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The pathogenesis of endomyocardial fibrosis (EMF) is poorly understood. EMF may result from autoimmune scarring of the endocardium. Clinically, EMF presents as a restrictive cardiomyopathy. EMF is commonly reported in tropical countries. In Western countries, EMF is associated with hypereosinophilia and reported as Loeffler endocarditis. We report a Caucasian patient with Crohn's disease and EMF, and discuss a possible linkage between the two conditions. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Vitamin D deficiency/insufficiency is significantly prevalent in chronic kidney disease. Data in the literature are however scarce about the effects of this deficiency on bone metabolism in hemodialysis (HD) patients. Moreover, it is still debated whether low vitamin D levels should be normalized in HD patients. In this paper, we report two cases showing the deleterious consequences of vitamin D deficiency in HD patients which is characterised by hypophosphatemia, hypocalcemia and osteomalacia (OM) leading to bone fractures. As vitamin D repletion is an easy way to treat OM, this report underlines the importance of monitoring and correction of vitamin D deficiency in this population. [ABSTRACT FROM AUTHOR]

Résumé: Le pharmacien d'officine est reconnu comme un acteur de la prévention et de l'éducation thérapeutique. Un projet pédagogique mené dans les officines du Nord-Pas-de-Calais et coordonné par la faculté de pharmacie de Lille avec le réseau Néphronor nous a permis de collecter des données permettant d'évaluer l'intérêt d'une évaluation pharmaceutique officinale de la MRC. Nous rapportons ici le résultat de l'intervention réalisée dans 109 pharmacies d'officine. Les entretiens pharmaceutiques ont concerné 2 populations de patients. Le groupe A concerne des patients se connaissant porteurs d'une IRC (entretien pharmaceutique d'optimisation thérapeutique). Le groupe B regroupe des patients à risque de MRC pour lesquels est proposée une stratégie de dépistage. Ainsi, 354 patients ont été inclus dans le groupe A, majoritairement des femmes (51,2 %), en stade 3 d'IRC, d'âge moyen 73 ans, diabétiques (44 %). Environ 70 % des patients avaient déjà été vus par un néphrologue et 45 % d'entre eux présentaient une bonne adhésion thérapeutique selon le questionnaire de Morisky Green. Par ailleurs, 20 % des patients n'avaient pas de traitement néphroprotecteur en stades 3 et 4 de la MRC et plus de la moitié ne connaissaient pas les situations à risque d'insuffisance rénale aiguë. Le groupe B a inclus 532 patients (âge moyen 70 ans). L'intervention pharmaceutique a permis de dépister 10 % de patients avec un DFG < 60 mL/min/1,73 m2. L'entretien pharmaceutique en officine a permis d'optimiser la prise en charge thérapeutique et l'information des patients IRC, ainsi que le dépistage précoce chez certains patients à risque. Chronic kidney disease (CKD) is a major concern of public health. The pharmacist is known as a health practitioner involved in prevention and therapeutic education. Our study aimed at defining the impact of community pharmacists' interventions for preventing and screening CKD. In our observational prospective study of 5 months conducted in 109 community pharmacy, we included 2 groups of patients: A (therapeutic optimization): CKD patients and B (CKD screening): population at risk. In group A, we included 354 patients, mainly women (51.2%), in stage 3 of CKD, mean age 73 years old, with hypertension alone (40.6%) or associated with diabetes (44%). About 70% of the patients had a follow up by a nephrologist and 45% of them were good adherent according to the Morisky Green self-report. However, approximately 20% of patients did not have nephroprotective treatments in their regimen although they were on stage 3 or 4 CKD patients, and about half of them were not aware of medical situations at risk. Concerning group B, 532 patients were included. The pharmaceutical interventions screened 10 % of patients with a GFR < 60 mL/min/1.73m2. The community pharmacists' interventions helped to optimize the therapeutic management of CKD patients and in the early screening of patients at risk. More studies are needed to extrapolate our observations to a larger population. [ABSTRACT FROM AUTHOR]

