Ali AlSahow

Filippo Pinto e Vairo

Hamad Ali

Mohamed Abu-Farha

Frontiers in Medicine

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TYPE EditorialPUBLISHED 11 May 2023DOI 10.3389/fmed.2023.1209571OPEN ACCESSEDITED AND REVIEWED BYMinnie M. Sarwal,University of California, San Francisco,United States*CORRESPONDENCEHamad Alihamad.ali@ku.edu.kwRECEIVED 20 April 2023ACCEPTED 28 April 2023PUBLISHED 11 May 2023CITATIONAli H, Pinto e Vairo F, AlSahow A andAbu-Farha M (2023) Editorial: Advances inchronic kidney disease diagnosis and therapy.Front. Med. 10:1209571.doi: 10.3389/fmed.2023.1209571COPYRIGHT© 2023 Ali, Pinto e Vairo, AlSahow andAbu-Farha. This is an open-access articledistributed under the terms of the CreativeCommons Attribution License (CC BY). The use,distribution or reproduction in other forums ispermitted, provided the original author(s) andthe copyright owner(s) are credited and thatthe original publication in this journal is cited, inaccordance with accepted academic practice.No use, distribution or reproduction ispermitted which does not comply with theseterms.Editorial: Advances in chronickidney disease diagnosis andtherapyHamad Ali1,2*, Filippo Pinto e Vairo3, Ali AlSahow4 andMohamed Abu-Farha21Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Health Sciences Center,Kuwait University, Jabriya, Kuwait, 2Research Division, Dasman Diabetes Institute, Dasman, Kuwait,3Department of Clinical Genomics, Center for Individualized Medicine, and Division of Nephrology andHypertension, Mayo Clinic, Rochester, MN, United States, 4Division of Nephrology, Al-Jahra Hospital,Ministry of Health, Al-Jahra, KuwaitKEYWORDSchronic kidney disease, glomerulopathy, tyrosine kinase inhibitors (TKI), ferroptosis 1,Receptor for Advanced Glycation End-product (RAGE), granulomatosis with polyangiitis(GPA), triglyceride-glucose indexEditorial on the Research TopicAdvances in chronic kidney disease diagnosis and therapyChronic kidney disease (CKD) continues to be a major challenge for health care systemsglobally. The disease is a direct contributor to morbidity and mortality, and a risk factorfor cardiovascular disease, a leading cause of death globally. Recent studies indicated thatCKD-related deaths were among the largest rises of causes of death between 2010 and 2019which could be attributed, in part, to the increased prevalence of CKD risk factors includingobesity, hypertension and diabetes (1). There is an urgent need to develop more effective andtargeted treatments for CKD that can prevent/slow disease progression and improve patientoutcomes. Furthermore, the identification of sensitive and reliable biomarkers is essential tomonitor disease progression accurately, assess the effectiveness of treatments, and identifypatients who may benefit from early interventions. Our Research Topic aimed to explorerecent advances in the field of CKD to improve our understanding of the disease, leading tobetter diagnosis, management, and treatment options for patients.Zhu et al. explored the relationship between Triglyceride-glucose (TyG) index and therisk of CKD. In their longitudinal observational study on more than 2,000 hypertensiveparticipants with a median follow up of 31 months, they found that individuals in thehighest quartile of TyG index had a 1.63-fold higher hazard ratio for the presence of CKDcompared to those in the lowest quartile. Furthermore, the relationship between TyG indexand CKD was found to be non-linear, with a rapid increase in risk beyond a TyG indexof 8.94. The study argued that early intervention of metabolic factors may prevent theoccurrence of CKD and reduce the incidence of cardiovascular disease and premature death.There is a bi-directional relationship between CKD and hypertension, as the latter can serveas both a result and a risk factor in the development and progression of CKD. Prasadet al. investigated the renal and cardiovascular outcomes associated with administration ofAngiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB)which are the preferred antihypertensive drug class in patients with CKD. Their findingsFrontiers inMedicine 01 frontiersin.orgAli et al. 10.3389/fmed.2023.1209571showed that utilization of ACEI/ARB correlated with a slowerdecline in eGFR among individuals with CKD stages 1–3.ACEI/ARBs administration also correlated with a reduced risk ofrenal outcomes and cardiovascular mortality.The Receptor for Advanced Glycation End-products (RAGE)is activated by multiple ligands such as AGEs, HMGB1, andS100 proteins. Its activation through these ligands triggersmultiple pathways that are involved in various diseases rangingfrom autoimmune diseases to cancers and infectious diseasesas well as the progression of both CKD and COVID-19.Curran and Kopp reviewed studies that can link RAGE ligandswith those diseases and highlighted the elevated mortalityrisk associated with COVID-19 patients with CKD. Theyalso reported the role played by the RAGE pathway inrenal cell injury and dysfunction. Based on these elaborateinvolvement of RAGE pathways in both CKD and COVID-19,the authors proposed that interventions to reduce RAGE andRAGE ligand plasma and tissue levels can provide a promisingtherapeutic target to delay or stop the progression