METABOLISM IN CHRONIC KIDNEY DISEASE Research Articles

Research hotspots and future trends in lipid metabolism in chronic kidney disease: a bibliometric and visualization analysis from 2004 to 2023.

Disorders of lipid metabolism play a key role in the initiation and progression of chronic kidney disease (CKD). Recently, research on lipid metabolism in CKD has rapidly increased worldwide. However, comprehensive bibliometric analyses in this field are lacking. Therefore, this study aimed to evaluate publications in the field of lipid metabolism in CKD over the past 20years based on bibliometric analysis methods to understand the important achievements, popular research topics, and emerging thematic trends. Literature on lipid metabolism in CKD, published between 2004 and 2023, was retrieved from the Web of Science Core Collection. The VOSviewer (v.1.6.19), CiteSpace (v.6.3 R1), R language (v.4.3.2), and Bibliometrix (v.4.1.4) packages (https://www.bibliometrix.org) were used for the bibliometric analysis and visualization. Annual output, author, country, institution, journal, cited literature, co-cited literature, and keywords were also included. The citation frequency and H-index were used to evaluate quality and influence. In total, 1,285 publications in the field of lipid metabolism in CKD were identified in this study. A total of 7,615 authors from 1,885 institutions in 69 countries and regions published articles in 466 journals. Among them, China was the most productive (368 articles), and the United States had the most citations (17,880 times) and the highest H-index (75). Vaziri Nosratola D, Levi Moshe, Fornoni Alessia, Zhao Yingyong, and Merscher Sandra emerged as core authors. Levi Moshe (2,247 times) and Vaziri Nosratola D (1,969 times) were also authors of the top two most cited publications. The International Journal of Molecular Sciences and Kidney International are the most published and cited journals in this field, respectively. Cardiovascular disease (CVD) and diabetic kidney disease (DKD) have attracted significant attention in the field of lipid metabolism. Oxidative stress, inflammation, insulin resistance, autophagy, and cell death are the key research topics in this field. Through bibliometric analysis, the current status and global trends in lipid metabolism in CKD were demonstrated. CVD and DKD are closely associated with the lipid metabolism of patients with CKD. Future studies should focus on effective CKD treatments using lipid-lowering targets.

Dysregulation of lipid metabolism in chronic kidney disease and the role of natural products.

Dysregulation of lipid metabolism plays a key role in the onset and progression of CKD, and a thorough understanding of its regulatory mechanisms is essential for the development of effective treatments. In recent years, an increasing number of studies have focused on the pharmacological activities of natural products and their application in the treatment of chronic diseases. Natural products, including plant extracts and bioactive compounds, have been shown to exert anti-inflammatory, antioxidant, antifibrosis, and anti-apoptotic effects through various signaling pathways in the treatment of CKD. Many natural products have been shown to target dysregulated lipid metabolism through various signaling pathways. This review summarizes the key regulatory factors and signaling pathways involved in the dysregulation of lipid metabolism in chronic kidney disease (CKD), highlighting their importance as potential therapeutic targets. Recently published research on the potential therapeutic benefits of natural products for the treatment of CKD was described. These studies have revealed the multi-target role of natural products in the regulation of lipid metabolism. Natural products show great potential in targeting lipid metabolism-related pathways, offering a novel research direction for the treatment of CKD while providing a scientific basis and experimental support for the development of new treatment strategies.

Assessment of regional and total skeletal metabolism using 18F-NaF PET/CT in patients with chronic kidney disease.

