JournalTOCs

Kidney Diseases
Number of Followers: 3

This is an Open Access Journal

Open Access journal
ISSN (Print) 2296-9381 - ISSN (Online) 2296-9357
Published by Karger

[120 journals]

Strategies to improve long-term outcomes for patients with chronic kidney
disease in China
- Abstract: Background: Chronic kidney disease (CKD) is an incurable disease requiring lifelong management. China has a high prevalence of CKD, which disproportionately affects older adults and those with chronic risk factors for CKD development. The rising prevalence of CKD in China places a substantial burden on the general population and the healthcare system. Summary: In China, there are currently many unmet needs for patients with CKD and high-risk individuals, resulting from a lack of education and support to reduce risk factors, delayed diagnoses, limited knowledge of CKD among primary care physicians and poor access to treatments among some patient populations. An integrated, nationwide approach is required to improve the current situation of CKD management in China. There are currently several national healthcare frameworks in place that focus on new major health policies to prevent disease and encourage people to adopt healthier lifestyles, and while they do not directly target CKD, they may have a positive indirect impact. We explore the unmet needs for patients with CKD in China and discuss the potential strategies that may be required to overcome them. Such strategies include improving physician and patient education, establishing a targeted screening programme, supporting patients to improve self-management behaviours, accelerating the creation of medical consortia and medical satellite centres, and migrating from hospital- to community-based management. In additional to policy-driven strategies, development of novel therapies will be key to providing new solutions for the long-term management of CKD.
  
  PubDate: Tue, 11 Apr 2023 09:55:38 +020
Efficacy and safety of SGLT2 inhibitors in nondiabetic patients with CKD:
a review of recent evidence
- Abstract: Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) were initially developed as glucose-lowering agents in patients with type-2 diabetes. However, available data from clinical trials and meta-analyses suggest that SGLT2i have pleiotropic benefits in reducing mortality and delaying the progression of chronic kidney disease (CKD) in both diabetic and nondiabetic patients. Thus, we herein review the current evidence regarding the efficacy and safety of SGLT2i in patients with nondiabetic CKD, and appraise the recently reported clinical trials that might facilitate the management of CKD in routine clinical practice. Summary: The benefits of SGLT2i on nondiabetic CKD are multifactorial and is mediated by a combination of mechanisms. The landmark DAPA-CKD trial revealed that dapagliflozin administered with renin-angiotensin system blockade drugs reduced the risk of a sustained decline (at least 50%) in the estimated glomerular filtration rate (eGFR), end-stage kidney disease (ESKD), or death from cardio-renal causes. The recent EMPA-KIDNEY trial showed that empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes. These benefits were consistent in patients with and without diabetes. Moreover, a meta-analysis of DAPA-HF and EMPEROR-Reduced trials confirmed reductions in the combined risk of cardiovascular death or worsening heart failure including composite renal endpoint. Key Messages: Considering the robust data available from DAPA-CKD, EMPA-KIDNEY and other trials such as EMPEROR-Preserved, DIAMOND that included nondiabetic patients, it may be necessary to update current guidelines to include SGLT2i as a first-line therapy for CKD and re-evaluate current CKD therapeutic approaches.
  
  PubDate: Tue, 11 Apr 2023 09:00:01 +020
From physiology to pathology: the role of mitochondria in acute kidney
injuries and chronic kidney diseases
- Abstract: Background: Renal diseases remain an increasing public health issue affecting millions of people. The kidney is a highly energetic organ that is rich in mitochondria. Numerous studies have demonstrated the important role of mitochondria in maintaining normal kidney function and in the pathogenesis of various renal diseases, including acute kidney injuries (AKI) and chronic kidney diseases (CKD). Summary: Under physiological conditions, fine-tuning mitochondrial energy balance, mitochondrial dynamics (fission and fusion processes), mitophagy, and biogenesis maintain mitochondrial fitness. While under AKI and CKD conditions, disruption of mitochondrial energy metabolism leads to increased oxidative stress. In addition, mitochondrial dynamics shift to excessive mitochondrial fission, mitochondrial autophagy is impaired, and mitochondrial biogenesis is also compromised. These mitochondrial injuries regulate renal cellular functions either directly or indirectly. Mitochondria-targeted approaches, containing genetic (microRNAs) and pharmaceutical methods (mitochondria-targeting antioxidants, mitochondrial permeability pore inhibitors, mitochondrial fission inhibitors, and biogenesis activators) are emerging as important therapeutic strategies for AKI and CKD. Key messages: Mitochondria play a critical role in the pathogenesis of AKI and CKD. This review provides an updated overview of mitochondrial homeostasis under physiological conditions and the involvement of mitochondrial dysfunction in renal diseases. Finally, we summarize the current status of mitochondria-targeted strategies in attenuating renal diseases.
  
