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Drug repurposing in autosomal dominant polycystic kidney disease: back to the future with pioglitazone
Zhiguo Mao, Manoj K Valluru, Albert C M Ong
doi : 10.1093/ckj/sfab062
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1715–1718
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of end-stage kidney failure. At present, only one drug, tolvaptan, has been approved for use to slow disease progression, but its use is limited by reduced tolerability and idiosyncratic liver toxicity. Thiazolidinediones were first developed as insulin-sensitizers but also regulate gene transcription in multiple tissues, leading to systemic effects on metabolism, inflammation and vascular reactivity. In this issue, Blazer-Yost et al. report the results of a single-centre Phase 1b double-blind placebo-controlled crossover study of the peroxisome proliferator-activated receptor ? (PPAR-?) agonist pioglitazone in 18 ADPKD patients. Encouragingly, there were no major safety signals, although evidence of efficacy could not be demonstrated due to the small sample size. We review the preclinical evidence for the use of PPAR-? agonists in ADPKD and speculate on the likely beneficial and adverse clinical effects of this interesting class of compounds in a future trial.
Fighting the unbearable lightness of neglecting kidney health: the decade of the kidney*
Raymond Vanholder, Lieven Annemans, Aminu K Bello, Boris Bikbov, Daniel Gallego, Ron T Gansevoort, Norbert Lameire, Valerie A Luyckx, Edita Noruisiene, Tom Oostrom, Christoph Wanner, Fokko Wieringa
doi : 10.1093/ckj/sfab070
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1719–1730
A brief comprehensive overview is provided of the elements constituting the burden of kidney disease [chronic kidney disease (CKD) and acute kidney injury]. This publication can be used for advocacy, emphasizing the importance and urgency of reducing this heavy and rapidly growing burden. Kidney diseases contribute to significant physical limitations, loss of quality of life, emotional and cognitive disorders, social isolation and premature death. CKD affects close to 100 million Europeans, with 300 million being at risk, and is projected to become the fifth cause of worldwide death by 2040. Kidney disease also imposes financial burdens, given the costs of accessing healthcare and inability to work. The extrapolated annual cost of all CKD is at least as high as that for cancer or diabetes. In addition, dialysis treatment of kidney diseases imposes environmental burdens by necessitating high energy and water consumption and producing plastic waste. Acute kidney injury is associated with further increases in global morbidity, mortality and economic burden. Yet investment in research for treatment of kidney disease lags behind that of other diseases. This publication is a call for European investment in research for kidney health. The innovations generated should mirror the successful European Union actions against cancer over the last 30?years. It is also a plea to nephrology professionals, patients and their families, caregivers and kidney health advocacy organizations to draw, during the Decade of the Kidney (2020–30), the attention of authorities to realize changes in understanding, research and treatment of kidney disease.
Step-by-step guide to setting up a kidney replacement therapy registry: the challenge of a national kidney replacement therapy registry
Guillermo Rosa-Diez, Mar?a Carlota Gonz?lez-Bedat, Rosario Luxardo, Mar?a Laura Ceretta, Alejandro Ferreiro-Fuentes
doi : 10.1093/ckj/sfab015
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1731–1737
Chronic kidney disease (CKD) has become one of the most important public health problems worldwide. Analysis, and understanding, of this global/national/regional reality would benefit from renal registry databases. The implementation of a CKD registry (including all categories) is difficult to achieve, given its high cost. On the other hand, patients with end-stage kidney disease (ESKD) are easily accessible and constitute the most severe subgroup in terms of comorbidities and healthcare costs. A kidney replacement therapy registry (KRTR) is defined as the systematic and continuous collection of a population-based data set from ESKD patients treated by dialysis/kidney transplant. The lack of available data, particularly in emerging economies, leaves information gaps on healthcare and outcomes in these patients. The heterogeneity/absence of a KRTR in some countries is consistent with the inequities in access to KRT worldwide. In 2014, the Pan American Health Organization (PAHO) proposed to determine the prevalence of patients on dialysis for at least 700 patients per million inhabitants by 2019 in every Latin American (LA) country. Since then, PAHO and the Sociedad LatinoAmericana de Nefrolog?a e Hipertensi?n have provided training courses and certification of KRTR in LA. The purpose of this manuscript is to provide guidance on how to set up a new KRTR in countries or regions that still lack one. Advice is provided on the sequential steps in the process of setting up a KRTR, personnel requirements, data set content and minimum quality indicators required.
