital or acquired. Recombinant human erythropoietin (epoetin) was introduced in 1989 for the treatment of anaemia of chronic kidney disease patients and has maintained an excellent therapeutic and safety record while treating hundreds of thousands of patients. A very rare, but serious adverse event associated with epoetin administration is a condition in which patients develop neutralising anti-erythropoietin antibodies and, consequently, PRCA. This condition is referred to as epoetin-induced PRCA (epo-PRCA). Since it is a rare condition, many haematologists and nephrologists around the world see the condition infrequently and may be uncertain about the diagnosis. For this reason, an ad hoc international working group of expert haematologists and nephrologists met together to derive new recommendations for the haematological diagnosis of epo-PRCA. These recommendations, which represent the consensus opinions of the working group, address haematological approaches to monitor and investigate suspected epo-PRCA and should help physicians differentiate between PRCA and other bone marrow diseases, as well as, between PRCA and epo-PRCA.

Autoantibodies↗
PubMed2003

Predialysis Survey on Anemia Management: patient referral.

BACKGROUND: The Predialysis Survey on Anemia Management was designed to assess the care given to predialysis patients within 3 months of the start of hemodialysis or peritoneal dialysis (PD) therapy. In this presentation, we focus on demographic data and patient referral practices of patients who enter kidney centers. METHODS: We conducted a retrospective chart review of patients who had started hemodialysis or PD therapy between August 1999 and April 2000. All patients (age, 16 to 99 years) who entered 1 of the 779 centers in 21 European countries, Israel, or South Africa were included, except those for whom dialysis therapy was only started during an acute episode. Demographic characteristics, referral to kidney centers, comorbidities, drug treatments, major clinical events, and use of epoetin were documented. RESULTS: Mean creatinine clearance rate at the first visit to the kidney center was 18.2 mL/min (0.303 mL/s). Of all patients, greater than 35% had a creatinine clearance less than 10.0 mL/min (<0.167 mL/s) at their first visit. Overall, 87% of patients were initiated on hemodialysis therapy, and 13% were started on PD therapy. PD was used more often the longer a patient was under the care of a nephrologist. Of 4,333 new dialysis patients, 68% had a hemoglobin concentration of 11.0 g/dL or less (< or =110 g/L) at the first visit. CONCLUSION: The majority of patients in the survey had been under the care of a nephrologist for more than 12 months before the start of dialysis therapy. Nevertheless, most of these patients were anemic, and only a minority were on epoetin treatment.

Adolescent↗
PubMed2003

PRE-dialysis survey on anaemia management.

BACKGROUND: The PRE-dialysis survey on anaemia management (PRESAM) was designed to assess the care given to pre-dialysis patients in the 12 months before haemodialysis or peritoneal dialysis, with emphasis on anaemia management. METHODS: For this epidemiological study, a retrospective chart review was conducted for patients who started haemodialysis or peritoneal dialysis between 1 August, 1999 and 6 April, 2000. All adult patients who entered one of the 779 participating centres in 21 European countries, Israel or South Africa were included, except for patients who underwent dialysis only during an acute episode. In addition to demographic characteristics, the study examined the prevalence of anaemia, anaemia management including the use of iron supplementation and epoetin, source of referral to the dialysis centre, comorbidities and major clinical events. RESULTS: A total of 4333 new dialysis patients were included in the survey. At the first visit to the dialysis centre, 68% of the patients had a haemoglobin (Hb) concentration < or = 11.0 g/dl; Hb concentration was positively correlated with creatinine clearance rate (r = 0.43, P < 0.01). Patients who received epoetin had a mean Hb concentration of 8.8 g/dl at the start of epoetin treatment, and 96% of these patients had an Hb concentration < or = 11.0 g/dl. Only 26.5% of the patients received epoetin before dialysis. The length of time under the care of a nephrologist was associated with meeting the European Best Practice Guidelines (EBPG) target Hb concentration, as well as receiving epoetin. CONCLUSIONS: Few pre-dialysis patients met the EBPG target for Hb concentration, despite regular nephrology care.

