Post-transplant donor specific antibody is associated with poor kidney transplant outcomes only when combined with both T-cell –mediated rejection and non-adherence
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. (Source: Kidney International)
Source: Kidney International - March 19, 2019 Category: Urology & Nephrology Authors: Aravind Cherukuri, Rajil Mehta, Akhil Sharma, Puneet Sood, Adriana Zeevi, Amit D. Tevar, David Rothstein, Sundaram Hariharan Tags: Clinical Investigation Source Type: research

Low levels of urinary epidermal growth factor  predict chronic kidney disease progression in children
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/1.73 m2. (Source: Kidney International)
Source: Kidney International - March 19, 2019 Category: Urology & Nephrology Authors: 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 Alp Tags: Clinical Investigation Source Type: research

An instrumental variable approach quantifies and confirms the duration of pre-transplant dialysis has negative impact on kidney transplant recipient survival
Dialysis prior to kidney transplantation may have a detrimental effect on post-transplant Outcomes. However, prior studies have not fully characterized the nature of this relationship and may have been subject to residual confounding. Here we investigated the association between pre-transplant dialysis duration and two post-transplant outcomes: all-cause death and death with functioning graft. This was a retrospective, population-based, cohort study in all deceased donor kidney transplants performed in Ontario, Canada, from April 1, 2002 to March 31, 2013. (Source: Kidney International)
Source: Kidney International - March 19, 2019 Category: Urology & Nephrology Authors: Rui Fu, S. Joseph Kim, Claire de Oliveira, Peter C. Coyte Tags: Clinical Investigation Source Type: research

Atypical and secondary hemolytic uremic syndromes have a distinct presentation and no common genetic risk factors
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%). (Source: Kidney International)
Source: Kidney International - March 15, 2019 Category: Urology & Nephrology Authors: Alice Le Clech, No émie 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, Vé Tags: Clinical Investigation Source Type: research

SON haploinsufficiency causes impaired pre-mRNA splicing of CAKUT genes and heterogeneous renal  phenotypes
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. (Source: Kidney International)
Source: Kidney International - March 15, 2019 Category: Urology & Nephrology Authors: Jung-Hyun Kim, Eun Young Park, David Chitayat, David L. Stachura, J örg Schaper, Kristin Lindstrom, Tamison Jewett, Dagmar Wieczorek, Jos M. Draaisma, Margje Sinnema, Christianne Hoeberigs, Maja Hempel, Kristine K. Bachman, Andrea H. Seeley, Joshua K. St Tags: Clinical Investigation Source Type: research

Clinicopathological spectrum of renal parenchymal involvement in B-cell lymphoproliferative disorders
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 Waldenstr öm’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%). (So...
Source: Kidney International - March 15, 2019 Category: Urology & Nephrology Authors: Vincent Javaugue, C éline 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, Céc Tags: Basic Research Source Type: research

Non-HLA Agonistic Anti-Angiotensin II Type 1 Receptor Antibodies Induce a Distinctive Phenotype of Antibody-mediated Rejection in Kidney Transplant Recipients
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. (Source: Kidney International)
Source: Kidney International - March 15, 2019 Category: Urology & Nephrology Authors: Carmen Lefaucheur, Denis Viglietti, Yassine Bouatou, Aur élie Philippe, Daniele Pievani, Olivier Aubert, Jean-Paul Duong Van Huyen, Jean-Luc Taupin, Denis Glotz, Christophe Legendre, Alexandre Loupy, Philip F Halloran, Duska Dragun Tags: Clinical Investigation Source Type: research

A Proliferation Inducing Ligand (APRIL) targeted antibody is a safe and effective treatment of murine IgA nephropathy
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 mo...
Source: Kidney International - March 15, 2019 Category: Urology & Nephrology Authors: 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 Wollacott, Yusuke Suzuki, Brian J.G. Pereira Tags: Basic Research Source Type: research

Strategies that improve renal medullary oxygenation during experimental cardiopulmonary bypass may mitigate postoperative acute kidney  injury
Renal medullary hypoxia may contribute to cardiac surgery –associated acute kidney injury. 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–1min–1 and target MAP of 70 mm ...
Source: Kidney International - March 15, 2019 Category: Urology & Nephrology Authors: Yugeesh R. Lankadeva, Andrew D. Cochrane, Bruno Marino, Naoya Iguchi, Sally G. Hood, Rinaldo Bellomo, Clive N. May, Roger G. Evans Tags: Basic Research Source Type: research

Comparison of organ donation and transplantation rates between opt-out and opt-in systems
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 nalysed 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 Transplanta...
Source: Kidney International - March 15, 2019 Category: Urology & Nephrology Authors: Adam Arshad, Benjamin Anderson, Adnan Sharif Tags: Clinical Investigation Source Type: research

