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BackgroundLupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with an induction immunosuppressive therapy (IST), followed by a maintenance IST, to target remission and avoid relapses. The optimal duration of maintenance IST for proliferative LN is unknown.ObjectivesThe WIN-Lupus trial tested whether IST discontinuation after 2-3 years in proliferative LN was non-inferior to IST continuation for 2 more years.MethodsWIN-Lupus is an investigator-initiated academic randomized controlled trial, conducted in 28 French centers. Patients on maintenance IST with azathioprine or mycophenolate mofetil for a minimum of 2 years and a maximum of 3 years, and who were taking Hydroxychloroquine, were randomized (1:1) between 2 groups: IST continuation and IST discontinuation. The primary endpoint was the relapse rate of proliferative LN at 24 months. Secondary endpoints were the rate of severe SLE flares, survival without renal relapse or severe flare, adverse events, kidney function, disease activity, corticosteroid exposure, patient-reported outcome and medico-economic impact.ResultsBetween 2011 and 2016, 125 patients were screened and 96 were randomized in the trial: 48 in the IST continuation group, 48 in the IST discontinuation group. In the per-protocol population, a relapse of proliferative LN occurred in 5/40 (10.4%) patients with IST continuation, and in 12/44 (25%) patients with IST discontinuation (difference 14.8%, 95%CI [-1.9; 31.5]). Non-inferiority was not demonstrated for relapse rate. Time to renal relapse did not differ between groups (p=0.092). Severe SLE flares (renal or extra-renal) were less frequent in patients with IST continuation compared to IST discontinuation (5/40 vs 14/44 patients, p=0.035). IST discontinuation was associated with lower health-related costs. Adverse events did not differ between groups.ConclusionNon-inferiority of maintenance IST discontinuation after 2 to 3 years was not demonstrated for renal relapse. IST discontinuation was associated with a higher risk of severe SLE flare.References[1]Moroni G et al. When and how is it possible to stop therapy in patients with lupus nephritis? Clin J Am Soc Nephrol. 2021. CJN.04830421. doi: 10.2215/CJN.04830421.[2]Fanouriakis A et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis. 2020;79(6):713-723.[3]Jourde-Chiche N et al. Proliferative lupus nephritis treatment: practice survey in nephrology and internal medicine in France. Nephrol Ther. 2014;10(3):170-6.[4]Zen M et al. Immunosuppressive therapy withdrawal after remission achievement in patients with lupus nephritis. Rheumatology (Oxford). 2021;keab373. doi: 10.1093/rheumatology/keab373.[5]Malvar A et al. Kidney biopsy-based management of maintenance immunosuppression is safe and may ameliorate flare rate in lupus nephritis. Kidney Int. 2020;97(1):156-162.AcknowledgementsGroupe Coopératif sur le Lupus Rénal (GCLR)Disclosure of InterestsNoemie JOURDE-CHICHE Speakers bureau: Vifor Pharma, Grant/research support from: Fresenius Medical Care: grant paid to my institution (AP-HM) for the CINEVAS study in ANCA-associated vasculitis, Nathalie Costedoat-Chalumeau Grant/research support from: AP-HP received a research support from ROCHE for the OBILUP trial, Karine Baumstarck: None declared, LAURENCE BOUILLET Speakers bureau: GSK, novartis, biocryst, takeda, behring, Paid instructor for: takeda, novartis, Consultant of: GSK, novartis, biocryst, takeda, behring, blueprint, Grant/research support from: takeda, gsk, sanofi, biocryst, novartis, Stéphane Burtey: None declared, Valerie Caudwell: None declared, Laurent Chiche Speakers bureau: BMS, Paid instructor for: BMS, Lionel Couzi Speakers bureau: Astellas, Chiesi, Novartis, Sandoz, Ostuka, GSK, Biotest, Consultant of: Biotest, Hansa, Novartis, Grant/research support from: Novartis, Astellas, Christophe DELIGNY: None declared, Bertrand Dussol Speakers bureau: Genzyme, Novonordisk, Grant/research support from: Shire, Stanislas Faguer Speakers bureau: Asahi, Vifor Pharma, Sanofi, Consultant of: Abyonyx Pharma, Pierre Gobert: None declared, Guillaume Gondran Speakers bureau: Pfizer, Novartis, Consultant of: Genzyme, Antoine Huart Speakers bureau: Janssen, Paid instructor for: Pfizer, Aurélie Hummel: None declared, Emilie Kalbacher: None declared, Alexandre Karras Speakers bureau: Vifor, GSK, Astra-Zeneca, Roche, Paid instructor for: Vifor, Sanofi, Alexion, Consultant of: Novartis, GSK, Bohringer-Ingelheim, Marc Lambert Speakers bureau: CHUGAI-ROCHE, BAYER, PFIZER, LEOPHARMA, Paid instructor for: CHUGAI-ROCHE, Consultant of: CHUGAI-ROCHE, BAYER, PFIZER, LEOPHARMA, Grant/research support from: CHUGAI-ROCHE, Véronique LE GUERN: None declared, Sandrine Loubiere: None declared, Helene Maillard: None declared, Francois Maurier: None declared, Micheline Pha: None declared, Viviane Queyrel Paid instructor for: GSK, Consultant of: Boehringer Ingelheim, Francoise Sarrot-Reynauld: None declared, David Verhelst: None declared, Eric Hachulla Speakers bureau: Johnson & Johnson, GSK, Roche-Chugai, Consultant of: Johnson & Johnson, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, Sanofi-Genzyme, Grant/research support from: CSL Behring, GSK, Roche-Chugai and Johnson & Johnson, Zahir Amoura Speakers bureau: GSK, CSL Behring, Consultant of: GSK, Grant/research support from: GSK, Eric Daugas Speakers bureau: GSK, Amgen, Paid instructor for: GSK, Astra Zeneca, Consultant of: GSK, Astra Zeneca, Amgen, Grant/research support from: ROCHE for the OBILUP trial (AP-HP)

