Search

We analyzed, by home blood pressure (BP) self-measurement and conventional predialytic measurement of BP, a cohort of haemodialysis patients in two hospital units between 2008 and 2010. All patients who already own a BP self-measurement device were included in this study. BP was recorded by the two methods for one week. The number of patients with a validated self-measurement device was 69 of 350 (21%) and 60 patients were included in analyses. These patients were divided into 23 (38%) permanent uncontrolled hypertensive (elevated BP at home and in hospital), 13 (22%) masked hypertensive (normal BP in hospital and elevated at home), eight (13%) white coat hypertensive (elevated BP in hospital and normal at home), and 16 (27%) permanent controlled normotensive (normal BP in hospital and at home). Patient compliance with all the self BP measurements was 95%. We did not find in this cohort the factors associated with masked hypertension in the general population such as being male, smoking and high body mass index. These results obtained in an in-hospital dialysis unit should be extrapolated with caution to all haemodialysis patients. However it is, to our knowledge, the first study on home BP self-measurement published in patients undergoing haemodialysis in France. A significant proportion of patients have masked hypertension. This should alert clinicians because of the poor cardiovascular prognosis associated with masked hypertension.

Introduction L’estimation de la volemie chez le patient dialyse chronique constitue un point cle de sa prise en charge. A l’heure actuelle, il n’existe pas de gold standard realisable en routine quotidienne malgre les outils de plus en plus nombreux comme la bioimpedancemetrie et l’echographie cardiaque trans-thoracique (ETT) et pulmonaire. Nous avons realise une etude prospective chez des patients hemodialyses chroniques dont le but est d’evaluer les performances diagnostiques de l’echographie pulmonaire et de l’examen clinique pour l’evaluation de la surcharge volemique en utilisant comme gold standard l’ETT. Patients et methodes Trente et un patients hemodialyses chroniques depuis plus de 3 mois en centre lourd ont ete inclus. Les patients presentant une fibrose pulmonaire n’ont pas ete inclus. L’evaluation volemique a ete realisee au debut de la deuxieme seance de dialyse hebdomadaire par : un score clinique (Criteres majeurs : dyspnee NYHA > III, orthopnee ; Criteres mineurs : turgescence jugulaire (TJ), reflux hepato-jugulaire (RHJ), crepitants a l’auscultation, œdemes peripheriques et HTA pre-dialyse) ; un score en ETT (diametre de la veine cave inferieure, rapport E/E’ et les pressions arterielles pulmonaires systoliques) ; et l’Echo-Comet score en echographie pulmonaire (nombre de lignes B anterieures et laterales sur 28 regions thoraciques). Resultats Cinq patients presentaient une surcharge a l’ETT. En comparaison a l’ETT, les performances diagnostiques du score de surcharge clinique presentent une sensibilite (Se) de 100 %, une specificite (Sp) de 81 %, une valeur predictive positive (VPP) de 50 % et une valeur predictive negative (VPN) : 100 %. Seulement l’orthopnee ( p = 0,008), la TJ ( p = 0,005) et le RHJ ( p = 0,008) etaient significativement associes au diagnostic de surcharge a l’ETT. Les performances diagnostiques de l’Echo-Comet score par echographie pulmonaire presentent une Se de 80 %, une Sp de 59 %, une VPP 26 % et un VPN 94 %. 10 patients (32,3 %) presentaient une augmentation de l’eau extra-pulmonaire pulmonaire sans signe de surcharge a l’ETT et a l’examen clinique. Conclusion Il s’agit de la premiere etude qui definit un score clinique pour evaluer la surcharge hydrosodee chez les patients hemodialyses chroniques. Ce score clinique presente des performances diagnostiques satisfaisantes en comparaison a l’ETT et serait facilement utilisable en routine clinique quotidienne pour ajuster le poids sec. L’evaluation de la surcharge par l’Echo-Comet score en echographie pulmonaire parait quant a elle mal correlee a la surcharge evaluee par ETT. En revanche, la presence d’eau extrapulmonaire non detectee par l’examen clinique et l’ETT reste un parametre a investiguer d’un point de vue diagnostique et pronostique chez les patients hemodialyses.

