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Kidney International

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https://www.readbyqxmd.com/read/29162294/early-detection-of-acute-tubulointerstitial-nephritis-in-the-genesis-of-mesoamerican-nephropathy
#1
Rebecca S B Fischer, Chandan Vangala, Luan Truong, Sreedhar Mandayam, Denis Chavarria, Orlando M Granera Llanes, Marcos U Fonseca Laguna, Alvaro Guerra Baez, Felix Garcia, Ramón García-Trabanino, Kristy O Murray
Mesoamerican nephropathy is a devastating disease of unknown etiology that affects mostly young agricultural workers in Central America. An understanding of the mechanism of injury and the early disease process is urgently needed and will aid in identification of the underlying cause and direct treatment and prevention efforts. We sought to describe the renal pathology in Mesoamerican nephropathy at its earliest clinical appearance in prospectively identified acute case patients in Nicaragua. We considered those with elevated (or increased at least 0...
November 18, 2017: Kidney International
https://www.readbyqxmd.com/read/29146277/lowering-ldl-cholesterol-reduces-cardiovascular-risk-independently-of-presence-of-inflammation
#2
Benjamin C Storey, Natalie Staplin, Richard Haynes, Christina Reith, Jonathan Emberson, William G Herrington, David C Wheeler, Robert Walker, Bengt Fellström, Christoph Wanner, Martin J Landray, Colin Baigent
Markers of inflammation, including plasma C-reactive protein (CRP), are associated with an increased risk of cardiovascular disease, and it has been suggested that this association is causal. However, the relationship between inflammation and cardiovascular disease has not been extensively studied in patients with chronic kidney disease. To evaluate this, we used data from the Study of Heart and Renal Protection (SHARP) to assess associations between circulating CRP and LDL cholesterol levels and the risk of vascular and non-vascular outcomes...
November 14, 2017: Kidney International
https://www.readbyqxmd.com/read/29137816/resuscitation-for-the-specialty-of-nephrology-is-cardionephrology-the-answer
#3
Janani Rangaswami, Roy O Mathew, Peter A McCullough
The specialty of nephrology faces major fellowship recruitment challenges, with ongoing declining interest among internal medicine residents. The field of Cardionephrology can help instill new interest and enthusiasm in choosing nephrology as a career amongst trainee physicians.
November 11, 2017: Kidney International
https://www.readbyqxmd.com/read/29132705/il-17a-improves-the-efficacy-of-mesenchymal-stem%C3%A2-cells-in-ischemic-reperfusion-renal-injury%C3%A2-by%C3%A2-increasing-treg-percentages-by-the%C3%A2-cox-2-pge2%C3%A2-pathway
#4
Ming Bai, Li Zhang, Bo Fu, Jiuxu Bai, Yingjie Zhang, Guangyan Cai, Xueyuan Bai, Zhe Feng, Shiren Sun, Xiangmei Chen
Mesenchymal stem cells (MSCs) are effective for the management of experimental ischemia-reperfusion acute kidney injury (IRI-AKI). Immune modulation is one of the important mechanisms of MSCs treatment. Interleukin-17A (IL-17A) pretreated MSCs are more immunosuppressive with minimal changes in immunogenicity in vitro. Here, we demonstrated that administration of IL-17A-pretreated MSCs resulted in significantly lower acute tubular necrosis scores, serum creatinine, and BUN of mice with IRI-AKI, compared with the administration of MSCs...
November 11, 2017: Kidney International
https://www.readbyqxmd.com/read/29129401/deletion-of-claudin-10-rescues-claudin-16-deficient-mice-from-hypomagnesemia-and-hypercalciuria
#5
Tilman Breiderhoff, Nina Himmerkus, Hoora Drewell, Allein Plain, Dorothee Günzel, Kerim Mutig, Thomas E Willnow, Dominik Müller, Markus Bleich
The tight junction proteins claudin-10 and -16 are crucial for the paracellular reabsorption of cations along the thick ascending limb of Henle's loop in the kidney. In patients, mutations in CLDN16 cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis, while mutations in CLDN10 impair kidney function. Mice lacking claudin-16 display magnesium and calcium wasting, whereas absence of claudin-10 results in hypermagnesemia and interstitial nephrocalcinosis. In order to study the functional interdependence of claudin-10 and -16 we generated double-deficient mice...
November 10, 2017: Kidney International
https://www.readbyqxmd.com/read/29102374/body-composition-is-associated-with-clinical-outcomes-in-patients-with-non-dialysis-dependent-chronic-kidney-disease
#6
Ting-Yun Lin, Ching-Hsiu Peng, Szu-Chun Hung, Der-Cherng Tarng
An inverse relationship between body mass index (BMI) and mortality (the obesity paradox) has been found in patients with non-dialysis-dependent chronic kidney disease (CKD). However, it is unclear whether increased muscle mass or body fat confers the survival advantage. To resolve this we investigated the impact of body makeup on a composite outcome of death or cardiovascular events in a prospective cohort of 326 patients with stage 3-5 CKD not yet on dialysis. Lean mass and body fat were determined using the Body Composition Monitor, a multifrequency bioimpedance spectroscopy device, and were expressed as the lean tissue or fat tissue index, respectively...