The study aims to assess regional and total bone metabolic activity in patients with chronic kidney disease using Na[18F]F PET and correlation between semi-quantitative indices and blood parameters. Seventy-two subjects (mean age 61.8 ± 13.8years) were included. Of these 24/72 patients had end-stage renal disease (ESRD) (GFR < 15mL/min/1.73 m2), 38/72 had chronic kidney disease (CKD) (GFR between 60 and 15mL/min/1.73 m2), and 10/72 were controls with normal renal function. All subjects underwent Na[18F]F PET-CT with a dose activity of 0.06mCi/Kg. Regional and total skeletal metabolism were assessed with mean SUVs in a skeletal volume of interest (VOI), bone to soft tissue index (B/S), global SUV mean (GSUV mean) of the whole bone, and uptake in the femoral neck. Statistically significant differences were observed in a number of 18F-NaF metrics like femoral neck metabolism in CKD and ERSD groups in comparison to control in right (P = 0.003) and left femur (P = 0.006), bone to soft tissue index in the femur (P = 0.016) and GSUV5 (P = 0.006). There is also a significant difference in SUV mean in lumbar vertebrae (L1-L4) among CKD, ESRD, and controls. There was a moderate correlation between 18F-NaF PET scan uptake and blood parameters such as ALP and PTH. Na[18F]F uptake parameters were significantly different in low versus high bone turnover state. The assessment of total skeleton and regional metabolism and bone turnover in CKD patients is feasible with Na[18F]F PET. Na[18F]F can help to detect early changes in bone metabolism and assess the progression of bone disease in this complex condition. Quantification with Na[18F]F PET might provide better assessment of the bone turnover. The difference in Na[18F]F uptake in CKD compared to controls is likely related to a change in bone turnover which, however, requires further validation.

Vitamin D metabolism in diabetic nephropathy

Diabetic nephropathy (DN) is a specific kidney involvement in diabetes mellitus (DM), caused by hemodynamic and metabolic factors. In the kidneys takes place an important step in the metabolism of vitamin D — 1α-hydroxylation, which results in the formation of its biologically active form. Reduced number of functioning nephrons in DN leads to impaired vitamin D metabolism, contributing to the development of a number of complications. In this review, we have focused in detail on both normal vitamin D metabolism and the features of vitamin D metabolism in chronic kidney disease (CKD). DN is the most common cause of CKD and, as a consequence, of kidney transplantation and one of the leading causes of cardiovascular morbidity and mortality in patients with DM. Bone mineral disorders resulting from abnormal vitamin D metabolism are also independent factors of high mortality among patients with DM. The final part of our review briefly highlights current approaches to vitamin D therapy in CKD and, in particular, in DN. It is worth noting that, despite the increasing number of patients with DN, there is currently no unified view on the use of vitamin D as a therapeutic agent in this pathology.

Hypomagnesemia: a potential underlooked cause of persistent vitamin D deficiency in chronic kidney disease.

Magnesium and vitamin D play important roles in most cells of the body. These nutrients act in a coordinated fashion to maintain physiologic functions of various organs, and their abnormal balance could adversely affect these functions. Therefore, deficient states of both nutrients may lead to several chronic medical conditions and increased cardiovascular and all-cause mortality. Chronic kidney disease (CKD) patients have altered metabolism of both magnesium and vitamin D. Some studies indicate that magnesium could have a role in the synthesis and metabolism of vitamin D, and that magnesium supplementation substantially reversed the resistance to vitamin D treatment in some clinical situations. Recent observational studies also found that magnesium intake significantly interacted with vitamin D status and, particularly with the risk of cardiovascular mortality. It is therefore essential to ensure adequate levels of magnesium to obtain the optimal benefits of vitamin D supplementation in CKD patients. In this review, we discuss magnesium physiology, magnesium and vitamin D metabolism in CKD, potential metabolic interactions between magnesium and vitamin D and its clinical relevance, as well as the possible role of magnesium supplementation to assure adequate vitamin D levels.

Metabolic profiling identifies the significance of caffeine metabolism in CKD.

Background: With the development of chronic kidney disease (CKD), there are various changes in metabolites. However, the effect of these metabolites on the etiology, progression and prognosis of CKD remains unclear. Objective: We aimed to identify significant metabolic pathways in CKD progression by screening metabolites through metabolic profiling, thus identifying potential targets for CKD treatment. Methods: Clinical data were collected from 145 CKD participants. GFR (mGFR) was measured by the iohexol method and participants were divided into four groups according to their mGFR. Untargeted metabolomics analysis was performed via UPLC-MS/MSUPLC-MSMS/MS assays. Metabolomic data were analyzed by MetaboAnalyst 5.0, one-way ANOVA, principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) to identify differential metabolites for further analysis. The open database sources of MBRole2.0, including KEGG and HMDB, were used to identify significant metabolic pathways in CKD progression. Results: Four metabolic pathways were classified as important in CKD progression, among which the most significant was caffeine metabolism. A total of 12 differential metabolites were enriched in caffeine metabolism, four of which decreased with the deterioration of the CKD stage, and two of which increased with the deterioration of the CKD stage. Of the four decreased metabolites, the most important was caffeine. Conclusion: Caffeine metabolism appears to be the most important pathway in the progression of CKD as identified by metabolic profiling. Caffeine is the most important metabolite that decreases with the deterioration of the CKD stage.