Value of renal gene panel diagnostics in adults waiting for kidney transplantation due to undetermined end-stage renal disease
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. (Source: Kidney International)
Source: Kidney International - March 15, 2019 Category: Urology & Nephrology Authors: Isabel Ottlewski, Johannes M ünch, Timo Wagner, Ria Schönauer, Anette Bachmann, Antje Weimann, Julia Hentschel, Tom H. Lindner, Daniel Seehofer, Carsten Bergmann, Rami Abou Jamra, Jan Halbritter Tags: Clinical Investigation Source Type: research

Novel 3D analysis using optical tissue clearing documents the evolution of murine rapidly progressive glomerulonephritis
Recent developments in optical tissue clearing have been difficult to apply for the morphometric analysis of organs with high cellular content and small functional structures, such as the kidney. Here, we establish combinations of genetic and immuno-labelling for single cell identification, tissue clearing and subsequent de-clarification for histoimmunopathology and transmission electron microscopy. Using advanced light microscopy and computational analyses, we investigated a murine model of crescentic nephritis, an inflammatory kidney disease typified by immune-mediated damage to glomeruli leading to the formation of hype...
Source: Kidney International - March 15, 2019 Category: Urology & Nephrology Authors: Victor G. Puelles, David Fleck, Lena Ortz, Stella Papadouri, Thiago Strieder, Alexander Boehner, James W. van der Wolde, Michael Vogt, Turgay Saritas, Christoph Kuppe, Astrid Fuss, Sylvia Menzel, Barbara M. Klinkhammer, Gerhard M üller-Newen, Felix Heyma Tags: Technical Notes Source Type: research

Disease-specific incident glomerulonephritis displays geographic clustering in under-serviced rural areas of British Columbia, Canada
There is little known about geographic variability in the incidence of glomerular disease and its potential implications for care delivery. To evaluate this, we performed a population-level cohort study using a provincial renal pathology database (2000-2012) to capture all incident cases of glomerulonephritis in British Columbia, Canada. This included 401 patients with membranous nephropathy (MN), 824 patients with IgA nephropathy (IgAN), 385 patients with focal segmental glomerulosclerosis (FSGS), 397 patients with lupus nephritis (LN) and 399 patients with ANCA-related glomerulonephritis (ANCA-GN). (Source: Kidney International)
Source: Kidney International - March 14, 2019 Category: Urology & Nephrology Authors: Mark Canney, Dilshani Induruwage, Lawrence C. McCandless, Heather N. Reich, Sean J. Barbour Tags: Clinical Investigation Source Type: research

Mineralocorticoid receptor antagonists and kidney diseases: pathophysiological basis
Chronic kidney disease (CKD) represent a global health concern, and its prevalence is increasing. The ultimate therapeutic option for CKD is kidney transplantation. However, the use of drugs that target specific pathways to delay or halt CKD progression such as ACEis, ARBs and SGLT-2 inhibitors is limited in the clinical practice. Mineralocorticoid receptor (MR) activation in non-classical tissues, such as the endothelium, smooth muscle cells, inflammatory cells, podocytes, and fibroblasts may have deleterious effects on kidney structure and function. (Source: Kidney International)
Source: Kidney International - March 12, 2019 Category: Urology & Nephrology Authors: Jonatan Barrera-Chimal, Sophie Girerd, Frederic Jaisser Tags: Review Source Type: research

Performance of creatinine- or cystatin C –based equations to estimate glomerular filtration rate in sub-Saharan African populations
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 Epi...
Source: Kidney International - March 11, 2019 Category: Urology & Nephrology Authors: Justine B. Bukabau, Eric Yayo, Appolinaire Gnionsah é, 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 Tags: Clinical Investigation Source Type: research

Calcimimetics maintain bone turnover in uremic rats despite the concomitant decrease in parathyroid hormone concentration
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. (Source: Kidney International)
Source: Kidney International - March 11, 2019 Category: Urology & Nephrology Authors: Juan M. D íaz-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 Loren Tags: Basic Research Source Type: research

Identification of 22 novel loci associated with  urinary biomarkers of albumin, sodium, and potassium excretion
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)...
Source: Kidney International - March 11, 2019 Category: Urology & Nephrology Authors: Daniela Zanetti, Abhiram Rao, Stefan Gustafsson, Themistocles L. Assimes, Stephen B. Montgomery, Erik Ingelsson Tags: Clinical Investigation Source Type: research

Cost-effectiveness of lipid lowering with statins and ezetimibe in chronic kidney disease
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 healthcare 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. (Source: Kidney International)
Source: Kidney International - March 11, 2019 Category: Urology & Nephrology Authors: Iryna Schlackow, Seamus Kent, William Herrington, Jonathan Emberson, Richard Haynes, Christina Reith, Rory Collins, Martin J. Landray, Alastair Gray, Colin Baigent, Borislava Mihaylova, SHARP Collaborative Group Tags: Clinical Investigation Source Type: research