Objective: The long-term outcome of allogenic islet transplantation is unknown. The aim of this study was to evaluate the 10-year outcome of islet transplantation in patients with type 1 diabetes and hypoglycemia unawareness and/or a functioning kidney graft.Research Design and Methods: We enrolled in this prospective parallel-arm cohort study 28 subjects with type 1 diabetes who received islet transplantation either alone (ITA) or after a kidney graft (IAK). Islet transplantation consisted of two or three intraportal infusions of allogenic islets administered within (median [interquartile range]) 68 days (43-92). Immunosuppression was induced with interleukin-2 receptor antibodies and maintained with sirolimus and tacrolimus. The primary outcome was insulin independence with A1C ≤6.5% (48 mmol/mol). Secondary outcomes were patient and graft survival, severe hypoglycemic events (SHEs), metabolic control, and renal function.Results: The primary outcome was met by (Kaplan-Meier estimates [95% CI]) 39% (22-57) and 28% (13-45) of patients 5 and 10 years after islet transplantation, respectively. Graft function persisted in 82% (62-92) and 78% (57-89) of case subjects after 5 and 10 years, respectively, and was associated with improved glucose control, reduced need for exogenous insulin, and a marked decrease of SHEs. ITA and IAK had similar outcomes. Primary graft function, evaluated 1 month after the last islet infusion, was significantly associated with the duration of graft function and insulin independence.Conclusions: Islet transplantation with the Edmonton protocol can provide 10-year markedly improved metabolic control without SHEs in three-quarters of patients with type 1 diabetes, kidney transplanted or not. [ABSTRACT FROM AUTHOR]

Summary: Background: Further study is needed on the prognostic impact of cirrhosis on haemodialysis patients. Aim: To evaluate cirrhosis' impact according to severity on survival and to provide therapeutic guidelines for haemodialysis cirrhotic patients. Methods: Patients with end‐stage renal failure treated with haemodialysis were included retrospectively from 01/01/2000 to 31/12/2004 and prospectively from 01/01/2005 to 31/12/2014 in our French Region. Clinical data, presence of cirrhosis and its severity were recorded at the beginning of haemodialysis. The primary endpoint was 2‐year survival. Results: Seven thousand three hundred and fifty‐four patients (96%) without cirrhosis and 304 patients (4%) with cirrhosis were included. Two‐year survival in noncirrhotic patients was higher than in cirrhotic patients (71.7% vs 54.4%, P < 0.0001). Patients with decompensated cirrhosis had a worse 2‐year outcome (44.1%) as compared to compensated cirrhotic (62.8%, P = 0.002) and noncirrhotic patients (71.7%, P < 0.0001). Compensated and decompensated cirrhosis were independent predictive factors of 2‐year mortality. In sensitivity analysis restricted to cirrhotic patients, 2‐year survival of Child‐Pugh A patients was higher than in Child‐Pugh B and C patients (65.5% vs 27.7% vs 0%, P < 0.0001). Development of predictive models based either on severity scores (MELD and Child‐Pugh) and extrahepatic comorbidities allowed correct classification of around 70% of patients in terms of mortality and may help to better stratify mortality risk in this population. Conclusions: Cirrhosis is independently associated with mortality in haemodialysis patients. Patients with severe cirrhosis have a poor 2‐year outcome. Severity of cirrhosis and presence of extrahepatic comorbidities should be considered when deciding to initiate renal replacement therapy. [ABSTRACT FROM AUTHOR]

Abstract: The study of calcineurin inhibitor (CNI) blood level variability to evaluate adherence in transplantation has improved over the years. The aim of our study was to assess factors associated with this variability using the coefficient of variation (CV). A cross‐sectional sample of kidney recipients grafted for more than 1 year was recruited. We recorded clinical data, data from a clinical pharmacist interview and from six questionnaires measuring adherence, satisfaction, behaviours, beliefs, perception of the illness and social vulnerability. A total of 408 recipients were enrolled (61.2% male, mean age 54) and divided into two groups: low variability CV < 30% (n = 302), high variability CV ≥ 30% (n = 106). In univariate analysis, hospital‐home distance, cyclosporine, time since transplantation and presence of discrepancies in drug regimen were associated with a greater risk of CV ≥ 30%. In contrast, tacrolimus QD conferred a lower risk of CV ≥ 30%. In multivariate analysis, only the presence of discrepancies remained significant: (OR 3.2 [1.21–9.01]; P = 0.022). Discrepancies in drug regimen appear as the main risk factor associated with CNI blood variability. The clinical pharmacist's input is an accurate and simple way of detecting non‐adherence which is not revealed in self‐report questionnaires. [ABSTRACT FROM AUTHOR]

