Pathogenesis Of Chronic Kidney Disease Research Articles

Thioredoxin-Interacting Protein: The Redoxissome Complex in Glomerular Lesion

Chronic Kidney Disease (CKD) affects millions of people worldwide and is a global health problem with few treatment options. The mechanisms underlying the pathogenesis of CKD include oxidative damage and inflammation. Damage to the glomeruli may be observed during the course of co-associated diseases such diabetes, but also in specific conditions such as focal segmental glomerulosclerosis. During its early manifestation, podocyte’s damage and death are key factors to glomerulopathies and its protection may represent an important therapeutic approach. Importantly, podocytes pathology involves inflammation and cellular damage, principally due to excessive oxidative stress. Underlying mechanisms associated to both inflammation and oxidative stress during the course of a renal lesion must be elucidated for the development of better clinical and research approaches to kidney physiology. Thus, here we discuss the role of the Thioredoxin system, an antioxidant mechanism, and TXNIP, a thioredoxin inhibitor linked to NRLP3 inflammasome activation, as a pivotal axis in the pathophysiology of glomerular lesions.

Contemporary understanding of the risk factors for chronic kidney disease in cold area

Abstract The management of chronic kidney disease (CKD) patients in cold areas is an important task in the daily practice of primary medical and health institutions. An important way to reduce the burden of CKD is to achieve early identification of and implement timely intervention on the relevant risk factors. Studies have shown that diet, alcohol, tobacco, air, sedentary and other factors in cold areas have negative impacts on human kidneys; yet, our current understanding of the effect of cold stimulation on CKD remains blurry. This paper introduces the research progress of risk factors related to CKD in cold areas and analytically summarizes the pathogenesis of CKD caused by cold stimulation, aiming to provide a reference work for the prevention, screening, evaluation, and management of CKD in cold areas.

In Memoriam: Anil K. Bidani, MD.

In Memoriam: Anil K. Bidani, MD.

Association of dietary inflammatory index with chronic kidney disease and kidney stones in Iranian adults: A cross-sectional study within the Ravansar non-communicable diseases cohort.

Chronic inflammation plays a central role in the pathogenesis of chronic kidney disease (CKD). The association of dietary inflammatory index (DII) with CKD remains underexplored. Thus, the present study aimed to determine the association between the DII, risk of CKD, and kidney stone formation using the data from the Ravansar non-communicable diseases (RaNCD) cohort study conducted in Kermanshah, Iran. The cross-sectional study was conducted using the recruitment phase data of the RaNCD cohort study comprising 9,824 individuals with an age range of 35–65 years. Food frequency questionnaires (FFQ) were used to evaluate the association between diet and DII scores. Renal function was assessed using estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), and serum creatinine (Cr) level. CKD was defined based on eGFR. The prevalence of kidney stones was evaluated by participants’ self-report. A total of 1,791 participants (18.24%) had kidney stones, while a majority were in the first quartile (27.69%). Out of 9,824 subjects, 1,747 subjects (eGFR: 18.50 ml/min per 1.73 m2; 95% CI: 17.72–19.30) had CKD. A significant trend for eGFR across all quartiles (Qs) of DII was observed. The odds ratio of CKD in the fourth quartile (pro-inflammatory diet) was 4.38-times higher than in the first quartile (anti-inflammatory diet) of DII (95% CI = 3.58–5.36). Women were found to be more likely to have less eGFR than men in the DII Qs. Collectively, the findings indicated that consumption of a pro-inflammatory diet was associated with a high occurrence of CKD. As a matter of interest, the results also revealed that a pro-inflammatory diet had no significant correlation with kidney stone development.

Molecular Mechanisms of Cellular Injury and Role of Toxic Heavy Metals in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a progressive disease that affects millions of adults every year. Major risk factors include diabetes, hypertension, and obesity, which affect millions of adults worldwide. CKD is characterized by cellular injury followed by permanent loss of functional nephrons. As injured cells die and nephrons become sclerotic, remaining healthy nephrons attempt to compensate by undergoing various structural, molecular, and functional changes. While these changes are designed to maintain appropriate renal function, they may lead to additional cellular injury and progression of disease. As CKD progresses and filtration decreases, the ability to eliminate metabolic wastes and environmental toxicants declines. The inability to eliminate environmental toxicants such as arsenic, cadmium, and mercury may contribute to cellular injury and enhance the progression of CKD. The present review describes major molecular alterations that contribute to the pathogenesis of CKD and the effects of arsenic, cadmium, and mercury on the progression of CKD.

