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Nephronophthisis (NPH) is an autosomal-recessive ciliopathy representing one of the most frequent causes of kidney failure in childhood characterized by a broad clinical and genetic heterogeneity. Applied to one of the worldwide largest cohorts of patients with NPH, genetic analysis encompassing targeted and whole exome sequencing identified disease-causing variants in 600 patients from 496 families with a detection rate of 71%. Of 788 pathogenic variants, 40 known ciliopathy genes were identified. However, the majority of patients (53%) bore biallelic pathogenic variants in NPHP1. NPH-causing gene alterations affected all ciliary modules defined by structural and/or functional subdomains. Seventy six percent of these patients had progressed to kidney failure, of which 18% had an infantile form (under five years) and harbored variants affecting the Inversin compartment or intraflagellar transport complex A. Forty eight percent of patients showed a juvenile (5-15 years) and 34% a late-onset disease (over 15 years), the latter mostly carrying variants belonging to the Transition Zone module. Furthermore, while more than 85% of patients with an infantile form presented with extra-kidney manifestations, it only concerned half of juvenile and late onset cases. Eye involvement represented a predominant feature, followed by cerebellar hypoplasia and other brain abnormalities, liver and skeletal defects. The phenotypic variability was in a large part associated with mutation types, genes and corresponding ciliary modules with hypomorphic variants in ciliary genes playing a role in early steps of ciliogenesis associated with juvenile-to-late onset NPH forms. Thus, our data confirm a considerable proportion of late-onset NPH suggesting an underdiagnosis in adult chronic kidney disease.

International audience; Human leukocyte antigen (HLA) mismatching and minimization of immunosuppression are two major risk factors for the development of de novo donor-specific antibodies, which are associated with reduced kidney graft survival. Antibodies do not recognize whole HLA antigens but rather individual epitopes, which are short sequences of amino acids in accessible positions. However, compatibility is still assessed by the simple count of mismatched HLA antigens. We hypothesized that the number of mismatched epitopes, or ("epitope load") would identify patients at the highest risk of developing donor specific antibodies following minimization of immunosuppression. We determined epitope load in 89 clinical trial participants who converted from cyclosporine to everolimus 3 months after kidney transplantation. Twenty-nine participants (32.6%) developed de novo donor specific antibodies. Compared to the number of HLA mismatches, epitope load was more strongly associated with the development of donor specific antibodies. Participants with an epitope load greater than 27 had a 12-fold relative risk of developing donor-specific antibodies compared to those with an epitope load below that threshold. Using that threshold, epitope load would have missed only one participant who subsequently developed donor specific antibodies, compared to 8 missed cases based on a 6-antigen mismatch. DQ7 was the most frequent antigenic target of donor specific antibodies in our population, and some DQ7 epitopes appeared to be more frequently involved than others. Assessing epitope load before minimizing immunosuppression may be a more efficient tool to identify patients at the highest risk of allosensitization.

Hypocomplementemic urticarial vasculitis is a rare systemic vasculitis, affecting small vessels, characterised by chronicle urticaria, hypocomplementemia, and systemic manifestations. Renal involvement, whose prevalence varies between 9% and 60%, is mainly glomerular. We here report the case of a 59 years old woman presenting kidney failure, associated with chronicle urticaria and arthralgias. Laboratory investigation showed haematuria, proteinuria, hypocomplementemia and anti-SSa antibody positivity. A percutaneous kidney biopsy revealed focal and segmental glomerulonephritis associated with an acute interstitial nephritis. Hypocomplementemic urticarial vasculitis diagnosis was established after identifying anti-C1q antibodies. The lack of a dry syndrome, the negativity of a Schirmer test and the lack of sialadenitis on a salivary gland biopsy excluded an associated Gougerot-Sjogren Syndrome. The patient was treated with hydroxychloroquine and low-dose steroids, enabling a clinical and biological recovery. Of the 82 cases in the literature describing hypocomplementemic urticarial vasculitis associated nephropathies, 72 (88%) were a glomerular impairment, most frequently secondary to membranoproliferative glomerulonephritis. Only 6 (7%) tubulo-interstitial nephritis have been reported, 4 of them being associated with a glomerulonephritis. Patients were more likely to be women, aged in their third decade. The most frequent renal manifestations were haematuria (60%), and proteinuria (52%). Kidney failure was rarely observed (22%), with a fairly good renal prognosis. Hypocomplementemic urticarial vasculitis was associated with a systemic disease in 11 (13%) patients. In the absence of recommendations, the treatment strategy remains to be defined.

BACKGROUND Renal cancer accounts for 3% of adult malignancies; renal cell carcinoma (RCC) represents 80% of all renal cancers, and is characterized by late recurrences. Recurrences after kidney transplantation are associated with a high mortality rate. We aimed to determine if recurrences are linked to tumor characteristics and to delays between diagnosis and transplantation. METHODS We retrospectively analyzed data from French kidney-transplanted patients with medical histories of pretransplant renal cancer, focusing on the most common histological subtypes: clear cell and papillary cancers. Characteristics of the tumors, patients, and kidney transplantations were documented, and posttransplant patient survival was analyzed. RESULTS Of 143 patients, 13 experienced cancer recurrence after kidney transplantation. The mean delay in recurrence was 3 ± 2.3 years posttransplantation, and the cumulative incidences of recurrence were 7.7% at 5 years and 14.9% at 10 years. The risk of recurrence was higher in patients with clear cell RCC (13% vs 0%, P = 0.015). There was no correlation between posttransplant recurrence and the interval before transplantation. Factors associated with a higher risk of cancer recurrence were histological clear cell RCC (P = 0.025), tumor stage pT2 (P = 0.002), and Fuhrman grade IV (P < 0.001). Recurrences were associated with a high mortality rate; 76.9% of patients with recurrences had died by the end of the follow-up period. CONCLUSIONS Recurrences of clear cell RCC are not uncommon after kidney transplantation and are associated with very poor prognoses. These results should be considered before listing patients with a history of renal cancer for transplantation.

