ケツエキ トウセキ カンジャ ノ チョウキ セイメイ ヨゴ ヨソク インシ トシテノ トウセキゴ ノ ケッショウANP ト BNPノウド ノ ユウヨウセイ : 15ネンカン ノ ヨゴ チョウサ

透析患者52人において心胸比を透析前に,収縮期血圧,血清アルブミン,血漿心房性ナトリウム利尿ペプチド(atrial natriuretic peptide ; ANP),脳性ナトリウム利尿ペプチド(brain natriuretic peptide ; BNP),血漿レニン活性(plasma renin activity ; PRA),血漿ノルアドレナリン(plasma noradrenaline ; PNA)濃度を透析直後に測定した.患者は上記測定の中央値で高低2群に分けてKaplan-Meier (KM)生存曲線を求め,両群の比較をLogrank法で行った.生存期間に及ぼす因子解析は測定値を説明変数,生存期間を目的変数としてCox比例hazard法で行った.いずれもp<0.05を有意と判定した. 15年間で43人が死亡し,うち40人が病死であった. KM生存曲線は高年齢群(p<0.001),高ANP群(p=0.006),高BNP群(p=0.039)で有意に生存期間が短く,心胸比,収縮期血圧,血清アルブミン, PRA, PNAにおいては高低2群間に有意差を認めなかった. Cox比例hazard法による単変量解析では年齢(p<0.001),心胸比(p=0.011), ANP (p=0.003), BNP (p=0.002)が生命予後の有意なリスク因子となり,多変量解析ではp値は年齢<0.001,心胸比0.965, ANP 0.055, BNP 0.041となり,年齢とBNPが生命予後の独立したリスク因子であった.以上より透析患者において透析直後の血漿BNP濃度は長期生命予後の独立したリスク因子であり,血漿ANP濃度もリスク因子としてBNPに次いで重要であることが示された.This study was designed to clarify the clinical significance of post-dialysis plasma vasoactive substances including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), plasma renin activity (PRA) and noradrenaline (PNA) as a survival predictor in chronic hemo-dialysis (HD) patients. Immediately after HD, blood samples were collected for the measurements of serum albumin, ANP, BNP, PRA and PNA in 52 HD patients. During 15-year follow-up period 43 patients died ; 40 of diseases, 2 accident, 1 suicide. Patients were divided into two groups using the median of their age and clinical and laboratory variables. Kaplan-Meier survival analysis revealed that the groups of older age, higher plasma ANP and BNP concentration had significantly lower survival rates as compared with each counterpart (p<0.001, p=0.006, p=0.039, respectively). Univariate and multivariate Cox proportional hazard regression analyses were used to assess the potential association of their age, and clinical and laboratory variables with a survival rate. As a result of Univariate Cox hazard analysis, age, cardiothoracic ratio (CTR), and plasma ANP, and BNP concentrations had significant relationship with overall mortality (p<0.001, p=0.011, p=0.003, and p=0.002, respectively). However, stepwise multivariate analysis revealed that the significant relationship with overall mortality was shown for their age (p<0.001) and BNP (p=0.041). These results demonstrated that the post-dialysis plasma BNP concentration was an independent risk factor for long-term survival and the post-dialysis plasma ANP concentration was also an important risk factor next to the BNP concentration

Living well with kidney disease by patient and care partner empowerment: kidney health for everyone everywhere

Living with chronic kidney disease (CKD) is associated with hardships for patients and their care partners. Empowering patients and their care partners, including family members or friends involved in their care, may help minimize the burden and consequences of CKD-related symptoms to enable life participation. There is a need to broaden the focus on living well with kidney disease and re-engagement in life, including an emphasis on patients being in control. The World Kidney Day (WKD) Joint Steering Committee has declared 2021 the year of ‘Living Well with Kidney Disease’ in an effort to increase education and awareness on the important goal of patient empowerment and life participation. This calls for the development and implementation of validated patient-reported outcome measures to assess and address areas of life participation in routine care. It could be supported by regulatory agencies as a metric for quality care or to support labeling claims for medicines and devices. Funding agencies could establish targeted calls for research that address the priorities of patients. Patients with kidney disease and their care partners should feel supported to live well through concerted efforts by kidney care communities including during pandemics. In the overall wellness program for kidney disease patients, the need for prevention should be reiterated. Early detection with a prolonged course of wellness despite kidney disease, after effective secondary and tertiary prevention programs, should be promoted. WKD 2021 continues to call for increased awareness of the importance of preventive measures throughout populations, professionals and policymakers, applicable to both developed and developing countries

