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The changing nature of COVID-19-associated AKI: where are we now?
Rebecca A Noble, Nicholas M Selby
doi : 10.1093/ndt/gfab326
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 201–202
How much time does it take to get cognitive impairment in kidney disease?
Davide Viggiano, Giovambattista Capasso
doi : 10.1093/ndt/gfab220
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 203–204
Amiloride and calciuria
Friedrich C Luft, Johan Sällström
doi : 10.1093/ndt/gfab221
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 205–207
Renal denervation for patients with chronic kidney disease and resistant hypertension: effective and safe but still not the panacea
Michel Burnier
doi : 10.1093/ndt/gfab208
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 208–210
The intersection of mineralocorticoid receptor activation and the FGF23–Klotho cascade: a duopoly that promotes renal and cardiovascular injury
Murray Epstein, Michael Freundlich
doi : 10.1093/ndt/gfab254
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 211–221
The nexus of chronic kidney disease (CKD) and cardiovascular disease (CVD) amplifies the morbidity and mortality of CKD, emphasizing the need for defining and establishing therapeutic initiatives to modify and abrogate the progression of CKD and concomitant CV risks. In addition to the traditional CV risk factors, disturbances of mineral metabolism are specific risk factors that contribute to the excessive CV mortality in patients with CKD. These risk factors include dysregulations of circulating factors that modulate phosphate metabolism, including fibroblast growth factor 23 (FGF23) and soluble Klotho. Reduced circulating levels and suppressed renal Klotho expression may be associated with adverse outcomes in CKD patients. While elevated circulating concentrations or locally produced FGF23 in the strained heart exert prohypertrophic mechanisms on the myocardium, Klotho attenuates tissue fibrosis, progression of CKD, cardiomyopathy, endothelial dysfunction, vascular stiffness and vascular calcification. Mineralocorticoid receptor (MR) activation in nonclassical targets, mediated by aldosterone and other ligands, amplifies CVD in CKD. In concert, we detail how the interplay of elevated FGF23, activation of the MR and concomitant reductions of circulating Klotho in CKD may potentiate each other’s deleterious effects on the kidney and heart, thereby contributing to the initiation and progression of kidney and cardiac functional deterioration, acting through multipronged, albeit complementary, mechanistic pathways.
The challenge of early glomerular filtration rate decline in response to antihypertensive treatment and chronic kidney disease outcomes
Lorenzo Signorini, Gianluigi Zaza, Giovanni Gambaro
doi : 10.1093/ndt/gfaa171
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 222–229
Hypertension and chronic kidney disease (CKD) are closely linked pathological processes. Combating high blood pressure (BP) is an essential part of preventing CKD progression and reducing cardiovascular (CV) risk. Data from recent randomized controlled trials on patients at high CV risk showed the beneficial effects of intensive action to meet BP targets on mortality related to CV disease. The impact of meeting such targets on renal function is still unclear, however, particularly for patients with CKD. This issue has been the object of several post hoc analyses because lowering BP definitely has a nephroprotective role, but the early decline in glomerular filtration rate (GFR) associated with antihypertensive therapies and strict BP targets is still a concern in nephrology clinical practice. The present review discusses the results of studies on this topic, focusing specifically on the clinical significance of early GFR decline in response to treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, or to different BP targets, in terms of renal and CV outcomes, and how this tips the balance towards continuing or discontinuing antihypertensive therapy.
Neutrophils are key mediators in crescentic glomerulonephritis and targets for new therapeutic approaches
Marilina Antonelou, Rhys D R Evans, Scott R Henderson, Alan D Salama
doi : 10.1093/ndt/gfaa206
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 230–238
Crescentic glomerulonephritis (CGN) results from a diverse set of diseases associated with immune dysregulation and the breakdown of self-tolerance to a wide range of autoantigens, some known and some that remain unknown. Experimental data demonstrate that neutrophils have an important role in the pathogenesis of CGN. Upon activation, neutrophils generate reactive oxygen species, release serine proteases and form neutrophil extracellular traps (NETs), all of which can induce direct tissue damage. In addition, serine proteases such as myeloperoxidase and proteinase 3, presented on NETs, can be processed and recognized as autoantigens, leading to the generation and maintenance of autoimmune responses in susceptible individuals. The basis of the specificity of autoimmune responses in different patients to NET proteins is unclear, but relates at least in part to differences in human leucocyte antigen expression. Conditions associated with CGN are often characterized by aberrant neutrophil activation and NETosis and, in some, impaired NET degradation. Targeting neutrophil degranulation and NETosis is now possible using a variety of novel compounds and may provide a promising therapeutic alternative to glucocorticoid use, which has been a mainstay of management in CGN for decades and is associated with significant adverse effects. In this review, we discuss the evidence supporting the role of neutrophils in the development of CGN and the pathways identified in neutrophil degranulation and NETosis that may translate to novel therapeutic applications.
