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Simulations with the chemistry-transport model WRF-Chem are compared to aerosol measurements performed at the puy de Dôme station with a compact Time-of-Flight Aerosol Mass Spectrometer (cToF-AMS) for two episodes in autumn 2008 and in summer 2010. The WRF-Chem model is used with the Volatility Basis Set (VBS) approach dedicated to the formation of secondary organic aerosol (SOA). The model systematically underestimates the observed concentrations of organic aerosol (OA), with significant differences observed for the summer case. For this event, where high OA concentrations were observed (12.5 µgm-3 in average), simulated OA mass concentration is 2.0µgm-3. For the autumn event, observed OA concentrations reached 2.6µgm-3. The simulated concentrations reached only 0.6µgm-3. During the summer event, several gas-phase volatile organic compounds (VOCs) were measured and were used to test the robustness of both emission/dry deposition and SOA formation processes. The concentrations of VOCs, and more specifically the anthropogenic ones, calculated by the model are estimated to be much lower than the observed ones. Hence, the emissions of all SOA precursors are multiplied by 2 in the model: this induces an increase of the mean OA mass concentration of 25% (+0.5µgm-3) and 18% (+0.4µgm-3), respectively for anthropogenic and bio-genic VOCs. The dry deposition of gas-phase organic condensable vapours (OCVs) is also critical to predict the SOA mass concentrations: dividing the deposition factor by 2 leads to an increase of OA mass by an additional 12% (+0.2µgm-3). However, these increases were not sufficient to explain the observed OA concentration, and the underestimation of the OA concentration levels seems to be principally related to a lack in the parameterization of SOA formation. Changing the oxidation rate of OCVs from 1.0x10-11 to 4.0x10-11 cm-3 molecule-1 s-1, doubling the SOA yields for anthropogenic VOCs and finally doubling the SOA yields for biogenic VOCs results in an increase of the mean OAmass concentration by 56% (+1.1 µgm-3), 61 % (+1.2µgm-3) and 40% (+0.8µgm-3), respectively. The consideration of both emission/dry deposition and SOA formation processes tests lead to a mean OA mass concentration of 10.7µgm-3 for 2010, a value that is close to the observations. For 2008, modifying solely the oxidation rate of OCVs and the SOA yields is sufficient to reproduce the observed level of mean OA mass (a mass of 2.4 µgm-3 is obtained by the model whereas a mass of 2.6 µgm-3 was observed). [ABSTRACT FROM AUTHOR]

Few studies have assessed the pharmacokinetics of mycophenolic acid (MPA) in non-transplanted patients treated with mycophenolate mofetil (MMF), and little information is available concerning a concentration-effect relationship between the MPA area under the curve (AUC) and the immunological parameters in patients treated for systemic lupus erythematosus (SLE). We evaluated the variations in pharmacokinetics for MPA in patients with SLE and the relationship between MPA-AUC and markers of disease activity. MPA blood concentrations were measured through enzyme-multiplied immunotechnique (T0, T30′, T1h, T2h, T3h and T4h) to determine the MPA AUC0-4h in patients treated with MMF since at least 4 weeks for SLE. Clinical examination, biochemical analyses and immunological analyses were performed on the same day. The relationship between MPA exposure and disease activity markers was assessed. A total of 20 patients were included in the study. The diagnosis of SLE had been made 87 ± 72 months before and patients had been treated with MMF for 31 ± 30 months. Mean dose of MMF on the day of the study was 1600 ± 447 mg/day. Mean MPA AUC0-4h was 28.4 ± 13.6 mg h/L, mean dose-normalised AUC0-4h was 35.5 ± 13.8 mg h/L and mean MPA C0 was 3.1 ± 2.2 mg/L. There was a high correlation between MPAAUC0-4h and MPA C0, (r = 0.80;P < 0.001).AUC0-4h tended to be lower in patientswho had low complement C3 concentration (<0.67 g/L) and low complement C4 concentration (<0.14 g/L). Moreover, there was a significant relationship between MPA trough levels and complement C4 concentrations (P = 0.043). We confirmed high inter-individual variability of MPA AUC in patients treated with MMF for SLE. This suggests that MPA exposure may be unpredictable with a fixed MMF dose. There was a concentration-effect relationship between MPA exposure (C0) and immunological disease activity parameters. [ABSTRACT FROM AUTHOR]

Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear Therefore, patients with TMA and native kidney biopsies were identified during 2009-2022 in 20 French hospitals and results evaluated. RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (median 184 vs 346 μmol/L) than RH-TMA. RL-TMA resulted from virtually all identified causes, more frequently from anti-VEGF treatment and hematological malignancies but less frequently from shigatoxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection, and even less frequently when three or more causes/triggers were combined (RL-TMA: 5%; RH-TMA: 12%). RL-TMA was associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median 28 months). Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 44%). Among the 69 patients with proven complement-mediated aHUS, eculizumab (anti-C5 therapy) was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other patients with aHUS, including 51% with RL-TMA, eculizumab was used in 29 but with unclear effects of this treatment. Thus, RL-TMA represents a very high proportion of patients with TMA and results from virtually all known causes of TMA and includes 25% of patients with complement-mediated aHUS. Adverse outcomes of RL-TMA are lower compared to RH-TMA but remain significant. Anti-C5 therapy was rarely used in RL-TMA, even in proven complement-mediated aHUS, and its effects remain to be assessed., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Hepatitis E virus (HEV) can cause chronic infection (≥3 months) and cirrhosis in immunocompromised patients, especially kidney transplant recipients. Low alanine aminotransferase (ALT) levels and high HEV intrahost diversity have previously been associated with evolution toward chronicity in these patients. We hypothesized that additional clinical and viral factors could be associated with the risk of chronic HEV infection., Methods: We investigated a series of 27 kidney transplant recipients with HEV infection, including 20 patients with chronic hepatitis E., Results: High tacrolimus trough concentration at diagnosis was the most relevant marker associated with chronic hepatitis E (9.2 vs. 6.4 ng/ml, P  = 0.04). Most HEV genetic changes selected during HEV infection were compartmentalized between plasma and feces., Conclusion: This compartmentalization highlights the diversity and complexity of HEV replication compartments. Tacrolimus trough concentration at diagnosis of HEV infection could allow an early identification of patients at high risk of chronic hepatitis E and guide treatment initiation., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Background: The 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., Aim: The prevalence and predictors of cerebral lesions appearing during the acute phase of iTTP and Shiga toxin-producing Escherichia coli-HUS or atypical HUS were evaluated in a prospective multicenter study., Methods: Univariate 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., Results: Among 73 TMA cases (mean age 46.9 ± 16 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, three 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., Conclusion: At the acute phase of iTTP or HUS, both symptomatic and covert ischemic lesions are detected in one third of cases on MRI. Diagnosis of iTTP and the presence of old infarcts on MRI are associated with the occurrence of such acute lesions as well as increased blood pulse pressure, that may represent a potential target to further improve the therapeutic management of these conditions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

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 the major 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.

Background: 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., Methods: 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., Results: 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)., Conclusion: 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., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Objective: 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., Methods: 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]., Results: 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., Conclusion: Low EDV explains high renal resistive index, and the mechanism-linking renal resistive index to the risk of death is through low EDV., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)