A randomized phase 1b cross-over study of the safety of low-dose pioglitazone for treatment of autosomal dominant polycystic kidney disease
Bonnie L Blazer-Yost, Robert L Bacallao, Bradley J Erickson, Michelle L LaPradd, Marie E Edwards, Nehal Sheth, Kim Swinney, Kristen M Ponsler-Sipes, Ranjani N Moorthi, Susan M Perkins, Vicente E Torres, Sharon M Moe
doi : 10.1093/ckj/sfaa232
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1738–1746
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common monogenetic disorders in humans and is characterized by numerous fluid-filled cysts that grow slowly, resulting in end-stage renal disease in the majority of patients. Preclinical studies have indicated that treatment with low-dose thiazolidinediones, such as pioglitazone, decrease cyst growth in rodent models of PKD.
The arteriovenous access stage (AVAS) classification
Peter Bal??, Jennifer Hanko, Hannah Magowan, Agnes Masengu, Katarina Lawrie, Stephen O’Neill
doi : 10.1093/ckj/sfaa189
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1747–1751
Key anatomical factors mean that individuals needing arteriovenous access are unique and have different possibilities for fistula creation. The aim of this article is to describe a new classification system for all patients needing haemodialysis vascular access in the upper extremity with the purpose to simplify sharing the information about suitability for surgical access creation depending on vascular anatomy.
How biocompatible haemodialysers can conquer the need for systemic anticoagulation even in post-dilution haemodiafiltration: a cross-over study
Floris Vanommeslaeghe, Iv?n Josipovic, Matthieu Boone, Arjan van der Tol, Annemie Dhondt, Wim Van Biesen, Sunny Eloot
doi : 10.1093/ckj/sfaa219
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1752–1759
While systemic anticoagulation is most widely used in haemodialysis (HD), contraindications to its use might occur in particular settings. The Solacea™ haemodialyser with an asymmetric triacetate membrane claims improved biocompatibility and has already shown promising results when used in combination with only half dose of anticoagulation. To quantify the performance of the Solacea™ when further decreasing anticoagulation to zero, fibre blocking was assessed by micro-computed tomography (micro-CT).
Hyperkalemia excursions are associated with an increased risk of mortality and hospitalizations in hemodialysis patients
Angelo Karaboyas, Bruce M Robinson, Glen James, Katarina Hedman, Carol P Moreno Quinn, Patricia De Sequera, Kosaku Nitta, Roberto Pecoits-Filho
doi : 10.1093/ckj/sfaa208
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1760–1769
Hyperkalemia is common among hemodialysis (HD) patients and has been associated with adverse clinical outcomes. Previous studies considered a single serum potassium (K) measurement or time-averaged values, but serum K excursions out of the target range may be more reflective of true hyperkalemia events. We assessed whether hyperkalemia excursions lead to an elevated risk of adverse clinical outcomes.
Real-world safety and effectiveness of sucroferric oxyhydroxide for treatment of hyperphosphataemia in dialysis patients: a prospective observational study
Marc G Vervloet, Ioannis N Boletis, Angel L M de Francisco, Philip A Kalra, Markus Ketteler, Piergiorgio Messa, Manuela Stauss-Grabo, Anja Derlet, Sebastian Walpen, Amandine Perrin, Linda H Ficociello, Jacques Rottembourg, Christoph Wanner, Jorge B Cannata-And?a, Denis Fouque
doi : 10.1093/ckj/sfaa211
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1770–1779
The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), is indicated to control serum phosphorus levels in patients with chronic kidney disease on dialysis.
