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Biomedical subjects

D Fouque

Publications and source records attributed to D Fouque.

At least 55 records · Page 3Linked to original sources
PubMed1996

Insulin-like growth factor 1 resistance in chronic renal failure.

Renal failure is characterized by endocrine and metabolic disorders, some of them being described as a state of resistance to growth hormone (GH) and/or insulin-like growth factor (IGF) 1. There is evidence for a reduced metabolic action of IGF-1 (formerly somatomedin C) in hemodialysis and kidney transplant children and in adults undergoing hemodialysis. Since the development of recombinant human (rh) IGF-1, despite strong metabolic actions, some experimental studies suggest a decrease in metabolic effects of rhIGF-1 in chronic renal failure (CRF). Preliminary reports in adult dialysis patients also stressed the possibility of a resistance to rhIGF-1 metabolic actions. The perturbed IGF-binding protein system in CRF may play an important role in modifying storage and IGF-I delivery to tissues. Also, by analogy with insulin, receptor and postreceptor defects may be involved in this condition, as suggested by rhIGF-1 resistance with aging or in obese Zucker rats. However, rhIGF-1 remains a potent anabolic factor in uremia. Further studies will therefore be necessary to clarify this IGF-1 resistance state. Such knowledge might allow physicians to reduce the amount of rhIGF-1 administered to the patients and improve the anabolic actions of rhIGF-1 during acute and chronic renal failure.

Acute Kidney Injury↗
PubMed1996

Effects of low-protein diet supplemented with ketoacids on plasma lipids in adult chronic renal failure.

We designed a short-term randomized controlled study in 12 adult patients with chronic renal failure to assess the metabolic effects of a low-protein diet (LPD) supplemented or not with ketoacids (Cetolog, Clintec Corp., France). Dietary survey included a monthly 3-day food record and a 24-hour urinary urea measurement. After a baseline period (1.11 g protein, 31.7 kcal/kg BW/day), patients reduced their protein intake (PI) to 0.71 g/kg BW/day. Energy intake (EI) was kept constant (31.4 kcal/kg BW/day) during the 3-month period. Baseline plasma lipids did not show overt hyperlipemia. After reducing PI, a significant increase in apolipoprotein AI and the Apo-AI/Apo-B ratio was observed. Plasma Lp(a) levels were elevated at baseline and did not change during the 3-month LPD period. There was no difference between groups receiving ketoacids or not. Thus, in adult chronic renal failure, under a sufficient EI, reducing PI by 40% had a beneficial effect on plasma lipid profile. This improvement in lipid profile might reduce the high cardiovascular risk in these patients.

Adult↗
PubMed1996

[Nephrotic syndrome and protein metabolism].

The adult protein turn-over daily affects 250 grammes, which is equivalent to four times the average daily protein intake. Regulation of synthesis and catabolism appears to occur by independent ways. These systems are altered during the nephrotic syndrome and ultimately lead to a loss of total body nitrogen and a risk for malnutrition. Indeed, during the nephrotic syndrome, muscle protein synthesis is further impaired as the urinary protein losses increase. This may suggest that anabolic compounds are lost in the urine of such patients. A moderate protein restriction (0.8 g/kg BW/day) allows a reduction in proteinuria, as well as pharmacological agents (ACE inhibitors) and should therefore slow the progressive renal insult.

Adult↗
PubMed1996

[Recombinant human growth hormone (rhGH) administration in a patient with chronic renal insufficiency: renal and metabolic effects].

We report the renal and metabolic effects of a 40 day administration of recombinant human growth hormone in a 31 years old diabetic and GH-deficient patient who underwent a kidney and pancreas transplantation. The data show an increase in glomerular filtration rate, tubular reabsorption of phosphate, and plasma hemoglobin level. Anabolism is suggested from a decrease in serum urea nitrogen and an increase in muscle mass (increase in plasma creatinine). These positive effects might be partly explained by an overcome of endogenous growth hormone resistance when administering pharmacological doses of recombinant growth hormone.

Adult↗
PubMed1995

Pharmacokinetics of recombinant human insulin-like growth factor-1 in dialysis patients.

Six maintenance hemodialysis (MHD), six continuous ambulatory peritoneal dialysis (CAPD) and six normal adults underwent pharmacokinetic studies of insulin-like growth factor-1 (IGF-1). Each subject received two separate subcutaneous injections of recombinant human IGF-1 (rhIGF-1) (50 or 100 micrograms/kg) in random order separated by 7 to 21 days. Two different responses were observed. With the 50 micrograms/kg dose, serum IGF-1 levels and the pharmacokinetic parameters were not different between the three groups. With the 100 micrograms/kg dose, peak serum IGF-1 concentrations were significantly greater in the MHD and CAPD patients than in normals. However, by 12 to 14 hours after injection, serum IGF-1 was not different in the three groups. Although the Tmax, area under the curve and serum clearance of IGF-1 were similar in the three groups, the half-life and volume of distribution of rhIGF-1 was significantly decreased in both MHD and CAPD patients. These data indicate that IGF-1 pharmacokinetics are abnormal in maintenance dialysis patients.

