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Biomedical subjects

Denis Fouque

Publications and source records attributed to Denis Fouque.

At least 19 recordsLinked to original sources
PubMed2007

Adiponectin and chronic kidney disease.

Enhanced chronic inflammation and reduced insulin sensitivity are often present in chronic kidney disease (CKD). Cardiovascular disease remains a major cause of morbidity and mortality in end-stage renal patients. Adiponectin (ADP) is a hormone exclusively produced by adipocytes and possesses anti-inflammatory and cardioprotective properties. Despite the high prevalence of insulin resistance and cardiovascular disease, levels of ADP are increased among end-stage renal disease patients on hemo or peritoneal dialysis but also among patients with moderate renal failure or with the nephrotic syndrome. Furthermore, lower ADP levels are associated with poor cardiovascular outcome. In this review, we examine ADP modifications in CKD and discuss the different factors that may have an impact on this adipokine metabolism in renal failure.

Adiponectin↗
PubMed2006

Recurrent idiopathic thrombotic thrombocytopenic purpura: a role for vaccination in disease relapse?

The presence of antibodies against a disintegrin-like metalloproteinase with thrombospondin type 1 motif, isoform 13 (ADAMTS 13 protease) is the main cause (70% to 80%) of idiopathic and recurrent thrombotic thrombocytopenic purpura (TTP). However, etiologic factors that trigger the onset and potential relapses of TTP remain unclear. Immunologic deregulation and infectious agents are suspected. We report the case of a 51-year-old white man presenting with idiopathic TTP caused by autoantibodies against ADAMTS 13 protease. The first acute TTP episode needed long-term plasma exchanges because of early relapses. Consequently, vincristine therapy and splenectomy were performed. Those treatments induced TTP remission for 18 months. Relapses occurred twice between 1 and 3 months after vaccination. However, those relapses were not as severe as the first acute episode and responded to short-course plasma exchanges. ADAMTS 13 antibodies and decreased ADAMTS 13 protease activity were searched for and detected first during the second relapse. This case challenges the role of vaccination as an etiologic factor in the recurrence of idiopathic TTP.

ADAM Proteins↗
PubMed2006

Relationship between serum carnitine, acylcarnitines, and renal function in patients with chronic renal disease.

BACKGROUND: Serum free carnitine is decreased and serum acylcarnitines are increased in maintenance hemodialysis (MHD) patients, and the causes for these abnormalities are not known. This study examined the role of renal failure in the occurrence of low serum carnitine and increased acylcarnitines in patients with advanced chronic kidney disease (CKD) by assessing the relationship between these compounds and renal function in normal individuals and patients with CKD. If these compounds decrease as glomerular filtration rate (GFR) decreases, this suggests that decreased intake or impaired synthesis in kidneys explain the low serum values. If serum compounds increase as GFR decreases, this suggests that impaired excretion may predispose to these values. METHODS: The study, conducted in Lyon, France (part A), and Los Angeles, California (part B), compared serum free carnitine and acylcarnitines to renal function in 20 normal patients, 65 CKD patients, and 29 MHD patients. GFR was measured using inulin (A) and iothalamate (B) clearances. Carnitine compounds were measured by tandem mass spectrometry (A) and electron spray mass spectrometry (B). RESULTS: There was no relationship between serum total carnitine or free carnitine and GFR in the normal subjects and CKD patients. In contrast, serum acylcarnitines were inversely correlated with GFR in these 2 groups. Serum free carnitine was significantly lower in MHD patients than in CKD patients and normal controls in study B, whereas acylcarnitines were significantly greater than controls in studies A and B and than in CKD patients in study A. CONCLUSIONS: Serum free carnitine is not reduced in CKD and decreases in MHD patients. Serum acylcarnitines increase in CKD and MHD patients primarily because of impaired excretory function in the failing kidney.

Adult↗
PubMed2006

Associations of body fat and its changes over time with quality of life and prospective mortality in hemodialysis patients.