Tubulo-interstitial microcalcifications in renal transplant are described with a wide difference of incidence (4–78%) according to time and goal of biopsies. Currently, staining procedures are used to deduce the composition of crystals and speculate about their aetiologies. Here we test the contribution of infrared microspectroscopy (IR-MS) in understanding kidney transplant crystal deposits. First, microcalcifications observed in 118 allograft biopsies are studied by IR-MS. The Fourier transform infrared signal shows that a major proportion (92%) of calcium phosphate crystals is in the pure or mixed form. Next, we compare 50 patients with calcifications to 100 without calcifications and show persistent hyperparathyroidism and tubular cell vacuolization as circumstances of crystal deposition. Finally, the graduation level of calcification by IR-MS appears to be correlated with the graft outcome. Graft survival seems to be worse in case of high microcalcification detection by IR-MS. These preliminary data suggest IR-MS as a great tool for clinicians to diagnose, characterize, and quantify microcalcifications in kidney allografts. [ABSTRACT FROM AUTHOR]

Immunosuppressive drugs are used in the treatment of inflammatory and autoimmune diseases, as well as in transplantation. Frequently prescribed in young people, these treatments may have deleterious effects on fertility, pregnancy outcomes and the unborn child. This review aims to summarize the main gonadal side effects of immunosuppressants, to detail the effects on fertility and pregnancy of each class of drug, and to provide recommendations on the management of patients who are seen prior to starting or who are already receiving immunosuppressive treatment, allowing them in due course to bear children. The recommendations for use are established with a rather low level of proof, which needs to be taken into account in the patient management. Methotrexate, mycophenolate, and le- and teri-flunomide, cyclophosphamide, mitoxanthrone are contraindicated if pregnancy is desired due to their teratogenic effects, as well as gonadotoxic effects in the case of cyclophosphamide. Anti-TNF-alpha and mTOR-inhibitors are to be used cautiously if pregnancy is desired, since experience using these drugs is still relatively scarce. Azathioprine, glucocorticoids, mesalazine, anticalcineurins such as cyclosporine and tacrolimus, ß-interferon, glatiramer-acetate and chloroquine can be used during pregnancy, bearing in mind however that side effects may still occur. Experience is limited concerning natalizumab, fingolimod, dimethyl-fumarate and induction treatments. Conclusion: At the time of prescription, patients must be informed of the possible consequences of immunosuppressants on fertility and of the need for contraception. Pregnancy must be planned and the treatment modified if necessary in a pre-conception time period adapted to the half-life of the drug, imperatively in relation with the prescriber of the immunosuppressive drugs. [ABSTRACT FROM AUTHOR]

Atypical hemolytic uremic syndrome (aHUS) is a rare renal thrombotic microan-giopathy commonly associated with rare genetic variants in complement system genes, unique to each patient/family. Here, we report 14 sporadic aHUS patients car-rying the same mutation, R139W, in the complement C3 gene. The clinical presen-tation was with a rapid progression to end-stage renal disease (6 of 14) and an unusually high frequency of cardiac (8 of 14) and/or neurologic (5 of 14) events. Although resting glomerular endothelial cells (GEnCs) remained unaffected by R139W-C3 sera, the incubation of those sera with GEnC preactivated with pro-inflammatory stimuli led to increased C3 deposition, C5a release, and procoagu-lant tissue-factor expression. This func-tional consequence of R139W-C3 re-sulted from the formation of a hyperactive C3 convertase. Mutant C3 showed an increased affinity for factor B and a re-duced binding to membrane cofactor pro-tein (MCP; CD46), but a normal regulation by factor H (FH). In addition, the fre-quency of at-risk FH and MCP haplotypes was significantly higher in the R139W-aHUS patients, compared with normal donors or to healthy carriers. These ge-netic background differences could ex-plain the R139W-aHUS incomplete pen-etrance. These results demonstrate that this C3 mutation, especially when associ-ated with an at-risk FH and/or MCP haplo-types, becomes pathogenic following an inflammatory endothelium-damaging event. (Blood. 2012;119(18):4182-4191) [ABSTRACT FROM AUTHOR]

