Patient survival on PAN/AN 69 membrane hemodialysis.
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Biomedical subjects
Publications and source records attributed to J Chanard.
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Nuclear medicine can make an efficient contribution to the diagnosis and monitoring of renal disease and to the assessment of therapeutic interventions in the field of renal transplantation. The new radio pharmaceutical MAG 3 labelled with 99mTc provides renal imaging of quality in patients with impaired renal function and enables quantitative evaluation of renal function. We report on radionuclide evaluation, with special emphasis on the analysis of the vascular component of the scintigram, in the different clinical situations (i.e. renal failure) that may compromise the outcome of a successful renal transplant.
Due to lack of structured epidemiological studies, the incidence of acute renal failure (ARF) cannot be established in France. An empirical approach method based on answered questionnaire sent by mail to nephrology centers affiliated or not to universities has been used to estimate the frequency of ARF requiring dialysis in 1991. We postulated that the French population was homogeneously distributed among the different regions and that the response rate of 74% could be extrapolated to 100%. We could therefore calculate an incidence of 64 ARF per million of inhabitants. However, this underestimates the exact incidence since the accurate evaluation of IRA in a controlled region (Champagne-Ardenne) is 104 per million of inhabitants. In addition, this study underlines the fact that many ARF are not treated in nephrology units, especially those associated with multiorgan failure requiring slow continuous hemofiltration and hemodialysis. It is suggested that the establishment of a national Registry for ARF and an adequate training of nephrologists are prerequisites to assess epidemiology and the global cost of ARF.
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Protein C has been measured by three different assays (antigenic, amidolytic and chronometric) in 27 end-stage renal insufficient patients before and after hemodialysis. Protein C levels have been compared with other coagulation inhibitors (antithrombin III, protein S) and fibrinolytic parameters. Baseline anticoagulant activity of protein C has been found impaired in eight cases whereas other inhibitors were normal. In four cases, both anticoagulant and antigenic levels were low. In one case, amidolytic method could also found a low activity. Hemodialysis leads to an increase of protein C activity and antigen level. Heparinemia after hemodialysis does not interfere with the chronometric measurement of protein C anticoagulant activity. Total protein level, hematocrit, protein S and antithrombin III are also elevated after hemodialysis. Baseline fibrinolytic parameters are normal and remain unchanged after hemodialysis. The clinical relevance of such modifications is discussed.
Cytomegalovirus (CMV) is the most common opportunistic pathogen following renal transplantation and remains a major concern in transplantation centers owing to its high morbidity and impact on renal allografts. Pending more effective antiviral drugs, efforts have been directed toward prevention strategies. We conducted a retrospective analysis to evaluate the efficacy of various prophylactic options used at our institution during the period April 1986 to August 1990. All CMV-negative patients with CMV-negative kidneys (D-R-) received screened, CMV-negative blood products (n = 19). CMV-specific immunoglobulins (CMV Ig) were used in 6 patients at increased risk for primary CMV infection and acyclovir was administered to 21 patients at an initial intravenous dose of 5 mg/kg body weight; then oral doses of 800-3200 mg per day were given according to the patients' estimated creatinine clearance. Thirty-two patients did not receive any CMV prophylactic treatment and served as controls. CMV monitoring of the patients during the first 6 months after transplantation showed an overall infection and disease rate of 81% and 38.1%, respectively, in the acyclovir-treated group. Compared with controls, the incidences of infection and disease were higher in the acyclovir-treated patients, with a significant difference for CMV infection (P = 0.002, generalized Wilcoxon test). Only 1 of the 19 D-R- patients presented with CMV infection. CMV Ig-treated patients tended to have less severe disease without any apparent reduction in infection incidence. Given the high rate of infection in patients at risk, we infer that high-dose acyclovir does not prevent CMV infection in our setting of renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