of COVID-19-associated CKD and perhaps non-COVID-19-associated CKD.As a result, more research is needed to advance this conceptand to investigate the clinical safety and efficacy of RAGE-targeted therapies.To better characterize and to identify the time-dependentrisk associated with granulomatosis with polyangiitis (GPA),a lethal primary systemic vasculitides disease characterizedby granulomatous and necrotizing inflammation affecting theupper respiratory tract, lungs, and kidneys, Lin et al. analyzedretrospective data from a nationally representative database inTaiwan for individuals with GPA. The analysis included GPApatients without end-stage kidney disease (ESKD) as well as theirsex, age, entry time, and comorbidities in a matched controlgroup at a 1:4 ratio (142 GPA patients and 568 controls). Theirfindings showed that GPA patients had the highest mortality ratewithin the first 6 months to a year and experienced incidence ofESKD exclusively in the first 3 years of diagnosis. In conclusion,the authors highlighted the need for close monitoring of GPApatients within the early years of the disease to protect againstESKD and to improve survival rate. To investigate the potentialbenefits of remote patient management (RPM) in reducing all-cause mortality among patients with heart failure (HF) andrenal impairment Naik et al. initiated a prospective, randomized,controlled multicenter trial. The trial included 1,538 patientswith stable heart failure from Germany between 2013 and 2017.Patients were randomized to either RPM plus usual care or usualcare alone. The primary endpoint was the percentage of lostunplanned days as a result of cardiovascular hospitalizations ordeath while the secondary outcome included hospitalizations, all-cause, and cardiovascular mortality. Overall, the study showedthat RPM can be a valuable approach in reducing all-causemortality in the high-risk population of patients with heart failureand CKD.Yang et al. reviewed the role of autophagy-dependentferroptosis in kidney diseases. Ferroptosis is a distinct type ofcell death that is mainly caused by iron toxicity and lipidperoxidation. In this review the authors provided a comprehensiveoverview of the role of ferroptosis in kidney disease, highlightingthe major role of autophagy-dependent ferroptosis in renalimpairment. ADAMTS9 is a metalloproteinase that has been shownto play a role in various kidney diseases. Pathogenic variantswithin this gene have been shown to cause nephronophthisis-related ciliopathies (NPHP-RC). In this issue, Yu et al. intendedto confirm whether ADAMTS9 dysfunction causes NPHP andglomerulopathy, utilizing ADAMTS9 knockout kidney organoidsand single-cell RNA sequencing highlighting the functional rolesof ADMATS9 in glomeruli and tubules. Their data showed thatthe podocyte clusters followed by the proximal tubules expressedthe highest levels of ADAMTS9. ADAMTS9 knockout resultedin the activation of multiple pathways in podocyte clusters,including the Wnt/PCP signaling pathway, which requires furtheranalysis. Tyrosine kinase inhibitors (TKIs) are effective tumortherapeutic targets but are associated with significant side effectssuch as hypertension, diarrhea, bleeding and proteinuria. Fuet al. were interested in evaluating the therapeutic value ofLiuwei Dihuang Pill (LDP), which is an ancient Chinese medicineformula. The authors showed in vitro that LDP mitigated TKI-related proteinuria through the attenuation of inflammatory injuryof podocytes.Although recent progress in CKD diagnosis andtherapy offers hope for better management, more targetedtreatments are urgently needed to prevent/slow diseaseprogression and improve patient outcomes. Additionally, thedevelopment of sensitive diagnostic and prognostic markersis critical for early detection and effective management,potentially reducing morbidity and mortality relatedto CKD.Author contributionsAll authors listed have made a substantial, direct, andintellectual contribution to the work and approved itfor publication.AcknowledgmentsWe extend our heartfelt appreciation to the Kuwait TransplantSociety for their invaluable contribution to the scientificcommunity and their dedication to improving patient outcomes.Conflict of interestThe authors declare that the research was conductedin the absence of any commercial or financial relationshipsthat could be construed as a potential conflictof interest.Publisher’s noteAll claims expressed in this article are solely thoseof the authors and do not necessarily represent those oftheir affiliated organizations, or those of the publisher,Frontiers inMedicine 02 frontiersin.orgAli et al. 10.3389/fmed.2023.1209571the editors and the reviewers. Any product that may beevaluated in this article, or claim that may be made byits manufacturer, is not guaranteed or endorsed by thepublisher.References1. Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney IntSuppl. (2011) 12:7–11. doi: 10.1016/j.kisu.2021.11.003Frontiers inMedicine 03 frontiersin.org

Editorial: Advances in chronic kidney disease diagnosis and therapy

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Editorial: Advances in chronic kidney disease diagnosis and therapy

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