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Citrulline AND kidney

Muthukumar Gunasekaran, Thin Thin Maw, Rowena Delos Santos, Surendra Shenoy, Jason Wellen, T Mohanakumar
BACKGROUND: Immune responses to tissue-restricted self-antigens are thought to play a role in chronic rejection after solid organ transplantation. De novo development of antibodies (Abs) to vimentin have been reported to be associated with interstitial fibrosis/tubular atrophy after kidney transplant, and it has been suggested that immunoglobulin isotype switching of Abs to vimentin may occur during this process. We aimed to determine the correlation between immunoglobulin isotype switching of Abs to vimentin and development of transplant glomerulopathy (TG) after kidney transplant, and to determine whether citrullinated modification of vimentin is required for de novo anti-vimentin development...
September 11, 2017: Transplant Immunology
Amy G Clark, Inge M Worni-Schudel, Francesca M Korte, Mary H Foster
A subset of autoimmune diseases result from autoantibodies targeting epitopes on matrix collagen. The most extensively studied are anti-glomerular basement membrane glomerulonephritis (or its systemic counterpart Goodpasture's disease) that destroys kidneys and lungs, and rheumatoid arthritis that leads to disabling arthritis. Autoantibodies in these disorders bind evolutionarily conserved conformational epitopes on the noncollagenous domain 1 (NC1) of the alpha3 chain of type IV [alpha3(IV)NC1] collagen in glomerular and alveolar basement membranes, and on native or citrullinated type II collagen (CII) in joint cartilage, respectively...
September 5, 2017: Molecular Immunology
Rui Li, Jinna Dai, Hui Kang
BACKGROUND: Serum creatinine, urea, and cystatin-c are standardly used for the evaluation of renal function in the clinic. However, some patients have chronic kidney disease but still retain kidney function; a conventional serum index in these patients can be completely normal. Serum amino acid levels can reflect subtle changes in metabolism and are closely related to renal function. Here, we investigated how amino acids change as renal impairment increases. METHODS: Subjects were divided into three groups by renal function glomerular filtration rate: healthy controls, patients with chronic kidney disease with normal kidney function, and patients with chronic kidney disease with decreased kidney function group...
June 23, 2017: Journal of Clinical Laboratory Analysis
Juan C Marini, Umang Agarwal, Jason L Robinson, Yang Yuan, Inka C Didelija, Barbara Stoll, Douglas G Burrin
The intestinal-renal axis for endogenous arginine synthesis is an interorgan process in which citrulline produced in the small intestine is utilized by the kidney for arginine synthesis. The function of this axis in neonates has been questioned because during this period the enzymes needed for arginine synthesis argininosuccinate synthase (ASS1) and lyase (ASL) are present in the gut. However, evidence of high plasma citrulline concentrations in neonates suggests otherwise. We quantified in vivo citrulline production in premature (10 days preterm), neonatal (7 days old), and young pigs (35 days old) using citrulline tracers...
August 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
Entai Hou, Na Sun, Fuchang Zhang, Chenyang Zhao, Kristie Usa, Mingyu Liang, Zhongmin Tian
Fumarase catalyzes the interconversion of fumarate and L-malate in the tricarboxylic acid cycle. The Dahl salt-sensitive (SS) rat, a model of salt-sensitive hypertension, exhibits fumarase insufficiencies. To investigate the mechanism mediating the effect of fumarase-related metabolites on hypertension, we considered the pathway in which L-malate can be converted to oxaloacetate, aspartate, argininosuccinate, and L-arginine, the substrate of nitric oxide (NO) synthase. The levels of aspartate, citrulline, L-arginine, and NO were significantly decreased in the kidneys of SS rats compared to salt-insensitive consomic SS...
