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Introduction: There are only scarce data regarding the cardiovascular impact of arteriovenous fistula after kidney transplantation depending on fistula flow. Methods: We performed a single‐center, prospective, cohort study including 49 patients with a functional fistula at 1 year from kidney transplantation. Patients were convened for a clinical work‐up, a biological analysis, a fistula's Doppler ultrasonography and an echocardiography. Main judgment criterion was comparison of echocardiography parameters between patients with relative (fistula flow >1 L/min and a fistula flow/cardiac output ratio >20%), absolute high‐flow fistula (fistula flow >2 L/min) and normal‐flow fistula. Results: High‐flow fistula frequency was 69%. Significantly higher left ventricular end‐diastolic and systolic diameters were observed in this group compared with the normal‐flow fistula group (53 ± 6 vs. 48 ± 7 mm; p = 0.04 and 33 ± 6 vs. 28 ± 8 mm; p = 0.02) and between the absolute and relative high‐flow fistula subgroups (56 ± 6 vs. 51 ± 6 mm; p = 0.009 and 35 ± 6 vs. 31 ± 5 mm; p = 0.01). The study showed no other significant differences. Conclusions: This study showed a significantly higher but not pathological left ventricular end‐diastolic and systolic diameters values in patients with high‐flow fistula compared with patients with normal‐flow fistula and between patients with respectively absolute and relative high‐flow fistula. [ABSTRACT FROM AUTHOR]

We assessed the risks of bleeding, acute kidney injury (AKI), and kidney failure associated with the prescription of antithrombotic agents (oral anticoagulants and/or antiplatelet agents) in patients with moderate‐to‐advanced chronic kidney disease (CKD). CKD‐REIN is a prospective cohort of 3022 nephrology outpatients with CKD stages 2–5 at baseline. We used cause‐specific Cox proportional hazard models to estimate hazard ratios (HRs) for bleeding (identified through hospitalizations), AKI, and kidney failure. Prescriptions of oral antithrombotics were treated as time‐dependent variables. At baseline, 339 (11%) patients (65% men; 69 [60–76] years) were prescribed oral anticoagulants only, 1095 (36%) antiplatelets only, and 101 (3%) both type of oral antithrombotics. Over a median (interquartile range [IQR]) follow‐up period of 3.0 (IQR, 2.8–3.1) years, 152 patients experienced a bleeding event, 414 patients experienced an episode of AKI, and 270 experienced kidney failure. The adjusted HRs (95% confidence interval [95% CI]) for bleeding associated with prescriptions of antiplatelets only, oral anticoagulants only, and antiplatelet + oral anticoagulant were, respectively, 0.74 (95% CI, 0.46–1.19), 2.38 (95% CI, 1.45–3.89), and 3.96 (95% CI, 2.20–7.12). An increased risk of AKI risk was associated with the prescription of oral anticoagulants (adjusted HR, 1.90, 95% CI, 1.47–2.45) but not the prescription of antiplatelets (HR, 1.24, 95% CI, 0.98–1.56). Kidney failure was not associated with the prescription of oral antithrombotics of any type. This study confirms the high risk of AKI associated with oral anticoagulants prescription in patients with CKD and also highlights the potential aggravating effect of combining vitamin K antagonist (VKA) and antiplatelets on the risk of bleeding. [ABSTRACT FROM AUTHOR]

Objective: Silica is an environmental substance strongly linked with autoimmunity. The aim of this study was to assess the prevalence of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and renal limited vasculitis, in a northeastern region of France and to evaluate whether there was a geospatial association between the localization of quarries in the region and the prevalence of these AAVs. Methods: Potential AAV patients were identified using 3 sources: hospital records, immunology laboratories, and the French National Health Insurance System. Patients who resided in the Alsace region of France as of January 1, 2016 and who fulfilled the American College of Rheumatology criteria for GPA or the 2012 Chapel Hill Consensus Conference definitions for GPA or MPA were included. Incomplete case ascertainment was corrected using a capture–recapture analysis. The spatial association between the number of cases and the presence of quarries in each administrative entity was assessed using regression analyses weighted for geographic region. Results: Among 910 potential AAV patients, we identified 185 patients fulfilling inclusion criteria: 120 patients with GPA, 35 patients with MPA, and 30 patients with renal limited vasculitis. The number of cases missed by any source as estimated by capture–recapture analysis was 6.4 (95% confidence interval [95% CI] 3.6–11.5). Accordingly, the estimated prevalence in Alsace in 2016 was 65.5 GPA cases per million inhabitants (95% CI 47.3–93.0), 19.1 MPA cases per million inhabitants (95% CI 11.3–34.3), and 16.8 renal limited vasculitis cases per million inhabitants (95% CI 8.7–35.2). The risk of AAV was significantly increased in communities with quarries (odds ratio 2.51 [95% CI 1.66–3.80]), and geographic‐weighted regression analyses revealed a significant spatial association between the proximity to quarries and the number of GPA cases (P = 0.039). In analyses stratifying the AAV patients by ANCA serotype, a significant association between the presence of quarries and positivity for both proteinase 3 ANCAs (P = 0.04) and myeloperoxidase ANCAs (P = 0.03) was observed. Conclusion: In a region with a high density of quarries, the spatial association between the presence of and proximity to quarries and the prevalence of AAVs supports the idea that silica may have a role as a specific environmental factor in this disease. [ABSTRACT FROM AUTHOR]