Summary The diabetes and renal phenotype of patients with maturity-onset diabetes of the young (MODY) on a transplantation waiting list is not known; neither is their outcome after pancreas (PT) and/or kidney transplantation (KT). Between 2002 and 2009, we screened 50 of 150 patients referred for kidney and pancreas transplantation to the Kremlin-Bicêtre center for HNF1B and HNF1A mutations if one or more of the following criteria was present (i) an atypical history of diabetes (ii) diabetes with at least one affected parent or two affected relatives, (iii) an absence of auto-antibodies at diagnosis (iv) a persistent secretion of fasting C peptide (v) a personal or a family history of renal cysts or dysplasia. Their phenotype and their outcome were analyzed. Four HNF1A (MODY3) and eight HNF1B mutations [renal cysts and diabetes (RCAD)] were identified. All MODY3 patients had diabetic nephropathy, but only 50% of RCAD patients. Four patients underwent a kidney and pancreas transplantation and two a kidney transplant alone. After 4.1 ± 1.1 years of follow-up, 83% of patients still have a functioning kidney and 75% a functioning pancreas. PT can be proposed with good results for MODY3 and RCAD patients. [ABSTRACT FROM AUTHOR]

Background: Use of a hospital pneumatic tube system may be associated with measurement errors.Methods: A venous blood sample was collected from 79 patients into a pair of lithium heparin tubes; one tube was sent to the laboratory by porter and the other was sent via the pneumatic tube system. Plasma lactate dehydrogenase concentrations were then assayed.Results: Lactate dehydrogenase concentrations were overestimated (median bias: 18.8%) when evacuated vacuum lithium heparin tubes were sent by pneumatic tube system. This bias was reduced by bubble-wrapping the standard lithium heparin tube or using Monovette lithium heparin tubes in aspiration mode (median bias: +8.7% and -0.3%, respectively).Conclusions: Cushioning and aspiration-mode sampling may limit pneumatic tube system-associated overestimation of lactate dehydrogenase concentrations. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To investigate the influence of primary graft function (PGF) on graft survival and metabolic control after islet transplantation with the Edmonton protocol. RESEARCH DESIGN AND METHODS -- A total of 14 consecutive patients with brittle type 1 diabetes were enrolled in this phase 2 study and received median 12,479 islet equivalents per kilogram of body weight (interquartile range 11,072-15,755) in two or three sequential infusions within 67 days (44-95). PGF was estimated 1 month after the last infusion by the [B-score, a previously validated index (range 0-8) based on insulin or oral treatment requirements, plasma C-peptide, blood glucose, and A1C. Primary outcome was graft survival, defined as insulin independence with A1C ≤6.5%. RESULTS-- All patients gained insulin independence within 12 days (6-23) after the last infusion. PGF was optimal (β-score ≥7) in nine patients and suboptimal (β-score ≤6) in five. At last follow-up, 3.3 years (2.8-4.0) after islet transplantation, eight patients (57%) remained insulin independent with A1C ≤6.5%, including seven patients with optimal PGF (78%) and one with suboptimal PGF (20%) (P = 0.01, log-rank test). Graft survival was not significantly influenced by HLA mismatches or by preexisting islet autoantibodies. A1C, mean glucose, glucose variability (assessed with continuous glucose monitoring system), and glucose tolerance (using an oral glucose tolerance test) were markedly improved when compared with baseline values and were significantly lower in patients with optimal PGF than in those with suboptimal PGF. CONCLUSIONS-- Optimal PGF was associated with prolonged graft survival and better metabolic control after islet transplantation. This early outcome may represent a valuable end point in future clinical trials. [ABSTRACT FROM AUTHOR]