FGF23 in Chronic Kidney Disease: Bridging the Heart and Anemia.

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone produced mainly in osteocytes. In chronic kidney disease (CKD) FGF23 levels increase due to higher production, but also as the result of impaired cleavage and reduced excretion from the body. FGF23 has a significant role in disturbed bone and mineral metabolism in CKD, which leads to a higher cardiovascular risk and mortality in these patients. Current research has emphasized the expression of FGF23 in cardiac myocytes, fibroblasts, and endothelial cells, and in addition to the effects on the kidney, its primary role is in cardiac remodeling in CKD patients. Recent discoveries found a significant link between increased FGF23 levels and anemia development in CKD. This review describes the FGF23 role in cardiac hypertrophy and anemia in the setting of CKD and discusses the best therapeutical approach for lowering FGF23 levels.

Iron deficiency in chronic kidney disease and the new generation of intravenous iron

Anemia is the most common complication of chronic kidney disease (CKD) and the main cause of poor prognosis in CKD patients. Iron deficiency (ID) is the second most important factor in the occurrence of anemia in CKD besides EPO deficiency, and iron is currently the main treatment for iron deficiency in patients with CKD anemia. Iron supplements are divided into intravenous iron and oral iron supplements. Oral iron is often ineffective due to its gastrointestinal side effects and low absorption efficiency. Traditional intravenous iron can only be administered in small single doses due to safety restrictions. New intravenous iron agents have emerged. This article provides a brief overview of current iron metabolism in chronic kidney disease, causes of iron deficiency, iron status and new intravenous iron agents available.

Uremic Myopathy and Mitochondrial Dysfunction in Kidney Disease.

Alterations in muscle structure and function in chronic kidney disease (CKD) patients are associated with poor outcomes. As key organelles in muscle cell homeostasis, mitochondrial metabolism has been studied in the context of muscle dysfunction in CKD. We conducted a study to determine the contribution of oxidative metabolism, glycolysis and fatty acid oxidation to the muscle metabolism in CKD. Mice developed CKD by exposure to adenine in the diet. Muscle of CKD mice showed significant weight loss compared to non-CKD mice, but only extensor digitorum longus (EDL) muscle showed a decreased number of fibers. There was no difference in the proportion of the various muscle fibers in CKD and non-CKD mice. Muscle of CKD mice had decreased expression of proteins associated with oxidative phosphorylation but increased expression of enzymes and transporters associated with glycolysis. In cell culture, myotubes exposed to uremic serum demonstrated decreased oxygen consumption rates (OCR) when glucose was used as substrate, conserved OCR when fatty acids were used and increased lactate production. In conclusion, mice with adenine-induced CKD developed sarcopenia and with increased glycolytic metabolism but without gross changes in fiber structure. In vitro models of uremic myopathy suggest fatty acid utilization is preserved compared to decreased glucose utilization.

Reno-Protective Effect of Low Protein Diet Supplemented With α-Ketoacid Through Gut Microbiota and Fecal Metabolism in 5/6 Nephrectomized Mice.