Resume Plusieurs modalites de traitement de l’insuffisance renale chronique terminale sont aujourd’hui disponibles. La transplantation renale a partir de donneurs vivants est la plus avantageuse pour les receveurs en termes de survie et de qualite de vie, en plus d’etre la plus economiquement viable pour la societe. Cette option souleve la question du devenir des donneurs vivants, sujets sains qui se soumettent a une procedure chirurgicale lourde. Plusieurs travaux ont ete menes comparant le devenir de donneurs de rein a celui de sujets controles. Les criteres d’evaluation etaient les potentielles complications de la nephrectomie a court comme a long termes : survenue d’une insuffisance renale, d’une hypertension arterielle, d’une proteinurie, possibilite de grossesse ulterieure, qualite de vie, survie du patient. Les resultats des premieres etudes ne mettaient pas en evidence de risque lie au don par rapport a celui existant dans la population generale. Mais depuis 2013, des publications ont rapporte l’existence d’un risque plus eleve d’insuffisance renale chronique, voire de mortalite, chez les donneurs de rein compares a des sujets controles selectionnes comme des candidats au don. Le risque lie au don est estime acceptable et minime, aux seules conditions d’une evaluation et d’une selection rigoureuse des candidats et d’un suivi regulier des donneurs indispensable.

Encapsulating peritoneal sclerosis is a rare but devastating complication of long-term peritoneal dialysis with a high mortality rate. The incidence is between 0.5 and 2.5%, decreasing with time. PSE is defined as a clinical syndrome with signs of gastrointestinal obstruction, inflammation parameters, radiological and macroscopic changes. The duration of treatment and the cessation of peritoneal dialysis are the main risks. About 75% occured in patients on hemodialysis or after kidney transplantation. Morphological alterations are disappearance of mesothelial layer, submesothelial fibrosis, interstitial sclerosis and vasculopathy. Ultrafiltration failure, fast transport status of the peritoneal membrane and loss of sodium sieving, the most powerful predictor, are the functional abnormalities. Biomarkers in peritoneal effluent include cancer antigen 125, interleukin-6. The pathophysiology is probably a consequence of a multiple-hit process in which expression of growth factors and cytokines play a central role. Medical strategies (corticosteroids, tamoxifen) in association with parenteral nutrition and/or surgery (enterolysis) are discussed. Prevention is the use of physiological peritoneal dialysis solutions, icodextrine instead of high glucose concentration solutions and peritoneal lavage after peritoneal dialysis stopping.

Hypocomplementemic urticarial vasculitis is a rare systemic vasculitis, affecting small vessels, characterised by chronicle urticaria, hypocomplementemia, and systemic manifestations. Renal involvement, whose prevalence varies between 9% and 60%, is mainly glomerular. We here report the case of a 59 years old woman presenting kidney failure, associated with chronicle urticaria and arthralgias. Laboratory investigation showed haematuria, proteinuria, hypocomplementemia and anti-SSa antibody positivity. A percutaneous kidney biopsy revealed focal and segmental glomerulonephritis associated with an acute interstitial nephritis. Hypocomplementemic urticarial vasculitis diagnosis was established after identifying anti-C1q antibodies. The lack of a dry syndrome, the negativity of a Schirmer test and the lack of sialadenitis on a salivary gland biopsy excluded an associated Gougerot-Sjögren Syndrome. The patient was treated with hydroxychloroquine and low-dose steroids, enabling a clinical and biological recovery. Of the 82 cases in the literature describing hypocomplementemic urticarial vasculitis associated nephropathies, 72 (88%) were a glomerular impairment, most frequently secondary to membranoproliferative glomerulonephritis. Only 6 (7%) tubulo-interstitial nephritis have been reported, 4 of them being associated with a glomerulonephritis. Patients were more likely to be women, aged in their third decade. The most frequent renal manifestations were haematuria (60%), and proteinuria (52%). Kidney failure was rarely observed (22%), with a fairly good renal prognosis. Hypocomplementemic urticarial vasculitis was associated with a systemic disease in 11 (13%) patients. In the absence of recommendations, the treatment strategy remains to be defined.

Introduction Although kidney transplantation carries a survival benefit compared with dialysis, mortality, especially the first year after transplantation, is high in recipients older than 70. The aim of this study was to evaluate early death and graft failure, and to determine the risk factors associated with these events in this specific population. Methods All patients older than 70 years who received a kidney transplant between January 2000 and December 2014 in the North-West of France were included (n = 171). Baseline characteristics and outcomes after transplantation were studied. Kaplan-Meier analysis was performed to assess patient and graft survival, and Cox regression analysis to evaluate risk factors for graft failure and patient death. Results The mean recipient age was 73.3 ± 2.5 years. Death-censored graft survival at 1, 3, and 5 years were 82.6%, 78.7%, and 75.4%, respectively. Patient survival at 1, 3, and 5 years was 90.1%, 82.5%, and 68.1%, respectively. One year after transplantation, 17 patients (9.9%) were dead, mainly from infectious (58.5%) or cardiovascular disease (29.4%). According to the Cox multivariate analysis, the independent risk factors for death or graft failure during the first year were arrhythmia (odds ratio [OR] 2.26; 95% confidence interval [CI] 1.08–4.8), left-ventricular ejection fraction (LVEF) under 56% (OR 2.38; 95% CI 1.18–4.83), human leucocyte antigen (HLA) antibodies (OR 2.1; 95% CI 1.04–4.2), deceased donor from cardiovascular cause (OR 5.18; 95% CI 1.22–6.3), and acute rejection (OR 2.77; 95% CI 1.2–6.3). Conclusion In kidney transplant recipients older than 70 years, cardiac evaluation and immunosuppression optimization seem to be crucial to improve short-term patient and graft survival., Graphical abstract