Xenobiotics Delivered by Electronic Nicotine Delivery Systems: Potential Cellular and Molecular Mechanisms on the Pathogenesis of Chronic Kidney Disease.

Chronic kidney disease (CKD) is characterized as sustained damage to the renal parenchyma, leading to impaired renal functions and gradually progressing to end-stage renal disease (ESRD). Diabetes mellitus (DM) and arterial hypertension (AH) are underlying diseases of CKD. Genetic background, lifestyle, and xenobiotic exposures can favor CKD onset and trigger its underlying diseases. Cigarette smoking (CS) is a known modified risk factor for CKD. Compounds from tobacco combustion act through multi-mediated mechanisms that impair renal function. Electronic nicotine delivery systems (ENDS) consumption, such as e-cigarettes and heated tobacco devices, is growing worldwide. ENDS release mainly nicotine, humectants, and flavorings, which generate several byproducts when heated, including volatile organic compounds and ultrafine particles. The toxicity assessment of these products is emerging in human and experimental studies, but data are yet incipient to achieve truthful conclusions about their safety. To build up the knowledge about the effect of currently employed ENDS on the pathogenesis of CKD, cellular and molecular mechanisms of ENDS xenobiotic on DM, AH, and kidney functions were reviewed. Unraveling the toxic mechanisms of action and endpoints of ENDS exposures will contribute to the risk assessment and implementation of proper health and regulatory interventions.

Targeting innate immunity-driven inflammation in CKD and cardiovascular disease.

Mortality among patients with chronic kidney disease (CKD) is largely a consequence of cardiovascular disease (CVD) and is a particular concern given the increasing prevalence of CKD. Sterile inflammation triggered by activation of the innate immune system is an important driver of both CKD and associated CVD. Several endogenous mediators, including lipoproteins, crystals such as silica, urate and cholesterol crystals, or compounds released from dying cells interact with pattern recognition receptors expressed on a variety of different cell types, leading to the release of pro-inflammatory cytokines. Disturbed regulation of the haematopoietic system by damage-associated molecular patterns, or as a consequence of clonal haematopoiesis or trained innate immunity, also contributes to the development of inflammation. In observational and genetic association studies, inflammation is linked to the progression of CKD and cardiovascular events. In 2017, the CANTOS trial of canakinumab provided evidence that inhibiting inflammation driven by NLRP3-IL-1-IL-6-mediated signalling significantly reduced cardiovascular event rates in individuals with and without CKD. Other approaches to target innate immune pathways are now under investigation for their ability to reduce cardiovascular events and slow disease progression among patients with atherosclerosis and stage 3 and 4 CKD. This Review summarizes current understanding of the role of inflammation in the pathogenesis of CKD and its associated CVD, and how this knowledge may translate into novel therapeutics.

Mechanisms of ferroptosis in chronic kidney disease.

Ferroptosis is a newly identified form of regulated cell death characterized by iron accumulation and lipid peroxidation. Ferroptosis plays an essential role in the pathology of numerous diseases and has emerged as a key area of focus in studies of chronic kidney disease (CKD). CKD is a major public health problem with high incidence and mortality that is characterized by a gradual loss of kidney function over time. The severity and complexity of CKD combined with the limited knowledge of its underlying molecular mechanism(s) have led to increased interest in this disease area. Here, we summarize recent advances in our understanding of the regulatory mechanism(s) of ferroptosis and highlight recent studies describing its role in the pathogenesis and progression of CKD. We further discuss the potential therapeutic benefits of targeting ferroptosis for the treatment of CKD and the major hurdles to overcome for the translation of in vitro studies into the clinic.

Molecular Dynamic Simulation Reveals Structure Differences in APOL1 Variants and Implication in Pathogenesis of Chronic Kidney Disease.