BackgroundLow protein supplemented with α-ketoacid diet (LKD) was recommended to be an essential intervention to delay the progression of chronic kidney disease (CKD) in patients who were not yet on dialysis. Aberrant gut microbiota and metabolism have been reported to be highly associated with CKD. However, the effect of LKD on gut microbiota and related fecal metabolism in CKD remains unclear.MethodsMice were fed with normal protein diet (NPD group), low protein diet (LPD group), and low protein diet supplemented with α-ketoacid (LKD group) after 5/6 nephrectomy. At the end of the study, blood, kidney tissues, and feces were collected for biochemical analyses, histological, 16S rRNA sequence of gut microbiome, and untargeted fecal metabolomic analyses.ResultsBoth LKD and LPD alleviate renal failure and fibrosis, and inflammatory statement in 5/6 nephrectomized mice, especially the LKD. In terms of gut microbiome, LKD significantly improved the dysbiosis induced by 5/6Nx, representing increased α-diversity and decreased F/B ratio. Compared with NPD, LKD significantly increased the abundance of g_Parasutterella, s_Parabacteroides_sp_CT06, f_Erysipelotrichaceae, g_Akkermansia, g_Gordonibacter, g_Faecalitalea, and s_Mucispirillum_sp_69, and decreased s_Lachnospiraceae_bacterium_28-4 and g_Lachnoclostridium. Moreover, 5/6Nx and LKD significantly altered fecal metabolome. Then, multi-omics analysis revealed that specific metabolites involved in glycerophospholipid, purine, vitamin B6, sphingolipid, phenylalanine, tyrosine and tryptophan biosynthesis, and microbes associated with LKD were correlated with the amelioration of CKD.ConclusionLKD had a better effect than LPD on delaying renal failure in 5/6 nephrectomy-induced CKD, which may be due to the regulation of affecting the gut microbiome and fecal metabolic profiles.

Effect of nutritional calcium and phosphate loading on calciprotein particle kinetics in adults with normal and impaired kidney function.

Plasma approaches metastability with respect to its calcium and phosphate content, with only minor perturbations in ionic activity needed to sustain crystal growth once nucleated. Physiologically, calcium and phosphate are intermittently absorbed from the diet each day, yet plasma concentrations of these ions deviate minimally post-prandially. This implies the existence of a blood-borne mineral buffer system to sequester calcium phosphates and minimise the risk of deposition in the soft tissues. Calciprotein particles (CPP), endogenous mineral-protein colloids containing the plasma protein fetuin-A, may fulfill this function but definitive evidence linking dietary mineral loading with their formation is lacking. Here we demonstrate that CPP are formed as a normal physiological response to feeding in healthy adults and that this occurs despite minimal change in conventional serum mineral markers. Further, in individuals with Chronic Kidney Disease (CKD), in whom mineral handling is impaired, we show that both fasting and post-prandial levels of CPP precursors are markedly augmented and strongly inversely correlated with kidney function. This study highlights the important, but often neglected, contribution of colloidal biochemistry to mineral homeostasis and provides novel insight into the dysregulation of mineral metabolism in CKD.

MO814: Sucroferric Oxyhydroxide versus Calcium Carbonate in the Treatment Bone Metabolism in Patients with Ckd3–5 Evaluated by 18F-NA Fluoride PET/CT and Biomarkers: A Randomized Crossover Study

Abstract BACKGROUND AND AIMS Non-invasive methods for assessing bone metabolism have been lacking in chronic kidney disease (CKD), and the effects of different treatments on bone metabolism are mostly unknown. However, fluorine-18 labeled sodium fluoride (18F-NaF) PET/CT scanning can assess bone turnover as skeletal plasma clearance of tracer (Ki) and bone volume/tissue volume (BV/TV) in CKD. In a randomized crossover study, we aimed to compare the 8-week treatment effects of a non-calcium-based phosphate binder, sucroferric oxyhydroxide (SO), with 8 weeks of treatment with a calcium-based phosphate binder, calcium carbonate (CC), on bone turnover and BV/TV. METHOD Whole body 18F-NaF PET/CT scans were performed at the end of the CC and SO treatment periods in each participant. Ki was determined by the single-point Patlak method with semi-population input functions. A recently established CKD-MDB population residual curve was applied. Estimation of BV/TV was made by CT-derived Hounsfield units (HU) in specified volumes of interest. Paired t-tests were used or non-parametric tests (Wilcoxon signed-ranks test) when data were not normally distributed. Statistical analyses were performed using SPSS 20. RESULTS Ki assessed by the 18F-NaF scan was not significantly different at the lumbar spine (CC: 0.030 ± 0.014 mL min–1 mL–1; SO: 0.031 ± 0.014 mL min–1 mL–1; P = .75) or any other site after short-term treatment with SO or CC. However, HU was significantly higher after CC treatment. CONCLUSION 18F-NaF PET/CT is a practical tool with which to evaluate bone metabolism in CKD. Short-term SO treatment did not affect Ki (turnover) differently than CC treatment, but BV/TV (volume) was significantly lower after SO treatment than after CC treatment.