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Plasma beta 2-microglobulin (beta 2m) is increased in chronically hemodialyzed patients and remains in a steady range once residual diuresis has stopped. Factors controlling such a steady state are unknown. We undertook metabolic studies to define whether plasma beta 2m is regulated by extrarenal proteolysis of the protein or by storage in a captation pool, a condition which may precede beta 2m-derived amyloidogenesis. Seventeen uremic patients on supportive therapy and five healthy controls were enrolled into the 6 to 10 day study. Using trace amounts of 131I-beta 2m and total body counting, half-life was between 2.4 and 8 days. 125I-beta 2m plasma kinetics was more suitable to calculate fractional catabolic rate and synthetic rate. A three compartment model was chosen to calculate turnover parameters in dialysis patients, whereas the regular two compartment model fitted best for healthy controls. beta 2m synthesis rate was increased in uremic patients when compared with controls (4.49 +/- 2.60 vs. 3.68 +/- 1.43 mg/kg/day, NS). The three compartment model did not integrate all the experimental data, since it was possible to calculate a captation compartment which accumulated beta 2m without fast proteolysis. The captation pool was positively correlated with plasma beta 2m concentration and comprised between 23% and 59% of the amount of the beta 2m disappearing from plasma per day. In conclusion, metabolic studies with radioiodinated beta 2m indicate a slight increase in beta 2m synthesis rate in uremic patients on supportive therapy, irrespective of the technique in use. Kinetic analysis requires a model taking into account a storage compartment which is more complex than the three compartment model.(ABSTRACT TRUNCATED AT 250 WORDS)
Interstitial renal fibrosis and gingival hypertrophy are frequent side-effects of cyclosporin A which have been attributed to a dysfunction of extracellular matrix synthesis. Endothelial cells might participate in the matrix accumulation observed. We studied the effects of increasing concentrations of cyclosporin A on protein synthesis by human umbilical vein endothelial cells. Collagen synthesis decreased significantly to 800 ng/ml in both medium and cell layer. The percentage of hydroxylation of its proline residues decreased significantly as from 400 ng/ml. The main proteins, analysed by SDS-PAGE, were thrombospondin, fibronectin and the alpha 1 and alpha 2 chains of type IV collagen. These fractions did not show any change after 24 hours exposure to 200 ng/ml of cyclosporin A. These results demonstrate an inhibitory effect of cyclosporin A on collagen synthesis by human umbilical vein endothelial cells. Consequently, matrix accumulation by increased collagen synthesis in cyclosporin A treated patient may not be directly related to the drug effect on endothelial cells.
The kinetics of beta 2-microglobulin (beta 2m) were studied in 17 anephric or functionally anephric hemodialyzed patients and five healthy subjects as controls. Highly purified beta 2m was radiolabeled with 125I and infused into patients. The radioactivity in plasma and dialysis fluids was measured during a week including two or three dialysis sessions. Patients were classified in four groups according to treatment: hemodialysis on Cuprophan (N = 5) or on AN69 membranes (N = 5), hemofiltration (N = 4) and CAPD (N = 3). Plasma activity was fitted to a three compartment model. In controls almost 100% of the radioactivity was recovered in urine within 96 hours and there was no extrarenal catabolism. In patients the fractional catabolic rate ranged from 0.0008 to 0.0022 min-1 versus 0.026 to 0.047 min-1 in controls. The synthetic rate was within the range of values from controls in 10 patients but higher in the seven others. It was correlated with plasma beta 2m concentration. Kinetic data indicate a retention of intact beta 2m. The original model was therefore modified with an additional compartment representing beta 2m captation. The amount of capted beta 2m was more elevated in hemodialyzed patients than in patients treated by hemofiltration or CAPD, in whom it could reach 5 mg/kg/day. Hemofiltration or CAPD may eliminate about 30 to 100% of beta 2m produced and therefore contribute to the low captation amount of these patients, as compared with that of patients treated by hemodialysis.