BK virus is near ubiquitous, with a seroprevalence of around 80% in the general population. Subsequent to an asymptomatic primary infection, BK virus then remains dormant in healthy subjects. Reactivation occurs in immunocompromised people. BKv is pathogenic mainly among patients who have received a kidney transplant, in whom the virus can cause specific tubulo-interstitial nephritis and even result in graft failure among approximately 20 to 30% of nephritic cases. Since the mid 90 s, incidence has increased with the use of new powerful immunosuppressor treatments. The cornerstone of BK virus infection or BK virus-associated nephropathy treatment is a decrease of the immunosuppressive regimen, which must then be offset with the risk of rejection. The use of several adjuvant therapies has been submitted (fluoroquinolones, leflunomide, intravenous immunoglobulins, cidofovir), with no sufficient proof enabling the recommendation of first-line prescription. The high frequency of this infection and its potential harmfulness argue for the use of prevention strategies, at least among patients presenting risk factors. Retransplantation is safe after a first kidney allograft loss caused by BK-virus nephropathy, on condition that a screening for viremia is frequently conducted.

Background Kidney graft survival in simultaneous pancreas–kidney (SPK) recipients is known to decrease after pancreas graft failure. Methods Sixty-three consecutive SPK recipients were retrospectively reviewed. Kidney graft function and proteinuria were evaluated at three months after the transplantation and at last follow-up. Histopathologic findings of protocol biopsies performed three months and one yr after transplantation were analyzed. Results Twelve patients lost the pancreas graft. Donors' characteristics were similar in patients with or without pancreas failure. After a median follow-up of 36 months, mean eGFR with a functional pancreas was 69.5 mL/min/1.73 m² vs. 56.3 mL/min/1.73 m² (p = 0.01) after pancreas loss. Patients who lost pancreas had a median proteinuria of 0.28 g vs. 0.13 g per 24 h (p = 0.02). Analysis of three-month protocol biopsies revealed more frequent isolated glomerulitis after pancreas failure (p = 0.0001), without peritubular capillaritis or C4d deposition. No donor-specific anti-HLA antibodies were detectable in these patients. Chronic tubulointerstitial changes were more frequent in patients with pancreas loss. There was no evidence of diabetic nephropathy recurrence. Conclusion SPK recipients develop an early kidney graft dysfunction after pancreas failure. Histopathologic findings revealed frequent glomerulitis without antibody-mediated rejection and early chronic changes.

Summary Background: Our objective was to clarify the clinical outcome of renal transplantation based on residual daily urine output (RDUO). Material/Methods: We retrospectively analyzed a prospective database of 276 patients who underwent renal transplantation (Tx) between January 2008 and December 2012. Patients had pre-transplantation daily urine output measurement of 24-h proteinuria and were clinically re-evaluated the day before transplantation. We included patients with no daily urine output and those with residual daily urine output. Real bladder capacity was not measured. We excluded patients with a history of lower urinary tract malformation, those treated by trans-ileal conduit or enterocystoplasty, and those with early graft thrombosis or graft primary non-function. Results: Sex ratio, age at Tx, pre-Tx MHC antibodies levels, donor age, and cold ischemia duration were not significantly different between the 2 groups. Dialysis duration was longer in group I (p

Nowadays, several treatments exist to treat terminal chronic renal failure. Best results for the recipients are obtained with kidney transplantation concerning mortality and quality of life. Transplantation is also the cheaper option for society. Living kidney donation raises the issue of the becoming of the donor, an absolutely healthy subject who gets to a surgical procedure. The becoming of living kidney donors has been compared with the one of controls subjects in several studies. The evaluations focused on the complications of nephrectomy in the short and long-term: kidney failure, hypertension, proteinuria, possibility of pregnancy, quality of life, and mortality. The first results did not show any risk linked to kidney donation, compared to general population. However, since 2013, kidney donors were found at higher risk for kidney failure and even for mortality, compared with controls selected like donor candidates. The risk of kidney donation is nevertheless acceptable and minimal, on the condition of rigorous selection of candidates and regular follow-up.

Encapsulating peritoneal sclerosis is a rare but devastating complication of long-term peritoneal dialysis with a high mortality rate. The incidence is between 0.5 and 2.5%, decreasing with time. PSE is defined as a clinical syndrome with signs of gastrointestinal obstruction, inflammation parameters, radiological and macroscopic changes. The duration of treatment and the cessation of peritoneal dialysis are the main risks. About 75% occured in patients on hemodialysis or after kidney transplantation. Morphological alterations are disappearance of mesothelial layer, submesothelial fibrosis, interstitial sclerosis and vasculopathy. Ultrafiltration failure, fast transport status of the peritoneal membrane and loss of sodium sieving, the most powerful predictor, are the functional abnormalities. Biomarkers in peritoneal effluent include cancer antigen 125, interleukin-6. The pathophysiology is probably a consequence of a multiple-hit process in which expression of growth factors and cytokines play a central role. Medical strategies (corticosteroids, tamoxifen) in association with parenteral nutrition and/or surgery (enterolysis) are discussed. Prevention is the use of physiological peritoneal dialysis solutions, icodextrine instead of high glucose concentration solutions and peritoneal lavage after peritoneal dialysis stopping.