Background: According to observational studies, two polymorphisms in the apolipoprotein L1 (APOL1) gene have been linked to an increased risk of chronic kidney disease (CKD) in Africans. One polymorphism involves the substitution of two amino-acid residues (S342G and I384M; known as G1), while the other involves the deletion of two amino-acid residues in a row (N388 and Y389; termed G2). Despite the strong link between APOL1 polymorphisms and kidney disease, the molecular mechanisms via which these APOL1 mutations influence the onset and progression of CKD remain unknown. Methods: To predict the active site and allosteric site on the APOL1 protein, we used the Computed Atlas of Surface Topography of Proteins (CASTp) and the Protein Allosteric Sites Server (PASSer). Using an extended molecular dynamics simulation, we investigated the characteristic structural perturbations in the 3D structures of APOL1 variants. Results: According to CASTp’s active site characterization, the topmost predicted site had a surface area of 964.892 Å2 and a pocket volume of 900.792 Å3. For the top three allosteric pockets, the allostery probability was 52.44%, 46.30%, and 38.50%, respectively. The systems reached equilibrium in about 125 ns. From 0–100 ns, there was also significant structural instability. When compared to G1 and G2, the wildtype protein (G0) had overall high stability throughout the simulation. The root-mean-square fluctuation (RMSF) of wildtype and variant protein backbone Cα fluctuations revealed that the Cα of the variants had a large structural fluctuation when compared to the wildtype. Conclusion: Using a combination of different computational techniques, we identified binding sites within the APOL1 protein that could be an attractive site for potential inhibitors of APOL1. Furthermore, the G1 and G2 mutations reduced the structural stability of APOL1.

Persistent DNA damage underlies tubular cell polyploidization and progression to chronic kidney disease in kidneys deficient in the DNA repair protein FAN1

Defective DNA repair pathways contribute to the development of chronic kidney disease (CKD) in humans. However, the molecular mechanisms underlying DNA damage-induced CKD pathogenesis are not well understood. Here, we investigated the role of tubular cell DNA damage in the pathogenesis of CKD using mice in which the DNA repair protein Fan1 was knocked out. The phenotype of these mice is orthologous to the human DNA damage syndrome, karyomegalic interstitial nephritis (KIN). Inactivation of Fan1 in kidney proximal tubule cells sensitized the kidneys to genotoxic and obstructive injury characterized by replication stress and persistent DNA damage response activity. Accumulation of DNA damage in Fan1 tubular cells induced epithelial dedifferentiation and tubular injury. Characteristic to KIN, cells with chronic DNA damage failed to complete mitosis and underwent polyploidization. Invitro and invivo studies showed that polyploidization was caused by the overexpression of DNA replication factors CDT1 and CDC6 in FAN1 deficient cells. Mechanistically, inhibiting DNA replication with Roscovitine reduced tubular injury, blocked the development of KIN and mitigated kidney function in these Fan1 knockout mice. Thus, our data delineate a mechanistic pathway by which persistent DNA damage in the kidney tubular cells leads to kidney injury and development of CKD. Furthermore, therapeutic modulation of cell cycle activity may provide an opportunity to mitigate the DNA damage response induced CKD progression.

Endoplasmic reticulum stress contributes to cisplatin-induced chronic kidney disease via the PERK-PKCδ pathway.

Cisplatin is an effective chemotherapeutic drug, but it may induce both acute and chronic kidney problems. The pathogenesis of chronic kidney disease (CKD) associated with cisplatin chemotherapy remains largely unclear. Mice and renal tubular cells were subjected to repeated low-dose cisplatin (RLDC) treatment to induce CKD and related pathological changes. The roles of endoplasmic reticulum (ER) stress, PERK, and protein kinase C-δ (PKCδ) were determined using pharmacological inhibitors and genetic manipulation. ER stress was induced by RLDC in kidney tubular cells in both in vivo and in vitro models. ER stress inhibitors given immediately after RLDC attenuated kidney dysfunction, tubular atrophy, kidney fibrosis, and inflammation in mice. In cultured renal proximal tubular cells, inhibitors of ER stress or its signaling kinase PERK also suppressed RLDC-induced fibrotic changes and the expression of inflammatory cytokines. Interestingly, RLDC-induced PKCδ activation, which was blocked by ER stress or PERK inhibitors, suggesting PKCδ may act downstream of PERK. Indeed, suppression of PKCδ with a kinase-dead PKCδ (PKCδ-KD) or Pkcδ-shRNA attenuated RLDC-induced fibrotic and inflammatory changes. Moreover, the expression of active PKCδ-catalytic fragment (PKCδ-CF) diminished the beneficial effects of PERK inhibitor in RLDC-treated cells. Co-immunoprecipitation assay further suggested PERK binding to PKCδ. These results indicate that ER stress contributes to chronic kidney pathologies following cisplatin chemotherapy via the PERK-PKCδ pathway.

