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Kidney International

Tzu-Ming Jao, Masaomi Nangaku, Chia-Hsien Wu, Mai Sugahara, Hisako Saito, Hiroshi Maekawa, Yu Ishimoto, Mari Aoe, Tsuyoshi Inoue, Tetsuhiro Tanaka, Bart Staels, Kazutoshi Mori, Reiko Inagi
Tubulointerstitial fibrosis is a strong predictor of progression in patients with chronic kidney disease, and is often accompanied by lipid accumulation in renal tubules. However, the molecular mechanisms modulating the relationship between lipotoxicity and tubulointerstitial fibrosis remain obscure. ATF6α, a transcription factor of the unfolded protein response, is reported to be an upstream regulator of fatty acid metabolism. Owing to their high energy demand, proximal tubular cells (PTCs) use fatty acids as their main energy source...
January 10, 2019: Kidney International
Daniela Verzola, Chiara Barisione, Daniela Picciotto, Giacomo Garibotto, Laetitia Koppe
The past two decades have witnessed tremendous progress in our understanding of the mechanisms underlying wasting and cachexia in chronic kidney disease (CKD) and in other chronic illnesses, such as cancer and heart failure. In all these conditions wasting is an effect of the activation of protein degradation in muscle, a response that increases the risk of morbidity and mortality. Major recent advances in our knowledge on how CKD and inflammation affect cellular signaling include the identification of the myostatin (MSTN)/activin system, and its related transcriptional program that promotes protein degradation...
December 28, 2018: Kidney International
Kinsuk Chauhan, Divya Anna Verghese, Veena Rao, Lili Chan, Chirag R Parikh, Steven G Coca, Girish N Nadkarni
Novel biomarkers are needed to predict kidney function decline in patients with type 2 diabetes, especially those with preserved glomerular filtration rate (GFR). There are limited data on the association of markers of endothelial dysfunction with longitudinal GFR decline. We used banked specimens from a nested case-control study in the Action to Control Cardiovascular Disease (ACCORD) trial (n=187 cases: 187 controls) and from a diverse contemporary cohort of type 2 diabetic patients from the Mount Sinai BioMe Biobank (n=871) to assess the association of plasma endostatin and kidney outcomes...
December 20, 2018: Kidney International
Avital Angel-Korman, Lauren Stern, Shayna Sarosiek, J Mark Sloan, Gheorghe Doros, Vaishali Sanchorawala, Andrea Havasi
Therapies for AL amyloidosis have dramatically improved, leading to longer patient survival; however, more AL amyloidosis patients are reaching end-stage renal disease (ESRD). There are no clear guidelines regarding eligibility for kidney transplantation in patients with AL amyloidosis, and data on outcomes are limited. We evaluated the clinical and laboratory data of 49 patients who were followed in the Amyloidosis Center at Boston University and underwent kidney transplantation at a center in the United States between 1987-2017...
December 20, 2018: Kidney International
Francisco Del Río, Amado Andrés, María Padilla, Ana I Sánchez-Fructuoso, María Molina, Ángel Ruiz, José M Pérez-Villares, Lorena Z Peiró, Teresa Aldabó, Rosa Sebastián, Eduardo Miñambres, Lidia Pita, Marcial Casares, Juan Galán, Cristina Vidal, Christel Terrón, Pablo Castro, Marga Sanroma, Elisabeth Coll, Beatriz Domínguez-Gil
Donation after uncontrolled circulatory death (uDCD) refers to donation from persons who have died following cardiac arrest and unsuccessful attempt at resuscitation. We report the Spanish experience of uDCD kidney transplantation, and identify factors related to short-term post-transplant outcomes. The Spanish CORE system compiles data on all donation and transplant procedures in the country. Between 2012-2015, 517 kidney transplants from 288 uDCD donors were performed. The incidence of primary non-function was 10%, and the incidence of delayed graft function was 76%...