We report the case of a human immunodeficiency virus-seropositive patient whose initial kidney transplant failed because of BK polyomavirus-induced nephropathy, and who underwent a second transplantation 3 years later. BK viruria was detected 1 day after transplantation. After 1 month, BK viremia developed along with a donor-specific antibody. After decreasing tacrolimus and mycophenolic acid and 2 courses of intravenous immunoglobulins, BK viremia and donor-specific antibody permanently disappeared, with stable renal function. This article is protected by copyright. All rights reserved.

International audience; BACKGROUND: POR*28 is a recently newly described allelic variant of the cytochrome P450 oxydoreductase (POR) which might be associated with an increased metabolic activity of P450 cytochromes (CYP) 3A5 and 3A4. Consequently, carriers of at least one allele of this polymorphism could require increased calcineurin inhibitors doses to reach the target residual concentrations (Co). The objective of this study is to test whether the allelic variant of POR, which is associated with an increased metabolic activity of CYP3A, impacts Tacrolimus (Tac) pharmacokinetics. METHODS: We tested this hypothesis in a population of 229 kidney transplant recipients (KTR) from a large, multicenter, prospective and randomized study. We have analyzed the association between POR*28 genotype and the proportion of individuals reaching the target Tac residual concentration (Tac Co) 10 days after transplantation. We have also measured the association between POR*28 and the Tac Co, and adjusted Tac Co (Tac Co/Tac dose) over time using generalized mixed linear models. RESULTS: Ten days after transplantation, there was no difference of frequencies of KTR within the target range of Tac Co (Co 10-15 ng/ml) according to the POR*28 genotype (p=0.8). The mean Tac Co at day 10 in the POR*1/*1 group was 15.3±9.7 ng/ml compared with 15.7±7.8 ng/ml in the POR*1/*28 group and 14.2 ±6.8 ng/ml, in the POR*28/*28 group, p=0.8. The adjusted Tac Co was not associated with POR*28 genotype over time (random effects model, p=0.9). When restricted to KTR expressing CYP3A5, POR*28 gentoype did not impact the proportion of individuals within the Tac Co target range neither the adjusted Tac Co (random effects model, p=0.1). CONCLUSIONS: POR*28 does not significantly influence Tac pharmacokinetic parameters in a large cohort of KTR. This study does not confirm recent findings indicating that POR*28 carriers require more Tac to reach target Co

Long-term outcomes in renal transplant recipients withdrawn from steroid and submitted to further minimization of immunosuppressive regimen after 1 year are lacking. In this multicenter study, 204 low immunological risk kidney transplant recipients were randomized 14.2 ± 3.7 months post-transplantation to receive either cyclosporine A (CsA) + azathioprine (AZA; n = 53), CsA + mycophenolate mofetil (MMF; n = 53), or CsA monotherapy (n = 98). At 3 years postrandomization, the occurrence of biopsy for graft dysfunction was similar in bitherapy and monotherapy groups (21/106 vs. 26/98; P = 0.25). At 10 years postrandomization, patients' survival was 100%, 94.2%, and 95.8% (P = 0.25), and death-censored graft survival was 94.9%, 94.7%, and 95.2% (P = 0.34) in AZA, MMF, and CsA groups, respectively. Mean estimated glomerular filtration rate was 70.4 ± 31.1, 60.1 ± 22.2, and 60.1 ± 19.0 ml/min/1.73 m(2), respectively (P = 0.16). The incidence of biopsy-proven acute rejection was 1.4%/year in the whole cohort. None of the patients developed polyomavirus-associated nephropathy. The main cause of graft loss (n = 12) was chronic antibody-mediated rejection (n = 6). De novo donor-specific antibodies were detected in 13% of AZA-, 21% of MMF-, and 14% of CsA-treated patients (P = 0.29). CsA monotherapy after 1 year is safe and associated with prolonged graft survival in well-selected renal transplant recipient (ClinicalTrials.gov number: 980654).

Resume Introduction Le fer dextran de bas poids moleculaire peut etre administre en une perfusion unique d’une dose totale correspondante a la carence en fer. L’objectif de cette etude observationnelle etait de determiner si l’administration unique d’une dose totale de fer dextran permettait de corriger la carence martiale du patient en dialyse peritoneale pendant une duree de quatre mois. Patients et methodes Les patients traites par dialyse peritoneale depuis plus de trois mois et ayant une anemie (hemoglobine Resultats Douze des dix-sept patients inclus terminaient l’etude. La dose totale moyenne administree etait de 742 ± 150 mg sans effet indesirable rapporte. Quatre mois apres l’injection on observait une augmentation significative de la moyenne de l’hemoglobinemie (10,1 ± 0,7 g/dL vs 11,4 ± 1,2 g/dL, p Conclusion Chez le patient traite par dialyse peritoneale, le fer dextran de faible poids moleculaire en injection unique d’une dose totale permet de corriger l’anemie ferriprive pendant une duree de quatre mois.

