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Kidney International

Shinji Tanaka, Yuki Sugiura, Hisako Saito, Mai Sugahara, Yoshiki Higashijima, Junna Yamaguchi, Reiko Inagi, Makoto Suematsu, Masaomi Nangaku, Tetsuhiro Tanaka
It is unclear whether long-term sodium-glucose cotransporter 2 (SGLT2) inhibition such as that during the treatment of diabetes has deleterious effects on the kidney. Therefore, we first sought to determine whether abnormal glucose metabolism occurs in the kidneys of 22-week-old BTBR ob/ob diabetic mice. Second, the cumulative effect of chronic SGLT2 inhibition by ipragliflozin and 30% calorie restriction, either of which lowered blood glucose to a similar extent, on renal glucose metabolism was evaluated. Mass spectrometry-based metabolomics demonstrated that these diabetic mice exhibited an abnormal elevation in the renal pools of tricarboxylic acid cycle metabolites...
July 13, 2018: Kidney International
David Harris, Christina M Wyatt, Agnes B Fogo, Pierre Ronco
No abstract text is available yet for this article.
July 10, 2018: Kidney International
Natsuko Tokonami, Tomoaki Takata, Jan Beyeler, Iris Ehrbar, Ayumi Yoshifuji, Erik I Christensen, Johannes Loffing, Olivier Devuyst, Eric G Olinger
Uromodulin, the most abundant protein in normal urine, is essentially produced by the cells lining the thick ascending limb. There it regulates the activity of the cotransporter NKCC2 and is involved in sodium chloride handling and blood pressure regulation. Conflicting reports suggested that uromodulin may also be expressed in the distal convoluted tubule (DCT) where its role remains unknown. Using microdissection studies combined with fluorescent in situ hybridization and co-immunostaining analyses, we found a significant expression of uromodulin in mouse and human DCT at approximately 10% of thick ascending limb expression levels, but restricted to the early part of the DCT (DCT1)...
July 7, 2018: Kidney International
Alain Meyrier, Patrick Niaudet
Minimal change disease accounts for 70% to 90% of cases of nephrotic syndrome in children. It also causes nephrotic syndrome in adults, including patients older than age 60. Renal function is altered moderately in approximately 20% to 30% of patients because foot-process fusion impairs filtration of water and solutes. The glomerular filtration rate is reduced by approximately 20% to 30% and returns to baseline with remission of proteinuria. Over the past 50 years, a number of publications have reported cases of acute kidney injury occurring in approximately one-fifth to one-third of adult cases in the absence of prior or concomitant renal disease...
July 3, 2018: Kidney International
Sanaz Sedaghat, Jie Ding, Gudny Eiriksdottir, Mark A van Buchem, Sigurdur Sigurdsson, M Arfan Ikram, Osorio Meirelles, Vilmundur Gudnason, Andrew S Levey, Lenore J Launer
Decreased glomerular filtration rate (GFR) and albuminuria may be accompanied by brain pathology. Here we investigated whether changes in these kidney measures are linked to development of new MRI-detected infarcts and microbleeds, and progression of white matter hyperintensity volume. The study included 2671 participants from the population-based AGES-Reykjavik Study (mean age 75, 58.7% women). GFR was estimated from serum creatinine, and albuminuria was assessed by urinary albumin-to-creatinine ratio. Brain MRI was acquired at baseline (2002-2006) and 5 years later (2007-2011)...
June 27, 2018: Kidney International
Marc Ghannoum, Robert S Hoffman, Sophie Gosselin, Thomas D Nolin, Valery Lavergne, Darren M Roberts
Historically, the clinical application of extracorporeal treatments (ECTRs), such as hemodialysis or hemoperfusion, was first intended for poisoned patients. With time, ECTRs were used almost indiscriminately to facilitate the elimination of many poisons, albeit with uncertain clinical benefit. To determine the precise role of ECTRs in poisoning situations, multiple variables need to be considered including a careful risk assessment, the poison's characteristics including toxicokinetics, alternative treatments, the patient's clinical status, and intricacies of available ECTRs, all of which are reviewed in this article...
June 26, 2018: Kidney International
Christoph Wanner, Charles A Herzog, Mintu P Turakhia
No abstract text is available yet for this article.
June 20, 2018: Kidney International
Anja Thorenz, Katja Derlin, Christoph Schröder, Lisa Dressler, Vijith Vijayan, Pooja Pradhan, Stephan Immenschuh, Anne Jörns, Frank Echtermeyer, Christine Herzog, Rongjun Chen, Song Rong, Jan Hinrich Bräsen, Cees van Kooten, Torsten Kirsch, Christian Klemann, Martin Meier, Andreas Klos, Hermann Haller, Bennet Hensen, Faikah Gueler
Severe ischemia reperfusion injury (IRI) results in rapid complement activation, acute kidney injury and progressive renal fibrosis. Little is known about the roles of the C5aR1 and C5aR2 complement receptors in IRI. In this study C5aR1-/- and C5aR2-/- mice were compared to the wild type in a renal IRI model leading to renal fibrosis. C5a receptor expression, kidney morphology, inflammation, and fibrosis were measured in different mouse strains one, seven and 21 days after IRI. Renal perfusion was evaluated by functional magnetic resonance imaging...