BACKGROUND: In maintenance hemodialysis (MHD) patients, a larger body size is associated with better survival but a worse self-reported quality of life (QoL). It is not clear whether muscle mass or body fat confers the survival advantage. OBJECTIVE: We hypothesized that both a low baseline body fat percentage and a loss of fat over time were independently associated with higher mortality but with a better QoL score. DESIGN: In 535 adult MHD patients, body fat was measured directly with the use of near infrared interactance and QoL was measured with a Short Form 36 questionnaire. The patients were followed for < or =30 mo. RESULTS: Across four 12% increments of body fat at baseline, the reported QoL scores were progressively lower (P < 0.01). After a multivariate adjustment for demographics and surrogates of muscle mass and inflammation (ie, midarm muscle circumference, serum creatinine, and proinflammatory cytokines), 46 patients with body fat of <12% had a death hazard ratio (HR) 4 times that of 199 patients with body fat content between 24% and 36% (HR: 4.01; 95% CI: 1.61, 9.99; P = 0.003). In 411 MHD patients whose body fat was remeasured after 6 mo, a fat loss (< or =-1%) was associated with a death risk 2 times that of patients who gained fat (> or =1%) after a multivariate adjustment (HR: 2.06; 95% CI: 1.05, 4.05; P = 0.04). CONCLUSIONS: A low baseline body fat percentage and fat loss over time are independently associated with higher mortality in MHD patients even after adjustment for demographics and surrogates of muscle mass and inflammation, whereas a tendency toward a worse QoL is reported by MHD patients with a higher body fat percentage. Obesity management in dialysis patients may need reconsideration.

Adipose Tissue↗
PubMed2006

Application of branched-chain amino acids in human pathological states: renal failure.

During renal failure, abnormalities of BCAA and branched-chain keto acid (BCKA) metabolism are due to both the lack of renal contribution to amino acid metabolism and the impact of renal failure and acidosis on whole-body nitrogen metabolism. Abnormal BCAA and BCKA metabolism result in BCAA depletion as reflected by low plasma BCAAs and cellular valine. BCAA metabolic disturbances can alter tissue activities, particularly brain function, and nutritional status. In dialysis patients, BCAA oral supplementation can induce an improvement of appetite and nutritional status. During chronic renal failure, the aims of nutritional interventions are to minimize uremic toxicity, avoid malnutrition and delay progression of kidney disease. BCAA and BCKA supplements have been proposed to decrease further protein intake while maintaining satisfactory nutritional status. In this setting, BCAAs or BCKAs have not been administrated solely but in association with other essential AA or keto analogs. Therefore, the proper effects of BCAAs and/or BCKAs have not been studied separately. Protein restriction together with keto acids and/or essential AAs has been reported to improve insulin sensitivity and hyperparathyroidism and to be compatible with a preservation of nutritional status. Nonetheless, a careful monitoring of protein-calorie intake and nutritional status is needed. A recent meta-analysis concluded that reducing protein intake in patients with chronic renal failure reduces the occurrence of renal death by approximately 40% as compared with larger or unrestricted protein intake. The additional effect of essential amino acids and keto acids on retardation of progression of renal failure has not been demonstrated.

Amino Acids, Branched-Chain↗
PubMed2005

Chronic dehydration may impair renal function in patients with chronic intestinal failure on long-term parenteral nutrition.

BACKGROUND & AIMS: Renal impairment is a documented complication in long-term parenteral nutrition (LTPN) patients. However, the aetiologies have remained elusive. The aim of this study was to evaluate the impact of parenteral nutrition, digestive status, and hydration level on renal function in LTPN patients. METHODS: In a prospective study of 40 LTPN patients, renal function and hydration level were assessed by measurement of inulin and creatinine clearances, plasma creatinine, urea, aldosterone and renin and urinary sodium/potassium ratio. Patients were assigned to one of two groups according to their inulin clearance (normal = Group 1, 20% decrease or more = Group 2). RESULTS: Of the patients, 52.5% (21/40) had a decrease in glomerular filtration rate (-38 +/- 15%), with age taken into consideration. Patient characteristics, parenteral nutrition composition or duration and intestinal status were not different between the two groups. Urologic or nephrologic diseases were more frequent in Group 2 patients. Moreover, in Group 2 patients, a urinary sodium/potassium excretion ratio of less than 1 in 8/21 patients and plasma renin (316 +/- 298 vs. 86 +/- 53% of normal value) and aldosterone (291 +/- 464 vs. 58 +/- 36 pmol/l) that were significantly higher than in Group 1 patients suggested a hypovolemic component. CONCLUSION: Decreased renal function is frequent (52.5%) in LTPN patients. A volemic component was associated in more than 70% of them. An elevation of serum creatinine or an inversion of the urinary Na/K ratio requires an evaluation of hydration equilibration and an oral rehydration and a modification in parenteral nutrition formulation.

