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Kidney International

Andrew A House, Christoph Wanner, Mark J Sarnak, Ileana L Piña, Christopher W McIntyre, Paul Komenda, Bertram L Kasiske, Anita Deswal, Christopher R deFilippi, John G F Cleland, Stefan D Anker, Charles A Herzog, Michael Cheung, David C Wheeler, Wolfgang C Winkelmayer, Peter A McCullough
The incidence and prevalence of heart failure (HF) and chronic kidney disease (CKD) are increasing, and as such a better understanding of the interface between both conditions is imperative for developing optimal strategies for their detection, prevention, diagnosis, and management. To this end, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international, multidisciplinary Controversies Conference titled Heart Failure in CKD. Breakout group discussions included (i) HF with preserved ejection fraction (HFpEF) and nondialysis CKD, (ii) HF with reduced ejection fraction (HFrEF) and nondialysis CKD, (iii) HFpEF and dialysis-dependent CKD, (iv) HFrEF and dialysis-dependent CKD, and (v) HF in kidney transplant patients...
April 30, 2019: Kidney International
Christopher T Chan, Peter J Blankestijn, Laura M Dember, Maurizio Gallieni, David C H Harris, Charmaine E Lok, Rajnish Mehrotra, Paul E Stevens, Angela Yee-Moon Wang, Michael Cheung, David C Wheeler, Wolfgang C Winkelmayer, Carol A Pollock
Globally, the number of patients undergoing maintenance dialysis is increasing, yet throughout the world there is significant variability in the practice of initiating dialysis. Factors such as availability of resources, reasons for starting dialysis, timing of dialysis initiation, patient education and preparedness, dialysis modality and access, as well as varied "country-specific" factors significantly affect patient experiences and outcomes. As the burden of end-stage kidney disease (ESKD) has increased globally, there has also been a growing recognition of the importance of patient involvement in determining the goals of care and decisions regarding treatment...
April 12, 2019: Kidney International
Sho Hasegawa, Etsuo A Susaki, Tetsuhiro Tanaka, Hirotaka Komaba, Takehiko Wada, Masafumi Fukagawa, Hiroki R Ueda, Masaomi Nangaku
The sympathetic nervous system is critical in maintaining the homeostasis of renal functions. However, its three-dimensional (3D) structures in the kidney have not been elucidated due to limitation of conventional imaging methods. CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis) is a newly developed tissue-clearing technique, which enables whole-organ 3D imaging without thin-sectioning. Comprehensive 3D imaging by CUBIC found that sympathetic nerves are primarily distributed around arteries in the mouse kidney...
April 4, 2019: Kidney International
Dominic M Taylor, J Andrew Bradley, Clare Bradley, Heather Draper, Christopher Dudley, Damian Fogarty, Simon Fraser, Rachel Johnson, Geraldine M Leydon, Wendy Metcalfe, Gabriel C Oniscu, Matthew Robb, Charles Tomson, Christopher J E Watson, Rommel Ravanan, Paul Roderick
Limited health literacy is common in patients with chronic kidney disease (CKD) and has been variably associated with adverse clinical outcomes. The prevalence of limited health literacy is lower in kidney transplant recipients than in individuals starting dialysis, suggesting selection of patients with higher health literacy for transplantation. We investigated the relationship between limited health literacy and clinical outcomes, including access to kidney transplantation, in a prospective UK cohort study of 2,274 incident dialysis patients aged 18-75 years...
March 27, 2019: Kidney International
Aravind Cherukuri, Rajil Mehta, Akhil Sharma, Puneet Sood, Adriana Zeevi, Amit D Tevar, David M Rothstein, Sundaram Hariharan
Post-transplant donor specific antibody (DSA) is associated with poor renal allograft outcomes. However, variable timing of DSA assessment and inclusion of patients who undergo desensitization treatments have hindered our understanding of its consequences and limited its predictive value. Here we prospectively studied non-desensitized patients to determine factors associated with poor four-year outcomes in patients who developed post-transplant DSA. Using serial monitoring, 67 of 294 patients were found to develop DSA by one year...