  PubDate: Tue, 04 Apr 2023 11:55:42 +020
Develop and Validate a Risk Score in Predicting Renal Failure in Focal
Segmental Glomerulosclerosis
- Abstract: Introduction The aim of this study is to develop and validate a risk score for end stage kidney disease (ESKD) in patients with focal segmental glomerulosclerosis (FSGS).Methods Patient with biopsy proven FSGS were enrolled. All the patients were allocated 1:1 to the two groups according to their baseline gender, age and baseline creatinine level by using a stratified randomization method. ESKD was the primary endpoint. Results We recruited 359 FSGS patients,177 subjects were assigned to group 1 and 182 to group 2. The clinicopathological variables were similar between two groups. There were 23 (13%) subjects reached to ESKD in group 1 and 22 (12.1%) in group 2. By multivariate Cox regression analyses we established risk scores (RS) 1 and RS 2 in groups 1 and 2, respectively. RS1 consists of five parameters including lower eGFR, higher urine protein, MAP, IgG level, and tubular-interstitial lesion (TIL) score; RS2 also consists of five predictors including lower C3, higher MAP, IgG level, hemoglobin and TIL score. RS1 and RS2 were cross-validated between these two groups, showing RS1 had better performance in predicting 5-year ESKD in Group1 [c statics, 0.86(0.74-0.98) vs 0.82(0.69-0.95] and Group2 [c statics, 0.91(0.83-0.99) vs 0.89(0.79-0.99)] compared to RS2. We then stratified the risk factors into four groups and Kaplan-Meier survival curve revealed that patients progressed to ESKD increased as risk levels increased. Conclusions A predictive model incorporated clinicopathological features was developed and validated for the prediction of ESKD in FSGS patients.
  
  PubDate: Tue, 28 Mar 2023 18:29:03 +020
Therapeutic potential targeting podocyte mitochondrial dysfunction in
focal segmental glomerulosclerosis
- Abstract: Background：Podocytes are essential components of the glomerular filtration barrier and essential for the proper filtration function of the glomerulus. Podocyte injury under various stress conditions is the primary pathogenesis and key determinant of focal segmental glomerulosclerosis (FSGS) with prominent clinical manifestations of proteinuria or nephrotic syndrome. Summary：Under physiological conditions, a highly coordinated mitochondrial quality control system, including antioxidant defenses, mitochondrial dynamics (fusion, fission and mitophagy), and mitochondrial biogenesis, guarantees the sophisticated structure and various functions of podocytes. However, under FSGS pathological conditions, mitochondria encounter oxidative stress, dynamics disturbances, and defective mitochondrial biogenesis. Moreover, mutations in mtDNA and mitochondria-related genes are also strongly associated with FSGS. Based on these evidences, bioactive agents that function to relieve mitochondrial oxidative stress and promote mitochondrial biogenesis have been proven effective in pre-clinical FSGS models. Targeting the mitochondrial network is expected to provide new therapeutic strategies for the treatment of FSGS and delay its progression to end-stage renal disease (ESRD). Key messages：Mitochondrial dysfunction plays a key role in podocyte injury and FSGS progression. This review summarized recent advances in the study of mitochondrial homeostatic imbalance and dysfunction in FSGS and discussed the potential of mitochondria-targeted therapeutics in improving FSGS and retarding its progression to ESRD.
  
