Search

Background: The risk of bleeding after percutaneous biopsy in kidney transplant recipients is usually low but may vary. A pre-procedure bleeding risk score in this population is lacking. Methods: We assessed themajor bleeding rate (transfusion, angiographic intervention, nephrectomy, hemorrhage/hematoma) at 8 days in 28,034 kidney transplant recipients with a kidney biopsy during the 2010–2019 period in France and compared them to 55,026 patients with a native kidney biopsy as controls. Results: The rate of major bleeding was low (angiographic intervention: 0.2%, hemorrhage/hematoma: 0.4%, nephrectomy: 0.02%, blood transfusion: 4.0%). A new bleeding risk score was developed (anemia = 1, female gender = 1, heart failure = 1, acute kidney failure = 2 points). The rate of bleeding varied: 1.6%, 2.9%, 3.7%, 6.0%, 8.0%, and 9.2% for scores 0 to 5, respectively, in kidney transplant recipients. The ROC AUC was 0.649 (0.634–0.664) in kidney transplant recipients and 0.755 (0.746–0.763) in patients who had a native kidney biopsy (rate of bleeding: from 1.2% for score = 0 to 19.2% for score = 5). Conclusions: The risk of major bleeding is low in most patients but indeed variable. A new universal risk score can be helpful to guide the decision concerning kidney biopsy and the choice of inpatient vs. outpatient procedure both in native and allograft kidney recipients.

BackgroundThe immune form of thrombotic thrombocytopenic purpura (iTTP) and the hemolytic and uremic syndrome (HUS) are two major forms of thrombotic microangiopathy (TMA). Their treatment has been recently greatly improved. In this new era, both the prevalence and predictors of cerebral lesions occurring during the acute phase of these severe conditions remain poorly known.AimThe prevalence and predictors of cerebral lesions appearing during the acute phase of iTTP and shigatoxin-producingEscherichia coli-HUS or atypical HUS were evaluated in a prospective multicenter study.MethodsUnivariate analysis was performed to report the main differences between patients with iTTP and those with HUS or between patients with acute cerebral lesions and the others. Multivariable logistic regression analysis was used to identify the potential predictors of these lesions.ResultsAmong 73 TMA cases (mean age 46.89 ± 15.99 years (range: 21-87 years) with iTTP (n = 57) or HUS (n= 16), one third presented with acute ischemic cerebral lesions on magnetic resonance imagery (MRI); two individuals also had hemorrhagic lesions. One in ten patients had acute ischemic lesions without any neurological symptom. The neurological manifestations did not differ between iTTP and HUS. In multivariable analysis, 3 factors predicted the occurrence of acute ischemic lesions on cerebral MRI: 1) the presence of old infarcts on cerebral MRI, 2) the level of blood pulse pressure, 3) the diagnosis of iTTP.ConclusionCerebral MRI is crucial to detect both symptomatic and covert ischemic lesions at the acute phase of iTTP and HUS and helps identify patients with old infarcts, at the highest risk of neurological worsening. The diagnosis of iTTP further increases the risk of ischemic lesions but also an increased level of blood pressure that may represent a potential target to further improve the therapeutic management of these conditions.Key points-One third of patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) or the hemolytic uremic syndrome (HUS) present with acute ischemic cerebral lesions on magnetic resonance imagery (MRI);-The cerebral manifestations on MRI did not differ between iTTP and HUS;-The presence of old infarcts on cerebral MRI, the level of blood pulse pressure and a diagnosis of iTTP predict the occurrence of acute ischemic lesions on cerebral MRI.

We describe five cases of severe necrotizing vasculitis following the RNA-based vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including four relapsing anti neutrophil cytoplasmic antibodies (ANCA) vasculitis, 27 days (1–60) after vaccination and one patient with quiescent chronic hepatitis B and de novo polyarteritis nodosa (PAN) 21 days after vaccination. Ten other cases were reported to the French national pharmacovigilance database: six patients with ANCA-associated vasculitis and four patients with PAN (first symptoms 19 days on average after vaccination). Five of these 10 patients developed kidney dysfunction. In conclusion, coronavirus disease 2019 (COVID-19) vaccines can be associated with de novo or recurrent ANCA vasculitis or PAN. Attention should be paid to patients with known ANCA vasculitis or patients with a history of hepatitis B infection.

Renal resistive index predicts the risk of death in many populations but the mechanism linking renal resistive index and death remains elusive. Renal resistive index is derived from end-diastolic velocity (EDV) and peak systolic velocity (PSV). However, the predictive value of EDV or PSV considered alone is unknown.We conducted a retrospective analysis of 2362 consecutive patients who received a kidney transplant from 1985 to 2017. EDV and PSV were measured at 3 months after transplantation, renal resistive index was calculated, and the risk of death was assessed [median follow-up: 6.25 years (0.25-29.15); total observation period: 13 201 patient-years].Doppler indices were available in 1721 of 2362 (78.9%) patients (exclusions: 113 who died or returned to dialysis before, 427 with no Doppler studies, 27 with renal artery stenosis, 74 missing values). Among them, 279 (16.4%) had diabetes before transplantation. Mean age was 51.5 ± 14.7, 1097 (63.7%) were male. During follow-up, 217 of 1721 (12.6%) patients died. Renal resistive index and EDV shared many determinants (notably systolic, diastolic and pulse pressure, recipient age and diabetes) unlike renal resistive index and PSV. EDV used as a binary [lowest tertile vs. higher values: (hazard ratio: 2.57 (1.96-3.36), P 0.001)] and as a continuous (the lower EDV, the greater the risk of death) variable was significantly associated with the risk of death. This finding was confirmed in multivariable analyses. Prediction of similar magnitude was found for renal resistive index. No association was found between PSV used as a binary or a continuous variable and the risk of death.Low EDV explains high renal resistive index, and the mechanism-linking renal resistive index to the risk of death is through low EDV.

International audience; BACKGROUND: The prevalence, prognostic role, and diagnostic value of blood pressure in immune-mediated thrombotic thrombocytopenic purpura (iTTP) and other thrombotic microangiopathies (TMAs) remain unclear. METHODS: Using a national cohort of iTTP (n = 368), Shigatoxin-induced hemolytic uremic syndrome (n = 86), atypical hemolytic uremic syndrome (n = 84), and hypertension-related thrombotic microangiopathy (n = 25), we sought to compare the cohort’s blood pressure profile to assess its impact on prognosis and diagnostic performances. RESULTS: Patients with iTTP had lower blood pressure than patients with other TMAs, systolic (130 [interquartile range (IQR) 118-143] vs 161 [IQR 142-180] mmHg) and diastolic (76 [IQR 69-83] vs 92 [IQR 79-105] mmHg, both p

Indications for kidney biopsy in adult IgA vasculitis (IgAV) remain debated and there are very few studies on this subject. The aim of this study was to establish a correlation between renal histological and clinical-laboratory data.A retrospective multicenter study was conducted using three databases from French hospitals, gathered between 1977 and 2020. The study included 294 adult patients with IgAV who had undergone kidney biopsy assessed according to the prognostic "Pillebout classification". Different statistical models were used to test the correlations between histological and clinical-laboratory data: Cochran Armitage, ANOVA, Kruskal-Wallis and logistic regression.The patients were primarily men (64%), with a mean age of 52 years. The main organs and tissues involved were: dermatological 100%, digestive 48% and rheumatological 61%. All had features of kidney involvement. The median serum creatinine was 96 µmol/L serum albumin 35 g/L, and C-reactive protein 28 mg/L. Of the patients, 86% (n = 254) had hematuria and median proteinuria was 1.8 g/day. The only statistically significant correlation between the pathological stages and the clinical-laboratory data was the presence of hematuria (p = 0.03, 66% class I to 92% class IV). In multivariate analysis, only albuminemia was associated with extracapillary proliferation (p = 0.02; OR 0.94) and only age was associated with stages 3-4 (p = 0.03; OR 1.02).Our study suggests that there is no strict baseline correlation between renal pathology and clinical-laboratory data. Given the current knowledge, it seems relevant to recommend a kidney biopsy in the presence of significant and persistent proteinuria or unexplained kidney function decline.