Traditional Chinese Medicine in the Treatment of Chronic Kidney Diseases: Theories, Applications, and Mechanisms.

Chronic kidney disease (CKD) is a common and progressive disease that has become a major public health problem on a global scale. Renal fibrosis is a common feature in the pathogenesis of CKD, which is mainly related to the excessive accumulation and deposition of extracellular matrix caused by various inflammatory factors. No ideal treatment has yet been established. In recent years, based on the traditional Chinese medicine (TCM) theory of CKD and its molecular mechanism, clinical evidence or experimental studies have confirmed that a variety of Chinese materia medica (CMM) and their effective components can delay the progress of CKD. TCM believes that the pathogenesis of CKD is the deficiency in the root and excess in the branch, and the deficiency and excess are always accompanied by the disease. The strategies of TCM in treating CKD are mainly based on invigorating Qi, tonifying the kidneys, promoting blood circulation, removing stasis, eliminating heat and dampness, removing turbidity, and eliminating edema, and these effects are multitargeted and multifunctional. This review attempts to summarize the theories and treatment strategies of TCM in the treatment of CKD and presents the efficacy and mechanisms of several CMMs supported by clinical evidence or experimental studies. In addition, the relationship between the macroscopic of TCM and the microscopic of modern medicine and the problems faced in further research were also discussed.

Renoprotective potentials of small molecule natural products targeting mitochondrial dysfunction.

Kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD), have become critical clinical, socioeconomic, and public health concerns worldwide. The kidney requires a lot of energy, and mitochondria act as the central organelle for the proper functioning of the kidney. Mitochondrial dysfunction has been associated with the pathogenesis of AKI and CKD. Natural products and their structural analogs have been sought as an alternative therapeutic strategy despite the challenges in drug discovery. Many studies have shown that small-molecule natural products can improve renal function and ameliorate kidney disease progression. This review summarizes the nephroprotective effects of small-molecule natural products, such as berberine, betulinic acid, celastrol, curcumin, salidroside, polydatin, and resveratrol. Treatment with small-molecule natural products was shown to attenuate renal oxidative stress and mitochondrial DNA (mtDNA) damage and restore mitochondrial biogenesis and dynamics in the kidneys against various injury stimuli. Therefore, small-molecule natural products should be recognized as multi-target therapeutics and promising drugs to prevent kidney diseases, particularly those with mitochondrial dysfunction.

Lysophosphatidic Acid Is a Proinflammatory Stimulus of Renal Tubular Epithelial Cells.

Chronic kidney disease (CKD) refers to a spectrum of diseases defined by renal fibrosis, permanent alterations in kidney structure, and low glomerular-filtration rate. Prolonged epithelial-tubular damage involves a series of changes that eventually lead to CKD, highlighting the importance of tubular epithelial cells in this process. Lysophosphatidic acid (LPA) is a bioactive lipid that signals mainly through its six cognate LPA receptors and is implicated in several chronic inflammatory pathological conditions. In this report, we have stimulated human proximal tubular epithelial cells (HKC-8) with LPA and 175 other possibly pathological stimuli, and simultaneously detected the levels of 27 intracellular phosphoproteins and 32 extracellular secreted molecules with multiplex ELISA. This quantification revealed a large amount of information concerning the signaling and the physiology of HKC-8 cells that can be extrapolated to other proximal tubular epithelial cells. LPA responses clustered with pro-inflammatory stimuli such as TNF and IL-1, promoting the phosphorylation of important inflammatory signaling hubs, including CREB1, ERK1, JUN, IκΒα, and MEK1, as well as the secretion of inflammatory factors of clinical relevance, including CCL2, CCL3, CXCL10, ICAM1, IL-6, and IL-8, most of them shown for the first time in proximal tubular epithelial cells. The identified LPA-induced signal-transduction pathways, which were pharmacologically validated, and the secretion of the inflammatory factors offer novel insights into the possible role of LPA in CKD pathogenesis.