Hypogammaglobulinemia (hypo-Ig) and low mannose binding protein (MBP) levels might be involved in the infectious risk in renal transplantation. In 152 kidney transplant recipients treated with calcineurin inhibitors (CNI) and mycophenolate mofetil (MMF), during the first year, we prospectively recorded the incidence of hypogammaglobulinemia, and low MBP levels. Their influence on infectious complications was evaluated in 92 patients at 3 and 12 months (T3 and T12). The proportion of deficiency increased significantly: hypo-IgG: 6% (T0), 45% (T3), and 30% (T12) ( P < 0.001); hypo-MBP: 5%, 11%, and 12% ( P = 0.035). Hypo-IgG at T3 was not associated with an increased incidence of first-year infections. A significantly higher proportion of patients with combined hypogammaglobulinemia [IgG+ (IgA and/or IgM)] at T3 and with isolated hypo-IgG at T0 developed infections until T3 compared with patients free of these deficits ( P < 0.05). Low MBP levels at T3 were associated with more sepsis and viral infections. Hypogammaglobulinemia is frequent during the first year after renal transplantation in patients treated with a CNI and MMF. Hypo-IgG at T0 and combined Igs deficts at T3 were associated with more infections. MBP deficiency might emerge as an important determinant of the post-transplant infectious risk. [ABSTRACT FROM AUTHOR]

Intra-operative parathyroid hormone (IOPTH) results are not known in the setting of tertiary hyperparathyroidism (HPT) after renal transplantation. A retrospective analysis of 35 tertiary HPT patients who all underwent subtotal parathyroidectomy and IOPTH monitoring was conducted. The mean follow-up time was 2.2±1.4 years. Thirty-four patients were cured; one patient (2.8%) had a persistent disease and was cured after reoperation. Median parathyroid hormone (PTH) (median percent decrease from highest) at baseline and at 5, 10, 20, and 30 min were 244, 78 (69%), 63 (75%), 53 (79%), and 49 pg/ml (83%), respectively. Four patients who were cured had a decrease of <50% at 5 min and two of them had a decrease of <50% at 10 min. The patient with persistent disease had a decrease of >50% at 10 min. The sensitivity of the test was 94% at 10 min using the Miami criteria. This study shows that IOPTH in tertiary hyperparathyroidism has a high sensitivity. However, because of the low risk of persistent hyperparathyroidism when a subtotal parathyroidectomy is performed, its potential impact on the overall success rate is very small. We therefore do not recommend the routine use of IOPTH in tertiary hyperparathyroidism. [ABSTRACT FROM AUTHOR]

We retrospectively reviewed our experience with 45 kidney transplant recipients (KTR) that were switched from CNI to SRL, mainly for chronic allograft dysfunction (CAD) (41/45). The mean serum creatinine at switch was 2.5 ± 0.8 mg/dl. At 1 year, patient survival was 93%. Death-censored graft survival was 67% at 1 year and 54% at 2 years. SRL was stopped because of severe side effects in 15 patients. Among these, eight patients developed ‘de novo’ high-grade proteinuria. Univariate analysis revealed that (1) a higher SRL level at 1 month was a predictor of SRL withdrawal due to severe side effects (P = 0.006), and (2) predictors of graft failure after SRL conversion were low SRL loading dose (P = 0.03) and a higher creatinine level at conversion (P = 0.003). [ABSTRACT FROM PUBLISHER]

A correction is presented to the article "Diabetes Care" which appeared in the May 2020 issue.

The article presents a single-arm, 5-year prospective, longitudinal study which examined the evolution of neuropathy after islet transplantation (IT) in patients with type 1 diabetes. The variables include continuous 24-hour mean blood pressure, continuous glucose monitoring (CGM), metabolic and sensory parameters. The study also used the kidney and lipid parameters, meanblood pressure and motor electrophysiological and cardiac autonomic neuropathy (CAN).