Nephrology Dialysis Transplantation




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Estimating tubular damage for predicting progression of chronic kidney disease—what are the implications for clinical practice and public health? 

Christoph Nowak, Johan Ärnlöv

doi : 10.1093/ndt/gfab009

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1769–1770

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Should renin–angiotensin–aldosterone system inhibition enablement be a therapeutic target in CKD patients?

Patrick Rossignol, Rajiv Agarwal

doi : 10.1093/ndt/gfab061

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1771–1772

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Idiopathic retroperitoneal fibrosis: an update for nephrologists

Valentina Raglianti, Giovanni M. Rossi, Augusto Vaglio

doi : 10.1093/ndt/gfaa083

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1773–1781

Idiopathic retroperitoneal fibrosis (IRF) is a rare condition characterized by the development of a peri-aortic and peri-iliac tissue showing chronic inflammatory infiltrates and pronounced fibrosis. Ureteral entrapment with consequent obstructive uropathy is one of the most common complications of IRF, which can lead to acute renal failure and, in the long term, to varying degrees of chronic kidney disease. IRF may be isolated or develop in association with autoimmune diseases (e.g. Hashimoto’s thyroiditis and psoriasis) and other fibro-inflammatory disorders (often within the spectrum of immunoglobulin G4-related disease), which suggests that it should be considered as a potentially systemic condition. IRF is an immune-mediated disease: genetic variants (e.g. human leukocyte antigen (HLA)-DRB1*03) and environmental agents (mainly exposure to asbestos and smoking) are strongly associated with an increased risk of developing the disease, while a complex network of chemokines (e.g. CXCL12 and C-C moti chemokine 11 (CCL11)) and cytokines [e.g. interleukin (IL)-6, IL-12 and IL-13] is likely to orchestrate the inflammatory response and simultaneously promote fibrosis. Glucocorticoids, alone or in combination with traditional immunosuppressants such as methotrexate and mycophenolate mofetil, are usually efficacious and promptly induce disease remission; however, up to 50% of patients relapse, thus requiring repeat immunosuppressive courses. Biologic drugs, namely rituximab, are being explored for the treatment of IRF. In addition to medical therapies, interventional procedures (mainly ureteral stenting) are required to relieve ureteral obstruction, whereas surgical ureterolysis is generally reserved to refractory cases. If appropriately treated, then the overall and renal prognosis of IRF are good, with <5% patients developing end-stage renal disease.

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Hypoxia in chronic kidney disease: towards a paradigm shift?

Anna Faivre, Carsten C. Scholz, Sophie de Seigneux

doi : 10.1093/ndt/gfaa091

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1782–1790

Chronic kidney disease (CKD) is defined as an alteration of kidney structure and/or function lasting for >3?months [1]. CKD affects 10% of the general adult population and is responsible for large healthcare costs [2]. Since the end of the last century, the role of hypoxia in CKD progression has controversially been discussed. To date, there is evidence of the presence of hypoxia in late-stage renal disease, but we lack time-course evidence, stage correlation and also spatial co-localization with fibrotic lesions to ensure its causative role. The classical view of hypoxia in CKD progression is that it is caused by peritubular capillary alterations, renal anaemia and increased oxygen consumption regardless of the primary injury. In this classical view, hypoxia is assumed to further induce pro-fibrotic and pro-inflammatory responses, as well as oxidative stress, leading to CKD worsening as part of a vicious circle. However, recent investigations tend to question this paradigm, and both the presence of hypoxia and its role in CKD progression are still not clearly demonstrated. Hypoxia-inducible factor (HIF) is the main transcriptional regulator of the hypoxia response. Genetic HIF modulation leads to variable effects on CKD progression in different murine models. In contrast, pharmacological modulation of the HIF pathway [i.e. by HIF hydroxylase inhibitors (HIs)] appears to be generally protective against fibrosis progression experimentally. We here review the existing literature on the role of hypoxia, the HIF pathway and HIF HIs in CKD progression and summarize the evidence that supports or rejects the hypoxia hypothesis, respectively.

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The consequences of altered microbiota in immune-related chronic kidney disease

Wei Ling Lau, Yongen Chang, Nosratola D. Vaziri

doi : 10.1093/ndt/gfaa087

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1791–1798

The normal gut microbiome modulates host enterocyte metabolism and shapes local and systemic immunity. Accumulation of urea and other waste products in chronic kidney disease induces gut dysbiosis and intestinal wall inflammation (leaky gut). There are decreased numbers of bacteria that generate short-chain fatty acids, which are an important nutrient source for host enterocytes and also contribute to regulation of the host immune system. Anaerobic proteolytic bacteria that express urease, uricase and indole and p-cresol enzymes, such as Enterobacteria and Enterococci, are increased. Microbial-derived uremic toxins such as indoxyl sulfate and trimethylamine N-oxide contribute to the pathophysiology of immune-related kidney diseases such as diabetic nephropathy, lupus nephritis and immunoglobulin A (IgA) nephropathy. Animal and clinical studies suggest potential benefits of dietary and probiotic interventions in slowing the progression of immune-related kidney diseases.