Background: Haemodialysis exposes patients to many potentially sensitizing allergens. Objectives: The primary objective of this study was to evaluate the prevalence of delayed hypersensitivity in a population of haemodialysis patients. Secondary objectives were to identify the possible risk factors for contact sensitization and to propose a series of skin tests adapted to haemodialysis patients. Methods: A prospective monocentric study was carried out in a nonselected population of haemodialysis patients. For each patient, medical history of atopy and allergic contact dermatitis, ongoing treatments (including topical ones), presence of eczema at the site of vascular access for haemodialysis were recorded. Allergological investigation included delayed hypersensitivity tests (European Environmental and Contact Dermatitis Research Group battery, tests GERDA, additional list and a battery of antiseptics and other dialysis-specific allergens) and latex skin prick test. Results: Seventy-five patients (41 men, 34 women, mean age of 65 years old), with a mean 3.8 years under dialysis, were included. Nineteen patients (25%) had at least one positive skin test and 13 (17%) a positive patch test to at least one allergen relative to dialysis process including eight tests to lidocaine–prilocaine cream and three to povidone–iodine. Tests results seemed clinically relevant since nine patients had localized pruritus at the fistula site and six patients active eczema around it. Conclusion: Contact sensitizations are frequent in haemodialysis patients and are linked to vascular access conditioning especially the use of lidocaine–prilocaine cream. Designing a specific test battery could help to diagnose the potential allergens and subsequently to give advice to avoid contact with sensitizing agents.

Resume L’heparinisation du circuit extracorporel en hemodialyse est particulierement difficile a mener chez les patients a risque hemorragique. Des doses excessives risquent de provoquer des saignements et des doses insuffisantes peuvent entrainer une coagulation du circuit. Il est donc fondamental de bien choisir la dose initiale d’heparine et de l’adapter au cours de la seance. Si l’observation clinique des lignes et du dialyseur est realisee de facon habituelle, aucun parametre biologique n’est utilise actuellement. Le delai d’obtention d’un resultat de laboratoire est trop long pour permettre une modification rapide et efficace de la dose d’anticoagulant. Un appareil de mesure delocalise, c’est-a-dire utilisable au sein du service pourrait repondre a cette attente. La societe Gamida distribue 2 appareils de la marque Hemochron® qui permettent de mesurer un temps de coagulation sur sang total : l’ACT (Activated Clotting Time). Nous avons teste chacun de ces 2 appareils, tant au niveau de leur manipulation qu’au niveau des resultats rendus. Onze patients ont ete inclus dans cette etude. Des mesures regulieres de l’ACT ont ete realisees en cours de seance simultanement avec chacun des 2 appareils. Les resultats obtenus ont ete compares et mis en parallele avec les mesures du TCA et de l’heparinemie rendues par le laboratoire. Les 2 appareils ont rendu des resultats satisfaisants mais c’est l’evaluation pratique qui a oriente nos conclusions. L’aspect economique de ce type de materiel est en cours d’evaluation.

Summary Objective: To determine whether Belzer solution (Viaspan®, Bristol-Myers Squibb, Brussels, Belgium), which is more expensive than Eurocollins solution, was better at preventing delayed graft function (DGF) and whether it was cost-effective as it could potentially reduce post-transplantation complications. Method: The risk of occurrence of complications associated with the use of these two rinsing and preserving solutions was estimated from a survey of 106 patients undergoing renal transplantation between 1 January 1993 and 31 March 1998. Both efficacy and adverse outcomes were recorded along with the costs directly associated with the transplantation procedure in the hospital setting: hospitalization, rinsing and preserving solutions, medical and technical interventions and diagnostic tests. Results: For the 45 kidney grafts rinsed and preserved with Eurocollins (strategy S1: n1 = 45) the cost/graft was estimated at 40 €. With Viaspan® (strategy S2: n2 = 61) the corresponding cost/graft was 424 €. Logistic regression analysis showed that Viaspan® was better than Eurocollins solution (eβ = 0·437; P = 0·05) in preventing DGF. Overall, S2 was less expensive than S1, from the hospital's perspective. The mean difference per patient was 278 €, which amounts to a saving of 2% of the total cost per renal transplantation. For rinsing and preserving kidney grafts Belzer solution is therefore preferable to Eurocollins solution.