Gueutin V, Ficheux M, Châtelet V, Lecouf A, Henri P, Hurault de Ligny B, Ryckelynck J-P, Lobbedez T. Hydration status of patients with end-stage renal disease after kidney transplantation. Clin Transplant 2011: 25: E656–E663. © 2011 John Wiley & Sons A/S. Abstract: Background: This study was carried out to estimate the modification of hydration status within the first three months of renal transplantation. Subjects and methods: Fifty patients who underwent a first kidney allograft were prospectively followed for three months after renal transplantation to assess hydration status by bioimpedance spectroscopy. Results: Two hours before the transplant procedure, 10/42 (23.8%) patients were overhydrated. Two days after surgery, 32/40 (80.0%) patients were overhydrated and at three months, 14/27 (51.9%) patients remained fluid-overloaded. Peritoneal dialysis (PD) patients had a lower hydration status (−0.60 L) than hemodialysis (HD) patients (0.70 L; p

Lymphomatoid granulomatosis (LYG) in renal transplant recipients is rare multisystemic angiocentric lymphoproliferative disorder with significant malignant potential. Here, we describe LYG in a 70-year-old renal allograft recipient who, 4 years after transplantation, on tacrolimus and mycophenolate mofetil and prednisone maintenance immunosuppression, complained of low-grade fever, persistent headache and gait disturbance. The MRI of the brain revealed diffuse periventricular cerebral and cerebellar contrast-enhanced lesions. The CT scan of the thorax showed multiple pulmonary nodular opacities in both lung fields. The patient was diagnosed LYG based on the cerebral biopsy showing perivascular infiltration of CD20-positive B-lymphocytes with granulomatous lesions and immunofluorescence staining with anti-EBV antibodies. With careful reduction of the immunossuppression combined with the use of rituximab, our patient showed a complete disappearance of LYG, and she is clinically well more than 4 years after the diagnosis, with good kidney function. No recurrence has been observed by radiological imaging until now. This is the first report of a durable (>4 years) complete remission of LYG after treatment with rituximab in renal transplantation.

Post-transplant diabetes mellitus (PTDM) is a well-known complication in renal transplant recipients (RTRs). While a number of risk factors for PTDM have been identified, the potential impact of pre-transplant dialysis modality on subsequent development of PTDM has not yet been explored. We performed a multicenter retrospective study on 2010 consecutive RTRs who did not have a history of diabetes prior to renal transplantation. PTDM was defined as a need for anti-diabetic therapy in an RTR without a history of diabetes prior to transplantation. Analysis of the risk factors for development of PTDM was performed with respect to pre-transplant dialysis modality. A total of 137 (6.8%) patients developed PTDM; 7% in the hemodialysis group and 6.5% in the peritoneal dialysis (PD) group (p = 0.85). In the multivariate analysis, age (p

Summary This study attempted to establish whether a calcineurin inhibitor (CNI)-free immunosuppressant regimen based on sirolimus (SRL) is associated with a preservation of conduit arteries endothelial function in kidney recipients or not. Twenty-nine kidney recipients were randomized to receive since transplantation SRL (n = 15) or cyclosporin A (CsA, n = 14) associated with mycophenolate mofetil (MMF) and steroids (6 months) in a parallel prospective study. Systolic, diastolic blood pressures, glomerular filtration rate (GFR) and radial artery flow-mediated dilatation (FMD) induced by postischaemic hyperaemia were assessed in a blind manner at one (M1) and 7 months (M7) after transplantation. Endothelium-independent dilatation was assessed by glyceryl trinitrate spray. There was no difference between the groups for all vascular parameters at M1. At M7, systolic blood pressure was lower (SRL: 119 ± 3 vs. CsA: 138 ± 4 mmHg, P

Long-term function of kidney allografts depends on multiple variables, one of which may be the compatibility in size between the graft and the recipient. Here, we assessed the long-term consequences of the ratio of the weight of the kidney to the weight of the recipient (KwRw ratio) in a multicenter cohort of 1189 patients who received a transplant between 1995 and 2006. The graft filtration rate increased by a mean of 5.74 ml/min between the third and sixth posttransplantation months among patients with a low KwRw ratio (

Background. Although cyclosporine maintenance therapy reduces the risk of acute rejection and increases short-term graft survival in renal transplant recipients, its associated nephrotoxicity increases the risk of chronic graft dysfunction. The dose that allows an optimal risk-to-benefit ratio has not been established. Methods. This multicentre study enrolled stable renal allograft recipients receiving cyclosporine and mycophenolate mofetil without corticosteroids in their second year post-transplant. Patients were randomized to a cyclosporine dose targeted to a standard area under the concentration–time curve (AUC)0–12 h (usual exposure, n =1 04) or 50% of the study standard AUC0–12 h (low exposure, n = 108) using a three-point pharmacokinetic sampling. The primary endpoint was the percentage of patients with treatment failure at 24 months (graft loss/acute rejection/ nephrotoxicity/>15% serum creatinine level increase). Results. Treatment failure was reported in 37 out of 101 (37%) patients in the usual-exposure and 19 out of 106 (18%) patients in the low-exposure groups (P = 0.003). Mean estimated glomerular filtration rate decreased from baseline to 2 years with usual exposure and increased with low exposure (P < 0.001). Mean systolic and diastolic blood pressures were lower with low exposure (P = 0.03 and P = 0.008, respectively). Conclusion. In renal transplant recipients receiving maintenance therapy without corticosteroids, a minimization strategy using three-point pharmacokinetic sampling to reduce and maintain cyclosporine exposure to 50% of the usual levels is safe and reduces the risk of graft dysfunction.