  PubDate: Tue, 28 Mar 2023 18:18:41 +020
Role of IL-6 family cytokines in organ fibrosis
- Abstract: Background: Organ fibrosis remains an important cause of high incidence rate and mortality worldwide. The prominent role of interleukin-6 (IL-6) family members represented by IL-6 in inflammation has been extensively studied, and drugs targeting IL-6 have been used clinically. Because of the close relationship between inflammation and fibrosis, researches on the role of IL-6 family members in organ fibrosis are also gradually emerging. Summary: In this review, we systematically reviewed the role of IL-6 family members in fibrosis and their possible mechanisms. We listed the role of IL-6 family members in organ fibrosis, and drew two diagrams to illustrate the downstream signal transductions of IL-6 family members. We also summarized the effect of some IL-6 family members' antagonists in a table.Key Messages: Fibrosis contributes to organ structure damage, organ dysfunction and eventually organ failure. Although IL-6 family cytokines have similar downstream signal pathways, different members play various roles in an organ-specific manner which might partly due to their different target cell populations. The pathogenic role of individual member in various diseases needs to be deciphered carefully.
  
  PubDate: Wed, 22 Mar 2023 12:05:39 +010
Hospitalizations of chronic dialysis patients: a national study in China
- Abstract: BackgroundPatients receiving chronic dialysis are usually with multiple comorbidities and at high-risk for hospitalization, which lead to tremendous healthcare resources utilization. This study aims to explore the characteristics of hospitalizations among chronic dialysis patients in China.MethodsHospital admissions from January 2013 to December 2015 were extracted from a national inpatient database in China. Chronic dialysis, including hemodialysis and peritoneal dialysis, were identified according to inpatients discharge records and International Classification of Diseases-10 (ICD-10) codes. The primary kidney disease, causes of admissions, modalities of dialysis, and comorbidities were analyzed. Multivariable Logistic regression model was used to assess the association of patient characteristics with multiple hospitalizations per year.ResultsAltogether, 266,636 hospitalizations from 124,721 chronic dialysis patients were included in the study. The mean age was 54.46±15.63 years and 78.29% of them were receiving hemodialysis. The leading cause of hospitalizations was dialysis access-related, including dialysis access creation (25.06%) and complications of access (21.09%). The following causes were non-access surgery (1.89%), cardiovascular disease (1.66%), and infectious diseases (1.43%). One fourth of the patients were hospitalized more than once per year. Multivariate Logistic regression models indicated that the primary kidney disease of diabetic kidney disease (odds ratio [OR]: 1.16, 95% confidence interval [CI]: 1.11-1.22) or hypertensive nephropathy (OR: 1.33, 95% CI: 1.27-1.40), coronary heart disease (OR: 1.09, 95% CI: 1.05-1.14), cancer (OR: 1.21, 95% CI: 1.13-1.30), or modality of peritoneal dialysis (OR: 2.67, 95% CI: 2.59-2.75) were risk factors for multiple hospitalizations.ConclusionOur study described characteristics and revealed the burden of hospitalizations of chronic dialysis patients in China. These findings highlight the importance of effective and efficient management strategies to reduce the high burden of hospitalization in dialysis population.
  
