[Renal stone disease: collaborative management between primary care and specialized physicians]. / Approche pratique de la lithiase rénale: duo entre généralistes et spécialistes.

Nephrolithiasis is a highly prevalent pathology with a 10% lifetime risk in the Western population. Although it is often minimized and qualified as "idiopathic" significant comorbidities are frequently observed, e.g. the metabolic syndrome, type 2 diabetes mellitus, hypertension and bone fragility. Therefore nephrolithiasis can be regarded as a systemic disorder. A specialized diagnostic and therapeutic approach should be offered to such patients with active kidney stone disease in order to prevent stone recurrence and favor early diagnosis of said comorbidities.

[Urinalysis: what a primary care physician needs to know]. / Analyse d'urines: l'ABC du praticien.

Dipstick urinalysis is a very useful diagnostic tool in primary care when used in a specific context (urinary complaints, follow-up of systemic diseases, or pregnancy), but not as a screening instrument. Urine collection in appropriate conditions, together with a correct interpretation of dipstick results, reduces the use of microscopic urinalysis and urine culture. Leucocyturia and positive nitrits indicate the presence of a urinary tract infection and do not generally require additional tests. Persistent haematuria or proteinuria need to be further explored (microscopic urinalysis and 24h urine collection). Presence of crystals in the microscopic urinalysis reflects the precipitation of the substance eliminated in the urinary tract, but does not systematically indicate a disease.

[Is kidney stone a bone disease?]. / La lithiase rénale est-elle une maladie osseuse?

Idiopathic calcium stone formation affects 10% of the adult western population in a lifetime and is, consequently, a real public health problem in these countries. Abnormalities of bone metabolism with osteopenia have been found in patients with idiopathic hypercalciuria. The type of diet (high protein intake, calcium restriction) and some mediators (cytokines, calcitriol) are involved in the pathophysiology of bone alterations. The purpose of this article is to discuss the link between calcium nephrolithiasis and bone density, factors implicated in bone loss and how to treat this pathology.

[The importance of education in the management of chronic kidney disease patient]. / Prise en charge du patient insuffisant rénal: intérêt d'une approche educative complémentaire au suivi médical.

Chronic kidney disease (CKD) is complex to manage, especially when a substitutive treatment has to be implemented. Strict medical follow-up is mandatory but not sufficient to provide optimal care to the CKD patients. Educational intervention gives more skills to the patients to cope with this chronic disease. In this approach, physicians and nurses help patients to have a greater acceptance of their illness and make their treatment their own. Therapeutic education is part of this patient-centred approach. Peer counselling is also used in our program as well as an educative journal.

[Nephrogenic systemic fibrosis: another problem for patients with chronic renal failure]. / Nouveau problème pour les insuffisants rénaux chroniques: la fibrose systémique néphrogénique.

Nephrogenic systemic fibrosis, another problem for patients with chronic renal failure Nephrogenic systemic fibrosis is a rare but severe disease described in patients with kidney failure. High morbidity ant mortality are associated with this new condition. Epidemiological studies strongly suggest a link between nephrogenic systemic fibrosis and gadolinium administration for magnetic resonance imaging enhancement. The disease is primarily cutaneous, with oedema affecting the limbs, later evolving to fibrosis that leads to joints contractures. The lesions can spread to the trunk and involve systemic organs like the heart, lungs and muscles. Given the lack of proved efficient therapy, careful evaluation of the risks and benefits of gadolinium administration should be done in patients with kidney disease. If really needed, a highly stable contrast media should be used.

[Magnesium metabolism disturbances]. / Dysmagnésémies.

Magnesium metabolism disturbances Magnesium (Mg) is the second most abundant intracellular cation. Only 1% of Mg is in the extracellular fluid and the plasma Mg concentration does not reflect a substantial tissue depletion. Hypomagnesemia is the most common abnormality of Mg balance. This disorder is often associated with hypocalcemia, hypokalemia and metabolic alkalosis. Hypomagnesemia must be suspected in any patient with alcoholism, chronic diarrhoea or on diuretic. The 24-hour urinary Mg excretion of greater than 10 to 30 mg (1 mmol) or a calculated fractional excretion of Mg of greater than 2% suggest inappropriate renal wasting. Symptomatic hypomagnesemia must be treated by intravenous Mg, following by oral intake of Mg salt and by Mg rich diet. Hypermagnesemia is rare and occurs in case of high load and/or when renal function is impaired.

[Nephrology]. / Néphrologie.

ABO incompatibility and positive cross match between the donor and the recipient are no longer considered absolute counter indications to renal transplantation. One-year and 5-years graft survival are similar to ABO compatible transplantation, although a higher incidence of acute humoral rejection is observed. Calcineurin inhibitors nephrotoxicity can be reduced since the introduction of new immunosuppressive drugs. Two forms of peritoneal dialysis are available: continuous ambulatory peritoneal dialysis and automated peritoneal dialysis. In each situation the treatment must be tailored to the patient. Various clinical and biological parameters allow to judge the adequacy of the peritoneal dialysis. The last guidelines fixed the minimal target value of one of them, the Kt/V, at 1.7.