Background Peripheral nerve system (PNS) involvement is common in Fabry's disease (FD), predominantly affecting the small nerve fibers that are difficult to investigate with conventional electrophysiological methods. Patients and methods Eighteen patients followed for Fabry's disease underwent a prospective series of electroneurophysiological explorations, including a study of the cardiac parasympathetic autonomic nervous system (ANS) and electrochemical skin conductance (ESC) tests. Data were compared with those obtained in 18 matched healthy controls. Results All patients had at least one clinical sign suggestive of neuropathy: 16 reported an acrosyndrome and 12 had dyshidrosis. Cold hypoesthesia was found in 15 patients and heat hypoesthesia in 13. Electroneurophysiological investigations and study of the cardiac parasympathetic ANS were normal in all patients. The ESC was significantly lower in FD patients compared with controls. Conclusion PNS involvement is common in FD and should be suspected in patients exhibiting an acrosyndrome, dyshidrosis and/or cold hypoesthesia. Conventional electrophysiological investigations are normal. New techniques, such as ESC, provide early diagnosis of small fiber involvement that currently requires more sophisticated tests difficult to apply in routine practice.

El diagnostico de una nefropatia glomerular se basa en elementos clinicos y biologicos simples. A partir de estos elementos (edemas, hipertension arterial, proteinuria, hematuria, etc.) se define un diagnostico semiologico: sindrome nefrotico (puro o impuro), sindrome nefritico, sindrome hematurico, glomerulonefritis rapidamente progresiva o glomerulonefritis cronica. De este diagnostico, que puede y debe definirse en la consulta de medicina primaria, se desprende la necesidad o no de recurrir al nefrologo y la urgencia que requiere. Por ejemplo, el diagnostico de sindrome de glomerulonefritis rapidamente progresiva supone recurrir al nefrologo con urgencia. Por el contrario, un sindrome de glomerulonefritis cronica en un paciente diabetico puede ser tratado en medicina general sin urgencia, ya que en la gran mayoria de los casos es indicio de una glomeruloesclerosis diabetica. En un segundo tiempo, la orientacion diagnostica se basa en la presencia o ausencia de signos extrarrenales (lesiones cutaneas o articulares, anticuerpos sericos de diversos tipos, etc.) y en los datos de la biopsia renal, cuyas indicaciones son amplias. El pronostico de las nefropatias glomerulares es sumamente variable. Depende de numerosos factores: etiologia, presentacion clinica y funcion renal en el momento del diagnostico, existencia o no de un tratamiento especifico y calidad de la respuesta al tratamiento especifico y respuesta al tratamiento nefroprotector. El espectro evolutivo abarca desde la curacion sin secuela durante el sindrome nefrotico hasta las lesiones glomerulares minimas o incluso la insuficiencia renal terminal rapida en algunas amiloidosis.