November 1, 2017: Kidney International
https://www.readbyqxmd.com/read/29102373/transcriptomic-analysis-uncovers-novel-synergistic-mechanisms-in-combination-therapy-for-lupus-nephritis
#7
Jia Fu, Zichen Wang, Kyung Lee, Chengguo Wei, Zhengzhao Liu, Mingchao Zhang, Minlin Zhou, Minchao Cai, Weijia Zhang, Peter Y Chuang, Avi Ma'ayan, John Cijiang He, Zhihong Liu
A recent clinical study showed that combination therapy consisting of mycophenolate mofetil, tacrolimus and steroids was shown to be more effective in achieving complete remission in patients with severe forms of lupus nephritis than conventional therapy consisting of intravenous cyclophosphamide and steroids. To explore the underlying molecular and cellular mechanisms of increased efficacy of the combination therapy regimen, we employed a mouse model of lupus nephritis, MRL/lpr mice, and treated them with monotherapies of prednisone, mycophenolate mofetil, or tacrolimus, or with their combination...
November 1, 2017: Kidney International
https://www.readbyqxmd.com/read/29102372/renal-potassium-physiology-integration-of-the-renal-response-to-dietary-potassium-depletion
#8
REVIEW
Kamel S Kamel, Martin Schreiber, Mitchell L Halperin
We summarize the current understanding of the physiology of the renal handling of potassium (K(+)), and present an integrative view of the renal response to K(+) depletion caused by dietary K(+) restriction. This renal response involves contributions from different nephron segments, and aims to diminish the rate of excretion of K(+) as a result of: decreasing the rate of electrogenic (and increasing the rate of electroneutral) reabsorption of sodium in the aldosterone-sensitive distal nephron (ASDN), decreasing the abundance of renal outer medullary K(+) channels in the luminal membrane of principal cells in the ASDN, decreasing the flow rate in the ASDN, and increasing the reabsorption of K(+) in the cortical and medullary collecting ducts...
November 1, 2017: Kidney International
https://www.readbyqxmd.com/read/29107361/race-but-not-hepatitis-c-co-infection-affects-survival-of-hiv-individuals-on-dialysis-in-contemporary-practice
#9
Deirdre Sawinski, Kimberly A Forde, Jayme E Locke, Jordana B Cohen, Joe Weldon, Justine Shults, Peter P Reese
Individuals with HIV infection are at elevated risk of developing end-stage renal disease. However, their outcomes after starting chronic dialysis in the contemporary era of widespread antiretroviral therapy are not well described. Using detailed data from a national dialysis provider, we determined HIV status by administrative codes and antiretroviral medication prescriptions, with hepatitis C virus (HCV) co-infection status provided by routinely measured serology. The survival on dialysis among 5348 individuals in the HIV(+) group and 1863 HIV(+)/HCV(+) individuals to a HIV(-)/HCV(-) reference cohort was compared...
October 26, 2017: Kidney International
https://www.readbyqxmd.com/read/29061334/neutrophil-peptidyl-arginine-deiminase-4-has-a-pivotal-role-in-ischemia-reperfusion-induced-acute%C3%A2-kidney-injury
#10
Wesley M Raup-Konsavage, Yanming Wang, Wei Wei Wang, Denis Feliers, Hong Ruan, W Brian Reeves
Ischemia/reperfusion is a common cause of acute kidney injury (AKI). However, mechanisms underlying the sudden loss in kidney function and tissue injury remain to be fully elucidated. Here, we investigated the role of peptidyl arginine deiminase-4 (PAD4), which converts arginine to citrulline and plays a role in epigenetic regulation and inflammation, in renal ischemia/reperfusion injury. PAD4 expression was highly induced in infiltrating leukocytes 24 hours following renal ischemia and reperfusion. This induction was accompanied by citrullination of histone H3 and formation of neutrophil extracellular traps in kidneys of wild-type mice...
October 20, 2017: Kidney International
https://www.readbyqxmd.com/read/29061333/novel-aspects-of-epitope-matching-and-practical-application-in-kidney-transplantation
#11
Wai H Lim, Germaine Wong, Sebastiaan Heidt, Frans H J Claas
This review describes the recent developments in the applicability and clinical significance of epitope matching in kidney transplantation. As incremental human leukocyte antigen (HLA) mismatches are associated with increased risk of rejection and allograft loss, HLA-matching remains one of the standard immunological triage tests to determine transplant suitability. Advancements in tissue-typing techniques have led to innovative concepts of HLA-matching at the epitope level. Epitopes are configurations of polymorphic amino acid residues that are recognized by B cells, and antibodies reactive with these epitopes lead to rejection and/or premature allograft loss...