Resume Introduction. Les transplantations d'organes sont associees a une nette augmentation du risque neoplasique. Plus que l'effet oncogene propre d'une classe therapeutique, c'est le poids total de l'immunosuppression qui semble etre le facteur favorisant predominant. Un oncogene viral est frequemment associe et profite de cet etat d'immunosuppression. Les neoplasies observees ont donc des caracteristiques histologiques, cliniques, evolutives et therapeutiques particulieres. Actualite et points forts. Les mecanismes de l'oncogenese chez les patients immunodeprimes sont progressivement eclaircis. Une infection virale est associee a chaque type neoplasique. Ainsi, les lymphomes B sont lies quasi systematiquement a une infection a Epstein-Barr virus. Les cancers cutanes et les cancers du col uterin succedent souvent a des dysplasies virales secondaires aux papillomavirus. L'augmentation importante de l'incidence des sarcomes de Kaposi montre le role du systeme immunitaire dans le controle de l'infection par le 8 e herpes virus humain. Les cancers hepatiques se rencontrent lors d'infections chroniques par les virus de l'hepatite B ou C. Perspectives et projets. Les complications neoplasiques vont representer un probleme important dans le suivi des transplantes. En effet, le nombre de patients transplantes augmente regulierement. Ces patients ont une duree de vie de plus en plus longue. En outre, les nouveaux medicaments immunosuppresseurs sont de plus en plus puissants. La connaissance precise des mecanismes de controle des cellules neoplasiques et de l'infection virale par le systeme immunitaire sera une etape importante pour permettre une prevention et un traitement efficace de ces cancers. L'etude des liens entre le systeme immunitaire et l'oncogenese virale doit etre un but important de la recherche en transplantation.

1. Adenosine acts on a family of G-protein-coupled receptors called purinoreceptors. 2. Four subtypes have been cloned and pharmacologically characterized. 3. The principal pharmacological data and structure-function relations for agonist interactions with P1 receptors are presented. 4. We conclude that the potent role of adenosine in the nervous system may be interesting for the development of drugs targeted at purines and their receptors.

Hemodialysis is an efficient therapy for endstage renal failure. This treatment, however, must be used in an optimal fashion, i.e., with the best technology and the most adequate schedules. Unfortunately and especially for economic reasons, these basic therapeutic principles are often not respected. As a consequence, morbidity and mortality in maintenance hemodialysis patients have increased. This article underlines four points that could influence mortality in maintenance hemodialysis patients: nutrition, adequacy of hemodialysis, blood pressure control and treatment time.

Introduction La glomerulonephrite a depots de C3 (GNC3) resulte d’anomalies de la voie alterne du complement et est caracterisee par des depots glomerulaires predominants de C3. Les frequences respectives de recidive de GNC3 (GNC3r) et de perte du transplant renal apres recidive sont de 66 % et 50 %. Deux cas de GNC3r traites apres transplantation par eculizumab (anticorps monoclonal anti-C5) ont ete decrits [1] . Un an apres traitement, un cas presentait une amelioration histologique, le second, une amelioration biologique. Nous rapportons un troisieme cas de traitement par eculizumab pour GNC3r. Patients et methodes Un homme de 17 ans a beneficie d’une premiere transplantation renale pour GNC3 a partir de sa demi-sœur. L’exploration quantitative des proteines de la voie alterne du complement etait normale avant transplantation. Quarante-deux jours apres, le patient presente une elevation de la creatininemie a 220 μmol/L versus 166 μmol/l (j22), et une micro-hematurie, sans proteinurie. L’examen anatomo-pathologique du transplant montre une GNC3r debutante (depots endomembraneux diffus exclusifs de C3). La creatininemie s’eleve progressivement jusqu’a 280 μmol/L (j64), sans proteinurie et les depots de C3 progressent, sans proliferation. Nous debutons a j77 un traitement par eculizumab apres nouvelle exploration des proteines de la voie alterne du complement, vaccination anti-meningococcique et antibioprophylaxie par oracilline, a raison de 900 mg par semaine pendant 4 semaines puis 1200 mg tous les 14 jours. La creatininemie s’eleve jusqu’a 330 μmol/L (j91) puis, entre les 3e et 7e injections d’eculizumab, diminue progressivement jusqu’a 126 μmol/L (j138), lors du dernier suivi. Discussion et conclusion Nous rapportons un cas de GNC3r precoce, dont l’evolution renale est favorable apres 61 jours de traitement par eculizumab. L’amelioration renale reste a confirmer et la duree du traitement, a definir. Les dernieres explorations du complement ont montre une concentration diminuee du facteur I et une mutation heterozygote du facteur I, rarement associee aux GNC3.