Summary The ANAES has defined four stages of chronic renal disease according to the presence of markers of kidney damage and to Cockcroft clearance (an estimate of endogeneous creatinine clearance). Renal insufficiency is defined by a Cockcroft clearance below 60 ml/min per 1.73 m2. Renal insufficiency is moderate if Cockcroft clearance is between 59 and 30 ml/min, severe between 29 and 15 ml/min, and end stage below 15 ml/min. Recommendations for the management of patients are given at each stage. The National Kidney Fundation has defined five stages of chronic kidney disease introducing mild renal insufficiency if estimated glomerular filtration rate is between 89 and 60 ml/min.

Summary Renal function is still evaluated in 2010 by the dosage of serum creatinine. Its main drawback is the lack of sensitivity to detect early renal insufficiency. Formulas allowing to estimate either endogeneous creatinine clearance (Cockcroft formula) or glomerular filtration rate (MDRD and CKD-EPI formulas) give good prediction of renal function. However, they are not accurate in patients with extreme age and body weight, and in patients with a low production of creatine or having normal renal function.

In earlier registry analyses, cyclosporine at doses of3 mg/kg/d at 1 year post-renal transplantation has been associated with significant graft loss or reduction in renal function. Improvements in cyclosporine formulation with increased bioavailability, plus the use of more efficient comedications, may now confer better outcomes. To determine the effect of the 1-year cyclosporine microemulsion (CsA-ME) dose on renal allograft function at 5 years, we analyzed data collected from 2889 patients with documented graft survival to year 5 in a prospective, multinational, observational study-Neoral MOST.Glomerular filtration rate (GFR) at year 1 was 63 +/- 20 mL/min and 59 +/- 22 mL/min at year 5. The multivariate analysis including year 1 CsA-ME dose as factor and GFR at 1 year as covariate revealed the most significant factors affecting GFR at year 5 were 1-year GFR, donor age60 years, and CsA-ME dose at 1 year. Risk factors associated with reduction in 5-year GFR (65 mL/min) included donor or recipient age60 years, delayed graft function, cadaveric donor, previous graft, and acute rejection. CsA-ME dose3 mg/kg/d was found to protect GFR. Analysis of GFR at each year posttransplantation (Wilcoxon model) found 1-year CsA-ME (cutoff 3 mg/kg/d) had a significant effect at each time point.Compared to higher doses, CsA-ME3 mg/kg/d at year 1 posttransplantation is associated with increased preservation of renal allograft function at year 5.

Background Long-term success of renal transplantation depends upon the quality of the donor organ, avoidance of peritransplant and early posttransplant damage (rejection), and optimal maintenance of graft function after the first 6-12 months. Glomerular filtration rate (GFR) at 1 year is a standard way to evaluate short-term success, whereas calculated GFR at 5 years gives a better appreciation of long-term outcomes. The objective of this study was to assess the effect of various demographic and transplant-related parameters on renal function via GFR at 1 year and 5 years post transplantation, using univariate and multivariate data analysis. Methods Data on 1-year GFR were available from 10,397 patients, whereas 2,889 patients provided data on both 1-year and 5-year GFR. All patients were enrolled in the Neoral Multinational Observational Study in Transplantation (Neoral-MOST), an ongoing, prospective, observational study of adult renal transplant recipients. Results One-year GFR was the most relevant predictor for 5-year GFR. In a multifactorial analysis (ANCOVA) using 1-year GFR as a continuous variable, the effects of several highly relevant parameters from univariate analysis (such as acute rejection and delayed graft function) on 5-year GFR appeared to be fully mediated by their influence on 1-year GFR, whereas immunological risk factors like HLA match or previous transplantation had an ongoing effect on graft function beyond year 1. Conclusions The findings of this study corroborate and augment data from previous registry surveys, and confirm the importance of observational studies in investigating the role of peritransplant parameters on long-term graft outcome.