Background and objectives The risk of major bleeding after percutaneous native kidney biopsy is usually considered low but remains poorly predictable. The aim of the study was to assess the risk of major bleeding and to build a preprocedure bleeding risk score. Design, setting, participants, & measurements Our study was a retrospective cohort study in all 52,138 patients who had a percutaneous native kidney biopsy in France in the 2010–2018 period. Measurements included major bleeding (i.e., blood transfusions, hemorrhage/hematoma, angiographic intervention, or nephrectomy) at day 8 after biopsy and risk of death at day 30. Exposures and outcomes were defined by diagnosis codes. Results Major bleeding occurred in 2765 of 52,138 (5%) patients (blood transfusions: 5%; angiographic intervention: 0.4%; and nephrectomy: 0.1%). Nineteen diagnoses were associated with major bleeding. A bleeding risk score was calculated (Charlson index [2–4: +1; 5 and 6: +2; >6: +3]; frailty index [1.5–4.4: +1; 4.5–9.5: +2; >9.5: +3]; women: +1; dyslipidemia: −1; obesity: −1; anemia: +8; thrombocytopenia: +2; cancer: +2; abnormal kidney function: +4; glomerular disease: −1; vascular kidney disease: −1; diabetic kidney disease: −1; autoimmune disease: +2; vasculitis: +5; hematologic disease: +2; thrombotic microangiopathy: +4; amyloidosis: −2; other kidney diagnosis: −1) + a constant of 5. The risk of bleeding went from 0.4% (lowest score group =0–4 points) to 33% (highest score group ≥35 points). Major bleeding was an independent risk of death (500 of 52,138 deaths: bleeding: 81 of 2765 [3%]; no bleeding: 419 of 49,373 [0.9%]; odds ratio, 1.95; 95% confidence interval, 1.50 to 2.54; P Conclusions The risk of major bleeding after percutaneous native kidney biopsy may be higher than generally thought and is associated with a twofold higher risk of death. It varies widely but can be estimated with a score useful for shared decision making and procedure choice.

Objective Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic small-vessel vasculitis characterized by asthma, hypereosinophilia and ANCA positivity in 40% of patients. Renal involvement is rare and poorly described, leading to this renal biopsy-proven based study in a large EGPA cohort. Methods We conducted a retrospective multicentre study including patients fulfilling the 1990 ACR criteria and/or the 2012 revised Chapel Hill Consensus Conference criteria for EGPA and/or the modified criteria of the MIRRA trial, with biopsy-proven nephropathy. Results Sixty-three patients [27 women, median age 60 years (18–83)] were included. Renal disease was present at vasculitis diagnosis in 54 patients (86%). ANCA were positive in 53 cases (84%) with anti-MPO specificity in 44 (83%). All patients had late-onset asthma. Peripheral neuropathy was present in 29 cases (46%), alveolar haemorrhage in 10 (16%). The most common renal presentation was acute renal failure (75%). Renal biopsy revealed pauci-immune necrotizing GN in 49 cases (78%). Membranous nephropathy (10%) and membranoproliferative GN (3%) were mostly observed in ANCA-negative patients. Pure acute interstitial nephritis was found in six cases (10%); important interstitial inflammation was observed in 28 (44%). All patients received steroids with adjunctive immunosuppression in 54 cases (86%). After a median follow-up of 51 months (1–296), 58 patients (92%) were alive, nine (14%) were on chronic dialysis and two (3%) had undergone kidney transplantation. Conclusion Necrotizing pauci-immune GN is the most common renal presentation in ANCA-positive EGPA. ANCA-negative patients had frequent atypical renal presentation with other glomerulopathies such as membranous nephropathy. An important eosinophilic interstitial infiltration was observed in almost 50% of cases.

Background Renal infarction (RI) is a rare disease with poor prognosis. Appropriate secondary prevention treatment is essential and requires an exhaustive etiological assessment. We aimed to determine whether invasive endovascular explorations may improve the diagnostic process and change the secondary prevention treatment strategy in RI patients. Methods We report a retrospective observational study of 25 RI patients referred to Tours University Hospital between 2011 and 2018 for etiological investigation including renal arteriography and intravascular ultrasonography (IVUS). We sought for antithrombotic treatment regimen, vital status, bleeding and ischemic outcomes during the median follow-up of 59 months. Results Invasive explorations showed local arterial disease in 14 patients (56%). This led to a diagnosis or change in diagnosis in 9 patients (36%) and to a change in antithrombotic strategy in 56% of cases, with an increased prescription of antiplatelet therapy. No patient died, only two patients (8%) had persistent mild renal insufficiency. One IVUS complication was reported and treated without any significant long-term consequences. Conclusion Invasive endovascular investigations of RI may modify the secondary prevention treatment through a better assessment of the aetiology of RI. Multicentric randomized studies are necessary to advocate the hypothesis that invasive exploration of renal artery can improve long-term prognosis.

Background Plasma iohexol clearance (CLiohexol) is a reference technique for glomerular filtration rate (GFR) determination. In routine practice, CLiohexol is calculated using one of several formulas, which have never been evaluated in kidney transplant recipients. We aimed to model iohexol pharmacokinetics in this population, evaluate the predictive performance of three simplified formulas and evaluate whether a Bayesian algorithm improves CLiohexol estimation. Methods After administration of iohexol, six blood samples were drawn from 151 patients at various time points. The dataset was split into two groups, one to develop the population pharmacokinetic (POPPK) model (n = 103) and the other (n = 48) to estimate the predictive performances of the various GFR estimation methods. GFR reference values (GFRref) in the validation dataset were obtained by non-compartmental pharmacokinetic (PK) analysis. Predictive performances of each method were evaluated in terms of bias (ME), imprecision (root mean square error [RMSE]) and number of predictions out of the ±10% or 15% error interval around the GFRref. Results A two-compartment model best fitted the data. The Bayesian estimator with samples drawn at 30, 120 and 270 min allowed accurate prediction of GFRref (ME = 0.47%, RMSE = 3.42%), as did the Brøchner-Mortensen (BM) formula (ME = − 0.0425%, RMSE = 3.40%). With both methods, none of the CL estimates were outside the ±15% interval and only 2.4% were outside the ±10% for the BM formula (and none for the Bayesian estimator). In patients with GFR ≤30 mL/min/1.73 m2, the BM formula performed very well, while the Bayesian method could not be evaluated in depth due to too small a number of patients with adequate sampling times. Conclusions GFR can be estimated with acceptable accuracy in kidney transplant patients using the BM formula, but also using a Bayesian algorithm.

Background The impact of blood pressure on neurological symptoms and risk of end-stage kidney disease (ESKD) is unknown in primary and secondary thrombotic microangiopathies (TMAs). Methods We measured baseline systolic (SBP) and diastolic (DBP) BP in consecutive 563 patients with adjudicated primary and secondary TMAs, and assessed its association with the risk of ESKD. Results Normal BP, grade 1, 2 and 3 hypertension were present in 243 (43.1%), 132 (23.4%), 101 (17.9%) and 88 (15.6%), respectively. Significant BP differences were noted in relation to the cause of TMA: highest BP values were found in patients with atypical hemolytic-uremic syndrome (aHUS), pregnancy, transplantation and auto-immune-related TMAs. Normal BP or grade 1 hypertension was found in 17/18 (94.4%) patients with thrombotic thrombocytopenic patients (only 1/18 (5.6%) had a SBP value>150 mmHg). In contrast, BP values could not differentiate isolated “essential” malignant hypertension (MH) from MH associated with aHUS (isolated MH (n=15): BP (median (IQR)): 220 (182-249)/132 (101-150) mmHg; MH with aHUS (n=5): BP: 223 (196-245)/131 (111-144) mmHg). The risk of vigilance disturbances (6.9%, 15.0%, 25.0%, respectively), epileptic seizures (1.5%, 4.0%, 12.5%, respectively) and posterior reversible encephalopathy syndrome (0.76%, 2.97%, 6.82%, respectively) increased with increasing baseline BP values from grade 1 to grade 3 hypertension. ESKD occurred in 35/563 (6.2%) patients (1.23%, 2.27%, 11.9% and 19.3% of patients with normal BP, grade 1, 2 and 3 hypertension, respectively). As compared to patients with normal BP ( Conclusions Baseline BP differs in primary and secondary TMAs. High BP reduces the neurological tolerance of TMAs and is a powerful independent risk factor of ESKD, even after adjustment on TMA’s cause.