October 20, 2017: Kidney International
https://www.readbyqxmd.com/read/29061332/human-plasmacytoid-dendritic-cells-acquire-phagocytic-capacity-by-tlr9-ligation-in-the-presence-of-soluble-factors-produced-by-renal-epithelial-cells
#12
Jurjen M Ruben, Gina Stella García-Romo, Eytan Breman, Sandra van der Kooij, Anke Redeker, Ramon Arens, Cees van Kooten
Plasmacytoid dendritic cells (pDCs) are antigen presenting cells specialized in viral recognition through Toll-like receptor (TLR)7 and TLR9, and produce vast amounts of interferon alpha upon ligation of these TLRs. We had previously demonstrated a strong influx of pDCs in the tubulointerstitium of renal biopsies at the time of acute rejection. However, the role of human pDCs in mediating acute or chronic allograft rejection remains elusive. pDCs are thought to have a limited capacity to ingest apoptotic cells, critical for inducing CD4(+) T cell activation via indirect antigen presentation and subsequent activation of antibody producing B cells...
October 20, 2017: Kidney International
https://www.readbyqxmd.com/read/29061331/screening-for-intracranial-aneurysms-in-autosomal-dominant-polycystic-kidney-disease-is-cost-effective
#13
Adrien Flahault, Denis Trystram, François Nataf, Marie Fouchard, Bertrand Knebelmann, Jean-Pierre Grünfeld, Dominique Joly
Intracranial aneurysm rupture is a dramatic complication of autosomal dominant polycystic kidney disease (ADPKD). It remains uncertain whether screening should be widespread or only target patients with risk factors (personal or familial history of intracranial aneurysm), with an at-risk profession, or those who request screening. We evaluated this in a single-center cohort of 495 consecutive patients with ADPKD submitted to targeted intracranial aneurysm screening. Cerebral magnetic resonance angiography was proposed to 110 patients with a familial history of intracranial aneurysm (group 1), whereas it was not our intention to propose it to 385 patients without familial risk (group 2)...
October 20, 2017: Kidney International
https://www.readbyqxmd.com/read/29054530/a-molecular-morphometric-approach-to-diabetic%C3%A2-kidney-disease-can-link-structure-to%C3%A2-function-and-outcome
#14
Viji Nair, Claudiu V Komorowsky, E Jennifer Weil, Berne Yee, Jeffrey Hodgin, Jennifer L Harder, Bradley Godfrey, Wenjun Ju, Carine M Boustany-Kari, Margrit Schwarz, Kevin V Lemley, Peter J Nelson, Robert G Nelson, Matthias Kretzler
Diabetic kidney disease is the leading cause of kidney failure. However, studies of molecular mechanisms of early kidney damage are lacking. Here we examined for possible linkage between transcriptional regulation and quantitative structural damage in early diabetic kidney disease in Pima Indians with type 2 diabetes. Tissue obtained from protocol kidney biopsies underwent genome-wide compartment-specific gene expression profiling and quantitative morphometric analysis. The ultrastructural lesion most strongly associated with transcriptional regulation was cortical interstitial fractional volume (VvInt), an index of tubule-interstitial damage...
October 18, 2017: Kidney International
https://www.readbyqxmd.com/read/29054532/a-randomized-clinical-trial-indicates-that-levamisole-increases-the-time-to-relapse-in-children-with-steroid-sensitive-idiopathic-nephrotic-syndrome
#15
Mariken P Gruppen, Antonia H Bouts, Marijke C Jansen-van der Weide, Maruschka P Merkus, Aleksandra Zurowska, Michal Maternik, Laura Massella, Francesco Emma, Patrick Niaudet, Elisabeth A M Cornelissen, Thierry Schurmans, Ann Raes, Johan van de Walle, Mieke van Dyck, Ashima Gulati, Arvind Bagga, Jean-Claude Davin
Levamisole has been considered the least toxic and least expensive steroid-sparing drug for preventing relapses of steroid-sensitive idiopathic nephrotic syndrome (SSINS). However, evidence for this is limited as previous randomized clinical trials were found to have methodological limitations. Therefore, we conducted an international multicenter, placebo-controlled, double-blind, randomized clinical trial to reassess its usefulness in prevention of relapses in children with SSINS. The efficacy and safety of one year of levamisole treatment in children with SSINS and frequent relapses were evaluated...