June 20, 2018: Kidney International
Dong Liu, Lide Lun, Qi Huang, Yichun Ning, Ying Zhang, Linna Wang, Zhiwei Yin, Yinping Zhang, Lihua Xia, Zhong Yin, Bo Fu, Guangyan Cai, Xuefeng Sun, Xiangmei Chen
The incidence of acute kidney injury (AKI) is high in elderly people, and is difficult to prevent and treat. One of its major causes is renal ischemia-reperfusion injury (IRI). A young systemic environment may prevent the senescence of old organs. However, it is unknown whether a young milieu may reduce renal IRI in the elderly. To examine this question, bilateral renal IRI was induced in old (24 months) mice three weeks after parabiosis model establishment. At 24 hours after IRI, compared to old wild-type mice, the old mice with IRI had significantly damaged renal histology, decreased renal function, increased oxidative stress, inflammation, and apoptosis...
June 20, 2018: Kidney International
Jasna Aleksova, Phillip Wong, Robert McLachlan, Kay Weng Choy, Peter R Ebeling, Frances Milat, Grahame J Elder
Gonadal hormones impact bone health and higher values of sex hormone-binding globulin (SHBG) have been independently associated with fracture risk in men without chronic kidney disease. People with chronic kidney disease have a greatly increased fracture risk, and gonadal dysfunction is common in men receiving dialysis treatment. Nevertheless, in these men the effect of gonadal steroids and SHBG on bone mineral density (BMD) and fracture risk is unknown. Here we investigate relationships between gonadal steroids, SHBG, BMD and fracture in men on long-term dialysis therapy, awaiting kidney or simultaneous pancreas kidney transplantation...
June 15, 2018: Kidney International
Angelo Karaboyas, Hairong Xu, Hal Morgenstern, Francesco Locatelli, Michel Jadoul, Kosaku Nitta, Indranil Dasgupta, Francesca Tentori, Friedrich K Port, Bruce M Robinson
The benefits of renin angiotensin-aldosterone system inhibitors (RAASi) are well-established in the general population, particularly among those with diabetes, congestive heart failure (CHF), or coronary artery disease (CAD). However, conflicting evidence from trials and concerns about hyperkalemia limit RAASi use in hemodialysis patients, relative to other antihypertensive agents, including beta blockers and calcium channel blockers. Therefore, we investigated prescription patterns and associations with mortality for RAASi and other antihypertensive agents using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS)...
June 13, 2018: Kidney International
Franz Schaefer, Gianluigi Ardissino, Gema Ariceta, Fadi Fakhouri, Marie Scully, Nicole Isbel, Åsa Lommelé, Varant Kupelian, Christoph Gasteyger, Larry A Greenbaum, Sally Johnson, Masayo Ogawa, Christoph Licht, Johan Vande Walle, Véronique Frémeaux-Bacchi
Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, life-threatening disease. The Global aHUS Registry collects real-world data on the natural history of the disease. Here we characterize end-stage renal disease (ESRD)-free survival, the rate of thrombotic microangiopathy, organ involvement and the genetic background of 851 patients in the registry, prior to eculizumab treatment. A sex-specific difference was apparent according to age at initial disease onset as the ratio of males to females was 1...
June 12, 2018: Kidney International
Quanxin Li, Ziying Wang, Yan Zhang, Jiaqing Zhu, Liang Li, Xiaojie Wang, Xiaoyang Cui, Yu Sun, Wei Tang, Chengjiang Gao, Chunhong Ma, Fan Yi
There is significant progress in understanding the structure and function of NLRC5, a member of the nucleotide oligomerization domain-like receptor family. However, in the context of MHC class I gene expression, the functions of NLRC5 in innate and adaptive immune responses beyond the regulation of MHC class I genes remain controversial and unresolved. In particular, the role of NLRC5 in the kidney is unknown. NLRC5 was significantly upregulated in the kidney from mice with renal ischemia/reperfusion injury...
June 12, 2018: Kidney International
Tanvi Arkatkar, Holly M Jacobs, Samuel W Du, Quan-Zhen Li, Kelly L Hudkins, Charles E Alpers, David J Rawlings, Shaun W Jackson
B cells are known to promote the pathogenesis of systemic lupus erythematosus (SLE) via the production of pathogenic anti-nuclear antibodies. However, the signals required for autoreactive B cell activation and the immune mechanisms whereby B cells impact lupus nephritis pathology remain poorly understood. The B cell survival cytokine B cell activating factor of the TNF Family (BAFF) has been implicated in the pathogenesis of SLE and lupus nephritis in both animal models and human clinical studies. Although the BAFF receptor has been predicted to be the primary BAFF family receptor responsible for BAFF-driven humoral autoimmunity, in the current study we identify a critical role for signals downstream of Transmembrane Activator and CAML Interactor (TACI) in BAFF-dependent lupus nephritis...
