Pub Date : 2024-06-07DOI: 10.3390/kidneydial4020010
Etienne Pays
Apolipoprotein L1 (APOL1) nephropathy results from several podocyte dysfunctions involving morphological and motility changes, mitochondrial perturbations, inflammatory stress, and alterations in cation channel activity. I propose that this phenotype results from increased hydrophobicity of the APOL1 risk variants, which induces two distinct types of podocyte dysfunctions. On one hand, increased hydrophobic interactions with APOL3 cause intracellular variant isoforms to impair both APOL3 control of Golgi PI(4)P kinase-B (PI4KB) activity and APOL3 control of mitochondrial membrane fusion, triggering actomyosin reorganisation together with mitophagy and apoptosis inhibition (hit 1). On the other hand, increased hydrophobic interactions with the podocyte plasma membrane may cause the extracellular variant isoforms to activate toxic Ca2+ influx and K+ efflux by the TRPC6 and BK channels, respectively (hit 2), presumably due to APOL1-mediated cholesterol clustering in microdomains. I propose that hit 2 depends on low HDL-C/high extracellular APOL1 ratio, such as occurs in cell culture in vitro, or during type I-interferon (IFN-I)-mediated inflammation.
{"title":"The Two Levels of Podocyte Dysfunctions Induced by Apolipoprotein L1 Risk Variants","authors":"Etienne Pays","doi":"10.3390/kidneydial4020010","DOIUrl":"https://doi.org/10.3390/kidneydial4020010","url":null,"abstract":"Apolipoprotein L1 (APOL1) nephropathy results from several podocyte dysfunctions involving morphological and motility changes, mitochondrial perturbations, inflammatory stress, and alterations in cation channel activity. I propose that this phenotype results from increased hydrophobicity of the APOL1 risk variants, which induces two distinct types of podocyte dysfunctions. On one hand, increased hydrophobic interactions with APOL3 cause intracellular variant isoforms to impair both APOL3 control of Golgi PI(4)P kinase-B (PI4KB) activity and APOL3 control of mitochondrial membrane fusion, triggering actomyosin reorganisation together with mitophagy and apoptosis inhibition (hit 1). On the other hand, increased hydrophobic interactions with the podocyte plasma membrane may cause the extracellular variant isoforms to activate toxic Ca2+ influx and K+ efflux by the TRPC6 and BK channels, respectively (hit 2), presumably due to APOL1-mediated cholesterol clustering in microdomains. I propose that hit 2 depends on low HDL-C/high extracellular APOL1 ratio, such as occurs in cell culture in vitro, or during type I-interferon (IFN-I)-mediated inflammation.","PeriodicalId":74038,"journal":{"name":"Kidney and dialysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141373605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.3390/kidneydial4020009
Dmitrii Balakhnin, I. Chermnykh, Artem Ivkin, E. Grigoriev
Cardiac surgery-associated acute kidney injury (CSA-AKI) is a complication of cardiopulmonary bypass surgery that frequently occurs in children. The increased availability of pediatric cardiac surgery leads to yearly increases in congenital heart disease (CHD) procedures performed worldwide. The number of complications, including pediatric CSA-AKI, has also increased. Children with CSA-AKI have worse postoperative periods and require more complex post-op intensive care. Thus, the timely commencement of interventions to prevent and to treat kidney injury in CHD children are one of a leading goals of pediatric cardiac intensive care.