Adult↗
PubMed2005

[Choosing between peritoneal dialysis and haemodialysis: a critical appraisal of the literature].

In France, incidence and prevalence of end-stage renal disease (ESRD) are increasing, requiring a more rational use of available replacement therapies. To help practitioners make their choice between treatment modalities of peritoneal dialysis (PD) and haemodialysis (HD), critical appraisal of relevant literature has been conducted. Although few absolute or relative contraindications for PD and HD exist, arguments in favour of one versus the other dialysis technique can be made. When patients receive adequate and complete information, their preference is neutral between PD and HD. To date, no trial presenting a convincing level of evidence has been published which demonstrates the superiority of one technique compared to the other. Relative to mortality, it appears that no difference can be observed between the two modalities. However, in those instances where patients expect a rapid transplantation, PD is the preferred technique. This analysis suggests that peritoneal dialysis and haemodialysis are not competitive but rather complementary treatments. It is therefore interesting to identify the reasons supporting the various choices between the two different treatment modalities amongst France's regions. Access to transplant, economic or organizational factors must be considered.

Contraindications↗
PubMed2005

Growth hormone induces anabolism in malnourished maintenance haemodialysis patients.

BACKGROUND: Growth hormone (GH) promotes anabolism in patients undergoing maintenance haemodialysis (MHD). However, no studies have examined the effects of GH on protein anabolism in MHD patients using full nitrogen-balance techniques. This study tested the hypothesis that recombinant human GH (rhGH) will induce an anabolic response, as assessed by long-term classic nitrogen-balance techniques, in malnourished MHD patients. METHODS: Six adult MHD patients with protein-energy malnutrition underwent nitrogen-balance studies in a general clinical research centre for 28-35 days each. Patients were maintained on a constant dialysis regimen and protein and energy intakes that were similar to their dialysis regimen and diet prior to hospitalization. The first 14-21 hospital days constituted a baseline phase; during the subsequent 8-21 days, patients were given daily subcutaneous injections of rhGH (0.05 mg/kg body weight/day). RESULTS: During treatment with rhGH, serum insulin-like growth factor-I (IGF-I) increased by approximately 225% (P = 0.002), nitrogen balance became strongly positive (+2.35 g/day; P = 0.034 vs baseline) and there was a reduction in serum urea nitrogen (-32%; P = 0.001). Two patients who became acutely ill and had the lowest dietary protein intakes developed a much smaller rise in serum IGF-I levels and increase in nitrogen balance when they received the rhGH treatment. In the remaining four responders, the decrease in nitrogen output was sustained throughout the entire period of treatment with rhGH. There was no change in body weight during the baseline or treatment phases of the study. CONCLUSIONS: Injections of rhGH induce a strong and sustained anabolic effect, as indicated by positive nitrogen balance, in MHD patients with protein-energy malnutrition. This response was attenuated in two patients who were acutely ill with low protein intakes, suggesting that they may have developed partial resistance to GH.

Adult↗
PubMed2005

Dialyzer membrane permeability and survival in hemodialysis patients.

BACKGROUND: We previously showed that nutritional protein concentrations were predictive of outcome, whereas variables reflecting body composition and dialysis dose were not, in a 30-month prospective follow-up of 1,610 hemodialysis patients. Information on dialysis membrane and erythropoietin use had to be evaluated in an additional follow-up. METHODS: A subset of 650 patients from the initial cohort of 1,610 was analyzed for survival in a 2-year extension of follow-up. Detailed data were collected: demographics; cause of renal failure; time on dialysis therapy; type of membrane; erythropoietin treatment; body mass index (BMI); predialysis albumin, prealbumin, and bicarbonate levels; and outcome. Normalized protein catabolic rate (nPCR), dialysis adequacy, and lean body mass were computed from predialysis and postdialysis urea and creatinine values. RESULTS: Patient characteristics were age of 61 +/- 16 years, 58% men, BMI of 22.7 +/- 4.4 kg/m2 , time on dialysis therapy of 102 +/- 73 months, and 8.8% had diabetes. Dialysis parameters were duration of 247 +/- 31 minutes, Kt/V of 1.4 +/- 0.3, and nPCR of 1.2 +/- 0.3 g/kg/d. Albumin level was 3.73 +/- 0.53 g/dL (37.3 +/- 5.3 g/L), and prealbumin level was 31 +/- 8 mg/dL. The survival rate was 78.7% after 2 years. Survival was influenced by age, presence of diabetes, use of high-flux membrane, and serum albumin level, but not other variables, including Kt/V and prealbumin level. Two-year variations in values for urea, creatinine, and weight were predictive of survival in univariate, but not multivariate, analyses. CONCLUSION: In patients on dialysis therapy for a long period, better survival was observed when high-flux dialysis membranes were used.