OBJECTIVE—Insulin resistance may be a risk factor for diabetic microangiopathy, which may have a familial component. We carried out a family-based study to determine which components of the insulin resistance syndrome are associated with diabetic retinopathy and nephropathy in type 1 diabetes. RESEARCH DESIGN AND METHODS—The Genesis France-Belgium Study is a multicenter binational study designed to investigate the genetic factors involved in the microvascular complications of type 1 diabetes using a family-based design. Probands were type 1 diabetic patients with diabetic retinopathy (classified as background, preproliferative, or proliferative) and possibly diabetic nephropathy (absent, incipient, established, or advanced). The insulin resistance score of their first-degree relatives was calculated according to their BMI and history of arterial hypertension, lipid disorders, and type 2 diabetes. RESULTS—The insulin resistance score of relatives was positively correlated with the albumin excretion rate (P = 0.0009) and fasting plasma glucose (P = 0.0003) and HbA1c (P < 0.0001) concentrations. This score was higher in the relatives of probands with than in those without diabetic nephropathy (P = 0.0370). Similarly, it was higher in relatives of subjects with proliferative diabetic retinopathy than in those of probands without, even after controlling for subjects with versus without diabetic nephropathy (P = 0.0379). However, the components of the insulin resistance score in relatives differed according to the severity of diabetic retinopathy or nephropathy in the probands. Obesity and history of arterial hypertension were most common in relatives of probands with proliferative diabetic retinopathy, whereas obesity and history of lipid disorders were most common in the relatives of probands with diabetic nephropathy. CONCLUSIONS—Familial insulin resistance segregates with diabetic complications: lipid disorders and obesity segregate with diabetic nephropathy, whereas arterial hypertension and obesity segregate with diabetic retinopathy.

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.

Introduction L’etiologie du lichen sclero-atrophique (LSA) n’est pas connue. Plusieurs facteurs seraient en cause, dont des mecanismes auto-immuns. Nous rapportons le cas d’une patiente presentant un lichen sclero-atrophique cutaneo-muqueux associe a des anticorps anti-NuMA. Observation Une patiente de 53 ans etait hospitalisee pour la prise en charge d’un LSA diffus. Ses antecedents etaient une insuffisance renale chronique terminale secondaire a une nephropathie interstitielle sur uropathie malformative et 3 fausses couches spontanees tardives. Elle ne prenait aucun medicament. L’examen clinique notait un LSA cutane diffus (abdomen, quatre membres, seins) ainsi qu’un LSA vulvaire severe avec fusion des petites levres et encapuchonnement du clitoris. Elle ne presentait pas de dysurie ni de dyspareunie. Le reste de l’examen clinique etait normal, il n’y avait notamment pas de photophobie, ni arthralgie ou autre manifestation systemique. Une biopsie cutanee du bras gauche revelait des remaniements histologiques du tissu conjonctif, un derme homogeneise avec un aspect fibreux et un collagene epaissi, l’ensemble confirmant le diagnostic de LSA. Le profil biologique auto-immun etait particulier, montrant des anticorps antinucleaires (AAN) a 1/320 avec des anticorps anti-NuMA de type 1. Les recherches d’anticorps anti-ADN, anti-ECT, anticardiolipine, anti-β2GP1 et d’anticoagulant circulant etaient negatives. Discussion Cette observation nous a semblee interessante en raison de l’association d’un LSA cutaneo-muqueux severe et d’un profil auto-immun atypique. L’etiologie du LSA n’est pas connue ; elle semble etre multifactorielle. Son association avec des pathologies inflammatoires et la presence d’auto-anticorps dans 40 % des cas sont en faveur, d’une part, auto-immune. Les anticorps anti-NUMA sont des auto-anticorps antinucleaires rares ( Conclusion Nous rapportons a notre connaissance la premiere observation de la presence d’anticorps anti-NuMA au cours d’un LSA cutaneo-muqueux. La realite et la signification de cette association ne pourront etre etablies qu’a la lumiere d’observations nouvelles.