Adult↗
PubMed1995

Impaired metabolic response to recombinant insulin-like growth factor-1 in dialysis patients.

The acute metabolic effects of recombinant human insulin-like growth factor-1 (rhIGF-1) were studied after an overnight fast in six maintenance hemodialysis (MHD) patients, six chronic peritoneal dialysis (PD) patients and six normal subjects. Each subject received a subcutaneous injection of rhIGF-1, 50 or 100 micrograms/kg body wt, given in random order on two occasions separated by 7 to 21 days. After the rhIGF-1 injection, plasma insulin, C-peptide, cortisol, amino acids and glucose decreased. The magnitude of the decrease was greater with the larger rhIGF-1 dose. The fall in plasma insulin, C-peptide and many amino acid concentrations was less and the decrease in glucose was similar in the MHD and CAPD patients as compared to normals. With 50 micrograms rhIGF-1/kg, plasma insulin and C-peptide decreased more quickly and often to a greater magnitude in normal individuals. With 100 micrograms rhIGF-1/kg, the decrease in plasma insulin, C-peptide and amino acids in the MHD and CAPD patients was almost as frequent as in the normal subjects, but the magnitude of the fall was often significantly less. This impaired response occurred in both MHD and CAPD patients even though, with the 100 micrograms rhIGF-1/kg dose, their plasma IGF-1 was significantly higher than in normals during most of the first four hours after injection. These results provide the first in vivo evidence for resistance to the metabolic effects of rhIGF-1 in patients with advanced renal failure.

Adult↗
PubMed1995

Insulin-like growth factor-1 and its binding proteins during a low-protein diet in chronic renal failure.

The effects of a low-protein diet on the serum insulin-like growth factor (IGF)-1 and IGF binding proteins (IGFBP) were investigated during a 3-month controlled study in 12 adult chronic renal failure patients. Six patients were randomly supplemented with keto acids (Cetolog, Clintec, Velizy, France). Protein intake was prescribed so that both groups were isonitrogenous. Dietary survey included a monthly 3-day food record and a 24-h urinary urea measurement. After a 4- to 6-wk equilibrium period (1.11 g of protein, 32 kcal/kg body wt per day), patients reduced their protein intake to 0.71 g protein/kg body wt per day. Energy intake was kept constant (31 kcal/kg body wt per day) during the 3-month period. Serum IGF-1 levels were in normal range and, for 11 of the 12 patients, were correlated with the GFR (P = 0.01). These serum IGF-1 values did not decrease after reducing the protein intake. By Western ligand blotting, serum IGFBP1, IGFBP2, and IGFBP4 levels were significantly higher than normal adults, whereas the IGFBP3 level was not increased. IGFBP were not modified when protein intake was reduced. The IGFBP1 level was elevated despite a normal insulin level. IGFBP4 changes were inversely correlated with IGF-1 variations. There was no difference between groups receiving or not receiving the keto acids. Thus, in adult chronic renal failure, reducing protein intake by 40% did not modify the growth hormone/IGF-1/IGFBP axis.

Adult↗
PubMed1994

Pharmacokinetics of ganciclovir in a patient undergoing chronic haemodialysis.

The pharmacokinetics of ganciclovir was evaluated in a 73-year old anuric, haemodialyzed patient given 1.25 mg.kg-1 at the end of each haemodialysis session, three times per week. A biexponential decrease in plasma ganciclovir was observed, with a peak concentration of 3.7 mg.l-1 followed by a steady state value of 2.6 mg.l-1 for almost 40 h. The total plasma clearance was 0.05 ml.min-1.kg-1, the volume of distribution at steady state was 0.6 l.kg-1, the elimination half life was 132 h, the area under curve was 372 micrograms.h.ml-1, the mean residence time was 190 h, and the percentage of ganciclovir cleared from plasma after a 5 h haemodialysis session was 52.1%. The simulated pharmacokinetics over one month, following the same scheme of administration, did not suggest marked accumulation of ganciclovir. These results were obtained after a reduction of 58% in the recommended dose in patients with impaired renal function.

Aged↗
PubMed1993

Wegener's granulomatosis with antiproteinase-3 antibodies occurring after Hodgkin's disease.