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Acute interstitial nephritis: aetiology and management

Juliet Schurder, David Buob, Peggy Perrin, Eric Thervet, Alexandre Karras, Alexandre Hertig

doi : 10.1093/ndt/gfz262

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1799–1802

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Glomerular disease in children: when to biopsy

Scott T. McEwen, Michelle N. Rheault

doi : 10.1093/ndt/gfz280

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1803–1805

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Acidosis and alkali therapy in patients with kidney transplant is associated with transcriptional changes and altered abundance of genes involved in cell metabolism and acid–base balance

Pedro H Imenez Silva, Anna Wiegand, Arezoo Daryadel, Giancarlo Russo, Alexander Ritter, Ariana Gaspert, Rudolf P Wüthrich, Carsten A Wagner, Nilufar Mohebbi

doi : 10.1093/ndt/gfab210

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1806–1820

Metabolic acidosis occurs frequently in patients with kidney transplant and is associated with a higher risk for and accelerated loss of graft function. To date, it is not known whether alkali therapy in these patients improves kidney function and whether acidosis and its therapy are associated with altered expression of proteins involved in renal acid–base metabolism.

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Comparison of treatment options in adults with frequently relapsing or steroid-dependent minimal change disease

Cihan Heybeli, Stephen B Erickson, Fernando C Fervenza, Marie C Hogan, Ladan Zand, Nelson Leung

doi : 10.1093/ndt/gfaa133

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1821–1827

Studies comparing all treatment options for frequently-relapsing/steroid-dependent (FR/SD) minimal change disease (MCD) in adults are lacking.

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Thiazide diuretics and the rate of disease progression in autosomal dominant polycystic kidney disease: an observational study 

Bart J Kramers, Iris W Koorevaar, Rudolf De Boer, Ewout J Hoorn, Michelle J Pena, Ron T Gansevoort, Esther Meijer, the DIPAK Consortium

doi : 10.1093/ndt/gfaa150

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1828–1836

In autosomal dominant polycystic kidney disease (ADPKD), hypertension is prevalent and cardiovascular events are the main cause of death. Thiazide diuretics are often prescribed as second-line antihypertensives, on top of renin–angiotensin–aldosterone system (RAAS) blockade. There is a concern, however, that diuretics may increase vasopressin concentration and RAAS activity, thereby worsening disease progression in ADPKD. We aimed to investigate the validity of these suggestions.

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Prognostic models for chronic kidney disease: a systematic review and external validation

Marieke H C van Rijn, Moniek van de Luijtgaarden, Arjan D van Zuilen, Peter J Blankestijn, Jack F M Wetzels, Thomas P A Debray, Jan A J G van den Brand

doi : 10.1093/ndt/gfaa155

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1837–1850

Accurate risk prediction is needed in order to provide personalized healthcare for chronic kidney disease (CKD) patients. An overload of prognosis studies is being published, ranging from individual biomarker studies to full prediction studies. We aim to systematically appraise published prognosis studies investigating multiple biomarkers and their role in risk predictions. Our primary objective was to investigate if the prognostic models that are reported in the literature were of sufficient quality and to externally validate them.

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Urine interleukin-9 and tumor necrosis factor-? for prognosis of human acute interstitial nephritis

Dennis G Moledina, F Perry Wilson, Lidiya Kukova, Wassim Obeid, Randy Luciano, Michael Kuperman, Gilbert W Moeckel, Michael Kashgarian, Mark A Perazella, Lloyd G Cantley, Chirag R Parikh

doi : 10.1093/ndt/gfaa169

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1851–1858

We previously demonstrated that urine interleukin (IL)-9 and tumor necrosis factor (TNF)-? can distinguish acute interstitial nephritis (AIN) from other causes of acute kidney injury. Here we evaluated the role of these biomarkers to prognosticate kidney function in patients with AIN.

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Differential metabolomic signatures of declining renal function in Types 1 and 2 diabetes

Maria Laura Manca, Anna Solini, Jani K Haukka, Niina Sandholm, Carol Forsblom, Per-Henrik Groop, Ele Ferrannini

doi : 10.1093/ndt/gfaa175

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1859–1866

Chronic kidney disease (CKD) shows different clinical features in Types1 (T1D) and 2 diabetes (T2D). Metabolomics have recently provided useful contribution to the identification of biomarkers of CKD progression in either form of the disease. However, no studies have so far compared plasma metabolomics between T1D and T2D in order to identify differential signatures of progression of estimated glomerular filtration rate (eGFR) decline.