BACKGROUND AND OBJECTIVES: In contrast to shigatoxin-associated Escherichia coli (STEC) causing hemolytic uremic syndrome, STEC-unrelated infections associated with thrombotic microangiopathy are less characterized. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our retrospective study in a four-hospital institution of 530 consecutive patients with adjudicated thrombotic microangiopathies during the 2009–2016 period studied STEC-unrelated infections’ epidemiology and major outcomes (death, acute dialysis, and major cardiovascular events). RESULTS: STEC-unrelated infection was present in 145 of 530 (27%) patients, thrombotic microangiopathies without infection were present in 350 of 530 (66%) patients, and STEC causing hemolytic and uremic syndrome was present in 35 of 530 (7%) patients. They (versus thrombotic microangiopathy without infection) were associated with age >60 years (36% versus 18%), men (53% versus 27%), altered consciousness (32% versus 11%), mean BP

International audience; Background and objectives - Thrombotic microangiopathies constitute a diagnostic and therapeutic challenge. Secondary thrombotic microangiopathies are less characterized than primary thrombotic microangiopathies (thrombotic thrombocytopenic purpura and atypical hemolytic and uremic syndrome). The relative frequencies and outcomes of secondary and primary thrombotic microangiopathies are unknown. Design, setting, participants, & measurements - We conducted a retrospective study in a four-hospital institution in 564 consecutive patients with adjudicated thrombotic microangiopathies during the 2009-2016 period. We estimated the incidence of primary and secondary thrombotic microangiopathies, thrombotic microangiopathy causes, and major outcomes during hospitalization (death, dialysis, major cardiovascular events [acute coronary syndrome and/or acute heart failure], and neurologic complications [stroke, cognitive impairment, or epilepsy]). Results - We identified primary thrombotic microangiopathies in 33 of 564 patients (6%; thrombotic thrombocytopenic purpura: 18 of 564 [3%]; atypical hemolytic and uremic syndrome: 18 of 564 [3%]). Secondary thrombotic microangiopathies were found in 531 of 564 patients (94%). A cause was identified in 500 of 564 (94%): pregnancy (35%; 11 of 1000 pregnancies), malignancies (19%), infections (33%), drugs (26%), transplantations (17%), autoimmune diseases (9%), shiga toxin due to (6%), and malignant hypertension (4%). In the 31 of 531 patients (6%) with other secondary thrombotic microangiopathies, 23% of patients had sickle cell disease, 10% had glucose-6-phosphate dehydrogenase deficiency, and 44% had folate deficiency. Multiple causes of thrombotic microangiopathies were more frequent in secondary than primary thrombotic microangiopathies (57% versus 19%

Background Hypocomplementemic urticarial vasculitis (HUV) is a rare systemic vasculitis. We aimed to describe the kidney involvement of HUV in a multicenter national cohort with an extended follow-up. Methods All patients with HUV (international Schwartz criteria) with a biopsy-proven kidney involvement, identified through a survey of the French Vasculitis Study Group (FVSG), were included. A systematic literature review on kidney involvement of HUV was performed. Results Twelve patients were included, among whom 8 had positive anti-C1q antibodies. All presented with proteinuria, from mild to nephrotic, and 8 displayed acute kidney injury (AKI), requiring temporary haemodialysis in 2. Kidney biopsy showed membrano-proliferative glomerulonephritis (MPGN) in 8 patients, pauci-immune crescentic GN or necrotizing vasculitis in 3 patients (with a mild to severe interstitial inflammation), and an isolated interstitial nephritis in 1 patient. C1q deposits were observed in the glomeruli (n = 6), tubules (n = 4) or renal arterioles (n = 3) of 8 patients. All patients received corticosteroids, and 9 were also treated with immunosuppressants or apheresis. After a mean follow-up of 8.9 years, 6 patients had a preserved renal function, but 2 patients had developed stage 3–4 chronic kidney disease (CKD) and 4 patients had reached end-stage kidney disease (ESKD), among whom 1 had received a kidney transplant. Conclusion Renal involvement of HUV can be responsible for severe AKI, CKD and ESRD. It is not always associated with circulating anti-C1q antibodies. Kidney biopsy shows mostly MPGN or crescentic GN, with frequent C1q deposits in the glomeruli, tubules or arterioles.

Background Renal resistive index (RI) predicts mortality in renal transplant recipients (RTR). However, its predictive value may be different according to the time of measurement. We analysed RI changes between 1 month and 3 months after transplantation and its predictive value for death with a functioning graft (DWFG). Methods We conducted a retrospective study in 1685 RTR between 1985 and 2017. The long-term predictive value of changes in RI value from 1 month to 3 months was assessed in diabetic and non-diabetic RTR. Results Best survival was observed in RTR with RI p p = 0.003) and when RI was ≥0.70 at 1 month and p = 0.006). In diabetic RTR, RI was significantly associated with an increased risk of death only in those with RI p = 0.040). RI considered as a continuous variable at 1 and 3 months was significantly associated with the risk of DWFG in nondiabetic but not in diabetic RTR. Conclusion RI changes overtime and this impacts differently diabetic and nondiabetic RTR. RI short-term changes have a strong prognosis value and refines the risk of DWFG associated with RI.

The anti–von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.

Introduction La mortalite cardiovasculaire est la premiere cause de deces chez les patients transplantes renaux. L’hypertension arterielle (HTA), dont la prevalence, est proche de 80 %, est le premier facteur de risque cardiovasculaire modifiable. Les pratiques concernant la prise en charge de l’HTA chez les patients transplantes renaux sont variees et les donnees scientifiques manquantes. L’objectif de cette etude est de decrire les pratiques, concernant la mesure et la prise en charge pharmacologique de l’HTA, et de confronter les resultats aux donnees recueillies aupres des patients transplantes renaux. Description Un questionnaire a ete diffuse aux medecins assurant le suivi de patients transplantes renaux en France et aux patients transplantes renaux. Methodes Les questions concernaient la mesure de la pression arterielle (PA), sa prise en charge therapeutique et l’observance. Resultats Les reponses obtenues proviennent de 77 nephrologues et 85 patients. Les inhibiteurs calciques suivis des inhibiteurs du systeme renine angiotensine sont les deux classes therapeutiques les plus souvent utilisees en premiere intention (55 % et 38 %), puis les diuretiques non epargneurs de potassium en troisieme intention (47 %) en l’absence de proteinurie. Concernant la mesure de la PA, les reponses des praticiens et des patients sont similaires pour 8 questions mais 5 questions comportent des differences significatives, notamment au sujet des mesures ambulatoires de PA ( Fig. 1 ). Une majorite de patients ressentent une amelioration de leur qualite de vie liee au traitement de l’HTA (88 %) et 79 % declarent etre observant. Conclusion La prise en charge therapeutique de l’HTA est majoritairement faite en adequation avec les recommandations KDIGO. La mesure de la PA ambulatoire est insuffisante et pourtant indispensable dans cette population a haut risque d’HTA resistante, d’HTA masquee et d’HTA nocturne. La mise en place d’etudes interventionnelles sur la mesure ambulatoire de PA chez les patients transplantes renaux semble interessante.

Main problem Recurrence of primary focal and segmental glomerulosclerosis following kidney transplantation (rFSGS) is a frequent and severe disease. Methods We studied the time to recurrence of FSGS and its impact on the response to plasma exchange (PE) and graft survival. Results Between 1990 and 2013, 2730 kidney transplants were performed, including 52 patients with a primary diagnosis of FSGS. Of these patients with primary FSGS, 34 (67%) developed rFSGS. We retrospectively divided these patients into two groups depending on the time to recurrence: early (up to three months after transplantation, n=26) or late (more than three months after transplantation, n=8). Survival did not significantly differ between the two groups. In cases of late recurrence, PE was started later, was performed less frequently and remission was achieved after more PE sessions and longer PE treatment than for the early group (p=0.01). In early recurrence, resistance to PE at 40 days was associated with no long-term response to PE. Conclusions PE should be performed as soon as possible after rFSGS. Patients with late rFSGS need to be offered the same treatment regime as those with early rFSGS.