Resume Bien que les resultats de la greffe renale avec donneur marginal en terme de survie du greffon soient en amelioration, de nombreux greffons juges marginaux sont refuses par les equipes de transplantation. L’objectif principal de notre etude retrospective etait d’evaluer le devenir des greffons renaux refuses a tort et transplantes dans d’autres centres. Dans le notre, l’acceptation ou le refus d’un greffon marginal reposait exclusivement sur le jugement clinique du nephrologue recevant la proposition. Un greffon transplante dans un autre centre etait considere comme refuse a tort si son debit de filtration glomerulaire estime (DFGe) etait superieur ou egal a 60 ml/min/1,73 m 2 un an apres la transplantation renale. Les caracteristiques des greffons et des receveurs etaient compares selon le DFGe a un an : groupe A : DFG ≥ 60 ml/min/1,73 m 2 , groupe B : DFG 2 . A posteriori, il etait calcule pour chaque donneur le score definissant les donneurs a criteres elargis (ECD) et le score Deceased Donor Score (DDS). Parmi les 304 propositions de reins refusees entre le 1 er janvier 2000 et le 31 decembre 2006, 55 reins n’ont pas ete acceptes par le nephrologue de garde car juges de mauvaise qualite sur la base du seul jugement clinique. Seulement 44 reins ont ete acceptes et transplantes dans un autre centre. Deux greffons ont ete perdus dans la premiere annee. A un an postgreffe, 42 greffons renaux etaient fonctionnels : 12 greffons pouvaient etre consideres comme refuses a tort car ayant un DFGe superieur ou egal a 60 ml/min/1,73 m 2 . En utilisant le score DDS, dix greffons sur 12 n’avaient pas les caracteristiques du greffon marginal dans le groupe A et 3 sur 30 dans le groupe B. La survie actuarielle des greffons censuree sur le deces des 42 greffons etait respectivement de 98 et de 93 % a un an et a deux ans. En conclusion, lorsque la decision d’acceptation d’un greffon marginal est basee uniquement sur le jugement clinique, la proportion de refus a tort est elevee. Notre etude montre que l’utilisation d’un score de qualite du greffon disponible au moment de la proposition de greffon comme outil d’aide a la decision medicale est une necessite.

Resume Le retour en dialyse apres echec de transplantation est un probleme emergent dans les centres de dialyse. L’objectif de cette etude est de determiner les conditions de prise en charge initiale en dialyse des patients en echec de greffe et leur devenir a court terme en epuration extrarenale. Patients et methodes Il s’agit d’une etude retrospective portant sur des patients ayant recu une greffe renale dans le centre regional de reference et retournant en dialyse apres plus de six mois en transplantation dans un centre de la region pendant la periode du 31 octobre 1986 au 03 mars 2004. La periode de suivi est de un an pour tous les patients. Resultats Parmi les 600 patients transplantes pendant la periode d’etude, 92 sont retournes en dialyse dont 69 apres une duree en transplantation de plus de six mois. A l’initiation de la dialyse la clairance moyenne de la creatinine etait de 13 ± 5 mL par minute. L’albuminemie moyenne etait de 34 ± 6 g/L et l’hemoglobinemie moyenne etait de 80,7 ± 10,7 g/L. La dialyse a ete debutee dans un contexte d’urgence pour 39 sur 57 (50 %) patients et sur catheter pour 14 sur 58 (25 %) patients. L’hemodialyse etait la methode de choix pour 59 sur 69 (85 %) patients, le retour dans la methode d’origine etait moins frequent chez les patients traites par la dialyse peritoneale que chez les patients traites par hemodialyse (7/13 versus 49/52 ; p Conclusion Malgre un suivi nephrologique regulier les patients en echec de greffe debutent frequemment la dialyse de facon non planifiee et en urgence. Une prise en charge plus precoce en dialyse des patients en echec de greffe est probablement necessaire.

BK virus is near ubiquitous, with a seroprevalence of around 80% in the general population. Subsequent to an asymptomatic primary infection, BK virus then remains dormant in healthy subjects. Reactivation occurs in immunocompromised people. BKv is pathogenic mainly among patients who have received a kidney transplant, in whom the virus can cause specific tubulo-interstitial nephritis and even result in graft failure among approximately 20 to 30% of nephritic cases. Since the mid 90 s, incidence has increased with the use of new powerful immunosuppressor treatments. The cornerstone of BK virus infection or BK virus-associated nephropathy treatment is a decrease of the immunosuppressive regimen, which must then be offset with the risk of rejection. The use of several adjuvant therapies has been submitted (fluoroquinolones, leflunomide, intravenous immunoglobulins, cidofovir), with no sufficient proof enabling the recommendation of first-line prescription. The high frequency of this infection and its potential harmfulness argue for the use of prevention strategies, at least among patients presenting risk factors. Retransplantation is safe after a first kidney allograft loss caused by BK-virus nephropathy, on condition that a screening for viremia is frequently conducted.