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Acute hepatitis C treatment in advanced renal failure using 8 weeks of pan-genotypic daclatasvir and reduced-dose sofosbuvir

Amit Goel, Dharmendra S Bhadauria, Anupma Kaul, Abhai Verma, Prachi Tiwari, Sumit Rungta, Praveer Rai, Amit Gupta, Rakesh Aggarwal

doi : 10.1093/ndt/gfaa187

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1867–1871

Sofosbuvir is not recommended in persons with estimated glomerular filtration rate (eGFR) <30?mL/min. We report the results of treatment with an off-label 8-week regimen of daclatasvir and half-dose sofosbuvir in patients with acute infection with hepatitis C virus ( HCV) and eGFR <30?mL/min.

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Routine serum biomarkers, but not dual-energy X-ray absorptiometry, correlate with cortical bone mineral density in children and young adults with chronic kidney disease

Alexander D Lalayiannis, Nicola J Crabtree, Charles J Ferro, Varvara Askiti, Andromachi Mitsioni, Lorenzo Biassoni, Amrit Kaur, Manish D Sinha, David C Wheeler, Neill D Duncan, Joyce Popoola, David V Milford, Jin Long, Mary Beth Leonard, Mary Fewtrell, Rukshana Shroff

doi : 10.1093/ndt/gfaa199

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1872–1881

Biomarkers and dual-energy X-ray absorptiometry (DXA) are thought to be poor predictors of bone mineral density (BMD). The Kidney Disease: Improving Global Outcomes guidelines suggest using DXA if the results will affect patient management, but this has not been studied in children or young adults in whom bone mineral accretion continues to 30?years of age. We studied the clinical utility of DXA and serum biomarkers against tibial cortical BMD (CortBMD) measured by peripheral quantitative computed tomography, expressed as Z-score CortBMD, which predicts fracture risk.

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Urinary excretion of epidermal growth factor and rapid loss of kidney function

Jon Viljar Norvik, Laura R Harskamp, Viji Nair, Kerby Shedden, Marit D Solbu, Bjørn O Eriksen, Matthias Kretzler, Ron T Gansevoort, Wenjun Ju, Toralf Melsom

doi : 10.1093/ndt/gfaa208

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1882–1892

Lower urinary excretion of the kidney tubule–specific biomarker epidermal growth factor (uEGF) is associated with increased risk of renal function [glomerular filtration rate (GFR)] loss in diabetes and in patients with established chronic kidney disease (CKD). We investigated whether uEGF is associated with rapid GFR decline or incident CKD in the general population.

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Renin–angiotensin system blocker discontinuation and adverse outcomes in chronic kidney disease

Carl P Walther, Wolfgang C Winkelmayer, Peter A Richardson, Salim S Virani, Sankar D Navaneethan

doi : 10.1093/ndt/gfaa300

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1893–1899

Treatment with renin–angiotensin system inhibitors (RASIs), angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) is the standard of care for those with chronic kidney disease (CKD) and albuminuria. However, ACEI/ARB treatment is often discontinued for various reasons. We investigated the association of ACEI/ARB discontinuation with outcomes among US veterans with non-dialysis-dependent CKD.

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Hypocalcemia and bone mineral changes in hemodialysis patients with low bone mass treated with denosumab: a 2-year observational study 

Rikako Hiramatsu, Yoshifumi Ubara, Naoki Sawa, Akinori Sakai

doi : 10.1093/ndt/gfaa359

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1900–1907

Increases in bone mineral density (BMD) following a single dose of denosumab and increased incidence of denosumab-associated acute hypocalcemia (DAAH) have been reported in chronic kidney disease patients. Little is known about clinical risk factors related to DAAH and the long-term effect of denosumab on BMD in hemodialysis patients.

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Dynapaenia and sarcopaenia in chronic haemodialysis patients: do muscle weakness and atrophy similarly influence poor outcome?

Jean-Sébastien Souweine, Grégoire Pasquier, Nils Kuster, Annie Rodriguez, Laure Patrier, Marion Morena, Eric Badia, Fabrice Raynaud, Lotfi Chalabi, Nathalie Raynal, Isabelle Ohresser, Maurice Hayot, Jacques Mercier, Moglie Le Quintrec, Fares Gouzi, Jean-Paul Cristol

doi : 10.1093/ndt/gfaa353

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1908–1918

Sarcopaenia, defined as a decline in both muscle mass and function, has been recognized as a major determinant of poor outcome in haemodialysis (HD) patients. It is generally assumed that sarcopaenia is driven by muscle atrophy related to protein-energy wasting. However, dynapaenia, defined as weakness without atrophy, has been characterized by a different disease phenotype from sarcopaenia. The aim of this study was to compare the characteristics and prognosis of sarcopaenic and dynapaenic patients among a prospective cohort of chronic HD (CHD) patients.