March 20, 2019: Kidney International
Karolis Azukaitis, Wenjun Ju, Marietta Kirchner, Viji Nair, Michelle Smith, Zhiyin Fang, Daniela Thurn-Valsassina, Aysun Bayazit, Anna Niemirska, Nur Canpolat, Ipek Kaplan Bulut, Fatos Yalcinkaya, Dusan Paripovic, Jerome Harambat, Nilgun Cakar, Harika Alpay, Francesca Lugani, Francesca Mencarelli, Mahmut Civilibal, Hakan Erdogan, Jutta Gellermann, Enrico Vidal, Yilmaz Tabel, Charlotte Gimpel, Pelin Ertan, Onder Yavascan, Anette Melk, Uwe Querfeld, Elke Wühl, Matthias Kretzler, Franz Schaefer
Urinary epidermal growth factor (uEGF) has recently been identified as a promising biomarker of chronic kidney disease (CKD) progression in adults with glomerular disease. Low levels of uEGF predict CKD progression and appear to reflect the extent of tubulointerstitial damage. We investigated the relevance of uEGF in pediatric CKD. We performed a post hoc analysis of the Cardiovascular Comorbidity in Children with CKD (4C) study, which prospectively follows children aged 6-17 years with baseline estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1...
March 20, 2019: Kidney International
Michael P Madaio, Istvan Czikora, Nino Kvirkvelia, Malgorzata McMenamin, Qiang Yue, Ting Liu, Haroldo A Toque, Supriya Sridhar, Katherine Covington, Rabei Alaisami, Paul M O'Connor, Robert W Caldwell, Jian-Kang Chen, Matthias Clauss, Michael W Brands, Douglas C Eaton, Maritza J Romero, Rudolf Lucas
In mice, the initial stage of nephrotoxic serum-induced nephritis (NTN) mimics antibody-mediated human glomerulonephritis. Local immune deposits generate tumor necrosis factor (TNF), which activates pro-inflammatory pathways in glomerular endothelial cells (GECs) and podocytes. Because TNF receptors mediate antibacterial defense, existing anti-TNF therapies can promote infection; however, we have previously demonstrated that different functional domains of TNF may have opposing effects. The TIP peptide mimics the lectin-like domain of TNF, and has been shown to blunt inflammation in acute lung injury without impairing TNF receptor-mediated antibacterial activity...
March 18, 2019: Kidney International
James R Myette, Toshiki Kano, Hitoshi Suzuki, Susan E Sloan, Kristy J Szretter, Boopathy Ramakrishnan, Hedy Adari, Ketan D Deotale, Frank Engler, Zachary Shriver, Andrew M Wollacott, Yusuke Suzuki, Brian J G Pereira
IgA nephropathy (IgAN) is the most prevalent primary chronic glomerular disease for which no safe disease-specific therapies currently exist. IgAN is an autoimmune disease involving the production of autoantigenic, aberrantly O-glycosylated IgA1 and ensuing deposition of nephritogenic immune complexes in the kidney. A Proliferation Inducing Ligand (APRIL) has emerged as a key B-cell-modulating factor in this pathogenesis. Using a mouse anti-APRIL monoclonal antibody (4540), we confirm both the pathogenic role of APRIL in IgAN and the therapeutic efficacy of antibody-directed neutralization of APRIL in the grouped mouse ddY disease model...
March 16, 2019: Kidney International
Isabel Ottlewski, Johannes Münch, Timo Wagner, Ria Schönauer, Anette Bachmann, Antje Weimann, Julia Hentschel, Tom H Lindner, Daniel Seehofer, Carsten Bergmann, Rami Abou Jamra, Jan Halbritter
End-stage renal disease (ESRD) of undetermined etiology is highly prevalent and constitutes a significant clinical challenge, particularly in the context of kidney transplantation (KT). Despite the identification of numerous rare hereditary nephropathies over the last few decades, patients with undetermined ESRD are not being systematically investigated for rare genetic causes in clinical practice. To address this, we utilized mutation analysis in patients on the kidney transplant waitlist and scrutinized underlying renal diagnoses of 142 patients in a single center KT-waitlist...
March 15, 2019: Kidney International
Adam Arshad, Benjamin Anderson, Adnan Sharif
Studies comparing opt-out and opt-in approaches to organ donation have generally suggested higher donation and transplantation rates in countries with an opt-out strategy. We compared organ donation and transplantation rates between countries with opt-out versus opt-in systems to investigate possible differences in the contemporary era. Data were analysed for 35 countries registered with the Organisation for Economic Co-operation and Development (17 countries classified as opt-out, 18 classified as opt-in) and obtained organ donation and transplantation rates for 2016 from the Global Observatory for Donation and Transplantation...
March 15, 2019: Kidney International
Carmen Lefaucheur, Denis Viglietti, Yassine Bouatou, Aurélie Philippe, Daniele Pievani, Olivier Aubert, Jean-Paul Duong Van Huyen, Jean-Luc Taupin, Denis Glotz, Christophe Legendre, Alexandre Loupy, Philip F Halloran, Duska Dragun
Anti-angiotensin II type 1 receptor (AT1R) antibodies have been associated with allograft rejection. We hypothesized that circulating AT1R antibodies might identify kidney transplant recipients at increased risk of allograft rejection and loss who are not identified by the HLA system. We prospectively enrolled 1845 kidney transplant recipients from two centers. Donor-specific HLA antibodies (DSAs) and AT1R antibodies were measured at the time of the first acute rejection episode or at 1 year post-transplant...