Background Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. Methods Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many operationally tolerant patients (TOL; defined as having a serum creatinine

Tobacco use increases the risk of mortality, cancers and cardiovascular diseases in transplanted patients. Transplanted patients are encouraged to quit tobacco use before and after renal transplantation. This study was carried out to evaluate the prevalence of tobacco consumption in transplanted patients in one French region. This survey was also conducted to identify factors associated with failure in smoking cessation.A questionnaire was sent by mail to transplanted patients followed in our center between the 1/01/95 and the 31/12/10. A second mail was sent to increase the response rate.During the study period, 544 questionnaires were sent to kidney transplant recipients. Among these 544 patients, there were 362 responders. Of these 362 patients, 121 patients (33.4%) were past smokers, and 21 (5.8%) were active smokers. Among the smokers, 20% were exposed to second-hand smoke, 48% had criteria for tobacco moderate to high dependency, and 13.4% were addicted to alcohol. In the multivariate analysis, exposure to second-hand smoke and living alone at home were associated with failure in smoking cessation.This study shows that the prevalence of tobacco use is not high in transplanted patients. Only 6% of our patients report tobacco use at the study time. Environmental factors are associated with failure in tobacco cessation. Living alone and exposure to second-hand smoke are associated with smoking. Therefore, in transplantation centers, programs devoted to tobacco cessation should be implemented and should take care of patients' lifestyle.

International audience; We present the results at 8 years of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in kidney transplant recipients at low immunologic risk. We assessed estimated glomerular filtration (eGFR), graft, patient, and death-censored graft survival (log-rank compared), de novo DSA appearance, risk of malignancy, post-transplant diabetes mellitus (PTDM), and anemia. Intent-to-treat and on-treatment analyses were performed. Graft survival was similar in both groups (sirolimus: 73.3%, cyclosporine: 77.7, P = 0.574). No difference was observed between treatment groups concerning patient survival (P = 0.508) and death-censored graft survival (P = 0.858). In conditional intent-to-treat analysis, mean eGFR was greater in sirolimus than in cyclosporine group (62.5 ± 27.3 ml/min vs. 47.8 ± 17.1 ml/min, P = 0.004), in particular because graft function was excellent in patients maintained under sirolimus (eGFR = 74.0 ml/min). Importantly, no detrimental impact was observed in patients in whom sirolimus has been withdrawn (eGFR = 49.5 ml/min). Overall, 17 patients showed de novo DSAs, with no difference between the two groups (P = 0.520). Malignancy did not differ by treatment. An initial maintenance regimen based on sirolimus provides a long-term improvement in renal function for kidney transplant patients, especially for those maintained on sirolimus.

Background The French healthcare system offers the possibility of increasing the use of peritoneal dialysis (PD) by involving in patient care nurses who work in the private system. Objective This study was conducted to evaluate the impact of a private home-nurse network on one dialysis program. Methods This was a retrospective study of 239 dialysis patients who started dialysis in our center between 1 January 1998 and 31 December 2003. Results Of these 239 patients, 142 were treated with hemodialysis and 97 with PD during the study period. Among the PD patients, 36 of 97 were treated with assisted PD and 61 of 97 with self-care PD. Assisted-PD patients were older (74 ± 10 vs 52 ± 18 years, p < 0.001) and presented more comorbidity (Charlson Comorbidity Index 7 ± 2.5 vs 4.3 ± 2.4, p < 0.05) compared with self-care patients. Continuous ambulatory PD was the modality of choice in the assisted group (32/36). Assisted patients were frequently hospitalized (31/36); actuarial survival free of hospitalization at 6 months was 46%. Patients with nurse assistance had a high risk of peritonitis (actuarial survival free of peritonitis: 52% at 1 year). Technique survival was 85% at 6 months and 58% at 1 year. Actuarial patient survival was 90% at 6 months and 83% at 1 year. Conclusion Assisted PD enables increased use of PD in incident dialysis patients. However, in view of the comorbidities of the assisted-PD patients, the need for frequent hospitalization has to be taken into account in such a program.

Peritonitis is still a frequent complication in peritoneal dialysis patients. Medical guidelines have been established to manage this infection. These guidelines do not provide any information regarding the requirement for hospitalization. The main objective of this study was to evaluate the impact of peritonitis episode on the hospitalization rate and on the hospitalization duration in a centre where peritoneal dialysis patients were hospitalized in case of peritonitis. This was a retrospective study of incident peritoneal patients over a six years period. Among 101 peritoneal dialysis patients 65% were hospitalized. Two hundred and twenty hospital stays were registered. The total duration of hospital stays was 2091 days. The hospitalization rate was 2 per patient and per year, the hospital duration was 19 days per patient per year. Of the 220 hospital stays, 67 (30%) were due to a peritoneal infection. Peritonitis episodes represent 581/2091 (28%) days of hospitalization. The mean duration of hospitalization for peritonitis was 8.7+/-7 days. Among the patients hospitalized for a peritonitis episode, 57% were assisted by a nurse at home to perform their peritoneal dialysis exchanges. Of the 67 peritonitis episodes, 91% were discharged from the hospital without any complication. This study emphases the fact that peritonitis has an important impact on the hospitalization rate and on the hospitalization duration in peritoneal dialysis patients. In an attempt to decrease the rate of hospitalization, educational programs are clearly needed in order to treat more peritonitis without any hospitalization requirement.

Background: Two hundred and forty cadaveric renal transplant recipients given anti-thymocyte globulin (Thymoglobulin®) as induction immunotherapy were followed up prospectively to review safety and efficacy. Methods: The median number of infusions was 10 [2–21] with a cumulative dose of 8.8 mg/kg [2.0–23.2 mg/kg]. During the fortnight following transplantation, 231 patients (96%) received a calcineurin inhibitor; all patients were given steroids and azathioprine or mycophenolate mofetil. At 1 yr, 60% of patients were on tripletherapy, 38% on bitherapy, and 2% on monotherapy; 20% had discontinued steroids. Results: Tolerance was excellent with no cases of anaphylaxis. The commonest adverse event was fever (55%). Eighteen patients developed serum sickness on median day 11 [10–14]. Seven patients had thrombocytopenia; six patients had severe neutropenia. All of these adverse events recovered spontaneously. The overall incidence of delayed graft function was 24%. At 1 yr patient and graft survival were 98 and 95%, respectively, and creatinine was 135 ± 43 μmol/L. Clinically suspected and biopsy-proven acute rejection were observed in 65 patients (27%) and 34 patients (14%), respectively. There were 62 non-cytomegalovirus (CMV) infections (two fatal) and 81 episodes of CMV infections. Eight malignancies were reported; two possibly related to immunosuppression. Conclusions: These results demonstrate that anti-thymocyte globulin has a safety profile with good tolerability and excellent efficacy.