{"title":"Cardiac Surgery-Associated Acute Kidney Injury in Children after Cardiopulmonary Bypass","authors":"Dmitrii Balakhnin, I. Chermnykh, Artem Ivkin, E. Grigoriev","doi":"10.3390/kidneydial4020009","DOIUrl":"https://doi.org/10.3390/kidneydial4020009","url":null,"abstract":"Cardiac surgery-associated acute kidney injury (CSA-AKI) is a complication of cardiopulmonary bypass surgery that frequently occurs in children. The increased availability of pediatric cardiac surgery leads to yearly increases in congenital heart disease (CHD) procedures performed worldwide. The number of complications, including pediatric CSA-AKI, has also increased. Children with CSA-AKI have worse postoperative periods and require more complex post-op intensive care. Thus, the timely commencement of interventions to prevent and to treat kidney injury in CHD children are one of a leading goals of pediatric cardiac intensive care.","PeriodicalId":74038,"journal":{"name":"Kidney and dialysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140994895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08DOI: 10.3390/kidneydial4020008
Yukie Kitajima
It is necessary to ensure adequate energy and protein intake in dialysis patients. However, in addition to the decline in dietary intake in older dialysis patients due to aging, the rate of anorexia is high in dialysis patients, which increases the risk of protein–energy wasting (PEW), sarcopenia, and frailty. There are many causes of anorexia in dialysis patients, including older dialysis patients, and approaches to improve the appetite of such patients have been reported; however, there has been no established approach to improve appetite adequately. Therefore, a key practical goal is to identify anorexia early and implement timely interventions before weight loss occurs. Appetite assessment tools and weight loss assessments are helpful for the screening and early identification of anorectic signs. Nutritional interventions include reducing dietary restrictions, using oral nutritional supplements, and intradialytic parenteral nutrition, as well as replenishing energy, protein, and zinc to prevent the development of nutritional disorders among older dialysis patients. Appetite assessments, early intervention, and dietary and nutritional counseling are key to improving appetite in these patients. The aging rate of dialysis patients in Japan is unprecedented globally, and I believe that this is a situation that will eventually occur in other countries as well. I discuss the factors that contribute to anorexia, especially in older dialysis patients, and Japan’s efforts to address this problem, such as the relaxation of dietary restrictions and the use of oral nutritional supplements.
{"title":"How Can We Improve the Appetite of Older Patients on Dialysis in Japan?","authors":"Yukie Kitajima","doi":"10.3390/kidneydial4020008","DOIUrl":"https://doi.org/10.3390/kidneydial4020008","url":null,"abstract":"It is necessary to ensure adequate energy and protein intake in dialysis patients. However, in addition to the decline in dietary intake in older dialysis patients due to aging, the rate of anorexia is high in dialysis patients, which increases the risk of protein–energy wasting (PEW), sarcopenia, and frailty. There are many causes of anorexia in dialysis patients, including older dialysis patients, and approaches to improve the appetite of such patients have been reported; however, there has been no established approach to improve appetite adequately. Therefore, a key practical goal is to identify anorexia early and implement timely interventions before weight loss occurs. Appetite assessment tools and weight loss assessments are helpful for the screening and early identification of anorectic signs. Nutritional interventions include reducing dietary restrictions, using oral nutritional supplements, and intradialytic parenteral nutrition, as well as replenishing energy, protein, and zinc to prevent the development of nutritional disorders among older dialysis patients. Appetite assessments, early intervention, and dietary and nutritional counseling are key to improving appetite in these patients. The aging rate of dialysis patients in Japan is unprecedented globally, and I believe that this is a situation that will eventually occur in other countries as well. I discuss the factors that contribute to anorexia, especially in older dialysis patients, and Japan’s efforts to address this problem, such as the relaxation of dietary restrictions and the use of oral nutritional supplements.","PeriodicalId":74038,"journal":{"name":"Kidney and dialysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141001565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-04DOI: 10.3390/kidneydial4010002
Braden Vogt, Ankur D. Shah
Urgent-start peritoneal dialysis (USPD) is defined as peritoneal dialysis initiated within 14 days of catheter insertion. In this review, the authors describe the most recent data on USPD, including outcomes, complications, barriers to implementation, and areas for future research. Outcomes appear similar between catheter insertion techniques, so patient factors and institutional workflow should guide practice. Mechanical complications may occur at a higher rate in USPD, but it does not impact technique survival or mortality. Infectious complications appear unchanged in USPD, and there may be fewer complications compared to urgent-start hemodialysis. Barriers to implementation are multifactorial, including physician and staff unfamiliarity and lack of institutional support. A significant limitation within the field includes lack of uniform terminology and definitions.
