Myocardiotoxicity of 5 fluorouracil.

We report a case of specific myocardiotoxicity due to 5 F.U. not previously described in man. A 41-year-old man was admitted to the ICU for heart and renal failure, appearing 24 h after 5 days treatment with 5 F.U. and cis-platinum. Dopamine was necessary to maintain blood pressure. Two-D echocardiography and a right heart catheterisation confirmed the alteration of myocardial contractility. After 2 weeks a complete cardiac recovery occurred.

Is erythropoietin treatment safe and effective in myeloma patients receiving hemodialysis?

Still few data are available on efficacy and safety of recombinant erythropoietin (rEPO) in patients with myeloma and end-stage renal failure (ESRF); two such hemodialysed patients are reported in whom only partial response was observed, despite iron, folic acid supplementation and, in one case, high doses of rEPO (320 IU/kg/week). Despite improvement in well being and no need of further transfusion, hemoglobin did not reach 80 g/l. One patient developed recurrence 4 weeks after starting rEPO. Patients with ESRF and myeloma should benefit from rEPO but particular attention should be paid to marrow proliferation.

[Metabolism and vascular effects of gammaglutamyl L-dopa on the isolated kidney of the rat]. / Métabolisme et effets vasculaires de la gammaglutamyl L-dopa sur le rein isolé de rat.

The gammaglutamyl L-dopa (or gludopa), a dopamine (DA) prodrug, may be usefull in antihypertensive therapy as an orally active specific renal vasodilator. Indeed, gludopa is selectively metabolized in vivo by the kidney. This is the consequence of the sequential action of two renal enzymes, gamma-glutamyl transpeptidase (gamma-GT) and aromatic L-amino acid decarboxylase. The aim of this work was to elucidate, in vitro, the factors regulating its metabolism and to characterize its renal vascular effects. The rat kidney was isolated and perfused at constant flow in a closed circuit with a modified Krebs-Henseleit solution (BSA 6g/100 ml). Gludopa injection (10(-5) M) led to generation of DA (measured by gaz chromatography/mass spectrometry) in the venous effluent (134 +/- 39 ng/ml, n = 3) and in the urine (257 +/- 107 ng/mn/g). In non filtering kidneys, the level of DA in recirculating medium was depressed (47 +/- 5 ng/ml, n = 5; p less than 0.05). Glomerular filtration and access to the gamma-GT localized on the brush border membrane of proximal tubular cells are thus important for optimal metabolism of gludopa. Vascular effects of gludopa were studied on the isolated rat kidney after reestablishing vascular tone by continuous perfusion with prostaglandin F2 alpha (10(-8) M/mn) and after inhibition of alpha- and beta-adrenoceptors. Gludopa (3 X 10(-6) to 4 X 10(-5) M) induced dose-dependent renal vasodilation. At 4 X 10(-5) M, the renal response (30 +/- 3 p. 100 of the relaxation induced by 10(-4) M of papaverine) was similar to that elicited by DA at 20 fold lower concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of apparent mineralocorticoid excess caused by type 2 11 beta- hydroxysteroid dehydrogenase deficiency]. / Un cas d'excès apparent de minéralocorticoïdes par déficit en 11 beta hydroxystéroïde-déshydrogénase de type 2.

The syndrome of apparent mineralocorticoid excess is a recessively inherited form of low renin hypertension. The syndrome is characterised by sodium retention and hypervolemia despite low plasma renin activity and aldosterone levels. Patients with this syndrome have mutations in the 11HSD2 gene which encodes the enzyme which normally converts cortisol in the renal tubule to its inactive form, cortisone. The unconverted cortisol is thus able to bind and activate the mineralocorticoid receptor, displacing its usual ligand, aldosterone, causing the apparent mineralocorticoid excess. We have studied a patient with severe hypertension, low renin and aldosterone, and a chronic hypokalemic alkalosis at age 4. The analysis of cortisone, cortisol and their metabolites showed the specific pattern of the apparent mineralocorticoid excess. In serum and urine, there was a dramatic decrease of cortisone and its metabolite, while cortisol and its metabolites were non affected.