May 23, 2017: Cell Reports
C Yzydorczyk, J B Armengaud, A C Peyter, H Chehade, F Cachat, C Juvet, B Siddeek, S Simoncini, F Sabatier, F Dignat-George, D Mitanchez, U Simeoni
Individuals born after intrauterine growth restriction (IUGR) have an increased risk of perinatal morbidity/mortality, and those who survive face long-term consequences such as cardiovascular-related diseases, including systemic hypertension, atherosclerosis, coronary heart disease and chronic kidney disease. In addition to the demonstrated long-term effects of decreased nephron endowment and hyperactivity of the hypothalamic-pituitary-adrenal axis, individuals born after IUGR also exhibit early alterations in vascular structure and function, which have been identified as key factors of the development of cardiovascular-related diseases...
May 2, 2017: Journal of Developmental Origins of Health and Disease
Dan-Qian Chen, Gang Cao, Hua Chen, Dan Liu, Wei Su, Xiao-Yong Yu, Nosratola D Vaziri, Xiu-Hua Liu, Xu Bai, Li Zhang, Ying-Yong Zhao
Changes in plasma concentration of small organic metabolites could be due to their altered production or urinary excretion and changes in their urine concentration may be due to the changes in their filtered load, tubular reabsorption, and/or altered urine volume. Therefore, these factors should be considered in interpretation of the changes observed in plasma or urine of the target metabolite(s). Fasting plasma and urine samples from 180 CKD patients and 120 age-matched healthy controls were determined by UPLC-HDMS-metabolomics and quantitative real-time RT-PCR techniques...
August 2017: Redox Biology
Antonin Ginguay, Luc Cynober, Emmanuel Curis, Ioannis Nicolis
Ornithine δ-aminotransferase (OAT, E.C. catalyzes the transfer of the δ-amino group from ornithine (Orn) to α-ketoglutarate (aKG), yielding glutamate-5-semialdehyde and glutamate (Glu), and vice versa. In mammals, OAT is a mitochondrial enzyme, mainly located in the liver, intestine, brain, and kidney. In general, OAT serves to form glutamate from ornithine, with the notable exception of the intestine, where citrulline (Cit) or arginine (Arg) are end products. Its main function is to control the production of signaling molecules and mediators, such as Glu itself, Cit, GABA, and aliphatic polyamines...
March 7, 2017: Biology
Hiroki Takeuchi, Teruaki Kawasaki, Kazuo Shigematsu, Kazuyuki Kawamura, Nobuyuki Oka
To clarify the roles of neutrophils in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitic neuropathy, we studied neutrophil extracellular traps (NETs) in peripheral nerve vasculitis. Stored nerve samples from 17 patients with microscopic polyangiitis (MPA) were immunohistochemically analyzed using antibodies for citrullinated histone H3 (citH3) and various neutrophil enzymes. We defined merged citH3 and extracellularly released myeloperoxidase (MPO) as NET formation. We also compared NET formation between MPO-ANCA-positive/negative MPA and rheumatoid arthritis (RA)-associated vasculitic neuropathy...
April 2017: Clinical Rheumatology
Samuele Cazzamalli, Alberto Dal Corso, Dario Neri
Small molecule-drug conjugates (SMDCs) are increasingly being considered as an alternative to antibody-drug conjugates (ADCs) for the selective delivery of anticancer agents to the tumor site, sparing normal tissues. Carbonic anhydrase IX (CAIX) is a membrane-bound enzyme, which is over-expressed in the majority of renal cell carcinomas and which can be efficiently targeted in vivo, using charged derivatives of acetazolamide, a small heteroaromatic sulfonamide. Here, we show that SMDC products, obtained by the coupling of acetazolamide with monomethyl auristatin E (MMAE) using dipeptide linkers, display a potent anti-tumoral activity in mice bearing xenografted SKRC-52 renal cell carcinomas...