Genetic testing in the diagnosis of chronic kidney disease: recommendations for clinical practice
Nine Knoers, Corinne Antignac, Carsten Bergmann, Karin Dahan, Sabrina Giglio, Laurence Heidet, Beata S Lipska-Zi?tkiewicz, Marina Noris, Giuseppe Remuzzi, Rosa Vargas-Poussou, Franz Schaefer for the ERA Working Group on Inherited Kidney Disorders (WGIKD), which is an official body of the ERA (European Renal Association), and the Molecular Diagnostics Taskforce of the European Rare Kidney Disease Reference Network (ERKNet)
doi : 10.1093/ndt/gfab218
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 239–254
The overall diagnostic yield of massively parallel sequencing–based tests in patients with chronic kidney disease (CKD) is 30% for paediatric cases and 6–30% for adult cases. These figures should encourage nephrologists to frequently use genetic testing as a diagnostic means for their patients. However, in reality, several barriers appear to hinder the implementation of massively parallel sequencing–based diagnostics in routine clinical practice. In this article we aim to support the nephrologist to overcome these barriers. After a detailed discussion of the general items that are important to genetic testing in nephrology, namely genetic testing modalities and their indications, clinical information needed for high-quality interpretation of genetic tests, the clinical benefit of genetic testing and genetic counselling, we describe each of these items more specifically for the different groups of genetic kidney diseases and for CKD of unknown origin.
Examination of the eye and retinal alterations in primary hyperoxaluria type 1
Johannes Birtel, Peter Charbel Issa, Philipp Herrmann, Bernd Hoppe, Anja Katrin Büscher
doi : 10.1093/ndt/gfaa101
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 255–257
What is the role of exercise in chronic kidney disease?
Vincenzo Bellizzi, Giuseppe Regolisti
doi : 10.1093/ndt/gfaa161
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 258–261
Identification of novel OCRL isoforms associated with phenotypic differences between Dent disease-2 and Lowe syndrome
Nana Sakakibara, Takeshi Ijuin, Tomoko Horinouchi, Tomohiko Yamamura, China Nagano, Eri Okada, Shinya Ishiko, Yuya Aoto, Rini Rossanti, Takeshi Ninchoji, Hiroyuki Awano, Hiroaki Nagase, Shogo Minamikawa, Ryojiro Tanaka, Takeshi Matsuyama, Koji Nagatani, Koichi Kamei, Kumiko Jinnouchi, Yasufumi Ohtsuka, Masafumi Oka, Yoshinori Araki, Toju Tanaka, Mari S Harada, Toru Igarashi, Hikaru Kitahara, Naoya Morisada, Shun-ichi Nakamura, Taro Okada, Kazumoto Iijima, Kandai Nozu
doi : 10.1093/ndt/gfab274
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 262–270
Although Lowe syndrome and Dent disease-2 are caused by Oculocerebrorenal syndrome of Lowe (OCRL) mutations, their clinical severities differ substantially and their molecular mechanisms remain unclear. Truncating mutations in OCRL exons 1–7 lead to Dent disease-2, whereas those in exons 8–24 lead to Lowe syndrome. Herein we identified the mechanism underlying the action of novel OCRL protein isoforms.
Acute kidney injury in patients hospitalized with COVID-19 from the ISARIC WHO CCP-UK Study: a prospective, multicentre cohort study
Michael K Sullivan, Jennifer S Lees, Thomas M Drake, Annemarie B Docherty, Georgia Oates, Hayley E Hardwick, Clark D Russell, Laura Merson, Jake Dunning, Jonathan S Nguyen-Van-Tam, Peter Openshaw, Ewen M Harrison, J Kenneth Baillie, ISARIC4C Investigators , Malcolm G Semple, Antonia Ho, Patrick B Mark
doi : 10.1093/ndt/gfab303
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 271–284
Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). This study investigated adults hospitalized with COVID-19 and hypothesized that risk factors for AKI would include comorbidities and non-White race.
Acute kidney injury is associated with subtle but quantifiable neurocognitive impairments
Jessica A Vanderlinden, Joanna S Semrau, Samuel A Silver, Rachel M Holden, Stephen H Scott, J Gordon Boyd
doi : 10.1093/ndt/gfab161
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 285–297
Acute kidney injury (AKI) is associated with long-term morbidity and mortality. The effects of AKI on neurocognitive functioning remain unknown. Our objective was to quantify neurocognitive impairment after an episode of AKI.