Immune reconstitution inflammatory syndrome (IRIS) is a rare entity that has been described recently in solid organ transplant (SOT) recipients. IRIS is characterized by an exuberant and dysregulated immune response following treatment of opportunistic infections. We describe here the case of a kidney transplant recipient who developed cryptococcal meningitis that was efficiently treated with antifungal therapy and decreased immunosuppression regimen. Eight months later, a paradoxical worsening of neurological symptoms and neuroradiological findings led to the diagnosis of IRIS. A short course of high-dose steroid therapy allowed complete resolution of neurological symptoms. This report highlights the challenge for physicians to distinguish IRIS from a relapsing cryptococcal infection. Clinical improvement of cryptococcosis-associated IRIS by anti-inflammatory drugs needs to be confirmed among SOT recipients.

Immunosuppressive regimens have lowered the rate of kidney rejection, but with increasing immunodeficiency-related complications. New cytomegalovirus (CMV) prophylaxis also has become available. The impact of these 2 developments on CMV diseases has not been well evaluated. We conducted a randomized trial comparing a drug regimen common in the 1980s, cyclosporin A (CsA) with azathioprine (Aza), with a drug combination used most today, tacrolimus (Tac) with mycophenolate mofetil (MMF), and we analyzed CMV risk factors in kidney transplant patients.The 300 patients included in the trial underwent the same universal prophylaxis and preemptive therapy. CMV events and risk factors were prospectively recorded.With preventive and preemptive strategies combined for 3 months, CMV replication was detected in 32.6% and CMV disease in 18.1% of patients. Multivariate analysis on risk factors for CMV disease were CMV donor (D)/recipient (R) matching and first month renal function (risk ratio [95% confidence interval]: 1.02 [1.01; 1.04]; P=0.011), but not the immunosuppressive regimen (P=0.35). The D+/R- combination increased the risk of CMV disease by a factor of 9 (P0.0001) when compared with D-/R- status, and a factor of 3.5 (P0.0001) when compared with all CMV-positive recipients. Despite the 50% rate of CMV disease in the D+/R- group, no asymptomatic CMV replication was detected with the preemptive strategy.With modern immunosuppression, a sequential quadritherapy with Tac/MMF, and a 3-month CMV prevention strategy, the risk for CMV disease remains close to that with CsA/Aza. A CMV-negative recipient transplanted from a CMV-positive donor (D+/R-) remains a major risk factor, calling for better CMV prophylaxis or matching in negative recipients. Preemptive strategy thus appeared inefficient for this high-risk group. Transplant recipients with altered renal function should also be considered at risk.

Cyclosporine A at pharmacological doses decreases the rate and yield of ATP synthesis in rat mitochondria. This action seems to be due to the mitochondrial calcium storage induced by the drug. If such an effect occurs in vivo, the ATP deficit will affect calcium extrusion pumps, so triggering vasoconstriction which is the major side effect of Cyclosporine A. Calcium antagonists (Nifedipine and Verapamil) at least partially correct this effect on ATP synthesis: this finding may be related with the beneficial clinical effect conferred on Cyclosporine A toxicity by calcium antagonists. This effect of calcium antagonists may be due to an interaction with Cyclosporine A at the level of mitochondrial calcium efflux.