June 12, 2018: Kidney International
Thitinun Anusornvongchai, Masaomi Nangaku, Tzu-Ming Jao, Chia-Hsien Wu, Yu Ishimoto, Hiroshi Maekawa, Tetsuhiro Tanaka, Akira Shimizu, Masayuki Yamamoto, Norio Suzuki, Ryoji Sassa, Reiko Inagi
Lipotoxicity plays an important role in the progression of chronic kidney damage via various mechanisms, such as endoplasmic reticulum stress. Several studies proposed renal lipotoxicity in glomerular and tubular cells but the effect of lipid on renal erythropoietin (EPO)-producing (REP) cells in the interstitium has not been elucidated. Since renal anemia is caused by derangement of EPO production in REP cells, we evaluated the effect of palmitate, a representative long-chain saturated fatty acid, on EPO production and the endoplasmic reticulum stress pathway...
June 7, 2018: Kidney International
Carla L Ellis, W Charles O'Neill
A variety of criteria exist for histopathologic diagnosis of calciphylaxis, also known as calcific uremic arteriolopathy but data on their specificity are limited. To assess this, histologic findings of 38 skin biopsies performed for a suspicion of calcific uremic arteriolopathy were compared with histologic findings in skin obtained from healthy margins of 43 amputations in patients with end-stage renal disease (ESRD) without evidence of calcific uremic arteriolopathy. Abnormalities in small arteries or arterioles were present in 35% of amputation specimens and 55% of skin biopsies, and among these only thrombosis but not calcification was significantly more prevalent in skin biopsies...
June 6, 2018: Kidney International
Carl D Langefeld, Mary E Comeau, Maggie C Y Ng, Meijian Guan, Latchezar Dimitrov, Poorva Mudgal, Mitzie H Spainhour, Bruce A Julian, Jeffrey C Edberg, Jennifer A Croker, Jasmin Divers, Pamela J Hicks, Donald W Bowden, Gary C Chan, Lijun Ma, Nicholette D Palmer, Robert P Kimberly, Barry I Freedman
African Americans carrying two apolipoprotein L1 gene (APOL1) renal risk variants have a high risk for nephropathy. However, only a minority develops end-stage renal disease (ESRD). Hence, modifying factors likely contribute to initiation of kidney disease such as endogenous (HIV infection) or exogenous (interferon treatment) environmental modifiers. In this report, genome-wide association studies and a meta-analysis were performed to identify novel loci for nondiabetic ESRD in African Americans and to detect genetic modifiers in APOL1-associated nephropathy...
June 6, 2018: Kidney International
Zivile D Békássy, Ann-Charlotte Kristoffersson, Johan Rebetz, Ramesh Tati, Anders I Olin, Diana Karpman
Certain kidney diseases are associated with complement activation although a renal triggering factor has not been identified. Here we demonstrated that renin, a kidney-specific enzyme, cleaves C3 into C3b and C3a, in a manner identical to the C3 convertase. Cleavage was specifically blocked by the renin inhibitor aliskiren. Renin-mediated C3 cleavage and its inhibition by aliskiren also occurred in serum. Generation of C3 cleavage products was demonstrated by immunoblotting, detecting the cleavage product C3b, by N-terminal sequencing of the cleavage product, and by ELISA for C3a release...
June 5, 2018: Kidney International
Jiun-Ruey Hu, Josef Coresh, Lesley A Inker, Andrew S Levey, Zihe Zheng, Casey M Rebholz, Adrienne Tin, Lawrence J Appel, Jingsha Chen, Mark J Sarnak, Morgan E Grams
Chronic kidney disease (CKD) involves significant metabolic abnormalities and has a high mortality rate. Because the levels of serum metabolites in patients with CKD might provide insight into subclinical disease states and risk for future mortality, we determined which serum metabolites reproducibly associate with mortality in CKD using a discovery and replication design. Metabolite levels were quantified via untargeted liquid chromatography and mass spectroscopy from serum samples of 299 patients with CKD in the Modification of Diet in Renal Disease (MDRD) study as a discovery cohort...
June 2, 2018: Kidney International
Karina Durlacher-Betzer, Alia Hassan, Ronen Levi, Jonathan Axelrod, Justin Silver, Tally Naveh-Many
The high serum fibroblast growth factor 23 (FGF23) levels in patients with acute kidney injury (AKI) and chronic kidney disease (CKD) are associated with increased morbidity and mortality. Mice with folic acid-induced AKI had an increase in bone FGF23 mRNA expression together with an increase in serum FGF23 and several circulating cytokines including interleukin-6 (IL-6). Dexamethasone partially prevented the increase in IL-6 and FGF23 in the AKI mice. IL-6 knock-out mice fed an adenine diet to induce CKD failed to increase bone FGF23 mRNA and had a muted increase in serum FGF23 levels, compared with the increases in wild-type mice with CKD...
May 31, 2018: Kidney International
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