January 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
Evelien P J G Neis, S Sabrkhany, I Hundscheid, D Schellekens, K Lenaerts, S W Olde Damink, E E Blaak, C H C Dejong, Sander S Rensen
Plasma levels of several amino acids are correlated with metabolic dysregulation in obesity and type 2 diabetes. To increase our understanding of human amino-acid metabolism, we aimed to determine splanchnic interorgan amino-acid handling. Twenty patients planned to undergo a pylorus preserving pancreatico-duodenectomy were included in this study. Blood was sampled from the portal vein, hepatic vein, superior mesenteric vein, inferior mesenteric vein, splenic vein, renal vein, and the radial artery during surgery...
January 2017: Amino Acids
Yoko Matsuda, Hideki Hamayasu, Atsuko Seki, Keisuke Nonaka, Tan Wang, Takumi Matsumoto, Yoshitomo Hamano, Hiroyuki Sumikura, Toshio Kumasaka, Shigeo Murayama, Akihiko Ishizu, Akira Shimizu, Takahiko Sugihara, Tomio Arai
A 76-year-old man was admitted with general fatigue, weight loss, fever, headache, renal failure, and a high serum level of myeloperoxidase-antineutrophil cytoplasmic antibody. Biopsy revealed citrullinated histone H3 (citH3)-positive neutrophils adherent to the temporal artery endothelium. Three days after completing pulse steroid therapy, he suffered from a sudden disturbance of consciousness and died. On autopsy, the kidneys showed the most severe vasculitis with dense infiltration of citH3-positive neutrophils...
August 2016: Pathology International
May Rabadi, Mihwa Kim, Vivette D'Agati, H Thomas Lee
We previously demonstrated that renal peptidyl arginine deiminase-4 (PAD4) is induced after renal ischemia and reperfusion (I/R) injury and exacerbates acute kidney injury (AKI) by increasing the renal tubular inflammatory response. Here, we tested whether genetic ablation of PAD4 attenuates renal injury and inflammation after I/R in mice. After renal I/R, PAD4 wild-type mice develop severe AKI with large increases in plasma creatinine, neutrophil infiltration, as well as significant renal tubular necrosis, apoptosis, and proinflammatory cytokine generation...
August 1, 2016: American Journal of Physiology. Renal Physiology
Saskia J H Brinkmann, Nikki Buijs, Mechteld A R Vermeulen, Efraim Oosterink, Henk Schierbeek, Albertus Beishuizen, Jean-Paul P M de Vries, Willem Wisselink, Paul A M van Leeuwen
Postoperative renal failure is a common complication after open repair of an abdominal aortic aneurysm. The amino acid arginine is formed in the kidneys from its precursor citrulline, and citrulline is formed from glutamine in the intestines. Arginine enhances the function of the immune and cardiovascular systems, which is important for recovery after surgery. We hypothesized that renal arginine production is diminished after ischemia-reperfusion injury caused by clamping of the aorta during open abdominal aortic surgery and that parenteral glutamine supplementation might compensate for this impaired arginine synthesis...
September 1, 2016: American Journal of Physiology. Renal Physiology
Na Mo, Ruogu Lai, Shizi Luo, Jianglin Xie, Xizi Wang, Lijuan Liu, Xiaoling Liu, Guangxing Chen
Objective. The purpose is to investigate the role of kidney deficiency and the association between kidney deficiency and a polymorphism FcγRIIb 695T>C coding for nonsynonymous substitution IIe232Thr (I232T) in rheumatoid arthritis (RA). Methods. Clinical parameters and autoantibodies were analyzed and genotyping was performed in 159 kidney deficiency and 161 non-kidney-deficiency RA patients. Results. The age of disease onset and disease duration exhibited significant differences between two groups (P < 0...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Ioana Alesutan, Martina Feger, Rashad Tuffaha, Tatsiana Castor, Katharina Musculus, Salvatore S Buehling, Christian L Heine, Makoto Kuro-O, Burkert Pieske, Kurt Schmidt, Andreas Tomaschitz, Winfried Maerz, Stefan Pilz, Andreas Meinitzer, Jakob Voelkl, Florian Lang
AIMS: Reduced homoarginine plasma levels are associated with unfavourable cardiovascular outcome in chronic kidney disease (CKD). Cardiovascular events in CKD are fostered by vascular calcification, an active process promoted by hyperphosphatemia and involving osteo-/chondrogenic transformation of vascular smooth muscle cells (VSMCs). The present study explored the effect of homoarginine on phosphate-induced osteo-/chondrogenic signalling and vascular calcification. METHODS AND RESULTS: Experiments were performed in hyperphosphatemic klotho-hypomorphic mice (kl/kl), in subtotal nephrectomy and vitamin D3-overload mouse calcification models and in primary human aortic smooth muscle cells (HAoSMCs)...