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Using a generic definition of cachexia in patients with kidney disease receiving haemodialysis: a longitudinal (pilot) study

Clare McKeaveney, Adrian Slee, Gary Adamson, Andrew Davenport, Ken Farrington, Denis Fouque, Kamyar Kalantar-Zadeh, John Mallett, Alexander P Maxwell, Robert Mullan, Helen Noble, Donal O’Donoghue, Sam Porter, David S Seres, Joanne Shields, Miles Witham, Joanne Reid

doi : 10.1093/ndt/gfaa174

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1919–1926

Research indicates that cachexia is common among persons with chronic illnesses and is associated with increased morbidity and mortality. However, there continues to be an absence of a uniformed disease-specific definition for cachexia in chronic kidney disease (CKD) patient populations.

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Pre-kidney transplant unintentional weight loss leads to worse post-kidney transplant outcomes

Meera N Harhay, Xiaomeng Chen, Nadia M Chu, Silas P Norman, Dorry L Segev, Mara McAdams-DeMarco

doi : 10.1093/ndt/gfab164

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1927–1936

Weight loss before kidney transplant (KT) is a known risk factor for weight gain and mortality, however, while unintentional weight loss is a marker of vulnerability, intentional weight loss might improve health. We tested whether pre-KT unintentional and intentional weight loss have differing associations with post-KT weight gain, graft loss and mortality.

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Multicenter registry analysis comparing survival on home hemodialysis and kidney transplant recipients in Australia and New Zealand

Isabelle Ethier, Yeoungjee Cho, Carmel Hawley, Elaine M Pascoe, Matthew A Roberts, David Semple, Annie-Claire Nadeau-Fredette, Germaine Wong, Wai H Lim, Matthew P Sypek, Andrea K Viecelli, Scott Campbell, Carolyn van Eps, Nicole M Isbel, David W Johnson

doi : 10.1093/ndt/gfaa159

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1937–1946

In the era of organ shortage, home hemodialysis (HHD) has been identified as the possible preferential bridge to kidney transplantation. Data are conflicting regarding the comparability of HHD and transplantation outcomes. This study aimed to compare patient and treatment survival between HHD patients and kidney transplant recipients.

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COVID-19 vaccination in haemodialysis patients: good things come in threes… 

Luc Frantzen, Sandrine Thibeaut, Julie Moussi-Frances, Monica Indreies, Clotilde Kiener, Yannick Saingra, Julien Santini, Paul Stroumza, Yohan El-Haik, Guilhem Cavaillé

doi : 10.1093/ndt/gfab224

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1947–1949

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SARS-CoV-2 vaccination in patients receiving kidney replacement therapies: where are we now with the protective immune response? 

Nestor Toapanta, Oriol Bestard, María José Soler

doi : 10.1093/ndt/gfab227

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1950–1954

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Amoxicillin crystalluria is associated with acute kidney injury in patients treated for acute infective endocarditis

Matthieu Jamme, Leopold Oliver, Julien Ternacle, Raphael Lepeule, Amina Moussafeur, Jean-Philippe Haymann, Sovannarith San, Antonio Fiore, Nicolas Mongardon, Michel Daudon, Pascal Lim, Emmanuel Letavernier

doi : 10.1093/ndt/gfab074

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1955–1958

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Changing the choice from dialysis to conservative care or vice versa in older patients with advanced chronic kidney disease 

Carlijn G N Voorend, Wouter R Verberne, Mathijs van Oevelen, Yvette Meuleman, Marjolijn van Buren, Willem Jan W Bos

doi : 10.1093/ndt/gfab162

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Pages 1958–1961

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Errata 

Dirk J W den Braanker, Rutger J Maas, Jeroen K Deegens, Cansu Yanginlar, Jack F M Wetzels, Johan van der Vlag, Tom Nijenhuis

doi : 10.1093/ndt/gfab021

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Page 1962

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Erratum to: COVID-19-related mortality in kidney transplant and dialysis patients: results of the ERACODA collaboration 

Luuk B Hilbrands, Raphaël Duivenvoorden, Priya Vart, Casper F M Franssen, Marc H Hemmelder, Kitty J Jager, Lyanne M Kieneker, Marlies Noordzij, Michelle J Pena, Hanne de Vries, David Arroyo, Adrian Covic, Marta Crespo, Eric Goffin, Mahmud Islam, Ziad A Massy, Nuria Montero, João P Oliveira, Ana Roca Muñoz, J Emilio Sanchez, Sivakumar Sridharan, Rebecca Winzeler, Ron T Gansevoort, ERACODA Collaborators

doi : 10.1093/ndt/gfab028

Nephrology Dialysis Transplantation, Volume 36, Issue 10, October 2021, Page 1962

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