Background. Hypertension and hyperuricaemia are common side-effects of cyclosporin A (CsA) treatment in renal transplant recipients. While it is well established that the calcium channel blocker amlodipine can control CsA-induced hypertension effectively in this patient population, recent evidence suggests amlodipine might also reduce hyperuricaemia. The present study was designed to compare the effects of the calcium channel blocker amlodipine (5–10 mg/day) and the � adrenoceptor antagonist tertatolol (5–10 mg/day) on CsA-induced hyperuricaemia in post-renal transplant recipients with hypertension. Methods. Forty-eight hypertensive renal transplant recipients on a stable dose of CsA were randomized in a double-blind, parallel-group manner to receive either amlodipine (n ¼ 24) or tertatolol (n ¼ 24) for 60 days. The primary outcome measure was the change from baseline in serum uric acid concentration. Secondary analyses of efficacy were based on changes in renal function and blood pressure. Results. Amlodipine significantly decreased serum uric acid levels from 483 ± 99 to 431 ± 110mmol/l (P < 0.001), while tertatolol significantly increased uric acid from 450 ± 98 to 476 ± 84mmol/l (P ¼ 0.006). Amlodipine also significantly increased glomerular filtration rate (P ¼ 0.0048) and the clearance rate of uric acid (P ¼ 0.023) and it reduced the fractional proximal tubular reabsorption of sodium (P < 0.001), compared with tertatolol. Renal plasma flow and filtered fraction were unaffected by both treatments, as was trough CsA blood concentration. Amlodipine lowered systolic blood pressure to a significantly greater extent than did tertatolol (P ¼ 0.007). The time-dependent profile of diastolic blood pressure did not differ significantly between treatment groups. Both drugs were well tolerated. Conclusions. Amlodipine could be more appropriate than tertatolol for CsA-induced hypertension and hyperuricaemia in renal transplant recipients.

Background. Induction therapy with antithymocyte globulin (ATG) reduces the incidence of acute rejection after transplantation. A study was undertaken to assess the efficacy and safety of ATG induction on tacrolimus-based and cyclosporine A (CsA)-based therapies compared with immediate tacrolimus triple therapy in kidney transplant recipients. Methods. In a 6-month, open-label, randomized, prospective study conducted in 30 European centers, 555 renal transplant patients were randomly assigned to tacrolimus triple therapy (Tac triple, n=185), ATG induction with tacrolimus (ATG-Tac, n= 186), or ATG induction with CsA microemulsion (ATG-CsA, n=184); all were combined with azathioprine, and corticosteroids. The primary endpoint was incidence and time to first acute rejection episode confirmed by biopsy. Results. Patient demographics and clinical parameters at baseline were similar. Patient and graft survival rates were similar in all groups. The incidence of clinically apparent acute rejection was significantly higher (P=0.003) for Tac triple (33.0%) compared with ATG-Tac (22.6%) and the incidence for ATG-Tac was significantly lower (P=0.004) than for ATG-CsA (37.0%). The incidences of acute rejection confirmed by biopsy (primary endpoint) were 25.4%, 15.1%, and 21.2% for Tac triple, ATG-Tac, and ATG-CsA, respectively (Tac triple vs. ATG-Tac, P=0.004). The incidences of corticosteroid-resistant acute rejection were 7.0% (Tac triple), 4.8% (ATG-Tac), and 10.9% (ATG-CsA) (ATG-Tac vs. ATG-CsA, P=0.038). In the ATG groups, the incidences of leukopenia, thrombocytopenia, serum sickness, fever, and cytomegalovirus infection were significantly higher (P

Acute graft rejection remains a major problem in renal transplant recipients, and there is no consensus on the optimal immunosuppressive strategy. Immunoprophylaxis with Thymoglobulin or basiliximab has significantly reduced the incidence of acute rejection episodes and graft loss following kidney transplantation. This open, randomized, multicenter study investigated the efficacy and tolerability of basiliximab (20mg day 0-day 4) plus early cyclosporine from day 0 (n = 50) compared with Thymoglobulin plus delayed cyclosporine (n = 50) in adult kidney transplant patients. In addition, all patients received steroids and mycophenolate mofetil (MMF) at standard doses from day 0. Patient and graft survival rates at 12 months were 98 and 94% in the basiliximab group, respectively, compared with 100 and 96% in the Thymoglobulin' group. The incidences of biopsy-confirmed acute rejection (8.0% in each group) and treatment failure (14% in the basiliximab group vs. 8% in the Thymoglobulin group) were comparable in the two groups. There was a non-significant tendency to more dialysis (14 vs. 6%), and fewer cytomegalovirus (CMV) infections (p = 0.005) in the basiliximab group, but the percentage of clinical CMV was not different between the two groups (6 vs. 12%). Both strategies give excellent results, despite the differences in patterns, in nonhyperimmunized patients receiving their first cadaveric renal allograft.