Acute decrease of urine calcium by amiloride in healthy volunteers under high-sodium diet
Dusan Harmacek, Anne Blanchard, Gregoire Wuerzner, Marc Maillard, Xavier Jeunemaitre, Michel Azizi, Olivier Bonny
doi : 10.1093/ndt/gfab159
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 298–303
Amiloride is a competitive blocker of the epithelial sodium (Na) channel in the renal collecting duct. It is a less potent diuretic than thiazides or loop diuretics, but is often used in association with its potassium (K)-sparing profile. Whether amiloride has a hypocalciuric effect similar to thiazides remains unclear. Animal studies and experiments on cell lines suggested that amiloride increases calcium (Ca) reabsorption in the distal nephron, but human studies are scarce.
Renal denervation in patients with versus without chronic kidney disease: results from the Global SYMPLICITY Registry with follow-up data of 3 years
Christian Ott, Felix Mahfoud, Giuseppe Mancia, Krzysztof Narkiewicz, Luis M Ruilope, Martin Fahy, Markus P Schlaich, Michael Böhm, Roland E Schmieder
doi : 10.1093/ndt/gfab154
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 304–310
Activity of the sympathetic nervous system is increased in patients with hypertension and chronic kidney disease (CKD). Here we compare short- and long-term blood pressure (BP)-lowering effects of renal denervation (RDN) between hypertensive patients with or without CKD in the Global SYMPLICITY Registry.
Renal comorbidities in collapsing variant focal segmental glomerulosclerosis: more than a coincidence?
Francois Gougeon, Harsharan K Singh, Volker Nickeleit
doi : 10.1093/ndt/gfaa327
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 311–317
Collapsing focal segmental glomerulosclerosis (FSGS) has various underlying etiologies and often leads to renal failure. The impact of biopsy-proven renal comorbidities in promoting collapsing glomerulopathy (CG) has not been systematically evaluated in large comparative studies. Those data are reported here.
Relationship between immunoglobulin A1 lectin-binding specificities, mesangial C4d deposits and clinical phenotypes in immunoglobulin A nephropathy
Alfons Segarra Medrano, Andrea Muijsemberg, David Wimbury, Marisa Martin, Elias Jatem, Jorge González, Laura Colás-Campás, Alicia García-Carrasco, Cristina Martínez, Jonathan Barratt
doi : 10.1093/ndt/gfaa356
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 318–325
The reason why mesangial C4d deposits are detected in only certain biopsies of immunoglobulin A nephropathy (IGAN) remains unclear. We analyse the association between IgA glycosylation patterns, mesangial C4 deposition and clinical phenotypes in IgAN.
Determining the optimal cholecalciferol dosing regimen in children with CKD: a randomized controlled trial
Arpana Iyengar, Nivedita Kamath, Hamsa V Reddy, Jyoti Sharma, Jyoti Singhal, Susan Uthup, Sudha Ekambaram, Sumithra Selvam, Anja Rahn, Dagmar-C Fischer, Mandy Wan, Rukshana Shroff
doi : 10.1093/ndt/gfaa369
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 326–334
The optimal treatment regimen for correcting 25-hydroxyvitamin D (25OHD) deficiency in children with chronic kidney disease (CKD) is not known. We compared cholecalciferol dosing regimens for achieving and maintaining 25OHD concentrations ?30 ng/mL in children with CKD stages 2–4.
Association of urinary sex steroid hormones with urinary calcium, oxalate and citrate excretion in kidney stone formers
Daniel G Fuster, Gaétan A Morard, Lisa Schneider, Cedric Mattmann, David Lüthi, Bruno Vogt, Nasser A Dhayat
doi : 10.1093/ndt/gfaa360
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 335–348
Sex-specific differences in nephrolithiasis with respect to both distribution of prevalence and stone composition are widely described and may be influenced by sex hormones.
Genetics-first approach improves diagnostics of ESKD patients <50 years old
Rozemarijn Snoek, Richard H van Jaarsveld, Tri Q Nguyen, Edith D J Peters, Martin G Elferink, Robert F Ernst, Maarten B Rookmaaker, Marc R Lilien, Eric Spierings, Roel Goldschmeding, Nine V A M Knoers, Bert van der Zwaag, Arjan D van Zuilen, Albertien M van Eerde
doi : 10.1093/ndt/gfaa363
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 349–357
Often only chronic kidney disease (CKD) patients with high likelihood of genetic disease are offered genetic testing. Early genetic testing could obviate the need for kidney biopsies, allowing for adequate prognostication and treatment. To test the viability of a ‘genetics-first’ approach for CKD, we performed genetic testing in a group of kidney transplant recipients aged <50?years, irrespective of cause of transplant.