Anemia↗
PubMed2002

[Renal involvement in scleroderma].

Scleroderma renal crisis occurs most often during the first years of the disease, in patients with systemic sclerosis and evolving cutaneous lesions. Clinically, it is responsible for severe hypertension, sometimes associated with cardiac failure or neurological symptoms. Laboratory tests disclose rapidly progressive renal failure, and often signs of thrombotic microangiopathy. If performed (which is rarely the case), renal biopsy shows scleroderma-induced chronic vascular lesions, but also vascular lesions that are secondary to malignant hypertension. The cornerstone of treatment is blood pressure control using angiotensin converting enzyme inhibitors, often in association with other antihypertensive agents. It has to be started as early as possible, in order to optimise vital and renal prognosis.

Antihypertensive Agents↗
PubMed2002

Chronic graft dysfunction in renal transplant patients: potential role of plasminogen activator inhibitor type 1.

BACKGROUND: Chronic allograft nephropathy is the main cause of long-term kidney graft loss. The plasminogen activator inhibitor type 1 (PAI-1) is a potential fibrogenic molecule whose secretion is regulated by several metabolic, inflammatory, and genetic factors. We aimed to determine whether PAI-1 secretion in renal transplant patients is correlated with the decline in renal function after transplantation. METHODS: Renal transplant patients (145 male/71 female) were included in the study 1-27 years after transplantation (median of follow-up: 7.35 years). At inclusion, routine clinical and biological data were collected, the 4G/5G polymorphism of the recipient PAI-1 gene was determined, and the PAI-1 plasma level was measured. RESULTS: The mean rate of decline in renal function was -4.26+/-0.30 ml/min/year. By multiple linear regression analysis, the rate of decline in renal function was significantly correlated with proteinuria (P=0.0176), occurrence of late acute rejection episodes (P=0.0001), and PAI-1 plasma level (P=0.0051). In addition, PAI-1 plasma level was also significantly correlated with body mass index (P=0.038), insulin (P<0.0001), platelet count (P<0.0001), and fibrinogen (P=0.024). The PAI-1 gene polymorphism tested did not influence the rate of decline in renal function after transplantation nor the plasma level of PAI-1 antigen. CONCLUSION: We conclude that PAI-1, whose secretion is determined in large part by metabolic and inflammatory factors, may be implicated in the rate of decline in renal function after transplantation.

Adult↗
PubMed2002

A combination of cis-acting elements is required to activate the pro-alpha 1(I) collagen promoter in tendon fibroblasts of transgenic mice.

The genes encoding the two type I collagen chains are selectively activated in few cell types, including fibroblasts and osteoblasts. By generating transgenic mice, we have previously shown that the activity of the mouse pro-alpha1(I) promoter was controlled by separate cell-specific cis-acting elements. In particular, a sequence located between -3.2 and -2.3 kb was needed to induce expression of the reporter gene at high levels in tendon fibroblasts. In the present work, by using the same transgenic approach, we have identified two short elements in this sequence, named tendon-specific element (TSE) 1 and TSE2, that were necessary to direct reporter gene expression selectively in tendon fibroblasts. Gel shift assays showed that TSE1 and TSE2 bound proteins specifically present in nuclear extracts from tendon fibroblasts and that the sequence of TSE2 binding a tendon-specific protein corresponded to an E-box. Analysis of transgenic mice further indicated that TSE1 and TSE2 needed to cooperate not only with each other but also with other cis-acting elements of the proximal promoter to activate reporter gene expression in tendon fibroblasts. Similarly, it pointed out that the so-called osteoblast-specific element had to interact with downstream sequences to drive reporter gene expression in osteoblasts of transgenic mice. Thus, expression of the mouse pro-alpha1(I) collagen gene in tendon fibroblasts appears to be the result of a unique combination of different cis-acting elements, including TSE1 and TSE2.

Animals↗