Introduction La TEP-TDM, initialement developpe en neurologie et en oncologie, a montre un interet certain dans les pathologies infectieuses (endocardites, osteites, infections de materiel, fievres d’orgine indeterminee). L’infection de kyste est une complication frequente de la polykystose renale autosomique dominante (PKRAD), dont le diagnostic est difficile avec les techniques d’imagerie standard, et impacte la duree et le type d’antibiotherapie a utiliser. La persistance d’une fievre sous antibiotiques necessite parfois l’identification du kyste infecte et sa ponction-drainage. L’objectif principal de cette etude etait d’evaluer la valeur diagnostique de la TEP-TDM au (18F)-fluorodesoxyglucose (FDG) dans le diagnostic des infections de kystes renaux ou hepatiques chez les patients porteurs d’une PKRAD, et la comparer a celle des autres techniques d’imagerie (scanner et IRM). Patients et methodes Les patients hospitalises au CHU de Marseille pour suspicion d’infection de kyste et ayant eu une TEP-TDM au FDG entre septembre 2006 et decembre 2013 ont ete inclus. Un groupe temoin constitue de patients porteurs d’une PKRAD, pour lesquels une TEP-TDM avait ete realise pour un autre motif, a egalement ete constitue. Le diagnostic d’infection de kyste etait retenu a posteriori sur l’index de suspicion clinique (fievre, douleurs lombaires/de l’hypochondre droit, germe retrouve dans les hemocultures ou la ponction de kyste), l’absence de diagnostic differentiel et l’evolution favorable sous antibiotherapie. La TEP-TDM etait considere comme positif en cas d’hypermetabolisme focal de la paroi d’un ou plusieurs kystes, avec rehaussement de la paroi apres injection de produit de contraste, et infiltration de la graisse adjacente. Resultats Trente-deux TEP-TDM au FDG ont ete realises pour suspicion d’infection de kyste chez 24 patients. Le diagnostic d’infection de kyste etait finalement retenu chez 18/32 patients : 14 avec TEP-TDM positive (vrais positifs) et 4 avec une TEP-TDM normale (faux negatifs). Il n’y avait pas de faux positif, et aucun des 9 patients polykystiques controles ne presentait d’hypermetabolisme de la paroi des kystes. La TEP-TDM avait une sensibilite de 77 %, une specificite de 100 %, une valeur predictive negative de 77 %. De plus, un diagnostic differentiel a ete mis en evidence chez 3 patients : une diverticulite et 2 lesions pulmonaires. Ces performances etaient superieures a celles du scanner et de l’IRM. En effet, sur les 21 scanners realises chez les memes patients (dont 18 avec injection de produit de contraste), 1 scanner etait 1 vrai positif, 11 faux negatifs, 7 vrais negatifs, 0 faux negatif (sensibilite : 7 %, valeur predictive negative : 35 %, p Conclusion Les performances diagnostiques de la TEP-TDM au FDG sont superieures a celles du scanner, pour une irradiation comparable et sans nephrotoxicite, dans les infections de kystes de la PKAD. La TEP-TDM pourrait devenir l’examen d’imagerie de premiere intention dans le diagnostic des infections de kystes chez les polykystiques, et permet d’identifier le ou les kystes a ponctionner en cas d’evolution defavorable sous antibiotiques.

Bartonella quintana is a reemerging pathogen responsible for trench fever, endocarditis, bacteremia, and bacillary angiomatosis. We previously reported the first case of a patient with B. quintana-induced chronic adenomegaly, and here we present a report on a second patient. A hemodialyzed patient with Sjögren's syndrome presented with mediastinal adenomegalies and secondary pancytopenia. All diagnostic investigations remained negative, except that a Bartonella-like microorganism was isolated from a bone marrow biopsy. The isolate was identified as B. quintana by a specific mouse polyclonal antibody and by determination of a partial gltA (citrate synthase-encoding) gene and 16S rRNA gene sequences. DNA of the pathogen was also detected in the adenomegaly and in the serum of the patient by PCR amplification of the gltA gene. Anti-B. quintana antibodies were never detected in the patient's serum throughout the 12-month follow-up but were detected in the serum of the patient's cat. The patient's outcome was favorable after treatment with gentamicin. Chronic adenomegaly in seronegative patients is a new clinical entity due to B. quintana.

Summary: A patient with hyperuricaemia and gouty arthritis due to a new variant of hypoxanthine–guanine phosphoribosyltransferase is described. The mutation (I136T, HPRT Marseille) is in the phosphoribosylpyrophosphate-binding region of the gene and leads to almost total loss of enzyme activity in erythrocytes, with 5% in lymphocytes. Nevertheless, the patient showed no neurological abnormality.

Health related quality of life (HRQOL) indicators take into account the personal perception of health, and are proposed as an alternative for efficacy indicators in medical and therapeutic decision making. They provide, due to elaboration and validation of a questionnaire, a standardised assessment of the health status perception. This paper provides a review of a variety of HRQOL instruments developed for patients suffering end-stage renal disease (ESRD). Generic instruments are designed to be applicable in general population and disease-targeted instrument are potentially more sensitive to the characteristics of a specific population. Among HRQOL instruments, we found 4 generic questionnaires (the Sickness Impact Profile, the SF 36, the Nottingham Health Profile and the EQ-5D), 3 disease-targeted questionnaires developed for ESRD patient undergoing dialysis (the Kidney Disease Quality of Life instrument, the Kidney Disease Questionnaire and the Choice Health Experience Questionnaire), 1 questionnaire specific for ESRD patients (the HRQOL questionnaire), and 2 specific disease-targeted instruments for renal transplant (the Kidney Transplant Questionnaire and the ESRD Symptom Checklist-Transplantation Module). In France, very few studies on the quality of life of ESRD patients were published; no specific questionnaire validated in French is yet published.