[Renal biopsy in the elderly]. / La biopsie rénale chez le sujet âgé.

Fifty years after the first percutaneous needle biopsies of the kidney, enough results have been obtained to evaluate indications in elderly patients, a population group we define as over 75 years of age. In approximately 50% of the patients in this group, the indication for renal biposy is a nephrotic syndrome. The lesions usually observed involve extramembranous glomerulonephritis or minimal change glomerulopathy. The biopsy may also reveal amylosis. Chronic renal failure is the predominant reason for nephrology consultation in the elderly. Although all of these patients do not undergo biopsy, in our experience, results show chronic glomerulopathies, mainly IgA, in about half of the case as well as chronic interstitial nephritis and nephroangiosclerosis. The aging process also leads to acute renal failure in many patients. Biopsy would not be indicated in case of shock, drug toxicity or obstruction but in approximately 10% of the cases histology can reveal a specific parenchymal lesion. The technique for renal biopsy is the same in elderly patients as in younger adults. Renal biopsy can be considered as a safe diagnostic tool of considerable importance when ordered by a nephrologist, performed by an experienced operator and read by a well-trained pathologist. In many cases it is essential to in order to provide patients over 75 with the same quality care as younger adults.

[Central catheters: a temporary access for a definitive use?]. / Cathéters centraux: un abord temporaire pour un usage définitif?

Central venous access is an important component of hemodialysis. New materials are presently available which, during the last years, have allowed for a long term use of central venous catheters (CVC). While patients with failing fistulas still represent the majority of cases, a growing number of patients are given CVC as a primary vascular access for hemodialysis. The experience is however too short and further studies should address the question of maintenance, as well as the cost-benefit ratio of such permanent CVC.

[Peritoneal dialysis in cases of associated pathology]. / Dialyse péritonéale en cas de pathologies associées.

There are two aspects to considerations of the value of peritoneal dialysis (PD) in the treatment of renal insufficiency with associated pathology. The first involves the effects of the treatment on the symptoms or evolution of the pathology. Examples include the improvement of dyspnea due to cardiac insufficiency (CI) and of cirrhotic ascites (CA). However, there is also an undefined risk of reactivation lupus. The second facet is the increased risk of peritoneal infection, particularly for patients who are HIV + or who are immunosuppressed due to lupus or myeloma. In certain types of case (lupus with intractable vascular thrombosis, intolerance of ultrafiltration in cases of CI, AC or generalised amyloidosis) PD has particular advantages. Nevertheless, there has been no appropriate prospective study to demonstrate or otherwise the advantages in terms of survival. The use of PD remains therefore a matter of choice for individual patients and experienced health care team.

Metabolism and vascular effects of gamma-L-glutamyl-L-dopa on the isolated rat kidney.

Gamma-L-glutamyl-L-dopa (or gludopa), a dopamine (DA) prodrug, is selectively metabolized in vivo by the kidney through the sequential action of two renal enzymes, gamma-glutamyl transpeptidase (gamma-GT) and aromatic L-amino acid decarboxylase (AADC). This study was designed to analyze, in vitro, the factors regulating gludopa metabolism and its renal vascular effects. Rat kidneys were perfused in closed circuit with a cell-free perfusion buffer containing 6% bovine serum albumin (BSA). Adding gludopa (final concentration 10(-5) M in the perfusate) led to the release of DA both into urine and perfusate (0.53 +/- 0.21 and 1.38 +/- 0.28 nmol/min/g kidney wt, respectively, during the first 5 min after substrate addition, N = 5, mean +/- SEM). Total DA release (urine plus perfusate) was 73.7 +/- 15.8 nmol/g kidney wt within 30 minutes of recirculation. In non-filtering kidneys, total DA release in the recirculating medium was lower (12.5 +/- 1.4 nmol/g kidney wt, P less than 0.01). Glomerular filtration and access to the gamma-GT on the brush border membrane of proximal tubular cells are therefore required for the maximal conversion rate of gludopa. On filtering kidneys, L-dopa was also converted to DA, but at a higher rate than gludopa (total DA formed within 30 min of recirculation = 131.2 +/- 31.9 nmol/g kidney wt) and this rate was not reduced in non-filtering kidneys (224.2 +/- 41.7 nmol/g kidney wt DA formed within 30 min). Metabolic conversion of L-dopa by AADC is thus preserved in the case of an approach via the basolateral side of the proximal tubular cells. The renal vascular effects of gludopa were studied after vascular tone had been restored by continuous perfusion of PGF2 alpha and after the inhibition of alpha- and beta-adrenoceptors. Gludopa (3.10(-6) to 4.10(-5) M) elicited concentration-dependent renal vasodilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