December 19, 2018: Kidney International
Reid H Whitlock, William D Leslie, James Shaw, Claudio Rigatto, Laurel Thorlacius, Paul Komenda, David Collister, John A Kanis, Navdeep Tangri
The Fracture Risk Assessment Tool (FRAX®) was developed to predict fracture risk in the general population, but its applicability to patients with chronic kidney disease (CKD) is unknown. Using the Manitoba Bone Mineral Density (BMD) Database, we identified adults not receiving dialysis with available serum creatinine measurements and bone densitometry within 1 year. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Incident major osteoporotic fractures and hip fractures were ascertained from population-based health care databases...
December 19, 2018: Kidney International
Zuo-Lin Li, Lin-Li Lv, Tao-Tao Tang, Bin Wang, Ye Feng, Le-Ting Zhou, Jing-Yuan Cao, Ri-Ning Tang, Min Wu, Hong Liu, Steven D Crowley, Bi-Cheng Liu
Hypoxia promotes tubulointerstitial inflammation in the kidney. Although hypoxia inducible factor-1α (HIF-1α) is a master regulator of the response to hypoxia, the exact mechanisms through which HIF-1α modulates the induction of tubulointerstitial inflammation are still largely unclear. We demonstrated tubulointerstitial inflammation and increased tubular HIF-1α expression in murine models of ischemia/reperfusion injury and unilateral ureteral obstruction. Increased expression of HIF-1α in tubular epithelial cells was associated with selective shedding of microRNA-23a (miRNA-23a)-enriched exosomes in vivo and systemic inhibition of miRNA-23a prior to ischemia/reperfusion injury attenuated tubulointerstitial inflammation...
December 7, 2018: Kidney International
Pauline Erpicum, Laurent Weekers, Olivier Detry, Catherine Bonvoisin, Marie-Hélène Delbouille, Céline Grégoire, Etienne Baudoux, Alexandra Briquet, Chantal Lechanteur, Gianni Maggipinto, Joan Somja, Hans Pottel, Frédéric Baron, François Jouret, Yves Beguin
Mesenchymal stromal cells (MSCs) exhibit anti-inflammatory and immune-regulatory properties, and preclinical studies suggest a potential benefit in solid organ transplantation. We report on the 1-year follow-up of an open-label phase I-II trial of a single infusion of third-party MSC post-kidney transplantation, in addition to standard immunosuppression. Ten kidney transplant recipients from deceased donors received third-party bone marrow MSCs (∼2 × 106 /kg) on day 3 ± 2 post-transplant and were compared to 10 concurrent controls...
December 6, 2018: Kidney International
Michaela Finsterbusch, M Ursula Norman, Pam Hall, A Richard Kitching, Michael J Hickey
Platelet-leukocyte interactions promote acute glomerulonephritis. However, neither the nature of the interactions between platelets and immune cells nor the capacity of platelets to promote leukocyte activation has been characterized in this condition. We used confocal intravital microscopy to define the interactions of platelets with neutrophils, monocytes, and endothelial cells in glomerular capillaries in mice. In the absence of inflammation, platelets underwent rapid on/off interactions with immune cells...
November 29, 2018: Kidney International
David Montero, Carsten Lundby
The production of erythropoietin (Epo) is modulated by renal tissue oxygen tension, which in principle depends on both arterial oxygen content (CaO2) and arterial oxygen tension (PaO2). Uncontrolled observational studies suggest that alterations in CaO2 fundamentally regulate Epo synthesis. We sought to establish whether reduced CaO2 enhances plasma Epo concentration independently of PaO2 . In a blinded crossover study, 8 healthy young subjects were exposed to three conditions: room air (normoxia); 11% oxygen balanced in nitrogen, which lowers both CaO2 and PaO2 (hypoxia); and carbon monoxide plus normoxia, which decreases CaO2 to the same degree as hypoxia while preserving PaO2 (hypoxemia)...