Factors affecting pre-end-stage kidney disease haemoglobin control and outcomes following dialysis initiation: a nationwide study
Yang Xu, Marie Evans, Peter Barany, Glen James, Arvid Sj?lander, Juan Jesus Carrero
doi : 10.1093/ckj/sfaa213
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1780–1788
Attaining the narrow haemoglobin (Hb) range recommended by European Renal Best Practice Guidelines renal anaemia guidelines may be difficult, and whether this leads to better outcomes following dialysis initiation is not known.
High-sensitivity troponins in dialysis patients: variation and prognostic value
Sunna Snaedal, Peter B?r?ny, Sigr?n H Lund, Abdul R Qureshi, Olof Heimbürger, Peter Stenvinkel, Christian L?wbeer, Karolina Szummer
doi : 10.1093/ckj/sfaa215
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1789–1797
Dialysis patients have a high prevalence of cardiovascular mortality but also elevated cardiac troponins (cTns) even without signs of cardiac ischaemia. The study aims to assess variation and prognostic value of high-sensitivity cTnI and cTnT in prevalent dialysis patients.
Pro-calcifying analysis of uraemic serum from patients treated with medium cut-off membrane in a prospective, cross-over study
Paola Ciceri, Giorgia Tettamanti, Andrea Galassi, Lorenza Magagnoli, Nicolas Fabresse, Jean-Claude Alvarez, Ziad A Massy, Piergiorgio Messa, Mario Cozzolino
doi : 10.1093/ckj/sfaa216
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1798–1807
The retention of a large number of solutes that are normally excreted or metabolized by the kidney is responsible for the symptoms typical in uraemic patients. These molecules are defined as uraemic toxins and can be classified into three groups: small water-soluble molecules, middle molecules and protein-bound toxins. Recently, efforts were put towards developing dialysis membranes that allow the removal of large middle molecules without clinically relevant albumin loss. These membranes are the medium cut-off (MCO) membranes that allow the removal of middle molecules up to ?50?000?Da.
Evaluation of potential drug interactions with sodium zirconium cyclosilicate: a single-center, open-label, one sequence crossover study in healthy adults
Mats N?g?rd, William G Kramer, David W Boulton
doi : 10.1093/ckj/sfaa222
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1808–1816
Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is an oral potassium binder for the treatment of hyperkalemia in adults. SZC acts in the gastrointestinal tract and additionally binds hydrogen ions in acidic environments like the stomach, potentially transiently increasing gastric pH and leading to drug interactions with pH-sensitive drugs. This study assessed potential pharmacokinetic (PK) interactions between SZC and nine pH-sensitive drugs.
Scope and heterogeneity of outcomes reported in randomized trials in patients receiving peritoneal dialysis
Karine E Manera, David W Johnson, Yeoungjee Cho, Benedicte Sautenet, Jenny Shen, Ayano Kelly, Angela Yee-Moon Wang, Edwina A Brown, Gillian Brunier, Jeffrey Perl, Jie Dong, Martin Wilkie, Rajnish Mehrotra, Roberto Pecoits-Filho, Saraladevi Naicker, Tony Dunning, Jonathan C Craig, Allison Tong
doi : 10.1093/ckj/sfaa224
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1817–1825
Randomized trials can provide evidence to inform decision-making but this may be limited if the outcomes of importance to patients and clinicians are omitted or reported inconsistently. We aimed to assess the scope and heterogeneity of outcomes reported in trials in peritoneal dialysis (PD).
Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes
Neus Roca, Alvaro Madrid, Mercedes Lopez, Gloria Fraga, Elias Jatem, Jorge Gonzalez, Cristina Martinez, Alfons Segarra
doi : 10.1093/ckj/sfaa265
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1826–1834
Idiopathic focal segmental glomerulosclerosis (FSGS) has been linked to immunological and inflammatory response dysregulations. The aim of this study was to find endotypes of FSGS patients using a cluster (CL) analysis based on inflammatory and immunological variables, and to analyse whether a certain endotype is associated with response to treatment with corticosteroids.