Background and Aims Caplacizumab, a bivalent Nanobody, targets the A1 domain of von Willebrand Factor, inhibiting the interaction between ultra-large vWF and platelets in the treament of Acquired Thrombotic Thrombocytopenic Purpura (aTTP). Results of the Phase 3 HERCULES study confirm that treatment with caplacizumab reduces the time to platelet count response, resulting in faster resolution of aTTP. Treatment with caplacizumab also resulted in a highly clinically meaningful reduction in aTTP-related death, recurrence of aTTP, or a major thromboembolic event during study drug treatment. Data from clinical practice confirming the clinical trial data is still scarce. We report here the first real world evidence collected in the French thrombotic microangiopathies network. Method Patients with an acute episode of aTTP were included in an observational prospective multicentric study. The diagnosis of aTTP was done according to the French score (platelet count < 30 g/l and serum creatinine< 200µmol/l) or ADAMTS13 activity if available. Adult patients were proposed to be treated with daily plasma exchange (PE) in addition to corticosteroid and frontline rituximab plus early initiation of caplacizumab. PE was stopped after 2 days of platelet count normalization. Results Fifty patients (36 females, median age of 46 years old) were treated for aTTP. 30 patients (60%) had cerebral involvement and 13 (26%) had cardiac involvement. Cardiac troponin I was above upper normal value for 61% of patients. Before treatment, median platelet count was 16 g/l and median serum creatinine was 86 µmol/l. Three initial clinical suspicions of aTTP were finally diagnosed as HUS (2 patients) or vitamin deficiency (1 patient) resulting in the stop of treatment. A median number of 6 plasma exchanges was administered (min:3 - max:16). 375mg/m rituximab injections (3 to 4 for 35/43 patients with reported data) were mostly initiated within 3 days after the first plasma exchange. Caplacizumab treatment was initiated early (37/42 patients with reported data within 2 days after 1st plasma exchange) with a total median duration of treatment of 33 days (min:18 - max:35). The median platelet count normalization was 5 days (min:4 - max:6). 6/41 (14,6%) experienced exacerbations. No deaths and no patients refractory to therapy were reported. Eight adverse events related to caplacizumab therapy were reported, all with good outcomes. Conclusion Concomitant start of additional treatments allow to target severe ADAMTS13 deficiency and platelet aggregation which causes early mortality. The clinical French score seems useful in clinical practices.

Background Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. Methods Clinical and outcome data from patients from 11 French centers over the 2007–2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. Results Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of > 4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

International audience; Introduction:Diagnosing the etiology of a rapidly progressive glomerulonephritis is of vital importance to guide appropriate therapeutic management. This case highlights the complexity involved in establishing diagnosis when presentation is atypical. In certain cases diagnosis cannot be established based on clinical presentation or biopsy findings alone, and critical analysis of biopsy findings in context of clinical presentation is crucial to guide the clinical decision-making process.Case presentation: A 47-year-old Hispanic male with history of granulomatosis with polyangiitis (GPA) in remission on azathioprine, presented with fatigue and lethargy. Physical examination was unremarkable. Laboratory data revealed elevated creatinine and otherwise normal electrolytes. Urinalysis showed numerous dysmorphic red blood cells with few red cell casts. His serologic results were all negative except anti-proteinase-3 antibody at very low titers. Kidney biopsy showed necrotizing crescentic glomerulonephritis with linear immunoglobulin G staining along the basement membrane.Conclusion: This case presented conflicting serologic and histopathologic findings. The presence of anti-proteinase-3 antibody supported diagnosis of recurrence of GPA. However, linear staining of immunoglobulin G (IgG) on immunofluorescence (IF) staining of renal biopsy supported anti-glomerular basement membrane (GBM) disease. The treatment of anti-GBM disease and GPA both involve immunosuppression with prednisone and cyclophosphamide. However, patients with anti-GBM disease are also treated with plasmapheresis early in the disease presentation to prevent further damage. The patient with GPA, on the other hand, was shown to benefit from plasmapheresis only in the case of severe renal disease (serum creatinine level more than 5 mg/dL) or pulmonary hemorrhage. In this case, since the patient did not have detectable circulating anti-GBM antibody, the decision was made not to proceed with plasmapheresis. The patient was treated with a standard immunosuppressive regimen consisting of prednisone and cyclophosphamide with partial renal recovery at 2 months.

Background Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is being more widely recognized but the precise epidemiology and outcome is lacking, particularly in Europe. We aimed to assess clinical, pathologic and outcome data of IRGN-IgA. Methods Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were retrospectively collected. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed correlation between histological presentation and outcome using the Chi square test (qualitative data) and Kruskal-Wallis test (quantitative data). Results Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Most of them had a Staphylococcus aureus infection (77.8%) and 44.4% were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine >4 mg/dL, and 16% had a hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis with tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression, found in 17.8% of the cases, was most frequently observed in biopsies with acute or subacute pattern and associated with a shorter delay between infection and renal biopsy compared to segmental and focal staining. After a median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions Infection-related glomerulonephritis with IgA deposits is usually associated with Staphyloccus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

International audience; Background: Renal patients with diabetes mellitus are at very high risk of death before and after chronic dialysis initiation. Risk factors for death in this population are not clearly identified. Methods: We performed a retrospective survival analysis in 861 patients with diabetes mellitus consecutively followed up in the 2000-13 period in a nephrology setting. Results: The mean age was 70 \,±\, 10 years [men 65.2%; diabetes duration 13.7 \,±\, 10.3\,years; mean estimated glomerular filtration rate (eGFR) 42.4 \,±\, 21.0\,mL/min/1.73 m2). During follow-up (median 60\,months; up 15\,years), 263 patients died (184 before and 79 after dialysis initiation) and 183 started chronic dialysis. In multivariate analyses, age, elevated systolic and low diastolic arterial pressures, peripheral artery disease, cancer, loop diuretic use and atrial fibrillation at baseline and acute kidney injury (AKI), heart failure (HF) and amputation during follow-up were identified as risk factors for death. After adjustments on these parameters, eGFRs at the time of the first outpatient visit-eGFR 80 years of age [HR 1.08 (95% CI 0.64-1.81), P\,=\,0.7793]. Conclusions: In patients with diabetes mellitus, high systolic and low diastolic arterial pressure, peripheral artery disease and development of AKI and HF are significant risk factors for death. In addition to these parameters, eGFR

Human parvovirus B19 has been associated with various cases of kidney injuries with different glomerular phenotypes. In immunocompromised individuals, insufficient production of neutralizing antibodies can lead to chronic PVB19 carriage and manifestations. However, PVB19 DNA has been detected in bone marrow and peripheral blood for months or years in seemingly immunocompetent individuals, despite the presence of neutralizing antibodies. We report here PVB19-induced recurrent anuric acute kidney failures in a 57-year-old man over a 7-year period with persistent PVB19 infection and then PVB19-associated cryoglobulinemia. Acute renal failures were preceded by influenza-like syndrome associated with arthralgia, skin rash, and low-grade fever. Serum, bone marrow, renal, and digestive PVB19 replication was found in the different episodes. Endocapillary proliferative glomerulonephritis evolved into membranoproliferative glomerulonephritis. Complete renal recovery occurred after each bout. Off-label subcutaneous immunoglobulin therapy resulted in disappearance of blood and bone marrow PVB19 viral load and stopped the glomerulonephritis recurrence. Subcutaneous immunoglobulin therapy withdrawal resulted in renal relapse with cryoglobulin-associated manifestations.