We describe the first association between Hodgkin's lymphoma and Wegener's granulomatosis, heralded by renal involvement. A 43-year-old man developed rapidly progressive glomerulonephritis requiring chronic hemodialysis 8 months after remission of Hodgkin's lymphoma. At that moment, no extrarenal involvement was found, despite extensive investigation. Antineutrophil cytoplasm antibodies were positive, without specificity for proteinase-3 or myeloperoxydase. Six months after beginning hemodialysis, multiple pulmonary nodules appeared, along with rapid clinical worsening. A surgical biopsy was performed which disclosed a giant cell granuloma. Antimyeloperoxydase antibodies remained negative, whereas proteinase-3 antibodies became positive. Wegener's granulomatosis was diagnosed and treatment with cyclophosphamide and steroids was started. Clinical and radiological improvement occurred promptly. Eleven months after treatment, both Wegener's disease and Hodgkin's lymphoma remained in remission.

Adult↗
PubMed1993

Sleep apnea syndrome and end-stage renal disease. Cure after renal transplantation.

We report two patients undergoing maintenance hemodialysis who presented with sleep apnea syndrome (SAS). The first patient is a 36-year-old man with a terminal Berger's glomerulopathy and associated obstructive sleep apnea syndrome (OSAS) (apnea-hypopnea index [AHI] = 80). He was receiving home hemodialysis and was treated by nasal continuous positive airway pressure (CPAP). After successful renal transplantation, his symptoms completely disappeared, and control polysomnography greatly improved (AHI = 9). The second patient had hypokalemic nephropathy with severe, uncontrolled hypertension and hypertensive myocardiopathy. He was receiving home dialysis and showed a central sleep apnea syndrome with an AHI of 51. He also was successfully treated by nasal CPAP. After renal transplantation, his sleep improved, insomnia disappeared, and polysomnography showed great improvement (AHI = 5). We discuss the role of periodic breathing related to end-stage renal disease associated metabolic abnormalities, as a pathogenetic factor of these SASs. Respiratory correction of chronic metabolic acidosis, "uremic toxins," "middle molecules," and hemodialysis are all evoked as etiologic factors and their own roles are discussed.

Adult↗
PubMed1992

Controlled low protein diets in chronic renal insufficiency: meta-analysis.

OBJECTIVE: To determine whether low protein diets retard the development of end stage renal disease. DESIGN: Meta-analysis of 46 trials since 1975, from which six randomised controlled trials were selected. SETTING: Five trials in Europe and one in Australia between 1982 and 1991. SUBJECTS: 890 patients with mild to severe chronic renal failure who were followed up for at least one year. 450 patients received a low protein diet and 440 a control diet. INTERVENTION: Difference in protein intake between control and treated groups of at least 0.2 g protein/kg/day. MAIN OUTCOME MEASURE: Number of renal deaths (the necessity to start dialysis or death of patient during study). RESULTS: 156 renal deaths were recorded, 61 in the low protein diet group and 95 in the control group, leading to an odds ratio of low protein to control of 0.54 with a 95% confidence interval of 0.37 to 0.79. CONCLUSIONS: This result, obtained on a large population of patients suffering from chronic renal insufficiency, strongly supports the effectiveness of low protein diets in delaying the onset of end stage renal disease.

Adolescent↗
PubMed1992

Increase of circulating insulin-like growth factor-I in chronic renal failure is reduced by low-protein diet.

We performed a nutritional trial to assess the variations of circulating insulin-like growth factor-I (IGF-I) in chronic renal failure (CRF). Eight patients suffering from mild renal failure (SCr = 374 +/- 52 mumol/l) were prescribed a standard diet for 1 month followed by 1 month of protein restriction. Mean protein intake was 0.77 and 0.46 g/kg BW/day, mean caloric intake 25 and 24.7 kcal/kg BW/day for the first and the second month, respectively. After each period of diet, nitrogen balances were negative (-1.2 +/- 1.6 and -1.6 +/- 0.9 g/N/day). Despite these low-caloric conditions, mean serum IGF-I level was at the upper level of normal (358 +/- 136 ng/ml) after 1 month of standard protein intake, and statistically reduced (289 +/- 122 ng/ml, p < 0.002) by the low-protein diet. No correlation was observed between serum IGF-I levels and protein, caloric intake, and nitrogen balances for the two periods. Estimation of the IGF-I binding by the ratio of extracted to nonextracted IGF-I value suggested abnormal binding in CRF. This binding was modified by reduced protein intake. In conclusion, larger studies are needed in CRF to assess the significance of IGF-I variations and the IGF-I binding proteins which modulate the bioactivity of this growth factor.

Adult↗
PubMed1990

[Is it possible to use creatinine for following the development of renal insufficiency?].

Accurate methods of measuring glomerular filtration rate are usually considered as expansive and time consuming. Therefore, alternative methods (creatinine clearance, either calculated or measured, reciprocal plasma creatinine, slopes of creatinine vs time) have frequently been used to assess the rate of progression of renal failure and predict the time of dialysis. The present review underlines the limitations of such techniques frequently underestimated in recent trials intending to evaluate the potential benefit of protein restriction. It delimitates the restrictive conditions in which such methods could be used for clinical but not research purposes.

Creatinine↗