POS-250 A RANDOMIZED TRIAL OF EFFECT OF CHOLECALCIFEROL SUPPLEMENTATION ON CARDIOVASCULAR DISEASE, INFLAMMATION, AND BONE METABOLISM MARKERS IN CKD: BASELINE CHARACTERISTICS OF FEASIBILITY PHASE

Studies have linked lower vitamin D levels with cardiovascular disease (CVD) and mortality in general population and chronic kidney disease (CKD). The preliminary evidence of vitamin D supplementation is encouraging but there is a huge void with respect to good quality long term data supporting the use of this promising intervention for translation into better outcomes for CVD in CKD. This study is exploring the effect of cholecalciferol supplementation on cardiovascular disease, markers of inflammation and bone metabolism in CKD. We present the baseline characteristics of feasibility phase of the trial. The study is a multicentric, prospective, randomized, placebo controlled, double blind trial in two parallel groups and feasibility phase is being done at Postgraduate Institute of Medical Education and Research, Chandigarh, India. The trial is registered at Clinical Trials Registry of India (CTRI/2019/05/019211). After a run-in period of 2 weeks, the enrolled subjects are randomized in 1:1 to receive either 60,000 IU/2 weeks of cholecalciferol or matching placebo. The subjects will be then followed up every three month till 3 years. The primary outcome of the study is a composite of major adverse cardiac events (MACE). Secondary outcome measures include all-cause mortality, need of RRT, change in hsCRP, IL-6, iPTH, FGF-23, bone specific alkaline phosphatase, and CTX-1. A total of 720 subjects have been screened till date. Out of 119 enrolled, 86 subjects have been randomized over 24 months period. 76% subjects have completed annual follow up at 12 months, 66% subjects - 15thmonths follow up, 40%- 18 months follow up, 26% subjects - 21 months follow up, 6% subjects – 24 months follow up. Baseline characteristics and serum biomarkers levels has been analysed in 80 subjects. Mean age of the subjects were 51.3 ± 12.2 years and 58.8 % were males. Serum haemoglobin levels were 11.6 ±1.7 g/dl. Mean eGFR was 26.3 (17.4, 35.1) ml/min/1.73m2. Outcome events were; MACE: 1 (due to CVD), death other than due to MACE: 1 (due to COVID 19), subjects with composite of all-cause death and non-fatal MACE: 2, subject with need of RRT:1 and subjects with composite of 50% decline in GFR or need of RRT: 3. 2 serious adverse events unrelated to study drug were reported during the course of study. Table: Baseline levels of various serum biomarkers Tabled 1CharacteristicsTotal (N = 80)Serum creatinine (mg/dL)2.7 ± 1.1Serum calcium (mg/dL)9.2 (8.8, 9.4)Serum inorganic phosphorous (mg/dL)3.8 (3.2, 4.2)Serum intact parathyroid hormone (pg/mL)172.0 (94.6, 327.9)Serum 25-hydroxyvitamin D3 (ng/mL)28.5 (22.6, 38.2)Bone alkaline phosphatase (U/L)29.7 (22.1, 43.7)Fibroblast growth factor-23 (pg/mL)131.0 (37.9, 139.7)C-reactive protein (ng/mL)4.4 (1.9, 7.6)Interleukin-6 (pg/mL)4.0 (2.1, 2.3)Carboxy terminal telopeptide (ng/mL)1.2 (0.2, 2.3) Open table in a new tab Despite COVID 19 related restrictions being in place for most of the last 18 months, the study has been able to screen and enrol participants. The follow ups have been ensured either through physical or remote (mobile/telephonic) means. Once in the multi-centric phase, the study will be able to test a relatively inexpensive intervention in the form of vitamin D supplementation for CVD in CKD.