Tissue inhibitor metalloproteinase-2 (TIMP-2) • IGF-binding protein-7 (IGFBP7) levels are associated with adverse outcomes in patients in the intensive care unit with acute kidney injury
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]&...
Source: Kidney International - March 9, 2019 Category: Urology & Nephrology Authors: Yun Xie, Ghada Ankawi, Bo Yang, Francesco Garzotto, Alberto Passannante, Andrea Breglia, Kumar Digvijay, Fiorenza Ferrari, Alessandra Brendolan, Raffaele Bonato, Davide Giavarina, Dario Gregori, Claudio Ronco Tags: Clinical Investigation Source Type: research

Lrig2 and Hpse2, mutated in urofacial syndrome, pattern nerves in the urinary bladder
Mutations in leucine-rich-repeats and immunoglobulin-like-domains 2 (LRIG2) or in heparanase 2 (HPSE2) cause urofacial syndrome, a devastating autosomal recessive disease of functional bladder outlet obstruction. It has been speculated that urofacial syndrome has a neural basis, but it is unknown whether defects in urinary bladder innervation are present. We hypothesized that urofacial syndrome features a peripheral neuropathy of the bladder. Mice with homozygous targeted Lrig2 mutations had urinary defects resembling those found in urofacial syndrome. (Source: Kidney International)
Source: Kidney International - March 8, 2019 Category: Urology & Nephrology Authors: Neil A. Roberts, Emma N. Hilton, Filipa M. Lopes, Subir Singh, Michael J. Randles, Natalie J. Gardiner, Karl Chopra, Riccardo Coletta, Zunera Bajwa, Robert J. Hall, Wyatt W. Yue, Franz Schaefer, Stefanie Weber, Roger Henriksson, Helen M. Stuart, H åkan H Tags: Basic Research Source Type: research

Matrix metalloproteinase-7 protects against acute kidney injury by priming renal tubules for survival and regeneration
In this study, we investigated the expression of MMP-7 and the impact of MMP-7 deficiency in several models of AKI. MMP-7 was induced in renal tubules following ischemia/ reperfusion injury or cisplatin administration, and in folic acid-induced AKI. (Source: Kidney International)
Source: Kidney International - March 8, 2019 Category: Urology & Nephrology Authors: Haiyan Fu, Dong Zhou, Haili Zhu, Jinlin Liao, Lin Lin, Xue Hong, Fan Fan Hou, Youhua Liu Tags: Basic Research Source Type: research

Plasma copeptin levels predict disease progression and tolvaptan efficacy in autosomal dominant polycystic kidney disease
In the TEMPO 3:4 Trial, treatment with tolvaptan, a vasopressin V2 receptor antagonist, slowed the increase in total kidney volume and decline in estimated glomerular filtration rate (eGFR) in autosomal dominant polycystic kidney disease (ADPKD). We investigated whether plasma copeptin levels, a marker of plasma vasopressin, are associated with disease progression, and whether pre-treatment copeptin and treatment-induced change in copeptin are associated with tolvaptan treatment efficacy. This post hoc analysis included 1,280 TEMPO 3:4 participants (aged 18-50 years, estimated creatinine clearance  ≥60 ml/min and t...
Source: Kidney International - March 8, 2019 Category: Urology & Nephrology Authors: Ron T. Gansevoort, Maatje D.A. van Gastel, Arlene B. Chapman, Jaime D. Blais, Frank S. Czerwiec, Eiji Higashihara, Jennifer Lee, John Ouyang, Ronald D. Perrone, Katrin Stade, Vicente E. Torres, Olivier Devuyst, TEMPO 3:4 Investigators Tags: Clinical Investigation Source Type: research

To transplant early or treat first?: A dilemma for Hepatitis C positive recipients
Kidney transplantation is a life-saving procedure for patients with end-stage kidney disease (ESKD)1. Despite the realisation that transplantation is clinically and economically superior to dialysis2, not all patients with ESKD will receive a transplant during their lifetime. Worldwide, the number of patients able to benefit from kidney transplantation is restricted by the shortage of deceased donor kidneys. In the United States (US), approximately 10% of those on dialysis (approximately 110,000 patients) are listed on the deceased donor transplant waiting list, and approximately 5000 patients die each year (around 4.5%) w...
Source: Kidney International - March 8, 2019 Category: Urology & Nephrology Authors: Germaine Wong, Toby Coates Tags: Make Your Diagnosis Source Type: research

Interleukin-17A blockade reduces albuminuria and  kidney injury in an accelerated model of diabetic nephropathy
Diabetic nephropathy (DN) is one of the most common complications of diabetes, and currently the first end-stage renal disease worldwide. New strategies to treat DN using agents that target inflammatory pathways have attracted special interest. Recent pieces of evidences suggest a promising effect of IL-17A, the Th17 effector cytokine. Among experimental DN models, mouse strain BTBR ob/ob (leptin deficiency mutation) develops histological features similar to human DN, which means an opportunity to study mechanisms and novel therapies aimed at DN regression. (Source: Kidney International)
Source: Kidney International - March 7, 2019 Category: Urology & Nephrology Authors: Carolina Lavoz, Yenniffer S ánchez Matus, Macarena Orejudo, J. Daniel Carpio, Alejandra Droguett, Jesús Egido, Sergio Mezzano, Marta Ruiz-Ortega Tags: Basic Research Source Type: research