[Could cystatine C replace creatinine as a market of glomerular filtration rate?]. / La cystatine C peut-elle remplacer la créatinine comme marqueur du taux de filtration glomérulaire?

Measurement of glomerular filtartion rate (GFR) is crucial for the detection and follow-up of an early renal impairment. Inulin clearance or radio-isotopes are the gold standard but they cannot be used routinely. Serum creatinine and creatinine clearance are the most widely used, but they lack sensibility to detect an early renal impairment and in cases of obesity, malnutrition or advanced age. Looking for a more reliable marker is necessary and cystatin C seems to be interesting. This molecule is constantly produced by nucleated cells, then freely filtrated and catabolized in the proximal tube. Clinical studies showed that cystatin C might be a more reliable marker of GFR in determined groups of patients. Moreover this molecule may have an other interest as a predictive risk factor or mortality, especially for cardiovascular events.

[Urine electrolytes: use and pitfalls to avoid]. / Le spot urinaire: utilité et pièges à éviter.

In clinical situations of electrolytic or acid-base disorders, the measure of electrolytes concentration and osmolality in a urine sample, which is called the urinary spot, is a simple way to guide the diagnosis and therapy. The interpretation of results must take into account the patient's history and clinical examination. The urine sodium concentration and urine osmolality are key elements in the diagnosis of dysnatremias and in renal failure. The urine chloride concentration is useful in the diagnosis of acid-base disorders. The potassium excretion in the urine, which is regulated mainly by aldosterone, is particularly helpful in the case of hypokaliemia. Finally, the determination of the transtubular potassium gradient is a valuable tool for the diagnosis of hypoaldosteronism.

[Nephrology]. / Néphrologie.

Alternative to nephrotoxic calcineurin inhibitors regimens are feasible in renal transplantation. Sirolimus is an effective immunosuppressive drug with less drug-induced nephrotoxicity. Enteric-coated mycophenolate sodium provides a safety and efficacy alternative to mycophenolate mofetil. In peritoneal effluent, cancer antigen 125 (Ca 125) is a mesothelial cell marker and of in vivo biocompatibility of the new dialysis solutions. Longterm PD and peritoneal sclerosis are associated with a low number of mesothelial cells and a low concentration of dialysate Ca 125. Exposure to glucose and degradation products (GDPs) is important in the genesis of mesothelial damage. Short results of the more biocompatible solutions are promising (increasing of Ca 125). In the future, exposure to glucose can be reduced by using combinations of various osmotic agents, each in a low concentration (glycerol and amino acid solution).

[Prevention of cortisone-induced osteoporosis]. / Prévention de l'ostéoporose cortisonique.

Osteoporosis and fractures are the frequent consequences of glucocorticoid therapy. Cancellous bone is primarily affected with a decrease of bone formation and an increase of bone resorption. Prevention of corticosteroid-induced osteoporosis is based upon general measures such as calcium and vitamine D supplementation, adequate protein intake, regular physical exercise, and upon specific therapies like those used in primary osteoporosis. Bisphosphonates which are potent bone resorption inhibitors have been shown to reduce bone mineral density and to decrease vertebral fracture rate. Therefore, they appear to be a first choice in the prevention of corticosteroid-induced osteoporosis.

Identification of plasma proteins adsorbed on hemodialysis tubing that promote Staphylococcus aureus adhesion.

Risk factors for Staphylococcus aureus infections in patients undergoing hemodialysis include underlying disease, material-induced host defects, and the presence of vascular access catheters. To determine the specific contribution of various potentially adsorbed plasma components in promoting S aureus adhesion to shunt tubing during chronic hemodialysis, we quantified their respective amounts by Western immunoblotting and densitometry and estimated their individual adhesion-promoting activities with specific adhesion-modified bacterial mutants. Fibrinogen, which was the only component consistently present in tubing protein extracts from all patients, was adsorbed in significantly higher amounts on predialyzer than on postdialyzer tubing segments. In contrast, fibronectin and von Willebrand factor were irregularly present in patients' tubing, whereas vitronectin or thrombospondin remained undetectable in all samples. The contribution of fibrinogen in promoting S aureus attachment to hemodialysis tubing was demonstrated by (1) the significantly lower adhesion of a cIfA mutant of strain Newman compared with its parent; (2) the increased attachment of strain 8325-4 after complementation with the cloned cIfA gene on the multicopy plasmid pCF4; and (3) the general tendency for strains Newman and 8325-4(pCF4) to express higher attachment on predialyzer compared with postdialyzer tubing segments in relationship with the higher content of fibrinogen on the former material. However, the specific S aureus attachment-promoting activity of both prefilter and postfilter tubing-adsorbed fibrinogen were much lower than that of the native in vitro-adsorbed protein and may reflect masking or inactivation of the in vivo-adsorbed protein by unknown mechanisms.