Insights into vitamin K metabolism in chronic kidney disease: more complicated than kale deficiency

Vascular calcification is a major manifestation of cardiovascular disease in advanced chronic kidney disease and is inhibited by vitamin K-dependent proteins. Clinical trials of vitamin K supplementation in chronic kidney disease have failed to demonstrate benefits on vascular calcification. Recent laboratory, human, and animal studies have shown that vitamin K handling and metabolism in chronic kidney disease is complex and suggest vitamin K2 subtype supplementation in isolation is unlikely to have significant clinical impact.

Cholesterol Metabolism in Chronic Kidney Disease: Physiology, Pathologic Mechanisms, and Treatment.

High plasma levels of lipids and/or lipoproteins are risk factors for atherosclerosis, nonalcoholic fatty liver disease (NAFLD), obesity, and diabetes. These four conditions have also been identified as risk factors leading to the development of chronic kidney disease (CKD). Although many pathways that generate high plasma levels of these factors have been identified, most clinical and physiologic dysfunction results from aberrant assembly and secretion of lipoproteins. The results of several published studies suggest that elevated levels of low-density lipoprotein (LDL)-cholesterol are a risk factor for atherosclerosis, myocardial infarction, coronary artery calcification associated with type 2 diabetes, and NAFLD. Cholesterol metabolism has also been identified as an important pathway contributing to the development of CKD; clinical treatments designed to alter various steps of the cholesterol synthesis and metabolism pathway are currently under study. Cholesterol synthesis and catabolism contribute to a multistep process with pathways that are regulated at the cellular level in renal tissue. Cholesterol metabolism may also be regulated by the balance between the influx and efflux of cholesterol molecules that are capable of crossing the membrane of renal proximal tubular epithelial cells and podocytes. Cellular accumulation of cholesterol can result in lipotoxicity and ultimately kidney dysfunction and failure. Thus, further research focused on cholesterol metabolism pathways will be necessary to improve our understanding of the impact of cholesterol restriction, which is currently a primary intervention recommended for patients with dyslipidemia.

Spectrally and Time-Resolved Fluorescence Imaging of 22-NBD-Cholesterol in Human Peripheral Blood Mononuclear Cells in Chronic Kidney Disease Patients.

The interaction of the fluorescent probe 22-NBD-cholesterol with membranes of human peripheral blood mononuclear cells (PBMC) was tested by time- and spectrally resolved fluorescence imaging to monitor the disturbance of lipid metabolism in chronic kidney disease (CKD) and its treatment with statins. Blood samples from healthy volunteers (HV) and CKD patients, either treated or untreated with statins, were compared. Spectral imaging was done using confocal microscopy at 16 spectral channels in response to 458 nm excitation. Time-resolved imaging was achieved by time-correlated single photon counting (TCSPC) following excitation at 475 nm. The fluorescence of 22-NBD-cholesterol was mostly integrated into plasmatic membrane and/or intracellular membrane but was missing from the nuclear region. The presence of two distinct spectral forms of 22-NBD-cholesterol was uncovered, with significant variations between studied groups. In addition, two fluorescence lifetime components were unmasked, changing in CKD patients treated with statins. The gathered results indicate that 22-NBD-cholesterol may serve as a tool to study changes in the lipid metabolism of patients with CKD to monitor the effect of statin treatment.

Relationship Between Dietary Phosphate Intake and Biomarkers of Bone and Mineral Metabolism in Australian Adults With Chronic Kidney Disease