Circulating factors cause proteinuria in parabiotic zebrafish
Proteinuria can be induced by impairment of any component of the glomerular filtration barrier. To determine the role of circulating permeability factors on glomerular damage, we developed a parabiosis-based zebrafish model to generate a common circulation between zebrafish larvae. A morpholino-mediated knockdown of a podocyte specific gene (nephronectin) was induced in one zebrafish larva which was then fused to an un-manipulated fish. Notably, proteinuria and glomerular damage were present in the manipulated fish and in the parabiotically-fused partner. (Source: Kidney International)
Source: Kidney International - March 7, 2019 Category: Urology & Nephrology Authors: J. M üller-Deile, H. Schenk, P. Schroder, K. Schulze, P. Bolaños-Palmieri, F. Siegerist, N. Endlich, H. Haller, M. Schiffer Tags: Basic Research Source Type: research

Improvements in albuminuria and chronic kidney disease progression with the appetite suppressant lorcaserin
Obesity is an established risk factor for chronic kidney disease (CKD) and has been associated with both impaired kidney function and albuminuria, reflecting a broad spectrum of underlying pathology (1). Proposed mechanisms include hemodynamic effects, with increased glomerular pressure leading to hyperfiltration and albuminuria with subsequent declines in kidney function, as well as possible adverse affects of adipokines on podocyte health (2). (Source: Kidney International)
Source: Kidney International - March 7, 2019 Category: Urology & Nephrology Authors: Peter Rossing, Frederik Persson, Marie Frimodt-M øller Tags: Nephrology Digest Source Type: research

Intensive BP control and incident kidney disease: what can we learn from urinary biomarkers?
The results of the Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that the intensive reduction in systolic blood pressure (SBP) to   (Source: Kidney International)
Source: Kidney International - March 6, 2019 Category: Urology & Nephrology Authors: T. Alp Ikizler, Jai Radhakrishnan, Germaine Wong Tags: Nephrology Digest Source Type: research

Regulated Necrosis in Kidney Ischemia-Reperfusion Injury
Ischemia-reperfusion injury (IRI) is the outcome of an inflammatory process that is triggered when an organ undergoes a transient reduction or cessation of blood flow, followed by re-establishment of perfusion. In the clinical setting, IRI contributes to significant acute kidney injury, patient morbidity and mortality and adverse outcomes in transplantation. Tubular cell death by necrosis and apoptosis is a central feature of renal IRI. Recent research has challenged traditional views of cell death by identifying new pathways in which cells die in a regulated manner but with the morphological features of necrosis. (Source:...
Source: Kidney International - March 6, 2019 Category: Urology & Nephrology Authors: Aspasia Pefanis, Francesco L. Ierino, James M. Murphy, Peter J. Cowan Tags: Review Source Type: research

Aberrant DNA methylation of mTOR pathway genes promotes inflammatory activation of immune cells in diabetic kidney disease
In this study, we tested the hypothesis that aberrant DNA methylation in peripheral immune cells contributes to DKD progression. We showed that levels of DNA methyltransferase 1 (DNMT1), a key enzyme for DNA methylation, were increased along with inflammatory activity of peripheral blood mononuclear cells in DKD patients. Inhibition of DNMT1 with 5-aza-2'-deoxycytidine (5-Aza) markedly increased the proportion of CD4+CD25+ regulatory T cells in peripheral blood mononuclear cells in culture and in diabetic animals. (Source: Kidney International)
Source: Kidney International - March 6, 2019 Category: Urology & Nephrology Authors: Guochun Chen, Huihui Chen, Shuyu Ren, Ming Xia, Jiefu Zhu, Yu Liu, Lei Zhang, Luosheng Tang, Lin Sun, Hong Liu, Zheng Dong Tags: Basic Research Source Type: research

Biological variation of measured and estimated glomerular filtration rate in patients with chronic kidney disease
When assessing changes in glomerular filtration rate (GFR) it is important to differentiate pathological change from intrinsic biological and analytical variation. GFR is measured using complex reference methods (e.g. iohexol clearance). In clinical practice measurement of creatinine and cystatin C are used in the Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) equations to provide estimated GFR. Here we studied the biological variability of measured and estimated GFR in twenty nephrology outpatients (10 male, 10 female; median age 71, range 50-80 years) with mod...
Source: Kidney International - March 6, 2019 Category: Urology & Nephrology Authors: Ceri Rowe, Alice J. Sitch, Jonathan Barratt, Elizabeth A. Brettell, Paul Cockwell, R Neil Dalton, Jon J. Deeks, Gillian Eaglestone, Tracy Pellatt-Higgins, Philip A. Kalra, Kamlesh Khunti, Fiona C. Loud, Frances S. Morris, Ryan S. Ottridge, Paul E. Stevens Tags: Clinical Investigation Source Type: research