The fibrogenic niche in kidney fibrosis: components and mechanisms.

Kidney fibrosis, characterized by excessive deposition of extracellular matrix (ECM) that leads to tissue scarring, is the final common outcome of a wide variety of chronic kidney diseases. Rather than being distributed uniformly across the kidney parenchyma, renal fibrotic lesions initiate at certain focal sites in which the fibrogenic niche is formed in a spatially confined fashion. This niche provides a unique tissue microenvironment that is orchestrated by a specialized ECM network consisting of de novo-induced matricellular proteins. Other structural elements of the fibrogenic niche include kidney resident and infiltrated inflammatory cells, extracellular vesicles, soluble factors and metabolites. ECM proteins in the fibrogenic niche recruit soluble factors including WNTs and transforming growth factor-β from the extracellular milieu, creating a distinctive profibrotic microenvironment. Studies using decellularized ECM scaffolds from fibrotic kidneys show that the fibrogenic niche autonomously promotes fibroblast proliferation, tubular injury, macrophage activation and endothelial cell depletion, pathological features that recapitulate key events in the pathogenesis of chronic kidney disease. The concept of the fibrogenic niche represents a paradigm shift in understanding of the mechanism of kidney fibrosis that could lead to the development of non-invasive biomarkers and novel therapies not only for chronic kidney disease, but also for fibrotic diseases of other organs.