Burden, Access, and Disparities in Kidney Disease

This article is being published in Kidney International and reprinted concurrently in several journals. The articles cover identical concepts and wording, but vary in minor stylistic and spelling changes, detail, and length of manuscript in keeping with each journals style. Any of these versions may be used in citing this article. Note that all authors contributed equally to the conception, preparation, and editing of the manuscript

Proposing a validation scheme for 13C metabolite tracer studies in high-resolution mass spectrometry

13C metabolite tracer and metabolic flux analyses require upfront experimental planning and validation tools. Here, we present a validation scheme including a comparison of different LC methods that allow for customization of analytical strategies for tracer studies with regard to the targeted metabolites. As the measurement of significant changes in labeling patterns depends on the spectral accuracy, we investigate this aspect comprehensively for high-resolution orbitrap mass spectrometry combined with reversed-phase chromatography, hydrophilic interaction liquid chromatography, or anion-exchange chromatography. Moreover, we propose a quality control protocol based on (1) a metabolite containing selenium to assess the instrument performance and on (2) in vivo synthesized isotopically enriched Pichia pastoris to validate the accuracy of carbon isotopologue distributions (CIDs), in this case considering each isotopologue of a targeted metabolite panel. Finally, validation involved a thorough assessment of procedural blanks and matrix interferences. We compared the analytical figures of merit regarding CID determination for over 40 metabolites between the three methods. Excellent precisions of less than 1% and trueness bias as small as 0.01–1% were found for the majority of compounds, whereas the CID determination of a small fraction was affected by contaminants. For most compounds, changes of labeling pattern as low as 1% could be measured.© The Author(s) 201

Identification and Functional Characterization of a Novel Susceptibility Locus for Small Vessel Vasculitis with MPO-ANCA

Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA+ AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 × 10−61, odds ratio (OR) 0.10; rs9277341, P = 1.5 × 10−44, OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 × 10−10, OR 2.9). MPO-ANCA+ AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 × 10−25, OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 × 10−7, OR 3.0), the latter a novel susceptibility locus for MPO-ANCA+ granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA+ AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types

PowerPoint Slides for: Distinct in vitro Complement Activation by Various Intravenous Iron Preparations

Background: Intravenous (IV) iron preparations are widely used in the treatment of anemia in patients undergoing hemodialysis (HD). All IV iron preparations carry a risk of causing hypersensitivity reactions. However, the pathophysiological mechanism is poorly understood. We hypothesize that a relevant number of these reactions are mediated by complement activation, resulting in a pseudo-anaphylactic clinical picture known as complement activation-related pseudo allergy (CARPA). Methods: First, the in-vitro complement-activating capacity was determined for 5 commonly used IV iron preparations using functional complement assays for the 3 pathways. Additionally, the preparations were tested in an ex-vivo model using the whole blood of healthy volunteers and HD patients. Lastly, in-vivo complement activation was tested for one preparation in HD patients. Results: In the in-vitro assays, iron dextran, and ferric carboxymaltose caused complement activation, which was only possible under alternative pathway conditions. Iron sucrose may interact with complement proteins, but did not activate complement in-vitro. In the ex-vivo assay, iron dextran significantly induced complement activation in the blood of healthy volunteers and HD patients. Furthermore, in the ex-vivo assay, ferric carboxymaltose and iron sucrose only caused significant complement activation in the blood of HD patients. No in-vitro or ex-vivo complement activation was found for ferumoxytol and iron isomaltoside. IV iron therapy with ferric carboxymaltose in HD patients did not lead to significant in-vivo complement activation. Conclusion: This study provides evidence that iron dextran and ferric carboxymaltose have complement-activating capacities in-vitro, and hypersensitivity reactions to these drugs could be CARPA-mediated