Higher serum phosphate is associated with increased adverse outcomes including cardiovascular disease. Abnormalities of bone and mineral metabolism in chronic kidney disease (CKD), including higher serum phosphate, are important risk factors for increased cardiovascular disease. Associations between dietary phosphate intake and biochemical and cardiovascular parameters in non-dialysis CKD patients, however, have not been adequately studied. This study aimed to explore associations between phosphate intake and biomarkers of bone and mineral metabolism and intermediate cardiovascular markers in adults with stage 3-4 CKD. One hundred thirty-two participants enrolled in the IMpact of Phosphate Reduction On Vascular End-points in Chronic Kidney Disease trial were invited to participate in this sub-study. At baseline, dietary phosphate intake and its source (animal, plant, or a mixture of animal and plant) were determined using a 7-day self-administered diet food record, and measurements were made of serum and urinary phosphate, serum calcium, parathyroid hormone, fibroblast growth factor-23, and the intermediate cardiovascular markers pulse wave velocity (PWV) and abdominal aortic calcification. The relationships between dietary phosphate intake and these bone metabolism and cardiovascular markers were explored using Pearson's correlation and linear regression. The effect of source of phosphate intake was analyzed using compositional data analysis. Ninety participants (age 64±12years, 68% male, estimated glomerular filtration rate 26.6±7.6mL/min/1.73m2, daily phosphate intake 1,544±347mg) completed the study. Correlations among dietary phosphate intake and biochemical measures, PWV, and abdominal aortic calcification ranged from r=-0.13 to r=+0.13. Linear regression showed no association between dietary phosphate measurements and biochemical or cardiovascular parameters. Source of phosphate intake was associated with PWV (P=.01), but not with other biomarkers of bone and mineral metabolism. Higher PWV values were associated with higher intake of plant-based relative to animal-based phosphate (1.058 [1.020-1.098], P=.003). Levels of total dietary phosphate intake measured by dietary food record show no statistically significant relationship with biochemical markers of bone and mineral metabolism or intermediate cardiovascular markers. Higher PWV levels associated with higher intake of plant-based relative to animal-based phosphate intake were an unexpected finding and further research is needed in this area.

Editorial introductions.

Current Opinion in Nephrology and Hypertension was launched in 1992. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of nephrology and hypertension are divided into 11 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Aline MartinAline MartinDr Aline Martin, PhD, MSc, is Associate Professor of Medicine in the Division of Nephrology and Hypertension at the Northwestern University Feinberg School of Medicine, Chicago, USA. She is a graduate of the University Jean Monnet, Saint-Etienne, France, and completed her postdoctoral training at the Jared Grantham Kidney Institute, Kansas University Medical Center, Kansas City, USA. Dr Martin conducts basic and translational science research in the area of bone and mineral metabolism disorders and actively mentors undergraduate, graduate and postdoctoral trainees. Dr Martin's research involves multiple national and international collaborations. She has received research support from the National Institute of Health and is a current member of the American Society for Bone and Mineral Research, American Society of Nephrology and American Heart Association. Tamara IsakovaTamara IsakovaDr Tamara Isakova, MD, MMSc, is Associate Professor of Medicine in the Division of Nephrology and Hypertension at the Northwestern University Feinberg School of Medicine, Chicago, USA. She is also Director of the Center for Translational Metabolism and Health within the Institute for Public Health and Medicine at Northwestern. She is a graduate of the State University of New York Downstate College of Medicine, USA, and she completed internal medicine training at the Massachusetts General Hospital, Boston, USA. She also received nephrology training in the combined Massachusetts General Hospital and Brigham & Women's Hospital nephrology fellowship program. Dr Isakova conducts clinical research in the area of disordered mineral metabolism in chronic kidney disease. She has received research support from the American Kidney Fund, the American Heart Association, the American Society of Nephrology, and the National Institute of Health. Dr Isakova provides clinical care for patients with chronic kidney disease, bone and mineral metabolism disorders, and kidney stones. Orson W. MoeOrson W. MoeDr Orson W. Moe received his medical degree from the University of Toronto, Canada and is currently Professor of Internal Medicine and Physiology at the University of Texas Southwestern Medical Center, Dallas, USA. He serves administratively as the Director of the Charles and Jane Pak Center of Mineral Metabolism and Clinical Research and Chief of the Division of Nephrology. He is an active clinician, researcher, and educator holding the Charles and Jane Pak Distinguished Chair in Mineral Metabolism Research and the Donald Seldin Professorship in Clinical Investigation. Dr Moe conducts both basic science and patient-oriented research on renal physiology and metabolism, as well as epithelial biology. His research strives to cross from the level of the whole patient, to animal and cell culture models, and down to single molecules. He is active in teaching at the undergraduate and post-graduate levels, nationally and internationally. In addition to editing Current Opinion in Nephrology and Hypertension, Dr Moe also edits the textbook, The Kidney: Physiology and Pathophysiology by Seldin and Giebisch. He is currently a member of the American Society of Clinical Research, American Association of Physicians, American Society of Nephrology, International Society of Nephrology, and the American Physiologic Society. Susan E. QuagginSusan E. QuagginSusan E. Quaggin, MD, FRCP(C), FASN, is a graduate of the University of Toronto, Canada, where she completed her residency and served as chief medical resident for the University's St. Michael's Hospital. She completed her nephrology fellowship at the University of Toronto and Yale University, USA, where she also completed research and post-doctoral training. Dr Quaggin's research focuses on fundamental processes needed to establish and maintain the integrity of the specialized vascular beds in the kidney and other organs. To understand and identify new therapeutic targets, she has worked to develop genetic mouse models that allow cell and time-specific manipulation of functional genes. Translation of her group's findings regarding the vasculature reveals pathogenic mechanisms and new therapeutic targets for a number of diseases, including diabetic kidney and eye disease, nephrotic syndrome, and glaucoma. She is currently the Charles Horace Mayo Professor of Medicine at Northwestern University, USA, where she serves as the Chief of the Division of Nephrology and Hypertension and the Director of the Feinberg Cardiovascular and Renal Research Institute, USA. Dr Quaggin was elected to the American Society for Clinical Investigation in 2006, the Association of American Physicians in 2013, and the National Academy of Medicine in 2019. She is also President of the American Society of Nephrology.