Introduction Le tolvaptan (JINARC®) est le premier traitement de la polykystose renale autosomique dominante (PKRAD) dont la Commission de la Transparence (HAS) a defini les criteres d’eligibilite en 2015. Description Cree en 2010, la cohorte GENKYST comprend 3200 patients dans 28 centres sur 13 departements du Grand Ouest Francais. Methodes Nous rapportons les resultats en vie reelle des patients Genkyst traites par tolvaptan suivis prospectivement depuis l’initiation du traitement. Pour chacun des patients, la pente du DFG en fonction du nombre de mois est calculee par regression lineaire, avant traitement puis apres debut du traitement. Resultats 108 patients ont ete traites dans 17 centres : âge moyen 47 ans, DFG moyen 55 ml/min. 89 % des patients traites etaient porteurs d’une mutation de PKD1. Le volume total renal moyen etait de 1422 ml/m (405 a 4643) : 96 % des patients avaient un score de la Mayo Clinic > 1 C et 70 % un score PRO-PKD > 3. La titration a ete hebdomadaire (25 %) ou mensuelle (56 %) et 72 % des patients ont pu atteindre et conserver la dose de 90-30 mg avec une duree moyenne de traitement de 22 mois. Au total, 30 % des patients ont du stopper le tolvaptan dont la moitie pour les effets aquaretiques. Trois cas d’augmentation importante des transaminases ont ete rapportes, spontanement resolutifs a l’arret du traitement. La perte moyenne de DFG etait de 5,16 ml/min/an avant traitement et passe a 3,48 ml/min/an apres traitement. En regression lineaire la moyenne des pentes par patient est significativement differente avant et apres traitement (p = 0,031). Conclusion Les indications de traitement ont ete globalement conformes aux indications de la HAS. Le traitement par tolvaptan en dehors de protocoles cliniques montre une tolerance plus faible (30 % d’arret). Pour la premiere fois, nous montrons une efficacite en vie reelle en comparant les donnees avant et apres traitement.

Kidney transplantation is one of the therapeutic options for end-stage renal disease (ESRD) in systemic sclerosis (SS). Current evidence demonstrates poorer patient and graft survival after transplantation in SS than in other primary kidney diseases. All the patients presenting ESRD associated with SS who had received a kidney allograft between 1987 and 2013 were systematically included from 20 French kidney transplantation centres. Thirty-four patients received 36 kidney transplants during the study period.. Initial kidney disease was scleroderma renal crisis in 76.4%. Extra-renal involvement of SS was generally stable, excepted cardiac and gastro intestinal involvements, which worsened after kidney transplantation in 45% and 26% of cases respectively. Patient survival was 100%, 90.3% and 82.5% at 1, 3, and 5 years post transplant respectively. Pulmonary involvement of SS was an independent risk factor of death after transplantation. Death-censored graft survival was 97.2% after 1 and 3 years, and 92.8% after 5 years. Recurrence of scleroderma renal crisis was diagnosed in 3 cases. In our study, patient and graft survivals after kidney transplantation can be considered as excellent. On this basis, we propose that in the absence of extra-renal contraindication, SS patients presenting with ESRD should be considered for kidney transplantation. This article is protected by copyright. All rights reserved.

Background Renal resistive index (RI) predicts mortality in renal transplant recipients, but we do not know whether this is true in diabetic patients. The objective of this study was to analyse the long-term predictive value of RI for death with a functioning graft (DWFG) in renal transplant recipients with or without pre-transplant diabetes. Methods We conducted a retrospective study in 1800 renal transplant recipients between 1985 and 2017 who were followed for up to 30 years (total observation period: 14 202 patient years). Donor and recipient characteristics at time of transplantation and at 3 months were reviewed. The long-term predictive value of RI for DWFG and the age–RI and arterial pressure–RI relationships were assessed. Results A total of 284/1800 (15.7%) patients had diabetes mellitus before transplantation. RI was Conclusion Our study indicates that RI is not a predictor of DWFG in diabetic renal transplant recipients, in contrast to non-diabetic recipients. These findings could be due to a different age–RI or pulse pressure–RI relationship.

International audience; High renal resistive index (RI) is observed in diabetes and is associated with poor patient survival, but whether it is primarily due to renal vascular resistance or systemic vascular alterations is unclear. The respective impact of kidney transplant from diabetic donors or to diabetic recipients on RI would shed some light on this issue. The objective of the study was to analyze the impact of donor and recipient diabetes on RI in order to understand the respective impact of the kidney and the vascular environment. The authors conducted a retrospective study in 1827 renal transplant recipients who received a kidney between 1985 and 2017, and had Doppler measurements at 3~months after transplant. Donor and recipient characteristics at the time of transplant and at 3~months were reviewed. Both donor diabetes and recipient diabetes were associated with RI in univariate analysis, but only recipient diabetes remained significantly associated in stepwise multivariate analyses (effect estimate on RI: +0.03~±~0.005, P~

Background Interconnections between major cardiovascular events (MCVEs) and renal events are recognized in diabetes, however, the specific impact of atrial fibrillation (AF), heart failure (HF) and acute coronary syndrome (ACS) on the risk of end-stage renal disease (ESRD) on top of established renal risk factors is unclear in type 2 diabetes mellitus. Methods We conducted a retrospective study in 861 consecutive patients followed in a nephrology setting during the 2000–13 period. Results The mean age was 70 ± 10 years, 65.1% were men and the estimated glomerular filtration rate (eGFR) was 42.4 ± 21.0 mL/min/1.73 m2. During follow-up (median 59 months), 194 patients reached ESRD. A history of AF, HF or ACS was associated with an increased risk of reduced baseline eGFR. In turn, reduced baseline eGFR resulted in a greater risk of new MCVE (especially HF) during follow-up. Finally, all new MCVEs were risk factors for subsequent acute kidney injury (AKI) {HF: hazard ratio [HR] 8.99 [95% confidence interval (CI) 7.06–11.4]; AF: HR 5.42 (3.91–7.52); ACS: HR 8.82 (6.24–12.5); all P Conclusions Past and new cardiovascular events (more HF and AF than ACS) have a strong, independent impact on the development of ESRD above and beyond established risk factors in diabetes.

Objective:Thrombotic microangiopathies (TMAs) constitute a group of diseases with a high renal risk. The epidemiological value of blood pressure (BP) is unknown in TMAs.Design and method:We measured baseline systolic (SBP) and diastolic (DBP) in consecutive 563 patients with adjudicated TMAs, and as

International audience; BACKGROUND AND OBJECTIVES: The complement inhibitor eculizumab has dramatically improved the outcome of atypical hemolytic uremic syndrome. However, the optimal duration of eculizumab treatment in atypical hemolytic uremic syndrome remains debated. We report on the French atypical hemolytic uremic syndrome working group's first 2-year experience with eculizumab discontinuation in patients with atypical hemolytic uremic syndrome.DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Using the French atypical hemolytic uremic syndrome registry database, we retrospectively identified all dialysis-free patients with atypical hemolytic uremic syndrome who discontinued eculizumab between 2010 and 2014 and reviewed their relevant clinical and biologic data. The decision to discontinue eculizumab was made by the clinician in charge of the patient. All patients were closely monitored by regular urine dipsticks and blood tests. Eculizumab was rapidly (24-48 hours) restarted in case of relapse.RESULTS: Among 108 patients treated with eculizumab, 38 patients (nine children and 29 adults) discontinued eculizumab (median treatment duration of 17.5 months). Twenty-one patients (55%) carried novel or rare complement genes variants. Renal recovery under eculizumab was equally good in patients with and those without complement gene variants detected. After a median follow-up of 22 months, 12 patients (31%) experienced atypical hemolytic uremic syndrome relapse. Eight of 11 patients (72%) with complement factor H variants, four of eight patients (50%) with membrane cofactor protein variants, and zero of 16 patients with no rare variant detected relapsed. In relapsing patients, early reintroduction (≤48 hours) of eculizumab led to rapid (

Summary Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) treatment strategy is based on immunosuppressive agents. Little information is available concerning mycophenolic acid (MPA) and the area under the curve (AUC) in patients treated for AAV. We evaluated the variations in pharmacokinetics for MPA in patients with AAV and the relationship between MPA–AUC and markers of the disease. MPA blood concentrations were measured through the enzyme-multiplied immunotechnique (C0, C30, C1, C2, C3, C4, C6 and C9) to determine the AUC. Eighteen patients were included in the study. The median (range) MPA AUC0–12 was 50·55 (30·9–105·4) mg/h/l. The highest coefficient of determination between MPA AUC and single concentrations was observed with C3 (P