Background: Podocalyxin (PODXL) is a highly sialylated adhesion glycoprotein that plays an important role in podocyte's physiology. Recently, missense and nonsense dominant variants in the PODXL gene have been associated with focal segmental glomerulosclerosis (FSGS), a leading cause of nephrotic syndrome and kidney failure. Their histologic description, however, was superficial or absent. Methods: We performed exome sequencing on a three‐generation family affected by an atypical glomerular nephropathy and characterized the disease by light and electron microscopy. Results: The disease was characterized by FSGS features and glomerular basement membrane duplication. Six family members displayed chronic proteinuria, ranging from mild manifestations without renal failure, to severe forms with end‐stage renal disease. Exome sequencing of affected twin sisters, their affected mother, healthy father, and healthy maternal uncle revealed a new nonsense variant cosegregating with the disease (c.1453C>T, NM_001018111) in the PODXL gene, which is known to be expressed in the kidney and to cause nephropathy when mutated. The variant is predicted to lead to a premature stop codon (p.Q485*) that results in the loss of the intracytoplasmic tail of the protein. Conclusion: This is the first description of a peculiar association combining a PODXL stop‐gain variant and both FSGS and membranoproliferative glomerulonephritis features, described by light and electron microscopy. [ABSTRACT FROM AUTHOR]

Thrombotic microangiopathy is a form of antibody-mediated rejection (ABMR): it is the main complication of ABO-incompatible (ABOi) kidney transplantation (KT). Herein, we report on two cases of ABMR with biological and histological features of thrombotic microangiopathy (TMA) that were treated by eculizumab after ABOi KT. The first patient presented with features of TMA at postoperative day (POD) 13. Because of worsening biological parameters and no recovery of kidney function, despite seven sessions of immunoadsorption, a salvage therapy of eculizumab was started on POD 23. Kidney function slightly improved during the first 4 months after transplantation. Eculizumab was stopped at month 4. However, kidney function worsened progressively, leading to dialysis at month 13 after transplantation. The second patient presented with features of TMA at POD 1. In addition to immunoadsorption therapy, eculizumab was started on POD 6. Kidney function improved. Eculizumab was stopped on POD 64 and immunoadsorption sessions were stopped on POD 102. At the last follow-up (after 9 months), eGFR was at 43 mL/min/1.73 m2. Our case reports show the beneficial effect of eculizumab to treat ABMR after ABOi KT. However, it should be given early after diagnosing TMA associated with ABMR. [ABSTRACT FROM AUTHOR]

The clinical merit of surveillance kidney graft biopsies remains controversial. A retrospective, multicenter analysis evaluated 12-month surveillance biopsies (SB, 154 patients) versus no SB (NSB, 138 patients (11 with diagnostic biopsy)) in patients >18 months posttransplant with estimated GFR (eGFR) ⩾30 mL/min. The primary objective was to describe renal function at 18 months post-transplant in patients with or without SB at month 12. Globally, most recipients in both cohorts were at low immunological risk (<10% of patients with PRA ⩾30%). The immunosuppressive regimen remained unchanged following more than half of SB that exhibited chronic lesions (18/33, 54.5%). Mean (SD) eGFR at month 18 (primary endpoint) was 56 (19) mL/min/1.73m2 with SB and 54 (15) mL/min/1.73m2 with NSB (P = 0.48). In the SB group, slight nonspecific changes were observed in 51 cases, rejection (acute or chronic) in 6 cases, CNI-related toxicity in 15 cases, recurrence of initial disease in two cases, and interstitial fibrosis/tubular atrophy (IF/TA) in 83 cases (71.6%), of which 35 cases (30.2%) were grade II/III lesions. eGFR <50 mL/min/1.73m2 at month 6 predicted IF/TA grade II or III (OR 3.85, 95% CI 1.64, 9.05, P < 0.002). SB at 12 months posttransplant did not prompt significant modification of immunosuppression, and no renal benefit was observed. [ABSTRACT FROM AUTHOR]

Courivaud C, Ladrière M, Toupance O, Caillard S, de Ligny BH, Ryckelynck J-P, Moulin B, Rieu P, Frimat L, Chalopin J-M, Chauvé S, Kazory A, Ducloux D. Impact of pre-transplant dialysis modality on post-transplant diabetes mellitus after kidney transplantation. Clin Transplant 2011: 25: 794-799. © 2010 John Wiley & Sons A/S. Abstract: 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 < 0.001), body mass index (BMI) (p < 0.001), use of tacrolimus (p = 0.002), and rejection episodes (p < 0.001) were identified as independent risk factors for development of PTDM. Patients in the PD group were younger (p = 0.004), had lower BMI (p = 0.07), and were less likely to have a history of hepatitis C (p = 0.007) and autosomal dominant polycystic kidney disease (p = 0.07). Adjustment for these variables did not modify the results. The results of this study suggest that pre-transplant dialysis modality does not have an impact on the subsequent development of PTDM in RTRs. [ABSTRACT FROM AUTHOR]