De novo expression of transforming growth factor-alpha in parathyroid gland tissue of patients with primary or secondary uraemic hyperparathyroidism.

BACKGROUND: The factors involved in abnormal parathyroid cell secretory function and growth in patients with primary and secondary hyperparathyroidism are still incompletely understood. PATIENTS AND METHODS: We studied the expression of transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF) and EGF receptor (EGF-R) at the gene message and the protein level in parathyroid tissue obtained from six patients with primary hyperparathyroidism, 15 patients with secondary uraemic hyperparathyroidism and five subjects with normal parathyroid tissue, using in situ hybridization and/or immunostaining technique. RESULTS: We found a consistent expression of TGF-alpha mRNA and protein in parathyroid endocrine cells of all six cases of primary parathyroid adenoma and in nearly all cases of secondary hyperplasia, in contrast to the absence of expression in normal parathyroid tissue. A marked expression of EGF-R mRNA and protein was also found in four of five tissue samples of primary parathyroid adenoma, in 13 of 15 tissue samples of secondary parathyroid hyperplasia and in most samples of normal parathyroid gland tissue. EGF mRNA and protein expression was undetectable in the majority of parathyroid tissue samples examined. CONCLUSION: Since TGF-alpha is known to bind to the EGF-R, the finding of an increased expression of TGF-alpha at the gene message and the protein level, together with a strong expression of EGF-R, in hyperplastic and adenomatous parathyroid glands suggests that this growth factor interacts with its receptor to promote parathyroid cell proliferation, perhaps by an autocrine mechanism.

Conformational changes of lipoxygenase (LOX) in modified environments. Contribution to the variation in specificity of soybean LOX type 1.

The addition of water-soluble cosolvents in the reaction medium of type 1 soybean lipoxygenase can modify the selectivity of the enzyme in the hydroperoxide synthesis reaction. This also results in changes in secondary reactions such as carbonyl compound formation. The possibility of a conformational change of the enzyme due to variations in its microenvironment was considered. Using enzyme immobilization and laser visible Raman spectroscopy, both indirect and direct observations of such a protein conformational rearrangement are described. Subtle modifications in the secondary and/or tertiary structures, for example in microenvironments of Tyr and Trp residues, in orientations of lateral side chains were evidenced, and their importance to enzyme specificity is discussed.

Soybean lipoxygenases-1, -2a, -2b and -2c do not contain PQQ.

Soybean isoenzymes lipoxygenases-1, -2a, -2b and -2c were examined spectroscopically for the presence of covalently bound pyrrolo quinoline quinone (PQQ) after derivatization by phenylhydrazine (PH), 2,4-dinitrophenylhydrazine (DNPH) and 3-methyl-2-benzothiazolinone hydrazone (MBTH). DNPH derivatization of PQQ after a pronase digestion step of lipoxygenase-1 in the presence of an anion exchange gel fixing the cofactor was also investigated. None of these experiments provided evidence for the presence of PQQ contrary to previous report by Van der Meer et al (1). We have checked, by EPR spectroscopy, that the three reactants used were able to reduce the active site ferric iron. Our results were confirmed by the absence of enzyme inhibition by cis- and trans-1,2-diaminocyclohexane or benzylamine in the presence of NaBH3CN which have been reported to react with PQQ and to inactivate quinoproteins (2,3).

Hexanal phenylhydrazone is a mechanism-based inactivator of soybean lipoxygenase 1.

Hexanal phenylhydrazone (1; 70:30 E:Z mixture) at micromolar concentration irreversibly inactivates soybean lipoxygenase 1 (L-1) in the presence of dioxygen. L-1 catalyzes the oxidation of 1 into its alpha-azo hydroperoxide 2 [C5H11CH(OOH)N = NC6H5]. 2 is an efficient inactivator of L-1. The aerobic reaction between 1 and L-1 follows a branched pathway leading to the release of 2 into the medium or to L-1 inactivation. The respective parameters corresponding to this inactivation by the (E)-1 and (Z)-1 isomers are Ki = 0.25 and 0.40 microM and kinact = 0.8 and 2.1 min-1. Linoleic acid protection agrees with a mechanism-based inactivation process. The oxidation of a minimum of 13 +/- 3 molar equiv of 1 is required for complete L-1 inactivation, but up to 70 equiv is necessary in the presence of a very large excess of 1. The inactivation is actually the result of two pathways: one is due to a reaction of 2 as soon as it is formed at the active site (20%); the other is due to 2 released into the medium and coming back to the active site (80%). The inactivation is accompanied by the oxidation of 1.8 +/- 0.8 methionine residues of the protein into the corresponding sulfoxide. The inactivated L-1 is electron paramagnetic resonance (EPR) silent with an effective magnetic moment of mu = 5.0 +/- 0.1 Bohr magnetons corresponding to an S = 2 spin state. An inactivation mechanism is proposed on the basis of EPR and magnetic susceptibility data obtained from the anaerobic and aerobic reactions of L-1 with 1 and 2.