Corticosteroid treatment exacerbates nephrotic syndrome in a zebrafish model of magi2a knockout
Recently, recessive mutations of MAGI2 were identified as a cause of steroid-resistant nephrotic syndrome (SRNS) in humans and mice. To further delineate the pathogenesis of MAGI2 loss of function, we generated stable knockout lines for the two zebrafish orthologues magi2a and magi2b by CRISPR/Cas9. We also developed a novel assay for the direct detection of proteinuria in zebrafish independent of transgenic background. Whereas knockout of magi2b did not yield a nephrotic syndrome phenotype, magi2a-/- larvae developed ascites, periorbital edema, and proteinuria, as indicated by increased excretion of low molecular weight p...
Source: Kidney International - March 5, 2019 Category: Urology & Nephrology Authors: Tilman Jobst-Schwan, Charlotte A. Hoogstraten, Caroline M. Kolvenbach, Johanna Magdalena Schmidt, Amy Kolb, Kaitlyn Eddy, Ronen Schneider, Shazia Ashraf, Eugen Widmeier, Amar J. Majmundar, Friedhelm Hildebrandt Tags: Basic Research Source Type: research

MicroRNA-214 promotes chronic kidney disease by disrupting mitochondrial oxidative phosphorylation
Mitochondria are critical in determining a cell ’s energy homeostasis and fate, and mitochondrial dysfunction has been implicated in the pathogenesis of chronic kidney disease (CKD). We sought to identify causative mitochondrial microRNAs. A microarray screen of kidney tissue from healthy mice identified 97 microRNAs that were enriched in the m itochondrial fraction. We focused on microRNA-214-3p (miR-214) because of a very high ratio of mitochondrial to cytoplasmic expression in the kidney compared to other organs. (Source: Kidney International)
Source: Kidney International - March 5, 2019 Category: Urology & Nephrology Authors: Mi Bai, Huimei Chen, Dan Ding, Ruihua Song, Jiajuan Lin, Yuanyuan Zhang, Yan Guo, Shuang Chen, Guixia Ding, Yue Zhang, Zhanjun Jia, Songming Huang, John Cijiang He, Li Yang, Aihua Zhang Tags: Basic Research Source Type: research

Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression
Human leukocyte antigen (HLA) mismatching and minimization of immunosuppression are two major risk factors for the development of de novo donor-specific antibodies, which are associated with reduced kidney graft survival. Antibodies do not recognize whole HLA antigens but rather individual epitopes, which are short sequences of amino acids in accessible positions. However, compatibility is still assessed by the simple count of mismatched HLA antigens. We hypothesized that the number of mismatched epitopes, or ( “epitope load”) would identify patients at the highest risk of developing donor specific antibodies f...
Source: Kidney International - March 5, 2019 Category: Urology & Nephrology Authors: Renaud Snanoudj, Nassim Kamar, Elisabeth Cassuto, Sophie Caillard, Marie Metzger, Pierre Merville, Antoine Thierry, Isabelle Jollet, Philippe Grimbert, Dany Anglicheau, Marc Hazzan, Gabriel Choukroun, Bruno Hurault De Ligny, B énedicte Janbon, Vincent Vu Tags: Clinical Investigation Source Type: research

CX3CL1 –CX3CR1 interaction mediates macrophage-mesothelial cross talk and promotes peritoneal fibrosis
Peritoneal dialysis (PD) is limited by chronic fibrotic remodeling of the peritoneal wall, a transforming growth factor- β (TGF-β)-mediated process. The fractalkine (CX3CL1) receptor CX3CR1 is expressed on macrophages and monocytes, where it is a marker of TGFβ expression. Detection of its ligand CX3CL1 on the peritoneal mesothelium led us to hypothesize a pathophysiologic role of CX3CL1-CX3CR1 interaction in perit oneal fibrosis. We found that CX3CL1 was expressed on peritoneal mesothelial cells from PD patients and in a murine PD model. (Source: Kidney International)
Source: Kidney International - March 5, 2019 Category: Urology & Nephrology Authors: Alexandra Helmke, Johannes Nordlohne, Michael S. Balzer, Lei Dong, Song Rong, Marcus Hiss, Nelli Shushakova, Hermann Haller, Sibylle von Vietinghoff Tags: Basic Research Source Type: research

Interaction between galectin-3 and cystinosin uncovers a pathogenic role of inflammation in kidney involvement of cystinosis
Inflammation is involved in the pathogenesis of many disorders. However, the underlying mechanisms are often unknown. Here, we test whether cystinosin, the protein involved in cystinosis, is a critical regulator of galectin-3, a member of the β-galactosidase binding protein family, during inflammation. Cystinosis is a lysosomal storage disorder and, despite ubiquitous expression of cystinosin, the kidney is the primary organ impacted by the disease. Cystinosin was found to enhance lysosomal localization and degradation of galectin-3. (Source: Kidney International)
Source: Kidney International - March 5, 2019 Category: Urology & Nephrology Authors: Tatiana Lobry, Roy Miller, Nathalie Nevo, Celine J. Rocca, Jinzhong Zhang, Sergio D. Catz, Fiona Moore, Lucie Thomas, Daniel Pouly, Anne Bailleux, Ida Chiara Guerrera, Marie-Claire Gubler, Cheung W. Wilson, Robert H. Mak, Tristan Montier, Corinne Antignac Tags: Basic Research Source Type: research