To determine whether Belzer solution (Viaspan, Bristol-Myers Squibb, Brussels, Belgium), which is more expensive than Eurocollins solution, was better at preventing delayed graft function (DGF) and whether it was cost-effective as it could potentially reduce post-transplantation complications.The risk of occurrence of complications associated with the use of these two rinsing and preserving solutions was estimated from a survey of 106 patients undergoing renal transplantation between 1 January 1993 and 31 March 1998. Both efficacy and adverse outcomes were recorded along with the costs directly associated with the transplantation procedure in the hospital setting: hospitalization, rinsing and preserving solutions, medical and technical interventions and diagnostic tests.For the 45 kidney grafts rinsed and preserved with Eurocollins (strategy S1: n1 = 45) the cost/graft was estimated at 40 euros. With Viaspan (strategy S2: n2 = 61) the corresponding cost/graft was 424 euros. Logistic regression analysis showed that Viaspan was better than Eurocollins solution (ebeta = 0.437; P = 0.05) in preventing DGF. Overall, S2 was less expensive than S1, from the hospital's perspective. The mean difference per patient was 278 euros, which amounts to a saving of 2% of the total cost per renal transplantation. For rinsing and preserving kidney grafts Belzer solution is therefore preferable to Eurocollins solution.

Background A pivotal role for Type I interferon (IFN) in SLE is supported by gene expression studies that identified the so-called type I IFN signature (IS). Objectives The aim of this study was to improve characterization of the blood-IFN signature in adult SLE patients. Methods Consecutive SLE patients fulfilling the ACR criteria were enrolled and followed-up prospectively. Microarray data were generated using Illumina beadchips. A modular transcriptional repertoire was employed as a framework for the analysis. Results Our repertoire of 260 modules, which consist of co-clustered gene sets, included 3 IFN-annotated modules (M1.2, M3.4 and M5.12) that were strongly up-regulated in SLE patients. At the individual level, a modular IS (ie, over-expression of at least 1 of the 3 IFN modules) was observed in 54/62 (87%) of patients or 131/157 (83%) of samples. The IFN signature was more complex than expected with each module displaying a distinct activation threshold (M1.2 Conclusions Modular repertoire analysis reveals complex IFN signatures in SLE, not restricted to the previous IFN-a signature, but involving also b and g IFNs. These modular IFN signatures may help in the design of disease activity biomarkers. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2405

Previous reports have demonstrated that Cyclosporine A (CyA) chronically administered induces an increase in adenosine plasma concentration by inhibiting adenosine uptake by red blood cells (RBC). We hypothesized that this effect may modulate, by a down regulation, the mRNA expression of adenosine receptors in rat kidney. Since high blood pressure (HBP) is a classical side effect of CyA treatment, nicardipine, a dihydropyridine calcium channel blocker, is often associated with CyA in treatment. To distinguish between the effects of CyA-induced HBP and the effects of CyA by itself, we have evaluated the effects of CyA and/or nicardipine on the mRNA expression of A1 and A2a adenosine receptors. The study was performed on five groups of rats (n= 8) receiving during 21 days either serum saline (0.5 ml i.p), CyA (12 mg/kg/day, i.p), nicardipine (1.2 mg/kg i.p) or nicardipine + CyA. The last (or fifth) group was injected with vehicle (0.5 ml i.p). Blood samples for adenosine assay were collected in the renal artery at day 21, just before the rat kidneys were removed for quantitation of adenosine A1 and A2a mRNA concentration by RT-PCR. We make two conclusions :i) Nicardipine induces a decrease in mRNA expression of A1 but not of A2a adenosine receptors. However, because nicardipine lowered both blood pressure and A1 mRNA expression, it is not possible to conclude if A1 mRNA decrease is implicated in the nicardipine effects on blood pressure.ii) CyA induces an increase in renal artery adenosine concentration and a decrease in mRNA expression of A1 and A2a adenosine receptors.