Effects of triangle grass decoction on bone metabolism in rats with chronic kidney disease complicated with mineral and bone abnormalities

Ethnopharmacological relevanceTriangle grass is a liliaceous Chlorophytum perennial herb of ChlorophytumlaxumR.Br. It is distributed mainly in Guangdong and Guangxi Provinces of China. The initial use of triangle grass was mainly to treat bone pain and swelling caused by a fall injury. Triangle grass tablets (NO. Z20070544) are also used as a preparation in our hospital because of their analgesic, anti-inflammatory, anti-snake venom and microcirculation improvement properties and other pharmacological effects (Mei et al., 2006). Triangle grass tablets have been widely used in our hospital to treat patients with bone pain from chronic kidney disease-mineral and bone disorder (CKD-MBD). However, the effects and mechanism of triangle grass on bone metabolism in chronic kidney disease complicated with mineral and bone abnormalities are unclear. Aim of the studyThe aim of the present study was to investigate the effects of a triangle grass decoction on bone metabolism in CKD-MBD rats. Materials and methodsCKD-MBD model rats were subjected to 5/6 nephrectomy combined with 0.5 g NaH2PO4/rat. Serum blood urea nitrogen (BUN), creatinine (Cr), phosphorus (P), calcium (Ca), and intact parathyroid hormone (iPTH) levels were measured with an automatic biochemical analyser. Bone mineral density was determined with a Viva CT 40 system. Bone morphogenetic protein 7(BMP-7),runt-related transcription factor 2 (Runx2) and Osterix protein levels were measured by Western blot analysis. Kidney, vertebra and thoracic aorta tissue samples were assessed by histopathology and immunohistochemistry (IHC). ResultsThe degrees of membrane thickening, necrosis, swelling and cast deposition were significantly reduced in high-dose rats and Low-dose rats. Serum BUN levels were significantly reduced in the Pre-H group (P < 0.05). Hypocalcaemia and hyperphos phataemia were detected in triangle grass (P < 0.05, P < 0.05). In addition, iPTH levels were significantly increased in the Pre-H group (P < 0.05). Alkaline phosphatase (ALP)levels were significantly decreased in the Pre-H group (P < 0.05). The bone mineral density was improved in the Pre-H and Pre-L groups. BMP-7 protein levels were significantly increased in the Pre-H group (P < 0.05). The pathological changes in muscle fibres in the thoracic aorta middle membranes were significantly alleviated in rats in the Pre-H and Pre-L groups. Changes in SM22α and SMα-act in protein levels were significantly attenuated in the Pre-H group (P < 0.05, P < 0.05). Changes in Runx2 and Osterix protein levels were also significantly attenuated in the Pre-H and Pre-L groups (P < 0.05, P < 0.05). ConclusionsTriangle grass can simultaneously ameliorate vertebral bone loss and abnormal calcification in the thoracic aorta. Triangle grass has a definite effect on bone metabolism disorder in CKD-MBD rats.

Editorial introductions

Editorial introductions