Creatinine determination in peritoneal dialysis: what method should be used?

The accuracy of methods for measurement of creatinine in plasma, urine and dialysate is of great importance in continuous ambulatory peritoneal dialysis (CAPD) patients, to assess the adequacy of CAPD (creatinine clearance) and to monitor the nutritional status (creatinine kinetic lean body mass). The methods most widely employed for creatinine determination are Jaffe's reaction and the enzymatic method, however these techniques may suffer from glucose interference, particularly for dialysate. We compared creatinine values obtained by Jaffe's reaction, the enzymatic method and high pressure liquid chromatography (HPLC) for three creatinine calibration curves prepared in three dialysis solutions with various concentrations of glucose and for plasma, urine and dialysate of 40 CAPD patients. High values of intercept of creatinine calibration curves were observed only with Jaffe's reaction and the enzymatic method in dialysis solutions. In plasma, urine and dialysate, creatinine values obtained by HPLC were always found to be lower than those measured by the other two methods. Concerning creatinine measurement in plasma and urine, Jaffe's reaction and the enzymatic method appeared equivalent. However it must be noted that, in dialysates, the enzymatic method may have glucose interference, and the use of a correcting factor for glucose with Jaffe's reaction is convenient. Nevertheless HPLC remains a method of reference. It is concluded that, for the CAPD patient, follow-up by creatinine kinetic lean body mass or creatinine clearance is possible provided that the same creatinine assay method is used in all biological fluids.

Effects of chronic renal failure on enzymes of energy metabolism in individual human muscle fibers.

In order to improve knowledge about the mechanisms underlying the alterations of energy metabolism recently observed in the skeletal muscle of patients suffering from chronic renal failure, this study was designed to test (1) whether changes in the activity of key enzymes of energy metabolism occur in the muscle of these patients, and if so (2) whether the different muscle fiber types are equally altered in their metabolic machinery. For this, the maximum activities of 14 enzymes were measured in individual muscle fibers microdissected from biopsies of rectus abdominis muscle obtained from seven normal subjects and seven patients with end-stage renal failure before renal replacement therapy. A large decrease in the activities of beta-hydroxyacyl-coenzyme A dehydrogenase, a key enzyme of the beta-oxidation pathway, of citrate synthase, which initiates the tricarboxylic acid cycle, and of fructose-1,6-bisphosphatase, which contributes to the synthesis of glycogen from lactate, was observed in the three fiber types (slow-twitch oxidative, fast-twitch oxidative-glycolytic, and fast-twitch glycolytic). A smaller reduction of the activities of phosphofructokinase and/or pyruvate kinase, two key enzymes of glycolysis, was also observed in slow-twitch oxidative and/or fast-twitch oxidative-glycolytic fibers. These results demonstrate that the abnormalities of muscle energy metabolism observed in patients with chronic renal failure are due, at least in part, to intrinsic changes in the key enzymes of major energy-providing pathways; they also offer a satisfactory explanation for the defect of oxidative metabolism recently demonstrated in the muscle of these patients.