{"title":"Urgent-Start Peritoneal Dialysis: Current State and Future Directions","authors":"Braden Vogt, Ankur D. Shah","doi":"10.3390/kidneydial4010002","DOIUrl":"https://doi.org/10.3390/kidneydial4010002","url":null,"abstract":"Urgent-start peritoneal dialysis (USPD) is defined as peritoneal dialysis initiated within 14 days of catheter insertion. In this review, the authors describe the most recent data on USPD, including outcomes, complications, barriers to implementation, and areas for future research. Outcomes appear similar between catheter insertion techniques, so patient factors and institutional workflow should guide practice. Mechanical complications may occur at a higher rate in USPD, but it does not impact technique survival or mortality. Infectious complications appear unchanged in USPD, and there may be fewer complications compared to urgent-start hemodialysis. Barriers to implementation are multifactorial, including physician and staff unfamiliarity and lack of institutional support. A significant limitation within the field includes lack of uniform terminology and definitions.","PeriodicalId":74038,"journal":{"name":"Kidney and dialysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139387240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-24DOI: 10.3390/kidneydial4010001
S. Van Laecke
Magnesium is an essential element with a pleiotropic role in human biology. Despite tight intestinal and renal regulation of its balance, insufficient intake can finally result in hypomagnesemia, which is a proxy of intracellular deficiency. Conditions such as diabetes, cancer, and infections are often associated with hypomagnesemia, which mostly predicts an unfavorable outcome. The effects of hypomagnesemia can either be direct and include neurological and cardiovascular symptoms or indirect, taking a mechanistic role in inflammation, endothelial dysfunction, and oxidative stress. The indication for intravenous magnesium as a treatment of torsades de pointes and pre-eclampsia is unrefuted, but new indications of peroral or intravenous supplementation, albeit with less supporting evidence, have emerged suggesting, respectively, an attenuation of vascular calcification in chronic kidney disease and improved rate control in atrial fibrillation. Other potential beneficial properties of magnesium, which were claimed by observational data, such as lipid lowering and renal protection, were not, or only partially, investigated in randomized controlled trials. Thus, the role of peroral supplementation of mild chronic asymptomatic hypomagnesemia should be separated from the more targeted prescription of magnesium in specific study populations. (Severe) hypermagnesemia is potentially life-threatening and occurs almost uniformly in subjects with severe renal failure exposed to either supplements or to magnesium-containing cathartics or antacids. Moderate hypermagnesemia is very common in pre-eclamptic women treated with intravenous magnesium. For most (but not all) studied endpoints, mild hypermagnesemia yields a survival benefit. Long-lasting concerns about the potential negative effects of mild hypermagnesemia on bone physiology and structure have so far not been unequivocally demonstrated to be troublesome.
{"title":"An Update on Hypomagnesemia and Hypermagnesemia","authors":"S. Van Laecke","doi":"10.3390/kidneydial4010001","DOIUrl":"https://doi.org/10.3390/kidneydial4010001","url":null,"abstract":"Magnesium is an essential element with a pleiotropic role in human biology. Despite tight intestinal and renal regulation of its balance, insufficient intake can finally result in hypomagnesemia, which is a proxy of intracellular deficiency. Conditions such as diabetes, cancer, and infections are often associated with hypomagnesemia, which mostly predicts an unfavorable outcome. The effects of hypomagnesemia can either be direct and include neurological and cardiovascular symptoms or indirect, taking a mechanistic role in inflammation, endothelial dysfunction, and oxidative stress. The indication for intravenous magnesium as a treatment of torsades de pointes and pre-eclampsia is unrefuted, but new indications of peroral or intravenous supplementation, albeit with less supporting evidence, have emerged suggesting, respectively, an attenuation of vascular calcification in chronic kidney disease and improved rate control in atrial fibrillation. Other potential beneficial properties of magnesium, which were claimed by observational data, such as lipid lowering and renal protection, were not, or only partially, investigated in randomized controlled trials. Thus, the role of peroral supplementation of mild chronic asymptomatic hypomagnesemia should be separated from the more targeted prescription of magnesium in specific study populations. (Severe) hypermagnesemia is potentially life-threatening and occurs almost uniformly in subjects with severe renal failure exposed to either supplements or to magnesium-containing cathartics or antacids. Moderate hypermagnesemia is very common in pre-eclamptic women treated with intravenous magnesium. For most (but not all) studied endpoints, mild hypermagnesemia yields a survival benefit. Long-lasting concerns about the potential negative effects of mild hypermagnesemia on bone physiology and structure have so far not been unequivocally demonstrated to be troublesome.","PeriodicalId":74038,"journal":{"name":"Kidney and dialysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139160099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-12DOI: 10.3390/kidneydial3040030
P. A. S. Vaz de Castro, Thomas Fujihara Ide, Fernando Crespo Torres, A. C. Simões e Silva
Nephrotic syndrome (NS) is a complex clinical entity characterized by proteinuria, hypoalbuminemia, and edema. In this review, we propose the view of NS as a podocytopathy, highlighting the importance of understanding the role of podocytes in the development of this condition. We discuss the various etiologies of NS, ranging from congenital to primary renal diseases, as well as secondary forms due to systemic diseases. We also delve into the mechanisms underlying podocyte injury, which plays a crucial role in the development of NS. By viewing NS as a podocytopathy, we suggest potential implications for the diagnosis and treatment of this condition, including the use of podocyte-specific biomarkers and targeted therapies. Our review provides a comprehensive overview of NS and its underlying mechanisms, emphasizing the importance of a multidisciplinary approach to the diagnosis and management of this condition. Further research is essential to better understand the complex interplay between podocyte injury and the development of NS, with the ultimate goal of improving patient outcomes.