Aged↗
PubMed2005

Multinutrient oral supplements and tube feeding in maintenance dialysis: a systematic review and meta-analysis.

BACKGROUND: This systematic review aims to determine the potential benefits of enteral multinutrient support (oral or tube) in patients with chronic kidney disease (CKD) receiving maintenance dialysis. METHODS: Studies of multinutrient oral supplements and enteral tube feeding that involved comparisons of nutritional support versus routine care (ie, usual diet), disease-specific formulae (with adapted macronutrient and micronutrient composition for use in maintenance dialysis patients) versus standard formulae, and enteral tube feeding versus parenteral nutrition are included in this review. The outcome measures sought were clinical (quality of life, complications, and mortality), biochemical (albumin and electrolyte levels), and nutritional (dietary intake and anthropometry). Meta-analyses were performed when possible. RESULTS: This review of 18 studies (5 randomized controlled trials [RCTs], 13 non-RCTs) suggests that enteral nutritional support increased total (energy and protein) intake and increased serum albumin concentration by 0.23 g/dL (2.3 g/L; 95% confidence interval, 0.037 to 0.418 g/dL [0.37 to 4.18 g/L]; 1 RCT, 2 non-RCTs), with little effect on electrolyte status (serum phosphate and potassium). Few studies reported clinical outcome, and there was insufficient information to compare disease-specific versus standard formulae or enteral versus parenteral nutrition. CONCLUSION: This systematic review suggests that enteral multinutrient support significantly increases serum albumin concentrations and improves total dietary intake. This may improve clinical outcome, especially in malnourished patients, but insufficient published data exist to examine this. Additional research is required to investigate clinical, economic, and nutritional consequences of using oral supplements and tube feeding (using standard or disease-specific feeds) in patients with CKD receiving maintenance dialysis.

Adult↗
PubMed2005

Leptin, adiponectin, and ghrelin dysregulation in chronic kidney disease.

In the past 10 years, 3 new metabolic compounds, leptin, adiponectin, and ghrelin, involved in energy metabolism, body composition, and appetite regulation, have been discovered. We have assessed their characteristics in 46 patients with stage 3 to 4 chronic kidney disease to evaluate the role of decreased renal function in the abnormal handling reported in more severe end-stage renal disease patients. In addition to the usual correlations with body mass index and body fat mass, the results show unexpected positive correlations between leptin and insulin, leptin and adiponectin, a weak inverse relationship between adiponectin and glomerular filtration rate, and no influence of C-reactive protein on either leptin or adiponectin in these noninflamed patients. Serum ghrelin was inversely correlated with body mass index and with glomerular filtration rate as measured by inulin clearance. Thus, ghrelin and leptin, 2 antagonist signals for energy balance, both seem to increase when glomerular filtration rate is reduced, potentially neutralizing their respective biologic effects in severe renal insufficiency.

Adiponectin↗
PubMed2004

Adiponectin in chronic kidney disease is related more to metabolic disturbances than to decline in renal function.