Rapid decline of anti-SARS-CoV-2 antibodies in patients on haemodialysis: the COVID-FRIAT study
Roberto Alc?zar-Arroyo, José Portolés, Paula L?pez-S?nchez, Felipe Zalamea, Karina Furaz, ?ngel Méndez, Luis Nieto, Rosa S?nchez-Hern?ndez, Soledad Pizarro, Alicia Garc?a, M?nica Pereira, Eduardo Gallego-Valc?rcel, Rosario Ll?pez-Carratala, Ignacio Gadea-Gironés, Roberto Mart?n, Blanca Miranda, COVID-FRIAT study group
doi : 10.1093/ckj/sfab048
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1835–1844
Coronavirus disease 2019 (COVID-19) patients on haemodialysis (HD) have high mortality. We investigated the value of reverse transcription polymerase chain reaction (RT-PCR) and the dynamic changes of antibodies (enzyme-linked immunosorbent assay immunoglobulin M (IgM) + IgA and/or IgG) in a large HD cohort.
Founding mutations explains hotspots of polycystic kidney disease in Southern Spain
Carmen Garc?a Rabaneda, Francisco Perea, Mar?a Luz Bellido D?az, Ana I Morales Garc?a, Margarita Mart?nez Atienza, Lisbeth Sousa Silva, Miguel ?ngel Garc?a Gonz?lez, Francisco Ruiz Cabello, Rafael J Esteban de la Rosa
doi : 10.1093/ckj/sfaa261
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1845–1847
Our group identified two pathogenic variants on the PKD1 gene, c.10527_10528delGA and c.7292T>A, from unrelated families. They came from two small counties in Granada, with 61 and 26 autosomal dominant polycystic kidney disease (ADPKD) individuals affected. To determine a common ancestor, healthy and ADPKD individuals from these families were genotyped by analysing four microsatellites located on chromosome 16. Our study identified a common haplotype in all ADPKD individuals. These findings underpin our hypothesis of the founder effect and explain why there is a high frequency of ADPKD in small regions. Determining hotspots of ADPKD will help to better plan healthcare in the future.
Systemic sclerosis and microscopic polyangiitis after systemic exposure to silicone
Claudia Carrera Mu?oz, Jorge Gonz?lez Rodr?guez, Annabel Ab? Rivera, Elena Estar?n, Jordi Roig C?rcel, Alfons Segarra Medrano
doi : 10.1093/ckj/sfab058
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1848–1850
The relationship between silicon breast implants (SBIs) and autoimmune/inflammatory syndrome induced by adjuvants (ASIA) has been extensively analysed, with discordant results. We present a 45-year-old woman with confirmed systemic exposure to SBI who developed systemic sclerosis (SSc) followed by anti-neutrophil cytoplasmic antibody anti-myeloperoxidase vasculitis with renopulmonary syndrome. The novelty of our case is, first, confirmation of systemic exposure to SBI and, second, chronologic development of not one, but two severe autoimmune diseases. Controversy may still remain regarding SBIs and ASIA because it is unclear that previous studies confirmed systemic exposure to silicon in their cohort of patients.
Simplified 8-site lung ultrasound examination to assess fluid overload in children on haemodialysis
Marco Allinovi, Wesley Hayes
doi : 10.1093/ckj/sfab041
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1851–1852
The non-steady state CKD-EPI calculator
Florian Buchkremer, Andreas Bock, Stephan Segerer
doi : 10.1093/ckj/sfab047
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1853–1856
The immunohistological profile of membranous nephropathy associated with syphilis infection
David Campos Wanderley, Precil Diego Miranda de Menezes Neves, Lect?cia Barbosa Jorge, Luiz Fernando Onuchic, Stanley Almeida Araujo
doi : 10.1093/ckj/sfab057
Clinical Kidney Journal, Volume 14, Issue 7, July 2021, Pages 1857–1858