{"title":"The View of Pediatric Nephrotic Syndrome as a Podocytopathy","authors":"P. A. S. Vaz de Castro, Thomas Fujihara Ide, Fernando Crespo Torres, A. C. Simões e Silva","doi":"10.3390/kidneydial3040030","DOIUrl":"https://doi.org/10.3390/kidneydial3040030","url":null,"abstract":"Nephrotic syndrome (NS) is a complex clinical entity characterized by proteinuria, hypoalbuminemia, and edema. In this review, we propose the view of NS as a podocytopathy, highlighting the importance of understanding the role of podocytes in the development of this condition. We discuss the various etiologies of NS, ranging from congenital to primary renal diseases, as well as secondary forms due to systemic diseases. We also delve into the mechanisms underlying podocyte injury, which plays a crucial role in the development of NS. By viewing NS as a podocytopathy, we suggest potential implications for the diagnosis and treatment of this condition, including the use of podocyte-specific biomarkers and targeted therapies. Our review provides a comprehensive overview of NS and its underlying mechanisms, emphasizing the importance of a multidisciplinary approach to the diagnosis and management of this condition. Further research is essential to better understand the complex interplay between podocyte injury and the development of NS, with the ultimate goal of improving patient outcomes.","PeriodicalId":74038,"journal":{"name":"Kidney and dialysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139009972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-06DOI: 10.3390/kidneydial3040029
Lauren Floyd, Joshua Storrar, Sanjeev Pramanik, Adam D. Morris, Smeeta Sinha, Silke R. Brix, Philip A. Kalra, Ajay P. Dhaygude
ANCA-associated vasculitides (AAV) are rare, autoimmune conditions associated with end-stage kidney disease (ESKD) and mortality. Data have predominately been from White populations of European ancestry although geographical differences are well documented. Few studies have looked at the incidence, phenotype and clinical outcomes of ethnic minority patients, in particular Indo-Asian populations. A two-center, retrospective cohort study was conducted of patients with ANCA-associated glomerulonephritis (AAGN), self-identifying as Indo-Asian in the North West, UK between 2009 and 2023. A control group of White patients was identified from the same databases and recruited consecutively in relation to the original cohort of Indo-Asian patients. A total of 66 patients were included, 24 patients of Indo-Asian ethnicity and a control cohort of 42 patients of White ethnicity. Indo-Asian patients had a lower median age at diagnosis (53.0 vs. 57.5 years, p = 0.15) and there was an increased prevalence of diabetes mellitus (33.3% vs. 4.8%, p = 0.002) and a higher incidence of previous TB exposure (12.5% vs. 0%, p = 0.019). Outcomes including relapse, ESKD and mortality were similar. We demonstrated an increased crude incidence of AAGN in Indo-Asian patients in the UK compared to similar epidemiological studies. Consideration needs to be given to epidemiological and genetic research, achieved by collaboration and broader recruitment in clinical trials.