First Author Spotlight

AnnouncementFirst Author SpotlightPublished Online:13 Jul 2022https://doi.org/10.1152/ajprenal.2022.323.1.AUMoreSectionsPDF (465 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat BOHAN CHENDivision of Nephrology, University of Toledo Medical Center, Toledo, OhioFigure 1.Bohan ChenDownload figureDownload PowerPointBohan Chen is a research fellow in Dr. Rujun Gong’s laboratory at the University of Toledo College of Medicine, where she studies the pathogenesis of chronic kidney diseases. She earned her MD degree at Zhengzhou University in China. In her spare time, she enjoys reading and outdoor activities [Photo: Fig. 1].https://doi.org/10.1152/ajprenal.00130.2022DOUGLASS B. CLAYTONDivision of Pediatric Urology, Department of Urology, Vanderbilt University Medical Center, Nashville, TennesseeFigure 2.Douglass ClaytonDownload figureDownload PowerPointDouglass Clayton, MD, is an Associate Professor of Urology at Vanderbilt University Medical Center and was mentored by Volker Haase, MD. His clinical work focuses on the care of children with urological problems. His research interest is centered on the role of the hypoxia-inducible factor pathway in bladder inflammation. In his spare time, he enjoys weightlifting, reading, and traveling [Photo: Fig. 2].https://doi.org/10.1152/ajprenal.00344.2021RYAN J. CORNELIUSDivision of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, OregonFigure 3.Ryan CorneliusDownload figureDownload PowerPointRyan Cornelius completed his PhD at the University of Nebraska Medical Center in Omaha, NE, mentored by Dr. Steve Sansom. In 2015, he came to Oregon Health and Science University as a postdoctoral fellow in David Ellison’s laboratory, where he studies electrolyte balance and kidney injury with a focus on the role of cullin-RING ligase regulation in the kidney. He spends his free time hiking and skiing with his wife, Sarah [Photo: Fig. 3].https://doi.org/10.1152/ajprenal.00436.2021JESSE A. DAVIDSONDepartment of Pediatrics, University of Colorado, Aurora, ColoradoFigure 4.Jesse DavidsonDownload figureDownload PowerPointJesse Davidson, MD, MPH, MSc, is an Associate Professor of Pediatrics at Children’s Hospital Colorado with dual board certification in pediatric cardiology/critical care. His research focuses on the systems biology and therapy of multiorgan injury after infant cardiac surgery, with a particular interest in leveraging metabolomic and proteomic techniques to explore the complex molecular pathways activated during postoperative injury and recovery [Photo: Fig. 4].https://doi.org/10.1152/ajprenal.00039.2022JULIAN D. C. SERNADepartment of Biochemistry, Chemistry Institute, Universidade de São Paulo, São Paulo, BrazilFigure 5.Julian SernaDownload figureDownload PowerPointJulian Serna is a PhD candidate at the Department of Biochemistry of Universidade de São Paulo, in Brazil. He completed his BS at Universidad del Valle in Chemistry. He is mentored by Dr. Alicia Juliana Kowaltowski. His research interest focuses on calcium signaling, metabolism, and mitochondrial biology. In his spare time, he enjoys learning about life on earth and doing pole sport [Photo: Fig. 5].https://doi.org/10.1152/ajprenal.00461.2021This article has no references to display. Download PDF Back to Top Next FiguresReferencesRelatedInformationRelated ArticlesThe Janus view: dual roles for hypoxia-inducible factor in renal repair after acute kidney injury 21 Jun 2022American Journal of Physiology-Renal PhysiologyInhibition of hypoxia-inducible factor-prolyl hydroxylation protects from cyclophosphamide-induced bladder injury and urinary dysfunction 21 Jun 2022American Journal of Physiology-Renal PhysiologyCOP9 signalosome deletion promotes renal injury and distal convoluted tubule remodeling 21 Jun 2022American Journal of Physiology-Renal PhysiologyMetabolomic profiling demonstrates evidence for kidney and urine metabolic dysregulation in a piglet model of cardiac surgery-induced acute kidney injury 21 Jun 2022American Journal of Physiology-Renal PhysiologyRegulation of kidney mitochondrial function by caloric restriction 21 Jun 2022American Journal of Physiology-Renal Physiology More from this issue > Volume 323Issue 1July 2022Pages i-ii Crossmark Copyright & PermissionsCopyright © 2022 the American Physiological Society.https://doi.org/10.1152/ajprenal.2022.323.1.AUHistory Published online 13 July 2022 Published in print 1 July 2022 Metrics

Research progress on regulation of mitophagy by traditional Chinese medicine in prevention and treatment of chronic kidney diseases

The prevalence of chronic kidney disease(CKD) increases year by year and has become a highly prevalent disease, seriously affecting the quality of life of patients and bringing heavy family burden. There are many diseases causing CKD, including va-rious primary and secondary glomerulonephritis, renal tubular injury, and renal vascular lesions. Although routine medical treatment for CKD can alleviate the clinical symptoms to a certain extent, it is sometimes difficult to prevent the progression of CKD. Traditional Chinese medicine(TCM) is advantageous in high safety, few adverse reactions, and definite clinical efficacy in the treatment of CKD. The active components contained can play a synergistic effect through multiple pathways and multiple targets to delay disease progression, but its mechanism of action has not been fully elucidated. As revealed by the literature in this field in China and abroad, abnormal mitophagy is a common feature of the pathogenesis of CKD of different types. In recent years, a large number of studies have proved that the regulation of mitophagy through the PINK1/Parkin signaling pathway and mitophagy receptor pathway could delay the progression of CKD and protect renal function. Therefore, the regulation of mitophagy by TCM in the prevention and treatment of CKD through related pathways has become a potential therapeutic target in recent years. This paper reviewed the research articles on the definite efficacy of TCM in preventing and treating CKD by regulating mitophagy through relevant pathways to provide new targets and stra-tegies for preventing and treating CKD and delaying their entry into end-stage renal diseases.