Organ transplantation is associated with an increased risk of neoplasia, which seems to be caused by the total effect of immunosuppression, i.e., the combination of factors involved, rather than by the use of a specific class of immunosuppressants. The presence and proliferation of viral oncogenes is frequently observed during this immunosuppressive state. The neoplasia in immunosuppressed patients therefore has particular histological, clinical, evolutive, and therapeutical characteristics.The oncogenic mechanisms in immunosuppressed patients have been progressively clarified. A viral infection is associated with each type of neoplasia: thus, B lymphoma are generally associated with Epstein-Barr viral infection. Skin and uterine cervical carcinomas frequently appear after viral dysplasia due to papillomavirus. The significant increase in the incidence of Kaposi sarcoma shows the role of the immune system in the control of the infection by the human herpes virus 8, which has been recently discovered. Liver cancer is associated with a history of hepatitis B or C chronic infection.Post-transplantation neoplasia constitutes a major problem in patient follow-up, as the number of transplant patients has increased and their survival rate has improved. In addition, there is an increasingly powerful new generation of immunosuppressive drugs. A precise knowledge of the immune system's control mechanisms regarding neoplasic cells and viral infection is an important step in the prevention and efficient treatment of these forms of cancer. Further research into the relationship between the immune system and viral oncogenesis should therefore be considered a major aim.

Lithostathine is a calcium carbonate crystal habit modifier. It is found precipitated under the form of fibrils in chronic calcifying pancreatitis or Alzheimer's disease. In order to gain better insight into the nature and the formation of fibrils, we have expressed and purified recombinant lithostathine. Analytical ultracentrifugation and quasi-elastic light scattering techniques were used to demonstrate that lithostathine remains essentially monomeric at acidic pH while it aggregates at physiological pH. Analysis of these aggregates by electron microscopy showed an apparently unorganized structure of numerous monomers which tend to precipitate forming regular unbranched fibrils. Aggregated forms seem to occur prior to the apparition of fibrils. In addition, we have demonstrated that these fibrils resulted from a proteolysis mechanism due to a specific cleavage of the Arg(11)-Ile(12) peptide bond. It is deduced that the NH(2)-terminal undecapeptide of lithostathine normally impedes fiber formation but not aggregation. A theoretical model explaining the formation of amyloid plaques in neurodegenerative diseases or stones in lithiasis starting from lithostathine is described. Therefore we propose that lithostathine, whose major function is unknown, defines a new class of molecules which is activated by proteolysis and is not involved in cytoskeleton nor intermediate filament functions.

This article summarise the main data in the literature on the role of bacteriological contamination of the dialysate fluid in inflammatory reactions in hemodialysis. Pyrogenic substances of small molecular weight from Gram-negative bacteria grown in dialysate can pass across intact dialyzer membrane to stimulate cytokine production by peripheral blood mononuclear cells. Cellulosic hemodialysis membranes are more permeable to endotoxins than synthetic membranes. Polysulfone membranes and polyamide membranes are able to adsorb bacterial toxins on the dialysate side. The diffusive transfer of bacterial products across dialysis membrane from dialysate fluid was demonstrated. Transmembrane passage of cytokine-inducing bacterial products across reprocessed dialyzers is greater than across new dialyzers. Bacteriological contamination of the dialysate fluid is a problem which must be considered with much more care by nephrologists, especially as LAL test is unable to detect all the bacterial products which can contaminate the dialysate fluid.

1. Adenosine acts on a family of G-protein-coupled receptors called purinoreceptors. 2. Four subtypes have been cloned and pharmacologically characterized. 3. The principal pharmacological data and structure-function relations for agonist interactions with P1 receptors are presented. 4. We conclude that the potent role of adenosine in the nervous system may be interesting for the development of drugs targeted at purines and their receptors.

Traveling can be dangerous for subjects with kidney insufficiency. Water loss or septic episodes can further increase renal dysfunction. Poor diet can lead to hyperkaliemia. Immunosuppression not only enhances the risk of infection but also complicates administration of live vaccines. Some antimalarial drugs are contraindicated (e.g. mefloquine) and others must be used with precaution. Prior to departure persons requiring hemodialysis should book sessions at centers listed in specialized guidebooks. In addition to infection, risks for hemodialysis patients include thrombosis of the arteriovenous fistula in case of dehydration or hypotension. In subjects with transplanted kidney, the risk of rejection can be enhanced either by poor compliance with immunodepressor treatment or by vaccination-induced antigenic stimulation. Pre-travel evaluation is necessary to determine metabolic, nutritional, and immune status. Subjects with kidney insufficiency and transplanted kidneys should be informed of the dangers and appropriate action in case of trouble.