{"title":"Clinical Phenotype and Outcomes of Indo-Asian Patients with ANCA-Associated Glomerulonephritis in the North West, UK","authors":"Lauren Floyd, Joshua Storrar, Sanjeev Pramanik, Adam D. Morris, Smeeta Sinha, Silke R. Brix, Philip A. Kalra, Ajay P. Dhaygude","doi":"10.3390/kidneydial3040029","DOIUrl":"https://doi.org/10.3390/kidneydial3040029","url":null,"abstract":"ANCA-associated vasculitides (AAV) are rare, autoimmune conditions associated with end-stage kidney disease (ESKD) and mortality. Data have predominately been from White populations of European ancestry although geographical differences are well documented. Few studies have looked at the incidence, phenotype and clinical outcomes of ethnic minority patients, in particular Indo-Asian populations. A two-center, retrospective cohort study was conducted of patients with ANCA-associated glomerulonephritis (AAGN), self-identifying as Indo-Asian in the North West, UK between 2009 and 2023. A control group of White patients was identified from the same databases and recruited consecutively in relation to the original cohort of Indo-Asian patients. A total of 66 patients were included, 24 patients of Indo-Asian ethnicity and a control cohort of 42 patients of White ethnicity. Indo-Asian patients had a lower median age at diagnosis (53.0 vs. 57.5 years, p = 0.15) and there was an increased prevalence of diabetes mellitus (33.3% vs. 4.8%, p = 0.002) and a higher incidence of previous TB exposure (12.5% vs. 0%, p = 0.019). Outcomes including relapse, ESKD and mortality were similar. We demonstrated an increased crude incidence of AAGN in Indo-Asian patients in the UK compared to similar epidemiological studies. Consideration needs to be given to epidemiological and genetic research, achieved by collaboration and broader recruitment in clinical trials.","PeriodicalId":74038,"journal":{"name":"Kidney and dialysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135636213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-03DOI: 10.3390/kidneydial3040028
Evdokia Bogdanova, Airat Sadykov, Galina Ivanova, Irina Zubina, Olga Beresneva, Olga Galkina, Marina Parastaeva, Vladimir Sharoyko, Vladimir Dobronravov
Chronic kidney disease—mineral and bone disorder (CKD-MBD) plays a significant role in causing cardiovascular morbidity and mortality related to CKD. CKD-MBD has been studied during advanced stages when changes in inorganic phosphate (Pi) and its hormonal regulation are obvious. The initial phases of myocardial remodeling (MR) in early CKD-MBD remain poorly understood. We induced mild CKD-MBD in spontaneously hypertensive rats using 3/4 nephrectomy. Animals were fed standard chow, containing 0.6% phosphate. In each animal, we analyzed indices of chronic kidney injury, bone turnover and Pi exchange, and assessed the myocardial histology and gene expression profile. Applied CKD-MBD models corresponded to human CKD S1-2 with low bone turnover and without an increase in systemic Pi-regulating factors (parathyroid hormone and fibroblast growth factor 23). In mild CKD-MBD models, we found MR features characterized by cardiomyocyte hypertrophy, interstitial and perivascular fibrosis, intramyocardial artery media thickening, along with alterations in Ppp3ca, Mapk1, Jag1, Hes1, Ptch1, Numb, Lgr4 and Bmp4 genes. Among other genes, the down-regulation of Jag1 was most tightly associated with either myocardial hypertrophy or fibrosis. Myocardial alterations concurrently occurred with mild CKD-MBD and comprised fibrosis preceding cardiomyocyte hypertrophy. The histological features of MR were associated with myocardial P accumulation in settings of low bone turnover, prior to a response of systemic Pi-regulating factors and with alterations in calcineurin, ERK1/2, Notch, BMP and Hedgehog genes.
{"title":"Myocardial Remodeling in Early Chronic Kidney Disease—Mineral and Bone Disorder Model with Low Bone Turnover","authors":"Evdokia Bogdanova, Airat Sadykov, Galina Ivanova, Irina Zubina, Olga Beresneva, Olga Galkina, Marina Parastaeva, Vladimir Sharoyko, Vladimir Dobronravov","doi":"10.3390/kidneydial3040028","DOIUrl":"https://doi.org/10.3390/kidneydial3040028","url":null,"abstract":"Chronic kidney disease—mineral and bone disorder (CKD-MBD) plays a significant role in causing cardiovascular morbidity and mortality related to CKD. CKD-MBD has been studied during advanced stages when changes in inorganic phosphate (Pi) and its hormonal regulation are obvious. The initial phases of myocardial remodeling (MR) in early CKD-MBD remain poorly understood. We induced mild CKD-MBD in spontaneously hypertensive rats using 3/4 nephrectomy. Animals were fed standard chow, containing 0.6% phosphate. In each animal, we analyzed indices of chronic kidney injury, bone turnover and Pi exchange, and assessed the myocardial histology and gene expression profile. Applied CKD-MBD models corresponded to human CKD S1-2 with low bone turnover and without an increase in systemic Pi-regulating factors (parathyroid hormone and fibroblast growth factor 23). In mild CKD-MBD models, we found MR features characterized by cardiomyocyte hypertrophy, interstitial and