Association of pre-ESKD hyponatremia with post-ESKD outcomes among incident ESKD patients
Maria V Marroquin, John Sy, Carola-Ellen Kleine, Justin Oveyssi, Jui-Ting Hsiung, Christina Park, Melissa Soohoo, Csaba P Kovesdy, Connie M Rhee, Elani Streja, Kamyar Kalantar-Zadeh, Ekamol Tantisattamo
doi : 10.1093/ndt/gfab203
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 358–365
Hyponatremia is one of the most common electrolyte disturbances in advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD) patients, and has been shown to be associated with higher mortality risk. However, the relationship between hyponatremia during late-stage CKD and the risk of poor outcomes after ESKD transition is unknown.
Circulating endotoxin and inflammation: associations with fitness, physical activity and the effect of a 6-month programme of cycling exercise during haemodialysis
Daniel S March, Ka-Bik Lai, Tracy Neal, Matthew P M Graham-Brown, Patrick J Highton, Darren R Churchward, Hannah M L Young, Maurice Dungey, David J Stensel, Alice C Smith, Nicolette C Bishop, Cheuk Chun Szeto, James O Burton
doi : 10.1093/ndt/gfab178
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 366–374
Intradialytic cycling (IDC) may provide cardiovascular benefits to individuals receiving haemodialysis, but the exact mechanism behind these improvements remains unclear. The primary aim of this study was to investigate the effect of a 6-month programme of IDC on circulating endotoxin (secondary analysis from the CYCLE-HD trial). Secondary aims were to investigate changes in circulating cytokines [interleukin-6 (IL-6), IL-10, tumour necrosis factor-?, C-reactive protein (CRP) and the IL-6:IL-10 ratio] and their associations with physical activity, fitness and cardiovascular outcomes.
Time-dependent evolution of IgG antibody levels after first and second dose of mRNA-based SARS-CoV-2 vaccination in haemodialysis patients: a multicentre study
Carla Santos-Araújo, Pedro Mota Veiga, Mário João Santos, Lidia Santos, Catarina Romãozinho, Mónica Silva, Carlos Lucas, Mary Luz Duarte, Mathias Haarhaus, Michael Haase, Fernando Macário
doi : 10.1093/ndt/gfab293
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 375–381
Vaccination programs are essential for the containment of the coronavirus disease 2019 pandemic, which has hit haemodialysis populations especially hard. Early reports suggest a reduced immunologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in dialysis patients, in spite of a high degree of seroconversion. We aimed to identify risk factors for a reduced efficacy of an mRNA vaccine in a cohort of haemodialysis patients.
Remnant cholesterol is prospectively associated with cardiovascular disease events and all-cause mortality in kidney transplant recipients: the FAVORIT study
Reuben William Horace, Mary Roberts, Theresa I Shireman, Basma Merhi, Paul Jacques, Andrew G Bostom, Simin Liu, Charles B Eaton
doi : 10.1093/ndt/gfab068
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 382–389
The cholesterol content of circulating triglyceride-rich lipoproteins is characterized as remnant cholesterol, although little is known about its role in the development of cardiovascular disease (CVD) outcomes, all-cause mortality or transplant failure in kidney transplant recipients (KTRs). Our primary aim was to investigate the prospective association of remnant cholesterol and the risk of CVD events in renal transplant recipients with secondary aims evaluating remnant cholesterol and renal graft failure and all-cause mortality among participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial.
Humoral response after SARS-CoV-2 vaccination in patients undergoing maintenance haemodialysis: loss of immunity, third dose and non-responders
Thomas Robert, Guillaume Lano, Matthieu Giot, Toscane Fourié, Xavier de Lamballeri, Océane Jehel, Dammar Bouchouareb, Philippe Brunet, Laetitia Ninove, Stéphane Burtey
doi : 10.1093/ndt/gfab299
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 390–392
French nationwide survey of undocumented end-stage renal disease migrant patient access to scheduled haemodialysis and kidney transplantation
Alice Doreille, Raphaël Godefroy, Jonas Martzloff, Clément Deltombe, Yosu Luque, Laurent Mesnard, Marc Hazzan, Michel Tsimaratos, Eric Rondeau, Maryvonne Hourmant, Bruno Moulin, Thomas Robert, Cédric Rafat
doi : 10.1093/ndt/gfab275
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Pages 393–395
Retraction Notice
doi : 10.1093/ndt/gfab029
Nephrology Dialysis Transplantation, Volume 37, Issue 2, February 2022, Page 396