Introduction Les microangiopathies thrombotiques (MAT) post-transplantation renale (TR) sont actuellement divisees entre recurrence d’une MAT primitive ou de MAT de novo sur le greffon. Methodes Decrire l’epidemiologie exhaustive des MAT post-TR dans un centre hospitalier universitaire. Une etude retrospective de 564 cas consecutifs adjudiques de MAT incidentes dans un groupe hospitalier entre 2009 et 2017 a permis l’identification de 50 cas de MAT post-TR. Les variables etudiees etaient le delai post-TR, l’etiologie de la MAT et la presentation clinique et biologique. L’analyse statistique univariee etait realisee par tests non parametriques. Resultats obtenus ou attendus L’analyse de la cohorte a permis d’identifier 3 differentes situations : un groupe precoce (n = 14, delai median = 2,5 jours [IQR = 0–9]), un groupe intermediaire (n = 18, delai median = 961 jours [IQR = 243–1439]) et un groupe terminal (n = 17, delai median = 3244 jours [IQR = 2555–6285]). L’etiologie etait multifactorielle dans 80 % des cas pour les groupes intermediaire et terminal et 100 % des cas precoces. Les principales causes de MAT etaient medicamenteuse (traitement par anticalcineurine et induction par thymoglobuline) et infectieuse (reactivation EBV chez 33 % des patients du groupe intermediaire). La survie des greffons apres un delai median de suivi de 45 mois (IQR = 30–68) et de 32 mois (IQR = 18–63) etait de 100 % et de 61 % dans les groupes precoces et intermediaires respectivement (4 rejets humoraux chroniques (cABMR) sur les 4 patients biopsies, 2 deces avec greffon fonctionnel). La perte de greffon dans le groupe terminal etait secondaire pour 13 patients (76 %) au cABMR (p = 0,001) avec un tableau de MAT clinique et biologique plus marque. Conclusion La cause de MAT post-TR varie en fonction du delai post-transplantation, qui devrait etre a prendre en consideration dans l’enquete etiologique. Le cABMR serait la cause principale de MAT sur le greffon a distance de la TR.

Introduction Nous rapportons ici les premieres donnees d’utilisation en vie reelle du caplacizumab, nanocorps anti-Willebrand, indique dans la prise en charge du purpura thrombotique thrombocytopenique acquis (PTTa). Methodes Etude observationnelle prospective multicentrique. Trois criteres presidaient a cette prise en charge nationale homogene : (i) diagnostic de PTTa selon le score clinique francais (ii) traitement par echanges plasmatiques (EP) quotidiens associe a un traitement par caplacizumab precoce et un traitement immunosuppresseur (corticotherapie et rituximab), (iii) arret des EP sans entretien apres normalisation plaquettaire durant 2 jours. Resultats obtenus ou attendus Vingt deux patients (17 femmes, âge median de 43 ans) ont ete traites pour un PTTa dans 14 centres. 12 patients avaient une atteinte cerebrale et 13 une atteinte cardiaque. A l’inclusion, le taux median de plaquettes etait de 10xG/l et la creatinine serique mediane de 85 μmol/l. Trois suspicions cliniques de PTTa en plus des 22 patients etudies ont ete finalement redressees en diagnostic de syndrome hemolytique et uremique associe a une shigatoxine (2 patients) ou en carence vitaminique (1 patient) justifiant l’arret des traitements. Le nombre median d’EP etait de 6 (min :3–max :16). Les injections de rituximab (3 a 4 pour 18/22 patients) etaient administrees majoritairement dans les 3 j post-EP. Le caplacizumab etait initie precocement ( Conclusion L’inititation conjointe de therapeutiques complementaires permet ainsi de cibler a la fois le deficit severe en ADAMTS13 et l’adhesion plaquettaire, cause de morbi-mortalite precoce. Le score clinique francais semble utilisable pour un diagnostic du PTTa en urgence.

Objective:High blood pressure and diabetes have a high morbidity and mortality rate and are the first causes for kidney diseases. In order to limit these complications, it is necessary to regularly monitor these patients, including close biological monitoring. In this study, we analyzed the serum cr

Introduction Le caplacizumab est un nanocorps anti-facteur Willebrand qui s’est montre efficace dans la prise en charge du purpura thrombotique thrombocytopenique acquis (PTTa) en association au traitement standard. Avec la mise a disposition dans le cadre d’une ATU du caplacizumab, nous rapportons ici les premieres donnees d’utilisation en vie reelle du produit. Patients et methodes Cette prise en charge nationale des patients traites pour un PTTa a ete preconisee selon les 3 criteres suivants : – diagnostic de PTTa reposant sur le score clinique francais (syndrome de MAT sans contexte associe, plaquettes – traitement par echanges plasmatiques (EP) quotidiens associe a un traitement par caplacizumab precoce et un traitement immunosuppresseur (corticotherapie 1,5 mg/kg/j et rituximab 375 mg/m2 3 a 4 injections) ; – arret des EP sans entretien apres normalisation du taux de plaquettes durant 2 jours. Le caplacizumab a ete administre a la dose de 10 mg IV avant le premier EP puis par voie sous-cutanee au decours de chaque EP puis pour une duree de 30 jours supplementaires apres le dernier EP. Les donnees des patients ont ete recueillies a la date du 21/12/18. Resultats Douze patients ont ete traites pour un PTTa dans 7 centres du CNR-MAT ; huit femmes et 4 hommes âges de 23 a 71 ans. Onze patients ont ete traites pour un premier episode, un patient etait traite pour une troisieme rechute. 10 patients avaient une atteinte cerebrale. Une seule suspicion d’infection a ete reportee. Une suspicion clinique de PTTa (plaquettes 20 × 109/l mais creatininemie 532 μmol/l) a ete finalement redressee en diagnostic de syndrome hemolytique et uremique associe a une shigatoxine au deuxieme jour de traitement et le patient a ete exclu de l’analyse. Les 11 patients finalement inclus avaient un taux de plaquettes a l’initiation des EP inferieur a 30 × 109/l et une creatinine serique inferieure a 200 μmol/l. Chez tous les patients, un deficit severe ( Conclusion Nous montrons sur ces premiers patients la possibilite d’utiliser le score clinique francais associant taux de plaquettes et creatinine serique pour diagnostiquer en urgence le PTTa. L’inititation conjointe des EP, du caplacizumab et du traitement immunosuppresseur en urgence permet ainsi de cibler a la fois le deficit severe en ADAMTS13 et les microthrombi, cause de morbimortalite precoce. Une evaluation des 50 premiers patients traites par ce nouveau standard therapeutique permettra de savoir si celui-ci diminue le taux de mortalite historique du PTTa qui demeure de 15 %.

To describe long-term CD4+ T-cell reconstitution after rabbit antithymocyte globulin (rATG) treatment and identify predictive factors following kidney transplantation. A single-center retrospective study analyzed lymphocyte subsets in rATG-treated kidney transplant recipients (1986–2009). 589 patients were analyzed (maximum follow-up 21 years). A comparator group (n = 298) received an anti-IL-2 receptor monoclonal antibody. CD4+ T-cell lymphopenia (40 years was identified as a cutoff point. CD4+ T-cell reconstitution following rATG treatment remains impaired even after 21 years. Most risk factors for long-term impaired CD4+ T-cell reconstitution may be evaluated pretransplant or are modifiable post-transplant.

Despite a large body of literature, the impact of chronic cytomegalovirus (CMV) infection in donor on long-term graft survival remains unclear, and factors modulating the effect of CMV infection on graft survival are presently unknown. In this retrospective study of 1279 kidney transplant patients, we analyzed long-term graft survival and evolution of CD8(+) cell population in donors and recipients by CMV serology and antigenemia status. A positive CMV serology in the donor was an independent risk factor for graft loss, especially among CMV-positive recipients (R(+) ). Antigenemia was not a risk factor for graft loss and kidneys from CMV-positive donors remained associated with poor graft survival among antigenemia-free recipients. Detrimental impact of donor's CMV seropositivity on graft survival was restricted to patients with full HLA-I mismatch, suggesting a role of CD8(+) cells. In R(+) patients with positive CMV antigenemia during the first year, CD8(+) cell count did not increase at 2 years posttransplantation, in contrast to R(-) recipients. In addition, marked CD8(+) -cell decrease was a risk factor of graft failure in these patients. This study identifies HLA-I full mismatch and a decrease of CD8(+) cell count at 2 years as important determinants of CMV-associated graft loss.