[Diseases associated with renal amyloidosis. Apropos of 216 cases]. / Maladies associées à l'amylose rénale. A propos de 216 cas.

Diseases associated with renal amyloidosis were evaluated in 216 patients observed between 1956 and 1989. The percentage of secondary amyloidosis decreased from 72 to 47%, where it has remained for the past 20 years, despite the clear diminution in the tuberculosis rate; this is due to its increased incidence of association with rheumatoid diseases. Dysglobulinemia was found in more than 75% of the patients with AL amyloidosis. Amyloidosis associated with this dysglobulinemia, of which 30% were myelomatous, represented more than 25% of the cases observed during the past decade and constituted, with rheumatoid arthritis, the two most common etiologies.

31P NMR spectroscopy investigation of muscle metabolism in hemodialysis patients.

Calf muscle metabolism of six patients with end-stage chronic renal failure undergoing maintenance hemodialysis and of six control subjects was studied using 31P nuclear magnetic resonance spectroscopy at 4.7 Tesla. Spectra were obtained at rest, during exercise and recovery. At rest, the inorganic phosphate, ATP and phosphocreatine concentrations, and the intracellular pH were similar in both groups of subjects. In the patients, the maximum workload achieved at the end of exercise led to a 84% and 46% depletion of phosphocreatine and ATP, respectively; under this condition, the intracellular pH fell to 6.50 +/- 0.09. In control subjects, a maximum workload caused no change in ATP concentration at the end of exercise, but a phosphocreatine depletion and an intracellular pH fall similar to those observed in the patients. Although the rate of phosphocreatine depletion during exercise was not different in the two groups of subjects, the decrease in intracellular pH was more rapid in the patients than in control subjects. At the end of maximum exercise, the rates of recovery of both phosphocreatine and intracellular pH were significantly reduced in the muscle of hemodialysis patients when compared to normal subjects. These results suggest that, in the calf muscle of hemodialysis patients, energy production via oxidative metabolism is impaired and compensated for by an increase in anaerobic glycolysis.

[National study of screening practices for hepatitis C among hemodialysis patients. Hepatitis Group]. / Etude nationale des pratiques de dépistage de l'hépatite C chez les patients hémodialysés. Hepatitis Group.

French and American consensus conferences on hepatitis C confirmed the burden of that disease, especially in high risk populations. In France, the seroprevalence of HCV is about 20% among haemodialysed patients. This study aimed at describing the French screening practices in haemodialysed patients. In 1995, 1213 self-administered questionnaires were sent to nephrologists working in 715 dialysis units. The response rate was 48% (585/1213) and 485 questionnaires were analysed. In 98% of questionnaires nephrologists answered that they prescribed screening test. Routine screening with alanine amino-transferase (ALT) was reported in 98% of questionnaires, usually once a month (57%) or four times a year (23%). Routine anti-HCV serology was reported by 96%, usually once (28%) or twice (46%) a year. The two main annual strategies combining ALT and anti-HCV serology were 12 ALT and 2 serologies (21%), or 12 ALT and 1 serology (14%) per year. HCV RNA detection was reported mainly in the case of positive anti-HCV serology (70%). The study suggested heterogeneity in screening practices and revealed the need to determine the cost-effectiveness ratios of the various strategies.

Renal transplantation at the University of Lyon.

Over the last 23 years, progress in renal transplantation has dramatically decreased mortality and transplant failures, especially during the first years following the transplant. Further improvement in immunosuppression or in induction of specific unresponsiveness should, in the future, limit the incidence of late failures. More experience in transplantation has led to reduced frequency and severity of most complications. This has resulted in acceptance of patients with risk factors such as old age or infancy, poor vascular status, hyperimmunization, or requirement for several transplants (kidney + pancreas, kidney + heart, kidney + liver, etc.). Optimum organ procurement facilities will be required to meet the increased demand for kidney transplants. It is hoped that this need will be stabilized when late transplant failures will become infrequent, thus decreasing the requirements for retransplantation.