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.

Assays of adenosine and its derivatives in biological fluids involve fluorimetric, radioimmunological or chromatographic analyses. Techniques currently used are tedious because they involve either an extraction using immunological methods or one or two freeze drying cycles when using high performance liquid chromatography (HPLC). In this context, we describe a “quick” HPLC method using a diode array detector for the spectral analysis and quantitation of adenosine and its derivatives in less than two hours following sampling. We compared our results to those obtained with an HPLC technique coupled to UV detection. Although there is a good correlation between the two techniques, the“quick” method provide values that are on average 30% higher than those obtained with the classical method. The absence of a lyophilization step in the classical method could explain this difference. The utilization of an HPLC system coupled to a diode array detector leads to a rapid and reliable assay of adenosine and its deriva...

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.

Background Delayed graft function (DGF) is a common complication after renal transplantation, and may affect graft function. The aim of this analysis was to evaluate risk factors for DGF, as well as parameters and events influencing graft function after DGF. We analyzed data collected in an ongoing international, prospective; observational study, the Neoral-MOST (Multinational Observational Study in renal Transplantation), and included in the analysis all patients with cadaveric kidney transplants for whom renal function at 1 year posttransplantation was documented ( N = 8950). Logistic regression was used to evaluate the risk factors for DGF occurrence, and multifactorial analysis of variance (ANCOVA) to assess the relevance of different factors for GFR at 1 year. Results Higher donor age, longer CIT, male recipients, Caucasian recipients, high recipients body mass index, and PRA were all associated with a higher risk for DGF. Renal function of former DGF kidneys at 1 year was lower in kidneys of elder donors, or which had experienced rejection or CMV infection. Variations of the maintenance regimen at 1 year posttransplantation were not associated with better graft function. Multifactorial analysis showed donor age and acute rejection as significant independent factors. Conclusions Most factors increasing the risk for DGF or having a negative impact on renal function at 1 year in grafts with DGF are predetermined. Additional posttransplant damage by acute rejection was associated with further reductions in GFR. Preventing acute rejection is an important step in achieving optimal function of DGF grafts.

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.

Hepatitis B (HBV) and hepatitis C (HCV) virus infections are major risk factors affecting long-term morbidity and mortality after renal transplantation. Hepatitis prevalence is subject to geographical variations.To compare and analyze the geographical prevalence, risk factors and impact of HBV and HCV infection in multinational cohorts of renal transplant recipients.From 1989 - 2002, data on 12,856 kidney transplant recipients in 37 countries were collected within the prospective MOST (Multinational Observational Study in Transplantation). Subgroup analyses of hepatitis-related prevalence, risk factors and impact were conducted on patients whose HBV and HCV status was available at time of transplantation. Countries were substratified according to population prevalence ofor = 5% HBV oror = 10% HCV.The prevalence of HBV was 2.9%, of HCV 8.7% and of HBV together with HCV 0.4%. Risk factors for hepatitis infection in renal transplant recipients were long dialysis time, retransplantation and blood transfusions. At each study endpoint up to 5 years after transplantation, no significant differences in graft function were observed, although the 1-year acute rejection rate tended to be lower in HCV+ patients. At 5 years post-transplant, there were no differences between the subgroups and regions regarding infections, post-transplant diabetes mellitus or malignancies including PTLD.Overall, HCV infections are more prevalent than HBV. Despite large geographical differences in prevalence, HBV and HCV status did not appear to have a significant impact on renal graft function, infections, malignancies and post-transplant diabetes mellitus up to 5 years after renal transplantation throughout the MOST countries.

Kidney involvement is frequent in hematologic malignancies. It is associated with adverse outcome and treatment difficulties. It can affect every area of the renal parenchyma (tubules, interstitium, glomerulus, vessels). Various mechanisms could be implicated: deposits of immunoglobulin fractions or crystals, renal infiltration by malignant cells, urinary tract obstruction, paraneoplastic or storage glomerulopathies… Diagnostic strategy relies on the clinical presentation: acute renal failure, chronic kidney disease, glomerular proteinuria with or without nephrotic syndrome, tubular proteinuria, hydroelectrolytic disorders. In this review, we detail the diagnostic tests that are needed for the detection and the follow-up of renal involvement in hematologic malignancies, and clarify the indications of renal biopsy. We propose diagnostic strategies of renal involvement in myeloma, Waldenström's disease, high grade lymphomas and acute leukemias, low grade lymphomas and chronic leukemias. The adverse effects of treatments (chemotherapy, radiotherapy, stem cell graft …) are not addressed in this review.