October 17, 2017: Kidney International
https://www.readbyqxmd.com/read/29054531/the-ammonia-transporter-rhcg-modulates-urinary-acidification-by-interacting-with-the-vacuolar-proton-atpases-in-renal-intercalated-cells
#16
Soline Bourgeois, Lisa Bounoure, Isabelle Mouro-Chanteloup, Yves Colin, Dennis Brown, Carsten A Wagner
Ammonium, stemming from renal ammoniagenesis, is a major urinary proton buffer and is excreted along the collecting duct. This process depends on the concomitant secretion of ammonia by the ammonia channel RhCG and of protons by the vacuolar-type proton-ATPase pump. Thus, urinary ammonium content and urinary acidification are tightly linked. However, mice lacking Rhcg excrete more alkaline urine despite lower urinary ammonium, suggesting an unexpected role of Rhcg in urinary acidification. RhCG and the B1 and B2 proton-ATPase subunits could be co-immunoprecipitated from kidney...
October 17, 2017: Kidney International
https://www.readbyqxmd.com/read/29042084/adenylyl-cyclase-5-deficiency-reduces-renal-cyclic-amp-and-cyst-growth-in-an-orthologous-mouse-model-of-polycystic-kidney-disease
#17
Qian Wang, Patricia Cobo-Stark, Vishal Patel, Stefan Somlo, Pyung-Lim Han, Peter Igarashi
Cyclic AMP promotes cyst growth in polycystic kidney disease (PKD) by stimulating cell proliferation and fluid secretion. Previously, we showed that the primary cilium of renal epithelial cells contains a cAMP regulatory complex comprising adenylyl cyclases 5 and 6 (AC5/6), polycystin-2, A-kinase anchoring protein 150, protein kinase A, and phosphodiesterase 4C. In Kif3a mutant cells that lack primary cilia, the formation of this regulatory complex is disrupted and cAMP levels are increased. Inhibition of AC5 reduces cAMP levels in Kif3a mutant cells, suggesting that AC5 may mediate the increase in cAMP in PKD...
October 14, 2017: Kidney International
https://www.readbyqxmd.com/read/29042083/aprotinin-prevents-proteolytic-epithelial-sodium-channel-enac-activation-and-volume-retention-in-nephrotic-syndrome
#18
Bernhard N Bohnert, Martina Menacher, Andrea Janessa, Matthias Wörn, Anja Schork, Sophie Daiminger, Hubert Kalbacher, Hans-Ulrich Häring, Christoph Daniel, Kerstin Amann, Florian Sure, Marko Bertog, Silke Haerteis, Christoph Korbmacher, Ferruh Artunc
Volume retention in nephrotic syndrome has been linked to activation of the epithelial sodium channel (ENaC) by proteolysis of its γ-subunit following urinary excretion of serine proteases such as plasmin. Here we tested whether pharmacological inhibition of urinary serine protease activity might protect from ENaC activation and volume retention in nephrotic syndrome. Urine from both nephrotic mice (induced by doxorubicin injection) and nephrotic patients exhibited high aprotinin-sensitive serine protease activity...
October 14, 2017: Kidney International
https://www.readbyqxmd.com/read/29042082/the-proto-oncogene-tyrosine-protein-kinase-src-is-essential-for-macrophage-myofibroblast-transition-during-renal-scarring
#19
Patrick Ming-Kuen Tang, Shuang Zhou, Chun-Jie Li, Jinyue Liao, Jun Xiao, Qing-Ming Wang, Guang-Yu Lian, Jinhong Li, Xiao-Ru Huang, Ka-Fai To, Chi-Fai Ng, Charing Ching-Ning Chong, Ronald Ching-Wa Ma, Tin-Lap Lee, Hui-Yao Lan
Src activation has been associated with fibrogenesis after kidney injury. Macrophage-myofibroblast transition is a newly identified process to generate collagen-producing myofibroblasts locally in the kidney undergoing fibrosis in a TGF-β/Smad3-dependent manner. The potential role of the macrophage-myofibroblast transition in Src-mediated renal fibrosis is unknown. In studying this by RNA sequencing at single-cell resolution, we uncovered a unique Src-centric regulatory gene network as a key underlying mechanism of macrophage-myofibroblast transition...
October 14, 2017: Kidney International
https://www.readbyqxmd.com/read/29042081/peritoneal-dialysis-is-associated-with-better-cognitive-function-than-hemodialysis-over-a-one-year-course
#20
Denise Neumann, Wilfried Mau, Andreas Wienke, Matthias Girndt
Impaired cognitive functioning in patients with end-stage renal disease may reduce their capabilities to adhere to complex medical or dietary regimens and to fully participate in medical decisions. With decreasing renal function, cognitive abilities are likely to decline, with cognitive dysfunction improving after initiation of dialysis and even being generally reversible after successful renal transplantation. However, little is known about cognitive changes particularly regarding different treatment modalities...
October 14, 2017: Kidney International
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