November 29, 2018: Kidney International
Martin R Späth, Malte P Bartram, Nicolàs Palacio-Escat, K Johanna R Hoyer, Cedric Debes, Fatih Demir, Christina B Schroeter, Amrei M Mandel, Franziska Grundmann, Giuliano Ciarimboli, Andreas Beyer, Jayachandran N Kizhakkedathu, Susanne Brodesser, Heike Göbel, Jan U Becker, Thomas Benzing, Bernhard Schermer, Martin Höhne, Volker Burst, Julio Saez-Rodriguez, Pitter F Huesgen, Roman-Ulrich Müller, Markus M Rinschen
Acute kidney injury (AKI) leads to significant morbidity and mortality; unfortunately, strategies to prevent or treat AKI are lacking. In recent years, several preconditioning protocols have been shown to be effective in inducing organ protection in rodent models. Here, we characterized two of these interventions-caloric restriction and hypoxic preconditioning-in a mouse model of cisplatin-induced AKI and investigated the underlying mechanisms by acquisition of multi-layered omic data (transcriptome, proteome, N-degradome) and functional parameters in the same animals...
November 29, 2018: Kidney International
Vivek Kasinath, Osman A Yilmam, Mayuko Uehara, Liwei Jiang, Farideh Ordikhani, Xiaofei Li, David J Salant, Reza Abdi
Crescentic glomerulonephritis is an inflammatory condition characterized by rapid deterioration of kidney function. Previous studies of crescentic glomerulonephritis have focused on immune activation in the kidney. However, the role of fibroblastic reticular cells, which reside in the stromal compartment of the kidney lymph node, has not been studied in this condition. We investigated the activation of kidney lymph node-resident fibroblastic reticular cells in nephrotoxic serum nephritis, a classic murine model of crescentic glomerulonephritis...
November 29, 2018: Kidney International
Takafumi Yagisawa, Toshiaki Tanaka, Satoshi Miyairi, Kazunari Tanabe, Nina Dvorina, Wayne M Yokoyama, Anna Valujskikh, William M Baldwin, Robert L Fairchild
Antibody mediated rejection (ABMR) is a major barrier to long-term kidney graft survival. Dysregulated donor-specific antibody (DSA) responses are induced in CCR5-deficient mice transplanted with complete major histocompatibility complex (MHC)-mismatched kidney allografts, and natural killer (NK) cells play a critical role in graft injury and rejection. We investigated the consequence of high DSA titers on kidney graft outcomes in the presence or absence of NK cell activation within the graft. Equivalent serum DSA titers were induced in CCR5-deficient B6 recipients of complete MHC mismatched A/J allografts and semi-allogeneic (A/J x B6) F1 kidney grafts, peaking by day 14 post-transplant...
November 29, 2018: Kidney International
Faik Imeri, Karen A Nolan, Andreas M Bapst, Sara Santambrogio, Irene Abreu-Rodríguez, Patrick Spielmann, Svende Pfundstein, Silvana Libertini, Lisa Crowther, Ilaria M C Orlando, Sophie L Dahl, Anna Keodara, Willy Kuo, Vartan Kurtcuoglu, Carsten C Scholz, Weihong Qi, Edith Hummler, David Hoogewijs, Roland H Wenger
Erythropoietin (Epo) is essential for erythropoiesis and is mainly produced by the fetal liver and the adult kidney following hypoxic stimulation. Epo regulation is commonly studied in hepatoma cell lines, but differences in Epo regulation between kidney and liver limit the understanding of Epo dysregulation in polycythaemia and anaemia. To overcome this limitation, we have generated a novel transgenic mouse model expressing Cre recombinase specifically in the active fraction of renal Epo-producing (REP) cells...
November 23, 2018: Kidney International
Aditi Sinha, Mamta Puraswani, Mani Kalaivani, Pragya Goyal, Pankaj Hari, Arvind Bagga
Both levamisole and mycophenolate mofetil (MMF) prevent relapses in patients with frequently relapsing nephrotic syndrome; however, their efficacy has not been compared prospectively. This single-center, randomized, open-label trial enrolled 149 children ages 6-18 years with frequently relapsing or steroid-dependent nephrotic syndrome. Participants were randomized in a 1:1 ratio to receive therapy with MMF (750-1000 mg/m2 daily) or levamisole (2-2.5 mg/kg on alternate days) for 1 year; prednisolone was discontinued by 2-3 months...