Resume Le but de cette etude est de comparer la nouvelle trousse de dosage du recepteur soluble a l'interleukine 2 (R IL2-S) des Laboratoires Immunotech a celle deja existant des Laboratoires T Cell Sciences. Nous avons teste ses qualites analytiques (performance, sensibilite, reproductibilite), les resultats que nous obtenons dans differents types de prelevement sont bien correles avec ceux donnes par la trousse de reference.

Summary Kidneys obtained from donors after cardiac death (DCD) are known to have higher rates of primary nonfunction and delayed graft function (DGF) than heart beating cadaveric donor (CAD) kidneys, but little is known about long-term function of DCD grafts that survive to 1 year. To investigate the outcomes of renal transplant recipients whose DCD graft functioned for at least 1 year, this study analyzed data collected from 326 DCD graft recipients and 340 CAD-matched controls enrolled in a prospective, multinational, observational study – Neoral®-MOST (Multinational Observational Study in Transplantation) (Novartis, Basel, Switzerland). No differences were found in the demographics or immunosuppression between the two groups. All patients received a Neoral®-based immunosuppressive regimen. Donors after cardiac death graft recipients had a higher incidence of DGF (40% vs. 27% CAD; P

Introduction. Mycophenolate mofetil (MMF) has greatly reduced the risk of acute rejection episodes (ARE) after renal transplantation, but dose reductions/withdrawals could jeopardize long-term results. Methods. The MOST database of de novo patients treated with MMF at month 1 and functioning grafts at month 12 were divided into 2 groups: groups 1, 2 g MMF at month 1 and month 12; and group 2, 2 g MMF at month 1 but MMF

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.

Background Peritransplant risk factors influence short-term and long-term graft survival, and 1-year serum creatinine is known to predict long-term graft survival. To examine interrelationships between risk factors, renal function at 1 year, and long-term graft function in patients maintained on cyclosporine, we analyzed data collected from 10,692 de novo or maintenance renal transplant recipients in an ongoing international, prospective, observational study—Neoral-MOST (Multinational Observational Study in renal Transplantation). The effect of donor age, delayed graft function, acute rejection, donor type, panel-reactive antibodies, and previous graft on 1- and 5-year renal function and their relationship to 1-year serum creatinine was assessed. Results Donor age, delayed graft function, acute rejection, and donor type significantly increased the risk for serum creatinine > 130 μmol/L at 1 year posttransplant, and 1-year serum creatinine was the strongest predictor of 5-year renal function. After adjustment for 1-year serum creatinine, an ongoing influence was observed for donor age, donor type, and previous graft. Delayed graft function and acute rejection had a significant effect on serum creatinine at year 1 but no additional impact on long-term graft function. Conclusions Serum creatinine at 1 year is influenced by risk factors known to affect overall graft survival and is predictive of 5-year renal graft function. The effects of delayed graft function and acute rejection appear to be limited to their influence on serum creatinine at 1 year, whereas donor type and previous graft predominantly affect later stages of graft life.

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.

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.

Malignant histiocytofibroma of the bladder is a rare (16 cases reported in the literature) and very aggressive sarcoma. It is sometimes associated with a haematological malignancy. The authors report a case of malignant histiocytofibroma of the bladder in a 72-year-old haemodialysed woman with a poor general status. She had a history of chemotherapy and radiotherapy for gastrointestinal lymphoma 6 years previously. Treatment consisted of palliative cystectomy for bladder pain and haematuria. A massive pelvic and abdominal wall recurrence occurred two months after cystectomy and the patient died. The authors review the 16 cases of malignant histiocytofibroma of the bladder reported in the literature. Histiocytofibroma is a tumour which requires aggressive treatment with a combination of radical surgery and systemic chemotherapy.

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.