March 15, 2019: Kidney International
Jung-Hyun Kim, Eun Young Park, David Chitayat, David L Stachura, Jörg Schaper, Kristin Lindstrom, Tamison Jewett, Dagmar Wieczorek, Jos M Draaisma, Margje Sinnema, Christianne Hoeberigs, Maja Hempel, Kristine K Bachman, Andrea H Seeley, Joshua K Stone, Hyun Kyung Kong, Lana Vukadin, Alexander Richard, Deepali N Shinde, Kirsty McWalter, Yue Cindy Si, Ganka Douglas, Ssang-Taek Lim, Lisenka E L M Vissers, Mathieu Lemaire, Eun-Young Erin Ahn
Although genetic testing is increasingly used in clinical nephrology, a large number of patients with congenital abnormalities of the kidney and urinary tract (CAKUT) remain undiagnosed with current gene panels. Therefore, careful curation of novel genetic findings is key to improving diagnostic yields. We recently described a novel intellectual disability syndrome caused by de novo heterozygous loss-of-function mutations in the gene encoding the splicing factor SON. Here, we show that many of these patients, including two previously unreported, exhibit a wide array of kidney abnormalities...
March 15, 2019: Kidney International
Yugeesh R Lankadeva, Andrew D Cochrane, Bruno Marino, Naoya Iguchi, Sally G Hood, Rinaldo Bellomo, Clive N May, Roger G Evans
Renal medullary hypoxia may contribute to cardiac surgery-associated acute kidney injury (AKI). However, the effects of cardiopulmonary bypass (CPB) on medullary oxygenation are poorly understood. Here we tested whether CPB causes medullary hypoxia and whether medullary oxygenation during CPB can be improved by increasing pump flow or mean arterial pressure (MAP). Twelve sheep were instrumented to measure whole kidney, medullary, and cortical blood flow and oxygenation. Five days later, under isoflurane anesthesia, CPB was initiated at a pump flow of 80 mL kg-1 min-1 and target MAP of 70 mm Hg...
March 15, 2019: Kidney International
Vincent Javaugue, Céline Debiais-Delpech, Mathilde Nouvier, Elise Gand, Sophie Chauvet, Laure Ecotiere, Estelle Desport, Jean-Michel Goujon, Vincent Delwail, Stéphanie Guidez, Cécile Tomowiak, Xavier Leleu, Arnaud Jaccard, Nathalie Rioux-Leclerc, Cécile Vigneau, Jean-Paul Fermand, Guy Touchard, Antoine Thierry, Frank Bridoux
The clinicopathological characteristics of kidney infiltration in B-cell lymphoproliferative disorders remain poorly described. We retrospectively studied 52 adults with biopsy-proven malignant B-cell kidney infiltration, including Waldenström's macroglobulinemia (n=21), chronic lymphocytic leukemia (n=11), diffuse large B-cell lymphoma (DLBCL) (n=8), other lymphoma (n=11), and multiple myeloma (n=1). Kidney disease varied according to the underlying lymphoproliferative disorder. In DLBCL, malignant kidney infiltration was prominent, resulting in acute kidney injury (AKI, 75%) and kidney enlargement (88%)...
March 15, 2019: Kidney International
Alice Le Clech, Noémie Simon-Tillaux, François Provôt, Yahsou Delmas, Paula Vieira-Martins, Sophie Limou, Jean-Michel Halimi, Moglie Le Quintrec, Ludivine Lebourg, Steven Grangé, Alexandre Karras, David Ribes, Noémie Jourde-Chiche, Eric Rondeau, Véronique Frémeaux-Bacchi, Fadi Fakhouri
Secondary hemolytic uremic syndrome (HUS) is a heterogeneous group of thrombotic microangiopathies associated with various underlying conditions. Whether it belongs to the spectrum of complement-mediated HUS remains controversial. We analysed the presentation, outcome, and frequency of complement gene rare variants in a cohort of 110 patients with secondary HUS attributed to drugs (29%), autoimmune diseases (24%), infections (17%), malignancies (10%), glomerulopathies (9%), extra-renal organ transplantation (8%), and pancreatitis (3%)...