International audience; Gas and aerosol chemistry of 10 km -resolution mesoscale models Meso-NH and WRF/CHEM were evaluated on three cases over Europe. These one-day duration cases were selected from Freney et al. (2011) and occurred on contrasted meteorological conditions and at different seasons: a cyclonic circulation with a well-marked frontal zone on winter, an anti-cyclonic situation with local storm precipitations on summer and a cold front in the northwest of Europe associated to a convergence of air masses over eastern Europe and conflicting air masses over Spain and France on autumn. To assess the performance of the two models, surface hourly databases from observation stations over Europe were used, together with airborne measurements. For both models, the meteorological fields were in good agreement with the measurements for the three days. Winds presented the largest normalized mean bias integrated over all European stations for both models. Daily gas chemistry was reproduced with normalized mean biases between -14 and 11 %, a level of accuracy that is acceptable for policy support. The two models performances were degraded during night-time quite likely due to the constant primary species emissions. The PM2.5 bulk mass concentration was overestimated by Meso-NH over Europe and slightly underestimated by WRF/CHEM. The absence of wet deposition in the models partly explains the local discrepancies with the observations. More locally, the systematic low mixing ratio of volatile organic compounds in the gas phase simulated by WRF/CHEM at three stations was correlated with the underestimation of OM (Organic Matter) mass in the aerosol phase. Moreover, this mass of OM was mainly composed of anthropogenic POA (Primary Organic Aerosols) in WRF/CHEM, suggesting a missing source for SOA (Secondary Organic Aerosols) mass in WRF/CHEM aerosol parameterization. The contribution of OM was well simulated by Meso-NH, with a higher contribution for the summer case. For Meso-NH, SOA made the major contribution to the OM mass. The simulation of the mass of SO42- in particles by both models was often overestimated and correlated with an underestimation of the SO2 mixing ratio. The simulated masses of NO3- and NH4+ in particles were always higher for Meso-NH than for WRF/CHEM, which was linked to a difference in NOX mixing ratio between the models. Finally, computations of model performance criterion and model performance goals show that both models can be considered acceptable for standard modelling applications. In particular, Meso-NH model, using a gaseous chemical mechanism designed to compute the organic precursors of aerosols, shows comparable simulated amounts of SOA to observations at local sites.

The high altitude Puy de Dome (PUY) research station, located at 1465 m a.s.l. in central France, hosts many instruments allowing continuous measurements and intensive campaigns to measure meteorological parameters, gas-phase species, aerosol and cloud properties. Aerosol chemical composition measurements provided by a compact Time-of-Flight Aerosol Mass Spectrometer (cToF-AMS) are used to evaluate the WRF-Chem model and more precisely its ability to simulate organic aerosol (OA) for a particular event in summer 2010. Using the Volatility Basis Set approach (VBS), dedicated to the formation of secondary organic aerosol (SOA), the WRF-Chem model strongly underestimates the high concentration levels of OA observed at the PUY station: 12.5 µg m–3 were observed and only 2.6 µg m–3 were simulated. By means of several measurements of gas-phase volatile organic compounds (VOCs), the robustness of both emissions and SOA formation processes in the WRF-Chem model was tested. The underestimation of the OA mass concentration appears to be mainly due to a misrepresentation of the oxidation rate of the organic condensable vapours (OCVs) and the SOA yields of both anthropogenic and biogenic VOCs in the VBS parameterization.

Organic aerosols (OA) represent a large fraction (from 20 to 90 %) of the submicron particulate mass and it is mainly composed of secondary organic aerosols (SOA). Despite the ubiquity of OA in the atmosphere, there are still large uncertainties in understanding the formation pathways of SOA. Consequently, OA sources and physico-chemical transformations during their transport are poorly represented in chemistry-transport models and large gaps still remain between simulated and measured OA concentrations. The ability of the WRF-CHEM model to reproduce the organic aerosol mass concentration originated from anthropogenic or/and biogenic emissions is evaluated. From this perspective, simulations for two contrasted air masses are performed with WFR-Chem using the Volatility Basis Set (VBS) approach dedicated to the formation of SOA. Simulations results are compared to aerosol measurements performed at the puy de Dome station with a compact Time-of-Flight Aerosol Mass Spectrometer for two episodes in autumn 2008 and in summer 2010. Moreover, measurements of both anthropogenic and biogenic VOCs are used to access the capacity of the WRF-Chem model to correctly simulate the concentrations levels of the gas precursors of the SOA.

Estimated glomerular filtration rate (eGFR) methods are not sufficiently reliable in renal transplant recipients (RTR) and should be replaced by iohexol plasma clearance measurement. However, this method has poor availability in health centers. The aim of our study was to develop a high-performance liquid chromatography (HPLC) method for plasma iohexol measurement in routine practice and to evaluate its plasma clearance as a reference of GFR. We developed an HPLC method using UV detection. We evaluated sample storage conditions to provide recommendations for routine practice. Then, we compared GFRbased on plasma iohexol clearance (GFR-iohexol) to eGFR using modification of diet in renal disease, Cockcroft and Gault, and CDK-EPIequations in 40 RTR. The method was validated over a concentration range of 15–300 μg/l. Excellent linearity (r > 0.998), inter- and intraday precision (CV 96.8%) were complied with ICH guidelines. We also demonstrated excellent samples stability (9 days). Although eGFR methods are not references in RTR, we found a correct concordance between eGFR and GFR-iohexol in our population. To conclude, our method is simple, rapid, accurate, and reliable for routine clinical and research use especially in RTR. J. Clin. Lab. Anal. 26:376-383, 2012. © 2012 Wiley Periodicals, Inc.

BACKGROUND Glomerular filtration rate (GFR) measurement is a major issue in kidney transplant recipients for clinicians. GFR can be determined by estimating the plasma clearance of iohexol, a nonradiolabeled compound. For practical and convenient application for patients and caregivers, it is important that a minimal number of samples are drawn. The aim of this study was to develop and validate a Bayesian model with fewer samples for reliable prediction of GFR in kidney transplant recipients. METHODS Iohexol plasma concentration-time curves from 95 patients were divided into an index (n = 63) and a validation set (n = 32). Samples (n = 4-6 per patient) were obtained during the elimination phase, that is, between 120 and 270 minutes. Individual reference values of iohexol clearance (CL(iohexol)) were calculated from k (elimination slope) and V (volume of distribution from intercept). Individual CL(iohexol) values were then introduced into the Brochner-Mortensen equation to obtain the GFR (reference value). A population pharmacokinetic model was developed from the index set and validated using standard methods. For the validation set, we tested various combinations of 1, 2, or 3 sampling time to estimate CL(iohexol). According to the different combinations tested, a maximum a posteriori Bayesian estimation of CL(iohexol) was obtained from population parameters. Individual estimates of GFR were compared with individual reference values through analysis of bias and precision. A capability analysis allowed us to determine the best sampling strategy for Bayesian estimation. RESULTS A 1-compartment model best described our data. Covariate analysis showed that uremia, serum creatinine, and age were significantly associated with k(e), and weight with V. The strategy, including samples drawn at 120 and 270 minutes, allowed accurate prediction of GFR (mean bias: -3.71%, mean imprecision: 7.77%). With this strategy, about 20% of individual predictions were outside the bounds of acceptance set at ± 10%, and about 6% if the bounds of acceptance were set at ± 15%. CONCLUSIONS This Bayesian approach can help to reduce the number of samples required to calculate GFR using Brochner-Mortensen formula with good accuracy.