Parameters of early failure in kidney transplantation have been analyzed from 507 transplantations with transplant loss in the first month, selected among the 7541 cadaveric kidney transplantations performed in France between 1985 and 1989. These failures represent 6.7 percent of the population transplanted over this period of time, 68.6 percent of the failures that occurred in the first 3 months post-grafting, and 47 percent of the total number of the first year failures. Comparing patients with and without transplant failure in the first month, sex of the donor and the recipient, ABO group of the donor and the recipient, origin of the kidney, cold ischemia time, HLA compatibility, dialysis duration, number of previous transplantations, showed no influence on the occurrence of early failure. Three parameters appeared to be significant risk factors: donor's age less than 5 years, P = 0.00001; recipient's age less than 5 years, P = 0.05; pregraft immunization, P = 0.002. Furthermore, multifactorial analysis showed that the absence of HLA compatibilities between donor and recipient in hyperimmunized patients also has a significant influence on early graft loss. However, comparison of these same parameters in patients with transplant failure within the first month and between 2 and 12 months post-grafting revealed that the influence of these 4 significant parameters is longstanding and that none of them is specific of the precocity of graft loss.
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Seven cases of legionellosis were observed in a series of 81 renal transplant recipients. In the 6 patients with functional graft, pneumonia occurred 17 days on average after the beginning of transplant rejection treatment. The diagnosis was made by bronchoalveolar lavage: the direct immunofluorescence antigen technique was positive in 5 cases and culture in 6 cases. Legionella pneumophila sero-groups 5 and 1 were identified in one and 5 patients respectively. Six of the 7 patients were treated with ofloxacin. This fluoroquinolone was effective in all cases. It was administered as single therapy in 3 patients and did not interfere with ciclosporin A metabolism. Ofloxacin given in mean doses of 400 mg per day adjusted to renal function proved to be a simple, effective and well tolerated treatment of legionellosis in transplant recipients receiving ciclosporin A.
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Fractional intestinal absorption of calcium (FACa) was measured using radioactive calcium and 200 mg of calcium carrier provided either by yogurt or by CaCl2 in 7 lactase-deficient (L(-] and 7 normal (L(+] subjects. During the control period prior to yogurt consumption, mean calcium intake was 819 mg per day in L(-) and 931 mg per day in L(+) subjects (NS). In both groups of subjects yogurt increased FACa from 20.8 +/- 3.9% to 26.9 +/- 7.2% (P = 0.065) in L(+) subjects and from 20.2 +/- 5.6% to 23.5 +/- 6.4% (P = 0.050) in L(-) subjects. The significant increase in FACa observed in L(-) subjects indicates that yogurt, which is an autodigesting source of lactose, does not impair calcium absorption. FACa increase could reflect the lower dietary calcium intake in L(-) subjects when compared with L(+) subjects, due to avoidance of milk and non-fermented dairy products which could cause intestinal discomfort. It is concluded that yogurt is a well-tolerated and efficient source of calcium in subjects with lactase deficiency.
The concentrations of cadralazine in plasma were studied in 101 hypertensive patients treated with oral doses of 10, 15, or 20 mg of cadralazine once daily. Most of the patients received additionally a beta-blocking drug (n = 87) and a diuretic (n = 52). Few blood samples were collected in each patient on several occasions during the treatment, which usually lasted for more than 6 months. No accumulation of cadralazine in plasma occurred in any of the patients and the maximum concentrations were similar to those recorded in a small sample of healthy volunteers. The terminal half-life of elimination (3.6 h) was longer than that observed in healthy subjects (approximately 2.5 h). Conversely, the total clearance (197 ml/min) was lower (285 ml/min in healthy). The half-life and the total clearance in plasma were not dose dependent. In the patients treated for more than 6 months, no change in the pharmacokinetics of cadralazine was detected. The description of the distribution of concentrations showed that one-half of the patients behaved similarly to healthy subjects concerning half-life and total clearance. The other half presented a slower elimination of the drug (t 1/2 = 4.4 h and ClT = 130 ml/min) and these patients were significantly older (p = 0.01) than the former. This suggests that special attention should be paid to old hypertensive patients when a dose higher than 15 mg once daily is prescribed. Though concentrations were proportional to the dose, the body weight was not found to be a determining factor for dose adjustment.(ABSTRACT TRUNCATED AT 250 WORDS)
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