Chronic administration of cyclosporin A induces nephrotoxicity in humans. This is related to a cyclosporin A-induced constriction of afferent glomerular arterioles and mesangial cells, which leads to a decrease in filtration pressure and creatinine clearance. Afterwards, cellular lesions are observed involving mainly tubular atrophy and interstitial fibrosis, both of which are nonspecific. The initial mechanism of its toxicity is not clearly explained. The current pharmacological approach is symptomatic in order to counteract or minimize the consequences of a prime cause, which still remains to be defined. However, cyclosporin A has a deletereous effect on mitochondrial functions and mainly on ATP synthesis, which occurs when Ca2+ accumulates in matrix mitochondria. The effects of trimetazidine, an antischemic drug used in the treatment of angina pectoris, have been assessed. This drug is effective in experimental models of hypoxia induced by cyclosporin A: it restores ATP synthesis previously decreased by Ca2+ and cyclosporin A, and releases a part of Ca2+ excess accumulated by mitochondria at concentrations reached in humans at usual dosage regimens. At higher concentrations, it reverses the mitochondrial permeability transition previously generated (opened) by Ca2+ and a pro-oxidant such as terbutylperoxide (t-BH). It was also observed that trimetazidine does not modify the immunosuppressive effects of cyclosporin A in various models. These data suggest that nephrotoxicity of cyclosporin A is not irrevocably linked to its immunosuppressive effect but that it may be possible to counteract at least partly its nephrotoxic effects without altering its effectiveness in preventing graft rejection.

We have prospectively studied in hemodialysis (HD) patients the evolution of hepatitis C virus (HCV) viremia and the putative relationships between the viremia and the biological markers of liver disease. For each of 22 HD patients having detectable antibodies to HCV (anti-HCV+), we looked four times for serum HCV-RNA by nested PCR (N-PCR), in April and November 1992, November 1993 and May 1994. We checked the transaminases (Trans) and the gamma glutamyl transpeptidase (gamma(GT)) levels on the same day as blood tests for the N-PCR. Abnormal Trans or gamma(GT)++ values were considered if they exceeded the upper limit of the normal level for our laboratory. Fifteen patients (68%) were intermittently N-PCR positive (N-PCR+): 3 patients were N-PCR+ at three determinations, 7 were N-PCR+ at two determinations and 5 only one time. Two patients (9%) were always N-PCR+ and five (23%) always negative. No correlation between an abnormal value of either Trans or gamma(GT) and viremia was evidenced at successive determinations. In conclusion, the majority (68%) of the anti-HCV+ patients had intermittent HCV N-PCR+. Among the anti-HCV+ patients, 77% were viremic. Since HCV viremia is often transitory and since there is no correlation between N-PCR positivity and the increase in Trans or gamma(GT) activities, HCV-RNA detection by N-PCR is probably not clinically relevant in anti-HCV+ HD patients.

To evaluate the morbidity of multiple artery renal transplants (1 artery) and to assess the value of this parameter as a risk factor for complications of renal transplantation in adults.140 renal transplants derived from brain dead donors with multiple arteries (2 arteries = 123, 3 arteries = 17) were reviewed with a mean follow-up of 3 years (6-120 months). Pedicle restoration was performed in 57 cases (end-to-side reimplantation of a polar artery = 17, composite aortic patch graft = 14, multiple procedures = 10, ligation of a polar artery = 8, arterial wound = 5, "gun barrel" anastomosis of 2 arteries = 4). Arteriography was performed systematically in 57 cases, in the absence of any signs suggestive of a vascular complication.2 recipients died from a vascular complication. 40% of transplants were functional at 5 years. 10 transplantectomies were performed for a vascular complication. 14 recipients returned to dialysis because of a vascular complication. 7.5% of systematic arteriographies revealed stenosis of the transplant artery. 54 transplants developed a vascular complication: thrombosis = 19, stenosis = 25. Three-artery transplants had a vascular morbidity of 50%. "Gun-barrel" anastomoses and polar reimplantations into the main trunk had a vascular morbidity of 40%. The urological morbidity was 10%.Multiple artery renal transplants, especially 3-artery transplants and certain pedicle restorations, are associated with a high risk of vascular complications. Arterial anatomy is a selection criterion for the donor and recipient which must be taken into account in renal transplantation.

We report the case of a 36 year-old-patient, hemodialyzed for idiopathic membranous glomerulonephritis, who suffers from type I membranoproliferative glomerulonephritis five years after a successful kidney transplantation. Etiologic evaluation evidenced chronic viral hepatitis C complicated by type III cryoglobulinemia. If hepatitis C induced membranoproliferative glomerulonephritis has yet been described among non transplanted patients, it is at our knowledge, the first observation in a renal transplant recipient.