November 22, 2018: Kidney International
Emily J See, Kushani Jayasinghe, Neil Glassford, Michael Bailey, David W Johnson, Kevan R Polkinghorne, Nigel D Toussaint, Rinaldo Bellomo
Reliable estimates of the long-term outcomes of acute kidney injury (AKI) are needed to inform clinical practice and guide allocation of health care resources. This systematic review and meta-analysis aimed to quantify the association between AKI and chronic kidney disease (CKD), end-stage kidney disease (ESKD), and death. Systematic searches were performed through EMBASE, MEDLINE, and grey literature sources to identify cohort studies in hospitalized adults that used standardized definitions for AKI, included a non-exposed comparator, and followed patients for at least 1 year...
November 22, 2018: Kidney International
David M Charytan, Jonathan Himmelfarb, T Alp Ikizler, Dominic S Raj, Jesse Y Hsu, J Richard Landis, Amanda H Anderson, Adriana M Hung, Rajnish Mehrotra, Shailendra Sharma, Daniel E Weiner, Mark Williams, Marcelo DiCarli, Hicham Skali, Paul L Kimmel, Alan S Kliger, Laura M Dember
The safety and efficacy of spironolactone is uncertain in end-stage renal disease. We randomized 129 maintenance hemodialysis patients to placebo (n=51) or spironolactone 12.5 mg (n=27), 25 mg (n=26), or 50 mg (n=25) daily for 36 weeks in a double-blind, placebo-controlled, multiple dosage trial to assess safety, tolerability and feasibility and to explore cardiovascular efficacy. The primary safety endpoints were hyperkalemia (potassium > 6.5 mEq/L) and hypotension requiring emergency department visit or hospitalization...
November 22, 2018: Kidney International
Simon C Johnson, Frank Martinez, Alessandro Bitto, Brenda Gonzalez, Cagdas Tazaerslan, Camille Cohen, Laure Delaval, José Timsit, Bertrand Knebelmann, Fabiola Terzi, Tarika Mahal, Yizhou Zhu, Philip G Morgan, Margaret M Sedensky, Matt Kaeberlein, Christophe Legendre, Yousin Suh, Guillaume Canaud
Mitochondrial diseases represent a significant clinical challenge. Substantial efforts have been devoted to identifying therapeutic strategies for mitochondrial disorders, but effective interventions have remained elusive. Recently, we reported attenuation of disease in a mouse model of the human mitochondrial disease Leigh syndrome through pharmacological inhibition of the mechanistic target of rapamycin (mTOR). The human mitochondrial disorder MELAS/MIDD (Mitochondrial Encephalopathy with Lactic Acidosis and Stroke-like Episodes/Maternally Inherited Diabetes and Deafness) shares many phenotypic characteristics with Leigh syndrome...
November 21, 2018: Kidney International
Justin J Kang, Nayiri M Kaissarian, Karl C Desch, Robert J Kelly, Liming Shu, Peter F Bodary, James A Shayman
Fabry disease results from loss of activity of the lysosomal enzyme α-galactosidase A (GLA), leading to the accumulation of globoseries glycosphingolipids in vascular endothelial cells. Thrombosis and stroke are life-threatening complications of Fabry disease; however, the mechanism of the vasculopathy remains unclear. We explored the relationship between GLA deficiency and endothelial cell von Willebrand factor (VWF) secretion in in vivo and in vitro models of Fabry disease. Plasma VWF was significantly higher at two months and increased with age in Gla-null compared to wild-type mice...
November 20, 2018: Kidney International
Isaac E Hall, Enver Akalin, Jonathan S Bromberg, Mona D Doshi, Tom Greene, Meera N Harhay, Yaqi Jia, Sherry G Mansour, Sumit Mohan, Thangamani Muthukumar, Peter P Reese, Bernd Schröppel, Pooja Singh, Heather R Thiessen-Philbrook, Francis L Weng, Chirag R Parikh
Deceased-donor acute kidney injury (AKI) is associated with organ discard and delayed graft function, but data on longer-term allograft survival are limited. We performed a multicenter study to determine associations between donor AKI (from none to severe based on AKI Network stages) and all-cause graft failure, adjusting for donor, transplant, and recipient factors. We examined whether any of the following factors modified the relationship between donor AKI and graft survival: kidney donor profile index, cold ischemia time, donation after cardiac death, expanded-criteria donation, kidney machine perfusion, donor-recipient gender combinations, or delayed graft function...
November 14, 2018: Kidney International
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