March 15, 2019: Kidney International
Iryna Schlackow, Seamus Kent, William Herrington, Jonathan Emberson, Richard Haynes, Christina Reith, Rory Collins, Martin J Landray, Alastair Gray, Colin Baigent, Borislava Mihaylova
Statin-based treatments reduce cardiovascular disease (CVD) risk in patients with non-dialysis chronic kidney disease (CKD), but it is unclear which regimen is the most cost-effective. We used the Study of Heart and Renal Protection (SHARP) CKD-CVD policy model to evaluate the effect of statins and ezetimibe on quality-adjusted life years (QALYs) and health care costs in the United States (US) and the United Kingdom (UK). Net costs below $100,000/QALY (US) or £20,000/QALY (UK) were considered cost-effective...
March 12, 2019: Kidney International
Justine B Bukabau, Eric Yayo, Appolinaire Gnionsahé, Dagui Monnet, Hans Pottel, Etienne Cavalier, Aliocha Nkodila, Jean Robert R Makulo, Vieux M Mokoli, François B Lepira, Nazaire M Nseka, Jean-Marie Krzesinski, Ernest K Sumaili, Pierre Delanaye
Glomerular filtration rate (GFR) is the best index for kidney function; however, the applicability of GFR estimating equations in sub-Saharan African populations remains unclear. In a cross-sectional study of adults living in Kinshasa, Democratic Republic of Congo (n=210) and Abidjan, Ivory Coast (n=284), we evaluated the performance of creatinine and cystatin C-based equations using plasma clearance of iohexol as the reference standard. The race coefficient did not improve the performance of creatinine-based GFR estimates; in fact, both the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology (CKD-EPI) equations performed better without the race coefficient in participants with GFR ≥60 mL/min/1...
March 12, 2019: Kidney International
Daniela Zanetti, Abhiram Rao, Stefan Gustafsson, Themistocles L Assimes, Stephen B Montgomery, Erik Ingelsson
Urine biomarkers reflecting kidney function and handling of dietary sodium and potassium are strongly associated with several common diseases including chronic kidney disease, cardiovascular disease, and diabetes mellitus. Knowledge about the genetic determinants of these biomarkers may shed light on pathophysiological mechanisms underlying the development of these diseases. We performed genome-wide association studies of urinary albumin: creatinine ratio (UACR), urinary potassium: creatinine ratio (UK/UCr), urinary sodium: creatinine ratio (UNa/UCr) and urinary sodium: potassium ratio (UNa/UK) in up to 218,450 (discovery) and 109,166 (replication) unrelated individuals of European ancestry from the UK Biobank...
March 12, 2019: Kidney International
Juan M Díaz-Tocados, María E Rodríguez-Ortiz, Yolanda Almadén, Carmen Pineda, Julio M Martínez-Moreno, Carmen Herencia, Noemi Vergara, M Victoria Pendón-Ruiz de Mier, Rafael Santamaría, Cristian Rodelo-Haad, Antonio Casado-Díaz, Víctor Lorenzo, Catarina Carvalho, João M Frazão, Arnold J Felsenfeld, William G Richards, Escolástico Aguilera-Tejero, Mariano Rodríguez, Ignacio López, Juan R Muñoz-Castañeda
Calcimimetics decrease parathyroid hormone (PTH) secretion in patients with secondary hyperparathyroidism. The decrease in PTH should cause a reduction in bone turnover; however, the direct effect of calcimimetics on bone cells, which express the calcium-sensing receptor (CaSR), has not been defined. In this study, we evaluated the direct bone effects of CaSR activation by a calcimimetic (AMG 641) in vitro and in vivo. To create a PTH "clamp," total parathyroidectomy was performed in rats with and without uremia induced by 5/6 nephrectomy, followed by a continuous subcutaneous infusion of PTH...
March 12, 2019: Kidney International
Yun Xie, Ghada Ankawi, Bo Yang, Francesco Garzotto, Alberto Passannante, Andrea Breglia, Kumar Digvijay, Fiorenza Ferrari, Alessandra Brendolan, Bonato Raffaele, Davide Giavarina, Dario Gregori, Claudio Ronco
The G1 cell cycle inhibitors tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as novel biomarkers for the prediction of moderate to severe acute kidney injury (AKI) risk. However, the prognostic value of [TIMP-2]•[IGFBP7] in predicting adverse outcomes in intensive care unit (ICU) patients with AKI was not previously described. To evaluate this, we conducted a cohort study, measuring [TIMP2]•[IGFBP7] levels in critically ill patients admitted to the ICU and classified the patients as NephroCheck (NC) (+) or NC (-) according to [TIMP-2]•[IGFBP7] values and AKI (+) or AKI (-) according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria...
March 9, 2019: Kidney International
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