Mononuclear phagocytes orchestrate prolyl hydroxylase inhibition-mediated renoprotection in chronic tubulointerstitial nephritis
Prolyl hydroxylase domain enzyme inhibitors (PHDi) stabilize hypoxia-inducible factors (HIF), and are protective in models of acute ischemic and inflammatory kidney disease. Whether PHDi also confer protection in chronic inflammatory kidney disease models remains unknown. Here we investigated long-term effects of PHDi treatment in adenine-induced nephropathy as a model for chronic tubulointerstitial nephritis. After three weeks, renal dysfunction and tubulointerstitial damage, including proximal and distal tubular injury, tubular dilation and renal crystal deposition were significantly attenuated in PHDi-treated (the isoqu...
Source: Kidney International - March 5, 2019 Category: Urology & Nephrology Authors: Gunnar Schley, Bernd Klanke, Joanna Kalucka, Valentin Schatz, Christoph Daniel, Marleen Mayer, Margarete Goppelt-Struebe, Martin Herrmann, Margret Thorsteinsdottir, Runolfur Palsson, Angelika Beneke, D örthe M. Katschinski, Nicolai Burzlaff, Kai-Uwe Ecka Tags: Basic Research Source Type: research

Organelle crosstalk in the kidney
Organelle damage can cause various kidney diseases. In particular, organelle stress such as decreased proteostatic activity in the endoplasmic reticulum (ER) and altered energy metabolism in mitochondria contribute to glomerular and tubulointerstitial damage, resulting in the progression and development of kidney diseases. The ER regulates protein quality control via the unfolded protein response (UPR) pathway. Pathogenic ER stress leads to dysregulation of this pathway, and a maladaptive UPR is highly deleterious to renal cell function, and thereby has been implicated in the pathophysiology of various kidney diseases. (So...
Source: Kidney International - March 4, 2019 Category: Urology & Nephrology Authors: Tsuyoshi Inoue, Hiroshi Maekawa, Reiko Inagi Tags: Review Source Type: research

Innovations in vascular access for hemodialysis
Worldwide, hemodialysis remains the prevalent dialysis modality for more than 2 million patients who require well-functioning vascular access for this procedure. Creation of an arteriovenous fistula for long-term hemodialysis was the first innovation since the Scribner shunt and was followed by the development of an arteriovenous graft and catheter. Bioengineered vessels were developed during the last century, but this field has been energized by recent technology relating to the creation of human vessels. (Source: Kidney International)
Source: Kidney International - March 4, 2019 Category: Urology & Nephrology Authors: Anil K. Agarwal, Nabil J. Haddad, Tushar J. Vachharajani, Arif Asif Tags: Review Source Type: research

Long-term trajectory of kidney function in autosomal-dominant polycystic kidney disease
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cyst and kidney growth, which is hypothesized to cause loss of functioning renal mass and eventually end-stage kidney disease. However, the time course of decline in glomerular filtration rate (GFR) is poorly defined. The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease study is a 14-year observational cohort study of 241 adults with ADPKD. As an estimate of the rate of kidney growth, participants were stratified into 5 subclasses based on baseline age and magnetic resonance imaging measurements of total kidney volume (TKV) accor...
Source: Kidney International - March 4, 2019 Category: Urology & Nephrology Authors: Alan S.L. Yu, Chengli Shen, Douglas P. Landsittel, Jared J. Grantham, Larry T. Cook, Vicente E. Torres, Arlene B. Chapman, Kyongtae Ty Bae, Michal Mrug, Peter C. Harris, Frederic F. Rahbari-Oskoui, Tiange Shi, William M. Bennett, Consortium for Radiologic Tags: Clinical Investigation Source Type: research

Bone mineral density, bone turnover markers, and  incident fractures in de novo kidney transplant recipients
Kidney transplant recipients are at increased risk of fractures. This prospective observational study investigated whether areal bone mineral density (aBMD) as assessed by dual-energy x-ray absorptiometry can predict incident fragility fractures in de novo kidney transplant recipients and whether bone turnover markers increase diagnostic accuracy. Parameters of bone mineral metabolism including parathyroid hormone (PTH), fibroblast growth factor 23, sclerostin, calcidiol and calcitriol, and bone turnover markers were assessed in blood samples collected immediately prior to kidney transplantation in 518 adult recipients. (S...
Source: Kidney International - March 4, 2019 Category: Urology & Nephrology Authors: Pieter Evenepoel, Kathleen Claes, Bjorn Meijers, Micha ël R. Laurent, Bert Bammens, Maarten Naesens, Ben Sprangers, Hans Pottel, Etienne Cavalier, Dirk Kuypers Tags: Clinical Investigation Source Type: research