Efficacy of Long-Term Treatment of Autosomal Recessive Hypercholesterolemia With Lomitapide: A Subanalysis of the Pan-European Lomitapide Study

Background and aim: Autosomal recessive hypercholesterolemia (ARH) is a rare autosomal recessive disorder of low-density lipoprotein (LDL) metabolism caused by pathogenic variants in the LDLRAP1 gene. Like homozygous familial hypercholesterolemia, ARH is resistant to conventional LDL-lowering medications and causes a high risk of atherosclerotic cardiovascular diseases (ASCVDs) and aortic valve stenosis. Lomitapide is emerging as an efficacious therapy in classical HoFH, but few data are available for ARH.Results: This is a subanalysis carried out on nine ARH patients included in the Pan-European Lomitapide Study. The age at starting lomitapide was 46 (interquartile range (IQR), 39.0-65.5) years, with a median treatment duration of 31.0 (IQR 14.0-40.5) months. At baseline, four (44.4%) patients had hypertension, one (11.1%) had diabetes mellitus, two (22.2%) were active smokers, and five (55.5%) reported ASCVD. The baseline LDL-C was 257.0 (IQR, 165.3-309.2) mg/dL. All patients were on statins plus ezetimibe, three were receiving Lipoprotein apheresis (LA), and one was also receiving proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i). The addition of lomitapide (mean dose, 10 mg) resulted in the achievement of a median on-treatment LDL-C of 101.7 mg/dL (IQR, 71.3-138.3; 60.4% reduction from baseline), with a best LDL-C value of 68.0 mg/dL (IQR, 43.7-86.7; 73.5% reduction from baseline). During follow-up, one patient stopped both PCSK9i and LA. Recurrence of ASCVD events was reported in one patient. The median on-treatment aspartate transaminase and alanine transaminase values were 31.1 (IQR, 22.6-48.3) U/L and 31.1 (IQR, 27.2-53.8) U/L, respectively. Among six ARH patients with available fibroscan examination, liver stiffness values recorded at the last visit were within the normal range (median, 4.7 KPa; IQR, 3.6-5.3 KPa).Conclusion: Lomitapide is effective and safe in ARH therapy as well as in classical HoFH

Supplementary Material for: Effect of Nocturnal Haemodialysis on Body Composition

Background: Haemodialysis patients have a high risk of malnutrition which is associated with increased mortality. Nocturnal haemodialysis (NHD) is associated with a significant increase in protein intake compared with conventional haemodialysis (CHD). It is unclear whether this leads to improved nutritional status. Therefore, we studied whether 1 year of NHD is associated with a change in body composition. Methods: Whole-body composition using dual-energy X-ray absorptiometry (DEXA) and normalised protein catabolic rate (nPCR) were measured in 11 adult patients before and 1 year after the transition from CHD (12 h dialysis/week) to NHD (28-48 h dialysis/week). Similar measurements were performed in a matched control group of 13 patients who stayed on CHD. Differences between groups were analysed with linear mixed models. Results: At baseline, nPCR, total mass, fat-free mass, and fat mass did not differ significantly between the CHD and NHD groups. nPCR increased in the NHD group (from 0.96 ± 0.23 to 1.12 ± 0.20 g/kg/day; p = 0.027) whereas it was stable in the CHD group (0.93 ± 0.21 at baseline and 0.87 ± 0.09 g/kg/day at 1 year, n.s.). The change in nPCR differed significantly between the two groups (p = 0.027). We observed no significant differences in the course of total mass, fat-free mass, and fat mass during the 1-year observation period between the NHD and CHD groups. Conclusions: One year of NHD had no significant effect on body composition in comparison with CHD, despite a significantly higher protein intake in patients on NHD