Background: In the multicenter, open-label Myriade study, renal transplant patients were randomized to early cyclosporine microemulsion (CsA-ME, day 0) or delayed CsA-ME (day 6) with enteric-coated mycophenolate sodium (EC-MPS), steroids and interleukin-2 receptor induction. One-yr results have been published previously. We now report the results of an extension study in which patients were followed up for a period of three yr post-transplant. Methods: All patients completing the one-yr core study on-treatment were eligible to enter the extension study. Results: Of the 203 patients, 153 completed the core trial on-treatment; 144 (94%) entered the extension study with a minimum follow-up of one yr (73 early CsA-ME, 71 delayed CsA-ME). In 75% of patients receiving EC-MPS during the extension, the recommended dose was administered (1440 mg/d). Median creatinine clearance remained constant (57 mL/min) at 12, 24 and 30 months post-transplant and was similar in the early and delayed CsA-ME groups as well as in subpopulations with or without delayed graft function. One patient in the early CsA-ME group died. No grafts were lost. The incidence of BPAR from time of transplant to the end of the extension study was 17% (24/139). Seven patients (5%) discontinued the extension study prematurely because of adverse events. Conclusion: These results suggest that a regimen of CsA-ME, EC-MPS and steroids results in excellent survival rates with stable renal function over a mean follow-up of 30 months. Immediate introduction of CsA-ME has no deleterious effect on long-term renal function, even among patients with delayed graft function. [ABSTRACT FROM AUTHOR]

Post-transplant lymphoproliferative disorders (PTLD) are severe complications after solid organ transplantation with no consensus on best treatment practice. Chemotherapy is a therapeutic option with a high response and a significant relapse rate leading to a low long-term tolerance rate. Currently, most centres use anthracycline-based drug combinations, such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). We assessed the efficacy and safety of a dose-adjusted ACVBP (doxorubicin reduced to 50 mg/m2, cyclophosphamide adjusted to renal function, vindesine, bleomycin, prednisone) regimen in patients failing to respond to a reduction in immunosuppressive therapy. Favourable responses were observed in 24 (73%) of the 33 treated patients. Fourteen (42%) patients died, mostly from PTLD progression. Actuarial survival was 60% at 5 years and 55% at 10 years. Survival prognostic factors were: number of involved sites ( P = 0·007), clinical stage III/IV ( P = 0·004), bulky tumour ( P < 0·0001), B symptoms ( P = 0·03), decreased serum albumin ( P = 0·03) and poor performance status ( P = 0·06). Both the international and the PTLD prognostic index were predictive for survival ( P = 0·001 and P = 0·002, respectively). Overall 128 cycles were given. Grade 3 or 4 neutropenia was recorded after 26 (20%) chemotherapy cycles in 19 (58%) patients. Forty-one (32%) infections were recorded in 26 (79%) patients. This study demonstrated that an individual dose-adjustment of ACVBP regimen was manageable in PTLD patients and favourably impacted on long-term survival. [ABSTRACT FROM AUTHOR]

Background: BK polyomavirus associated nephropathy (BKPyVAN) is a significant clinical issue in kidney transplant (KT) recipients. No specific therapy is currently available, although treatment with leflunomide may be part of the therapeutic strategy. Here, we sought to examine the impact of leflunomide on the evolution of BKPyVAN. Methods: This was an observational retrospective study conducted in 3 French transplant centers. KT recipients who developed BKPyVAN and received leflunomide after failure of other treatment approaches were deemed eligible. Graft function, viral clearance, patient survival, rejection rates, treatment tolerability, and immunosuppression levels served as the main outcome measures. Results: A total of 55 patients were included. Treatment with leflunomide was started after a mean of 1.4 ± 4.1months  after BKPyVAN diagnosis. Between the introduction of leflunomide and the end of follow‐up, creatinine levels increased by 31 ± 118% (P = 0.04), whereas viremia decreased by 79 ± 37% (P < 0.001). Blood viral clearance was observed in 76% of the study patients. Rejection episodes occurred in 33% of the participants. Eleven patients lost their graft (9 of which because of BKPyVAN). Ten patients developed adverse effects and 3 discontinued leflunomide. Conclusion: We cannot conclude about the exact place of leflunomide in the therapeutic strategy of BKPyVAN. It may be a part of the therapy to promote BK polyomavirus clearance in cases of BKPyVAN who fail to improve after immunosuppression lowering alone. Unfortunately, a significant decline in renal function and high rejection rates remain major clinical challenges. [ABSTRACT FROM AUTHOR]