Multifactorial functions of the inflammasome component NLRP3 in pathogenesis of chronic kidney diseases
The NLRP3 inflammasome is a cytosolic multiprotein caspase-activating complex platform involved in innate immunity required for the maturation and release of interleukin (IL)-1 β and IL-18. Both cytokines activate their respective receptors present on cells inside and outside kidneys, resulting in the release of other proinflammatory cytokines to set up an inflammatory milieu both within the kidney and systemically. The canonical NLRP3–ASC–caspase-1–IL-1β–IL-18 a xis has been shown to contribute to the pathophysiology of several kidney diseases by regulating renal necroinflammation. (Sourc...
Source: Kidney International - March 4, 2019 Category: Urology & Nephrology Authors: Shrikant R. Mulay Tags: Review Source Type: research

Fluid management in the critically ill
Fluid therapy, which is provided to restore and maintain tissue perfusion, is part of routine management for almost all critically ill patients. However, because either too much or too little fluid can have a negative impact on patient outcomes, fluid administration must be titrated carefully for each patient. The “salvage, optimization, stabilization, de-escalation” (SOSD) mnemonic should be used as a general guide to fluid resuscitation, and fluid administration should be adapted according to the course of the disease. (Source: Kidney International)
Source: Kidney International - March 4, 2019 Category: Urology & Nephrology Authors: Jean-Louis Vincent Tags: Review Source Type: research

Big science and big data in nephrology
There have been tremendous advances during the last decade in methods for large-scale, high-throughput data generation and in novel computational approaches to analyze these datasets. These advances have had a profound impact on biomedical research and clinical medicine. The field of genomics is rapidly developing toward single-cell analysis, and major advances in proteomics and metabolomics have been made in recent years. The developments on wearables and electronic health records are poised to change clinical trial design. (Source: Kidney International)
Source: Kidney International - March 4, 2019 Category: Urology & Nephrology Authors: Julio Saez-Rodriguez, Markus M. Rinschen, J ürgen Floege, Rafael Kramann Tags: Review Source Type: research

Poor accordance to a DASH dietary pattern is associated with higher risk of ESRD among adults with moderate chronic kidney disease and hypertension
We examined whether a DASH diet is associated with lower risk of ESRD among 1,110 adults aged  ≥ 20 years with hypertension and CKD (estimated glomerular filtration rate, eGFR 30-59 ml/min/1.73 m2) enrolled in the National Health and Nutrition Examination Survey (1988-1994). (Source: Kidney International)
Source: Kidney International - March 4, 2019 Category: Urology & Nephrology Authors: Tanushree Banerjee, Deidra C. Crews, Delphine S. Tuot, Meda E. Pavkov, Nilka Rios Burrows, Austin G. Stack, Rajiv Saran, Jennifer Bragg-Gresham, Neil R. Powe, Centers for Disease Control and Prevention Chronic Kidney Disease Surveillance Team Tags: Clinical Investigation Source Type: research

The C5a/C5aR1 axis promotes progression of renal tubulointerstitial fibrosis in a mouse model of renal ischemia/reperfusion injury
C5a is a potent proinflammatory agonist that mediates renal ischemia/reperfusion injury, but the potential for modulating chronic post-ischemic fibrosis and use of therapeutic antagonist are undefined. Here we determine whether C5a receptor 1 (C5aR1) signaling is essential to the development of post-ischemic fibrosis and if it is a valid target for therapeutic blockade with soluble receptor antagonist. C5aR1 is required for the development of renal tubulointerstitial fibrosis in a murine model of renal ischemia/reperfusion injury. (Source: Kidney International)
Source: Kidney International - March 4, 2019 Category: Urology & Nephrology Authors: Qi Peng, Weiju Wu, Kun-Yi Wu, Bo Cao, Cui Qiang, Ke Li, Steven H. Sacks, Wuding Zhou Tags: Basic Research Source Type: research

The motor protein Myo1c regulates transforming growth factor- β-signaling and fibrosis in podocytes
Transforming growth factor- β (TGF-β) is known to play a critical role in the pathogenesis of many progressive podocyte diseases. However, the molecular mechanisms regulating TGF-β signaling in podocytes remain unclear. Using a podocyte-specific Myo1c knockout, we demonstrate whether Myo1c is critical for TGF-β-signaling i n podocyte disease pathogenesis. Specifically, podocyte-specific Myo1c knockout mice were resistant to fibrotic injury induced by Adriamycin or nephrotoxic serum. Further, loss of Myo1c also protected from injury in the TGF-β-dependent unilateral ureteral obstruction mouse model ...
Source: Kidney International - March 4, 2019 Category: Urology & Nephrology Authors: Ehtesham Arif, Ashish K. Solanki, Pankaj Srivastava, Bushra Rahman, Brian R. Tash, Lawrence B. Holzman, Michael G. Janech, Ren é Martin, Hans-Joachim Knölker, Wayne R. Fitzgibbon, Peifeng Deng, Milos N. Budisavljevic, Wing-Kin Syn, Cindy Wang, Joshua H. Tags: Basic Research Source Type: research