Summary Pulse pressure and urinary albumin excretion were recently identified as risk factors of new-onset diabetes after renal transplantation (NODAT), suggesting that microvascular injury may be implicated in NODAT. However, the relationship between of microvascular injury and NODAT is unknown. In the present long-term (median follow-up: 5.7 years; observation period: 4908 patient-years) retrospective study in 656 renal transplant recipients, the association between baseline renal resistance index (RI, used as a marker of widespread microvascular damage) and the incidence of NODAT was assessed. The incidence of NODAT was 11.2% and 14.6% at 5 and 10 years, respectively, after transplantation. RI at 3 months was a risk factor for NODAT [hazard ratio (HR) per 0.1: 2.19 (1.55–3.09), P 0.75 (vs. 0 ≤ 0.75) was a potent a predictor of NODAT [HR: 3.29 (1.91–5.67), P

Introduction L’eculizumab est un anticorps therapeutique qui neutralise le composant C5 du complement et ainsi inhibe la voie finale commune du complement. Il est le traitement de reference des SHU atypiques. Son schema de prescription, qui ne prend en compte que l’âge du patient, impose des perfusions toutes les 2 semaines. Le cout est tres eleve (> 300 000 euros/an/patient). La mesure des concentrations residuelles d’eculizumab, qui doivent etre superieures a 75–100 mg/L pour assurer une neutralisation complete du complement, pourrait permettre d’adapter le schema d’administration de l’eculizumab. Patients et methodes Nous avons collecte 156 serums (39 patients) traites par eculizumab pour des SHU atypiques (7 centres). Apres avoir valide une technique Elisa de mesure, la concentration residuelle d’eculizumab a ete mesuree sur 154 echantillons. Une analyse pharmacocinetique de population a ete realisee a partir des concentrations d’eculizumab determinees chez 37 patients dont les donnees clinicobiologiques etaient disponibles. Resultats Les concentrations d’eculizumab presentaient une grande variabilite interindividuelle (mediane = 474 mg/L, etendue = 131–1292 mg/L), mais une faible variabilite intra-individuelle (CV = 13,3 ± 7,5 %). Trente-six sur 39 (92 %) patients presentaient des concentrations residuelles d’eculizumab superieures a 150 mg/L. Trois de ces 36 patients avaient des perfusions realisees seulement toutes les 3 semaines. Parmi les covariables etudiees en analyse multivariee (poids, sexe, taille), seul le poids etait associe a la concentration residuelle d’eculizumab (R2 = 0,26, p = 0,002) et a la clairance de l’eculizumab (R2 = 0,40, p = 0,0002). Une simulation des concentrations residuelles montre que 95 % et 85 % des patients presenteraient des concentrations residuelles d’eculizumab superieures a 100 mg/L pour une posologie respectivement de 1200 mg toutes les 3 ou 4 semaines. Discussion Nous confirmons dans cette etude pharmacologique multicentrique nos resultats anterieurs [1] . Ainsi les concentrations residuelles d’eculizumab, stables chez un meme patient, sont superieures a la cible indicative chez une large majorite des patients. Conclusion Un suivi therapeutique pharmacologique de l’eculizumab devrait permettre une diminution de la posologie chez la plupart des patients, sans risque de sous-exposition, et une reduction importante des couts.

BACKGROUND The predictive value of doubling of serum creatinine (DSC) has never been assessed in renal transplantation. We evaluated it in terms of its use for clinical trials, cost-effectiveness studies, and individual patients. METHODS Retrospective longitudinal study in 896 renal transplant recipients. RESULTS Death-censored graft loss occurred in 133 patients, during follow-up (up to 21 years). DSC was a risk factor for graft loss; however, the relative risk was different in patients with glomerular filtration rate less than 40 vs. more than or equal to 40 mL/min (hazard ratio: 14.5 [95% confidence interval: 7.4-28.4] vs. 47.8 [28.4-80.6], P=0.0051). Parameters influencing creatinine value (weight, age, sex) did not modify DSC's predictive value. The use of the composite endpoint DSC or death-censored graft loss instead of death-censored graft loss alone in clinical trials would reduce sample size by 7.1% to 9.0%. The annual probability of DSC to graft loss transition decreased from 76% (follow-up

Resume L’infection urinaire chez l’insuffisant renal est frequente et particuliere dans sa prise en charge diagnostique et therapeutique. Il faut donc etre rigoureux pour etablir son diagnostic precis. Les prelevements bacteriologiques sont precieux et indispensables. Y sont associes les recueils des donnees anamnestiques et cliniques permettant d’affirmer l’infection urinaire et de preciser son tableau clinique. L’urologue est souvent amene a traiter par antibiotiques des insuffisants renaux. Avant de debuter une antibiotherapie, il faut s’astreindre a caracteriser l’insuffisance renale : sa realite, son stade et son caractere aigu ou chronique. Cela doit permettre de choisir une antibiotherapie adaptee a chaque situation clinique et d’eviter des incidents iatrogenes.

Risk factors for new-onset diabetes after transplantation (NODAT) need to be assessed in large cohorts. We retrospectively evaluated the impact of early (3 and 6 months after transplantation) proteinuria, urinary albumin excretion (UAE) and arterial pressure on NODAT in 828 Caucasian renal transplant recipients (median follow-up: 5.3 years; 5832 patient-years). The 10- and 20-year incidence of NODAT was 15.0% and 22.0%, respectively. Low-grade (1 g/day) (HR: 2.04 [1.25-3.33], p = 0.0042) and very low-grade (0.3 g/day) (HR: 2.21 [1.32-3.70], p = 0.0025) proteinuria were independent risk factors for NODAT. There was a dose-dependent relationship across UAE categories (increasing risk from normoalbuminuria to macroalbuminuria) with NODAT. Tacrolimus, sirolimus and beta-blockers (HR: 1.86 [1.07-3.22], p = 0.0277) were significantly associated with NODAT even after multiple adjustments, but not diuretics, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Systolic arterial pressure (HR per 10 mmHg: 1.16 [1.03-1.29], p = 0.0126) and pulse pressure (HR: 1.26 [1.12-1.43], p = 0.0002) were associated with NODAT. Only pulse pressure remained significant after adjustments. Patients at highest risks had early proteinuria and pulse pressure60 mmHg. Early low-grade proteinuria and pulse pressure (in addition to beta-blockers) constitute independent risk factors for NODAT; they may be markers of the metabolic syndrome and/or vascular damage in renal transplant recipients.

Summary New-onset diabetes after transplantation (NODAT) is a growing concern in transplantation. All modifiable risk factors are not yet identified. We assessed the relationship between baseline clinical and biochemical parameters and NODAT. Eight-hundred and fifty-seven in-Caucasian renal transplant recipients were included. Charts were individually reviewed. The follow-up was 5.3 years (ranges: 0.25–20.8; 5613 patient-years). The incidence of NODAT was 15.0%, 18.4% and 22.0% at 10, 15 and 20 years following transplantation. Age, body mass index (BMI), glucose (all P

International audience; The annual cost of eculizumab maintenance therapy in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic-uremic syndrome (aHUS) exceeds $300,000 per patient. A better understanding of eculizumab pharmacokinetics and subsequent individual dose adjustment could reduce this cost. We measured the trough eculizumab concentration in 9 patients with maintenance therapy (aHUS, n = 7; PNH, n = 2) and determined: 1) the intra- and inter-individual variability; 2) the influence of weight on eculizumab pharmacokinetics; and 3) the rate of elimination of eculizumab following discontinuation. A one-compartment model was developed to describe the pharmacokinetics of eculizumab and predicted complement activity by body weight. Trough eculizumab concentrations were >50 µg/mL in 9/9, >100 µg/mL in 8/9, and >300 µg/mL in 5/9 of patients. Intra-individual variability was low but eculizumab concentrations, closely correlated with patient weight (R(2) = 0.66, p = 0.034), varied broadly (55 ± 12 to 733 ± 164 µg/mL). Pharmacokinetic modeling showed that the elimination half-life varied greatly, with an increase from 7.8 d in a patient weighing 100 kg to 19.5 d in a 40 kg patient. We predicted that infusions of 1200 mg could be spaced every 4 or 6 weeks in patients weighing