  PubDate: Mon, 20 Mar 2023 11:10:49 +010
Nephropathy is aggravated by fatty acids in diabetic kidney disease
through tubular epithelial cell necroptosis and is alleviated by an RIPK-1
inhibitor
- Abstract: Introduction: Diabetic kidney disease (DKD), one of the leading causes of end-stage renal disease, has complex pathogenic mechanisms and few effective clinical therapies. DKD progression is accompanied by the loss of renal resident cells, followed by chronic inflammation and extracellular matrix deposition. Necroptosis is a newly discovered form of regulated cell death and is a major form of intrinsic cell loss in certain diabetic complications such as cardiomyopathy, intestinal disease, and retinal neuropathy; however, its significance in DKD is largely unknown. Methods: In this study, the expression of necroptosis marker phosphorylated MLKL (p-MLKL) in renal biopsy tissues of patients with DKD was detected using immunofluorescence and semiquantified using immunohistochemistry. The effects of different disease-causing factors on necroptosis activation in human HK-2 cells were evaluated using immunofluorescence and western blotting. db/db diabetic mice were fed a high-fat diet to establish an animal model of DKD with significant renal tubule damage. Mice were treated with RIPK1 inhibitor RIPA-56 to evaluate its renal protective effects. mRNA transcriptome sequencing was used to explore the changes in signaling pathways after RIPA-56 treatment. Oil red O staining and electron macroscopy were used to observe lipid droplet accumulation in renal biopsy tissues and mouse kidney tissues.Results: Immunostaining of phosphorylated RIPK1/RIPK3/MLKL verified the occurrence of necroptosis in renal tubular epithelial cells (RTECs) of patients with DKD. The level of the necroptosis marker p-MLKL correlated positively with the severity of renal functional, pathological damages, and lipid droplet accumulation in patients with DKD. High glucose and fatty acids were the main factors causing necroptosis in human renal tubular HK-2 cells. Renal function deterioration and renal pathological injury were accelerated, and the necroptosis pathway was activated in db/db mice fed a high-fat diet. Application of RIPA-56 effectively reduced the degree of renal injury, inhibited the necroptosis pathway activation, and reduced necroinflammation and lipid droplet accumulation in the renal tissues of db/db mice fed a high-fat diet. Conclusion: The present study revealed the role of necroptosis in the progression of DKD and might provide a new therapeutic target for the treatment of DKD.
  
  PubDate: Fri, 17 Mar 2023 10:19:54 +010
A panoramic view of ferroptosis in cardiovascular disease
- Abstract: Background: Cardiovascular disease (CVD) remains the leading cause of disease burden worldwide. Ferroptosis, an iron-dependent form of programmed cell death, is characterized by the lethal accumulation of lipid peroxidation, which is morphologically, biochemically and genetically distinct from apoptosis, necrosis and pyroptosis. Emerging evidence provides exciting novel insights to allow for a deeper understanding of the physiology and pathology of ferroptosis in CVD. Summary: The rapidly evolving insights into ferroptosis have revealed its role in the pathogenesis of diverse forms of CVD, including cardiomyopathy, heart failure, atherosclerosis, pulmonary arterial hypertension and cerebrovascular disease. Various types of metabolic pathways are involved in the regulation of ferroptosis, including iron metabolism, lipid metabolism and oxidative metabolism. Modulators of ferroptosis, such as several clinical drugs, preclinical compounds and other emerging materials, have been applied as promising approaches in the prevention and treatment of CVD. Key message: In this review, we provide a 360-degree view of the latest progress in the field of ferroptosis in CVD, highlight the pathogenic role of ferroptosis in CVD and also discuss the importance and future directions of targeting ferroptosis in CVD.
  
  PubDate: Wed, 15 Mar 2023 10:39:01 +010
Impact of Angiopoietin-2 on Kidney Diseases
- Abstract: Background: Angiopoietins (Ang) are essential angiogenic factors involved in angiogenesis, vascular maturation, and inflammation. The most studied angiopoietins, angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), behave antagonistically to each other in vivo to sustain vascular endothelium homeostasis. While Ang-1 typically acts as the endothelium-protective mediator, its context-dependent antagonist Ang-2 can promote endothelium permeability and vascular destabilization, hence contributing to a poor outcome in vascular diseases via endothelial injury, vascular dysfunction, and microinflammation. The pathogenesis of kidney diseases is associated with endothelial dysfunction and chronic inflammation in renal diseases. Summary: Several preclinical studies report overexpression of Ang-2 in renal tissues of certain kidney disease models; additionally, clinical studies show increased levels of circulating Ang-2 in the course of chronic kidney disease, implying that Ang-2 may serve as a useful biomarker in these patients. However, the exact mechanisms of Ang-2 action in renal diseases remain unclear. Key Messages: We summarized the recent findings on Ang-2 in kidney diseases, including preclinical studies and clinical studies, aiming to provide a systematic understanding of the role of Ang-2 in these diseases.
  Kidney Dis
  PubDate: Tue, 14 Mar 2023 14:01:59 +010