perivascular fibrosis, intramyocardial artery media thickening, along with alterations in Ppp3ca, Mapk1, Jag1, Hes1, Ptch1, Numb, Lgr4 and Bmp4 genes. Among other genes, the down-regulation of Jag1 was most tightly associated with either myocardial hypertrophy or fibrosis. Myocardial alterations concurrently occurred with mild CKD-MBD and comprised fibrosis preceding cardiomyocyte hypertrophy. The histological features of MR were associated with myocardial P accumulation in settings of low bone turnover, prior to a response of systemic Pi-regulating factors and with alterations in calcineurin, ERK1/2, Notch, BMP and Hedgehog genes.","PeriodicalId":74038,"journal":{"name":"Kidney and dialysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135695614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-06DOI: 10.3390/kidneydial3030027
Kenji Nakata, N. Joki
Cardiovascular medicine, especially for ischemic heart disease, has evolved and advanced over the past two decades, leading to substantially improved outcomes for patients, even those with chronic kidney disease. However, the prognosis for patients with end-stage kidney disease (ESKD) has not improved so greatly. Recent studies have reported that myocardial fibrosis in chronic kidney disease patients is characterized by patchy and interstitial patterns. Areas of fibrosis have been located in the perivascular space, and severe fibrotic lesions appear to spread into myocardial fiber bundles in the form of pericellular fibrosis. These findings are fully consistent with known characteristics of reactive fibrosis. In hemodialysis patients, a greater extent of myocardial fibrosis is closely associated with a poorer prognosis. In this review, we focus on non-ischemic cardiomyopathy, especially reactive myocardial fibrosis, in ESKD patients.
{"title":"Non-Ischemic Myocardial Fibrosis in End-Stage Kidney Disease Patients: A New Perspective","authors":"Kenji Nakata, N. Joki","doi":"10.3390/kidneydial3030027","DOIUrl":"https://doi.org/10.3390/kidneydial3030027","url":null,"abstract":"Cardiovascular medicine, especially for ischemic heart disease, has evolved and advanced over the past two decades, leading to substantially improved outcomes for patients, even those with chronic kidney disease. However, the prognosis for patients with end-stage kidney disease (ESKD) has not improved so greatly. Recent studies have reported that myocardial fibrosis in chronic kidney disease patients is characterized by patchy and interstitial patterns. Areas of fibrosis have been located in the perivascular space, and severe fibrotic lesions appear to spread into myocardial fiber bundles in the form of pericellular fibrosis. These findings are fully consistent with known characteristics of reactive fibrosis. In hemodialysis patients, a greater extent of myocardial fibrosis is closely associated with a poorer prognosis. In this review, we focus on non-ischemic cardiomyopathy, especially reactive myocardial fibrosis, in ESKD patients.","PeriodicalId":74038,"journal":{"name":"Kidney and dialysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49301550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.3390/kidneydial3030026
Brett T. Burrows, Ashley M. Morgan, Alexis C. King, Rosalba Hernandez, K. Wilund
Nonadherence to exercise-related trials in hemodialysis (HD) patients is a significant burden worldwide. To address this issue, we assessed the feasibility and preliminary efficacy of a combined pre-habilitative virtual-reality-based mindfulness (VRM) program and a personalized activity prescription (PARx) in HD patients with elevated depressive symptoms. Ten HD patients (age = 59.60 ± 13.66) with elevated depressive symptoms completed a 10-week intervention. Participants were randomized into either a VRM+PARx (n = 6) or PARx alone (n = 4) group. During the 2-week prehabilitation, the VRM+PARx group completed our VRM program, while the PARx alone group received usual HD care. Post-prehabilitation, both groups began our 8-week PARx program. Feasibility was assessed by rates of recruitment, retention, adherence, and acceptability and adoption. Preliminary efficacy was measured using metrics of depressive symptoms, mindfulness, fatigue, and physical activity (PA) energy expenditure. A 25% recruitment rate was documented, with 90% retention. A 75% exercise adherence rate was observed and PARx demonstrated high perceived autonomy support (M = 27.6 ± 2.1). Post-prehabilitation, the VRM+PARx group showed significant between-group improvement in mindfulness (p = 0.02) and a significant within-group reduction in depressive symptoms (p = 0.05); however, no difference between groups was observed (p = 0.07). Post-PARx, no between-group difference was evident in PA energy expenditure; however, within the VRM+PARx group, a significant increase in PA energy expenditure was observed (p < 0.01). Fatigue remained unchanged. Our VRM and PARx programs demonstrated feasibility and potential efficacy for HD patients. However, to validate these findings, future trials should consider a larger sample size and a longer duration.
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