BACKGROUND: Adiponectin, a newly discovered collagen-like protein of the collectin family exclusively produced by adipocytes, possesses anti-inflammatory properties. Plasma adiponectin is associated with a decreased cardiovascular risk in non-renal patients, and is reduced in obesity and insulin-resistant states. Although reports show an increase in the adiponectin level in maintenance haemodialysis, peritoneal dialysis and end-stage renal disease, there is no documentation of adiponectin levels and regulation in the early stages of chronic kidney disease (CKD). METHODS: We prospectively measured glomerular filtration rate (GFR) in 48 patients with CKD using inulin clearance. Fasting blood was drawn to determine insulin, leptin, adiponectin and C-reactive protein (CRP) levels. Body fat mass was calculated using skinfold thickness measurements. RESULTS: The patients' mean GFR was 53.5+/-24.9 (SD) ml/min/1.73 m2. Adiponectin was in the normal range in men (9.8+/-2.9 mg/l) and women (16.6+/-5.0 mg/l) with CKD, being significantly higher in women than men (P<0.001). Serum leptin was above normal (10.4+/-10.7 microg/l), whereas serum insulin and CRP were within their normal ranges (3.5+/-3.3 microU/ml and 2.6+/-5.0 mg/l, respectively). In linear regression analysis, adiponectin was negatively correlated with GFR (P = 0.02), fat mass (P = 0.03) and body mass index (P = 0.002), and strongly positively correlated with serum leptin (P = 0.003). A positive relationship was also found between plasma adiponectin and the urinary albumin/creatinine ratio (P = 0.007). No relationship was found between adiponectin and insulin or adiponectin and CRP. In multiple regression analysis, adiponectin was significantly positively correlated with leptin (P<0.0001), negatively with body mass index (P<0.0001) and only weakly with GFR (P = 0.04). CONCLUSIONS: Despite an adverse metabolic environment in chronic renal insufficiency, serum adiponectin increases in non-obese patients when renal function deteriorates. Adiponectin is only weakly affected by renal function per se, but appears influenced by proteinuria, and more significantly by body mass index and the change in serum leptin that accompanies decline in renal function.

Adiponectin↗
PubMed2004

Outcome research, nutrition, and reverse epidemiology in maintenance dialysis patients.

High morbidity and mortality of maintenance dialysis patients have led to an increase in interest in outcome research in an attempt to identify causes for this adverse outcome. It has been proposed that a substantial amount of this risk can be explained by protein energy malnutrition, chronic inflammation, or concurrent combination of both, known as malnutrition-inflammation complex syndrome (MICS). Elements of overnutrition, such as increased weight or high serum cholesterol levels, which are deleterious in the general population, paradoxically are protective in dialysis patients. Conversely, a low body mass index and low serum levels of cholesterol, creatinine, and possibly homocysteine are risk factors for poor outcome in dialysis-dependent populations. These reverse or paradoxical relationships between nutritional markers and outcome are referred to as reverse epidemiology. The MICS appears to be a main contributor to the reverse epidemiology and poor outcome. Mortality is the most definitive and objective clinical outcome, whereas hospitalization and quality of life (QoL) are additional relevant but somewhat less objective outcome measures in dialysis populations. A systematic classification of outcome measures and their related epidemiologic and statistical assessment tools in dialysis patients are reviewed. The effect of MICS on outcome can be examined by epidemiologic studies that are based on large samples of dialysis patients, use multivariate techniques, and, as long as they follow strict methodologic requirements, provide an invaluable economical alternative to expensive clinical trials.

Cardiovascular Diseases↗
PubMed2003

Nutritional requirements in maintenance hemodialysis.

There is a high prevalence of nutritional disorders in maintenance hemodialysis patients. This fact has been recently confirmed because larger routine assessments of MHD patients body composition are now performed. Food records and dietary interviews show spontaneous low intakes of protein and energy in many patients. An increasing dialysis dose above a Kt/V (single pool) of 1.5 may not improve patients nutritional intakes. Inflammation may further impair the balance between protein synthesis and catabolism and cause anorexia. In response to these abnormalities, the management of energy, protein, vitamins, and trace elements intake will be discussed with special emphasis on calcium, phosphorus, enteral support, and parenteral nutrition.

Calcium, Dietary↗
PubMed2003

Advances in anabolic interventions for malnourished dialysis patients.

Malnutrition is a frequent state during maintenance dialysis. Among a variety of reasons, chronic catabolic events as well as resistance to anabolic compounds do induce an imbalance in protein metabolism and favor a chronic loss in protein mass. Anabolic effects have been obtained in pilot studies with recombinant growth hormone and insulin-like growth factor-1 in adult dialysis patients. More recently, the come back of androgen therapy provided reports of a positive impact on body composition and physical activity during maintenance dialysis. Strong improvement in nutritional status has also been obtained by more frequent dialysis sessions, either during long nocturnal or short daily schedules. Thus, promising new therapies are emerging to fight the important incidence of malnutrition in dialysis patients.

Androgens↗