RNA-Seq and protein mass spectrometry in microdissected kidney tubules reveal signaling processes initiating lithium-induced nephrogenic diabetes insipidus
Lithium salts, used for treating bipolar disorder, frequently induce nephrogenic diabetes insipidus (NDI) thereby limiting therapeutic success. NDI is associated with loss of expression of the gene coding for the molecular water channel, aquaporin-2, in the renal collecting duct (CD). Here, we use systems biology methods in a well-established rat model of lithium-induced NDI to identify signaling pathways activated at the onset of polyuria. Using single-tubule RNA-Seq, full transcriptomes were determined in microdissected cortical collecting ducts of rats after 72 hours without or with initiation of lithium chloride admini...
Source: Kidney International - March 4, 2019 Category: Urology & Nephrology Authors: Chih-Chien Sung, Lihe Chen, Kavee Limbutara, Hyun Jun Jung, Gabrielle G. Gilmer, Chin-Rang Yang, Shih-Hua Lin, Sookkasem Khositseth, Chung-Lin Chou, Mark A. Knepper Tags: Basic Research Source Type: research

Proteomic analysis of neutrophils in ANCA-associated vasculitis reveals a dysregulation in proteinase 3-associated proteins such as annexin-A1 involved in apoptotic cell clearance
Granulomatosis with polyangiitis (GPA) is an autoimmune vasculitis associated with anti-neutrophil-cytoplasmic antibodies (ANCA) against proteinase 3 leading to kidney damage. Neutrophils from those patients have increased expression of membrane proteinase 3 during apoptosis. Here we examined whether neutrophils from patients with GPA have dysregulated protein expressions associated with apoptosis. A global proteomic analysis was performed comparing neutrophils from patients with GPA, with healthy individuals under basal conditions and during apoptosis. (Source: Kidney International)
Source: Kidney International - March 4, 2019 Category: Urology & Nephrology Authors: Judith Everts-Graber, Katherine R. Martin, Nathalie Thieblemont, Julie Mocek, Arnaud Roccabianca, Philippe Chafey, Morgane le Gall, Pascale Tacnet-Delorme, Chris Reutelingsperger, Jean-Marc Naccache, Bernard Bonnotte, Alexandre Karras, Xavier Pu échal, L Tags: Basic Research Source Type: research

The effect of dry-weight reduction guided by lung ultrasound on ambulatory blood pressure in hemodialysis patients: a randomized controlled trial
Approximately 85% of hemodialysis patients are hypertensive, but less than 30% achieve adequate blood pressure (BP) control. Reduction of volume overload is fundamental for BP control, but clinical criteria to estimate dry-weight are inaccurate. In the present study we examined the effect of dry-weight reduction with a lung-ultrasound-guided strategy on ambulatory BP in 71 clinically euvolemic hemodialysis patients with hypertension. Patients were equally randomized into an active group, following a strategy for dry-weight reduction guided by pre-hemodialysis lung ultrasound, and a control group with standard-of-care treat...
Source: Kidney International - March 4, 2019 Category: Urology & Nephrology Authors: Charalampos Loutradis, Pantelis A. Sarafidis, Robert Ekart, Christodoulos Papadopoulos, Vasileios Sachpekidis, Maria Eleni Alexandrou, Dorothea Papadopoulou, Giorgos Efstratiadis, Aikaterini Papagianni, Gerard London, Carmine Zoccali Tags: Clinical Trial Source Type: research

An open-label, randomized trial indicates that everolimus with tacrolimus or cyclosporine is comparable to standard immunosuppression in de novo kidney transplant patients
This is a randomized trial (ATHENA study) in de novo kidney transplant patients to compare everolimus versus mycophenolic acid (MPA) with similar tacrolimus exposure in both groups, or everolimus with concomitant tacrolimus or cyclosporine (CsA), in an unselected population. In this 12-month, multicenter, open-label study, de novo kidney transplant recipients were randomized to everolimus with tacrolimus (EVR/TAC), everolimus with CsA (EVR/CsA) or MPA with tacrolimus (MPA/TAC), with similar tacrolimus exposure in both groups. (Source: Kidney International)
Source: Kidney International - March 1, 2019 Category: Urology & Nephrology Authors: Claudia Sommerer, Barbara Suwelack, Duska Dragun, Peter Schenker, Ingeborg A. Hauser, Oliver Witzke, Christian Hugo, Nassim Kamar, Pierre Merville, Martina Junge, Friedrich Thaiss, Bj örn Nashan, Athena Study Group Tags: Clinical Trial Source Type: research