Ethnic disparities in the association between low-grade inflammation biomarkers and chronic kidney disease: The HELIUS Cohort Study

AimsEthnic differences exist in the prevalence and progression of chronic kidney disease (CKD). However, underlying mechanisms remain unclear. It has been proposed that chronic low-grade inflammation plays an important role in CKD pathogenesis. In the current analysis, we study the association between systemic inflammatory biomarkers and CKD prevalence in different ethnic groups. MethodsWe examined cross-sectional associations between biomarkers of low-grade inflammation, including serum high-sensitive (hs)-CRP, fibrinogen, and D-dimer, and CKD prevalence in different ethnic groups residing in Amsterdam, the Netherlands. We included 5740 participants (similar-sized Dutch, African Surinamese, South-Asian Surinamese, Ghanaian, Turkish and Moroccan populations) aged 18 to 70 years of the Healthy Life in an Urban Setting study (HELIUS) cohort. ResultsIn the fully adjusted models, adjusted for ethnicity-specific cut-off values, elevated fibrinogen [odds ratio 2.50 (95 % confidence interval 1.10–5.78)] and D-dimer [2.99 (1.28–7.00)] were significantly associated with CKD in Dutch. In South-Asian Surinamese, a significant association with elevated D-dimer [2.66 (1.32–5.37)] was found. ConclusionsOur study shows that there are both differences in biomarker levels and the association with CKD across ethnic groups. Future research to identify potential drivers of the differential associations and susceptibility of CKD among ethnic groups to reduce the CKD burden is necessary.

Identification of circulating lncRNA in chronic kidney disease based on bioinformatics analysis.

Chronic kidney disease (CKD) is a high mortality disease and generally remains asymptomatic in the early stages. Long non-coding RNA (lncRNA) is defined as a non-protein-coding transcript more than 200 nucleotides which participate in numerous biological processes and have been identified as novel diagnostic markers for many diseases. Detection of circulating lncRNAs is a rapidly evolving, new area of molecular diagnosis. The purpose of our research was to identify circulating lncRNA expression profiles and possible molecular mechanisms involved in CKD. Blood samples were obtained from patients with CKD and healthy volunteers, and high-throughput sequencing was performed to identify differentially expressed (DE) lncRNAs and mRNAs. DE lncRNAs and mRNAs in peripheral blood mononuclear cells (PBMCs) were confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) to ensure the reliability and validity of RNA-seq data. Bioinformatics analysis was used to obtain biological functions and key pathways related to the pathogenesis of CKD. The interaction and co-expression functional networks for DE lncRNAs and mRNAs were also constructed. Our data showed that of the 425 DE lncRNAs detected, 196 lncRNAs were upregulated, while that of 229 lncRNAs were downregulated. A total of 433 DE mRNAs were identified in patients with CKD compared to healthy individuals. GO analysis revealed that DE lncRNAs were highly correlated with binding and pathway regulation. KEGG analysis suggested that DE lncRNAs were obviously enriched in regulatory pathways, such as antigen processing and presentation. We successfully constructed a potential DE lncRNA-mRNA co-expression network and analyzed the target genes of DE lncRNAs to predict cis- and trans-regulation in CKD. 100 lncRNAs that corresponded to 14 transcription factors (TFs) were identified in the TF-lncRNA binary network. Our findings on the lncRNA expression profiles and functional networks may help to interpret the possible molecular mechanisms implied in the pathogenesis of CKD; the results demonstrated that lncRNAs could potentially to be used as diagnostic biomarkers in CKD.

Metabolic Syndrome-Related Kidney Injury: A Review and Update.

Metabolic syndrome (MetS) includes visceral obesity, hyperglycemia, dyslipidemia, and hypertension. The prevalence of MetS is 20-25%, which is an important risk factor for chronic kidney disease (CKD). MetS causes effects on renal pathophysiology, including glomerular hyperfiltration, RAAS, microalbuminuria, profibrotic factors and podocyte injury. This review compares several criteria of MetS and analyzes their differences. MetS and the pathogenesis of CKD includes insulin resistance, obesity, dyslipidemia, inflammation, oxidative stress, and endothelial dysfunction. The intervention of MetS-related renal damage is the focus of this article and includes controlling body weight, hypertension, hyperglycemia, and hyperlipidemia, requiring all components to meet the criteria. In addition, interventions such as endoplasmic reticulum stress, oxidative stress, gut microbiota, body metabolism, appetite inhibition, podocyte apoptosis, and mesenchymal stem cells are reviewed.