June 1, 2016: Cardiovascular Research
Huan Wang, Li-Li Sha, Tian-Tian Ma, Lu-Xia Zhang, Min Chen, Ming-Hui Zhao
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of life-threatening disorders, and frequently affects the kidneys. This study investigated whether the circulating neutrophil extracellular traps (NETs) levels were associated with disease activity of AAV. We collected serum samples from 34 patients with AAV in active stage and 62 patients with AAV in remission. Cell free DNA in serum was quantified using the Quant-iT PicoGreen assay. NETs associated MPO-DNA complexes, citrullinated-histone H3-DNA (cit-H3-DNA) complexes and the concentration of deoxyribonuclease I (DNase I) were quantified using ELISA...
2016: PloS One
Masaharu Yoshida, Muneharu Yamada, Yasuyo Sudo, Tadasu Kojima, Tomohiro Tomiyasu, Noriko Yoshikawa, Takashi Oda, Michiyuki Yamada
Anti-neutrophil cytoplasmic antibody (ANCA) is associated with small-vessel vasculitis particularly in the kidneys and can induce the formation of neutrophil extracellular traps (NETs) from primed neutrophils. Recently we have reported that the induction of NETs correlates with ANCA affinity for myeloperoxidase (MPO) and disease activity in patients with MPO-ANCA-associated microscopic polyangiitis. To investigate whether MPO-ANCA affinity is associated with the formation of NETs in vivo, we examined the occurrence of NETs in the renal tissues of patients with MPO-ANCA-associated microscopic polyangiitis and ANCA affinity by double immunofluorescence staining for NET components of citrullinated histone, MPO and PAD4 and by ELISA competition with MPO, respectively...
July 2016: Nephrology
You-Lin Tain, Jaap A Joles
Adulthood hypertension can be programmed in response to a suboptimal environment in early life. However, developmental plasticity also implies that one can prevent hypertension in adult life by administrating appropriate compounds during early development. We have termed this reprogramming. While the risk of hypertension has been assessed in many mother-child cohorts of human developmental programming, interventions necessary to prove causation and provide a reprogramming strategy are lacking. Since the developing kidney is particularly vulnerable to environmental insults and blood pressure is determined by kidney function, renal programming is considered key in developmental programming of hypertension...
December 25, 2015: International Journal of Molecular Sciences
I-Chun Lin, Chien-Ning Hsu, Mao-Hung Lo, Shao-Ju Chien, You-Lin Tain
Arginine (ARG) and citrulline (CIT) are essential for nitric oxide (NO) synthesis. Their metabolites are interrelated, and involved in blood pressure (BP) control, chronic kidney disease (CKD), and cardiovascular disease (CVD). Although CVD is the leading cause of mortality in CKD, little is known about subclinical CVD in early-stage childhood CKD. Twenty-four-hour ambulatory BP monitoring and arterial stiffness assessment allows the earlier possible detection of subclinical CVD. We investigated whether urinary CIT and ARG metabolites and their ratios are correlated with BP load and vascular abnormalities in children and adolescents with early-stage CKD...
February 2016: Journal of the American Society of Hypertension: JASH
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