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Background: Kidney function can be impaired in patients with inflammatory bowel diseases (IBD), including Crohn's diseases (CD) and ulcerative colitis (UC). However, the causal relationship between IBD and chronic kidney diseases (CKD) remains unclear. Methods: We determined the causal association between IBD and CKD by performing two‐sample bidirectional mendelian randomization (MR) analyses. Independent genetic variants were selected as instrumental variables (IVs) of the exposure from open‐access genome‐wide association studies (GWAS) among European ancestry. IVs–outcome estimates were extracted from three separate GWAS for IBD and two for CKD, respectively. Inverse‐variance‐weighted model was used as the primary MR method. The pleiotropic effect and heterogeneity were evaluated. For either direction, analyses were performed per outcome database and were subsequently meta‐analysed. Results: Genetically predicted IBD was associated with higher risk of CKD (OR: 1.045, 95% CI: 1.016–1.073, P = 0.002) by including 42 344 IBD cases and 229 164 controls. Further analyses showed genetic liability to CD increased the risk of CKD (OR: 1.057, 95% CI: 1.027–1.087, p < 0.001) whereas UC did not (OR: 0.999, 95% CI:0.969–1.031, p = 0.970). In contrast, genetically predicted CKD was not associated with IBD (OR: 1.010, 95% CI: 0.965–1.056, p = 0.676), UC (OR: 1.011, 95% CI: 0.948–1.078, p = 0.746) and CD (OR: 1.024; 95% CI: 0.963–1.089, p = 0.447). Conclusions: We concluded that CD, but not UC, can increase the risk of CKD causally. CD, but not UC, can increase the risk of chronic kidney disease causally. These findings enhance our understanding of the differential impact of IBD subtypes on CKD. It may be necessary to monitor kidney function regularly in patients with CD. Summary at a Glance: Crohn's diseases, but not ulcerative colitis, can increase the risk of chronic kidney diseases (CKD) causally.CKD were not associated with the risk of inflammatory bowel diseases casually. [ABSTRACT FROM AUTHOR]

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Introduction: Long working hours are likely associated with the decreased of kidney function, while physical activity (PA) was linked to improvements in kidney function. However, whether PA can offset the negative impact of long working hours on kidney function was unclear, which is the focus of this study. Methods: A cross-sectional study was conducted. Three approaches were adopted to distinguish the association between long working hours and regular working hours. Moderate to vigorous physical activity (PA) was assessed by a structured questionnaire. eGFR and chronic kidney disease (CKD) or not were utilized to evaluate the kidney function. Linear and logistic regression analyses were conducted to assess the association between weekly working hours, PA, and kidney function. Results: A total of 18,431 adults were enrolled in this study, including 9981 males (54.2%) and 8450 females (45.8%). The average eGFR was (99.54 ± 17.55 mL/min/1.73m2). The people worked more than 40 h/wk (98.89 ± 17.06 mL/min/1.73 m2) had lower eGFR compared to those worked less than 40 h/wk (99.93 ± 17.83 mL/min/1.73 m2) (p < 0.05). Individuals working longer hours exhibited lower eGFR (b = -0.772, 95% CI: -1.241, -0.303, for > 40 h/wk compared to working = 40 h/wk). Engagement in moderate to vigorous PA was associated with higher eGFR values (b = 1.159, 95% CI: 0.699, 1.619) compared to low PA (< 150 minutes/wk), but this association did not reach statistical significance for the prevalence of CKD. Furthermore, PA was insufficient to reverse the decline of eGFR related to prolonged working hours. Discussion: Prolonged working hours were associated with a decline in eGFR, while PA was found to have a protective effect on kidney function. However, PA alone may not fully mitigate the negative impact of prolonged working hours on renal health. More robust measures to protect renal function should be implemented to mitigate the damage caused by prolonged working hours. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the frequency of familial relationships and genetic predispositions to kidney disease, analyzing their correlation with chronic kidney disease (CKD). Methods: This observational study included individuals aged 18-70 years (at the time of this study) from October 2009 to 2015. 2576 patients with diverse kidney diseases [mean age: 47 ± 16 years; 1455 men (56.5%)], were compared with 853 healthy individuals with an employed questionnaire. Variables such as siblings, familial kidney disease history, consanguineous marriage, etiology of CKD, age at the time of the study, and diagnosis were compared between groups. Results: Parental consanguinity frequency was similar between groups [n = 174 (6.8%) in the patient group vs. n = 74 (8.7%) in the control group, P = .06]. Kidney disease due to family history was significantly higher in the patient group than in the control group (466 [18.1%] vs. 72 [8.4%], P < .001). Parental consanguinity frequency was notably higher in patients with congenital anomalies of the kidney and urinary tract (CAKUT) (n = 31/234; 13.2%) and vesicoureteral reflux (VUR) nephropathy (n = 27/131, 20.5%) compared to controls (8.7%) (P = .036 and P < .001, respectively). Multivariate analysis indicated that predictors of parental consanguinity were kidney disease due to family history (OR: 5.712; 95% CI, 4.136-7.890; P < .001), age at kidney disease diagnosis (OR: 0.968; 95% CI, 0.957-0.979; P < .001), and kidney disease replacement therapy (OR: 1.441; 95% CI, 1.020-2.038; P = .038). Conclusion: The CAKUT and VUR nephropathy risks are increased in consanguineous marriages. Patients with parental consanguinity develop the disease earlier and face a higher risk of kidney failure requiring replacement therapy. Consanguineous marriage might impact the severity of kidney diseases. [ABSTRACT FROM AUTHOR]

Hypertension is a risk factor for developing chronic kidney disease (CKD). Studies of adult participants in the USA reported that hypertension increased the risk of developing CKD even in the non-diabetic population. However, studies in non-diabetic populations are limited and additional studies in other races are required. This study aimed to examine the relationship between hypertension and the development of CKD in non-diabetic Asian adults. In this longitudinal study, non-diabetic Japanese adults who took annual checkups from 1998 to 2023 were included. CKD was defined as <60 mL/min/1.73 m2, and hypertension was classified into four levels according to the guidelines of the American College of Cardiology/American Heart Association. The Weibull accelerated failure time model was selected because the proportional hazards assumption was violated. Of the 7363 (men: 40.3%) people in the final cohort, 2498 (men: 40.1%) developed CKD after a mean follow-up of 7.99 years. Elevated blood pressure (BP) and hypertension stage 2 had a 9% (95% confidence interval [CI]: 1%–16%) and 11% (95% CI: 5%–17%) shorter survival time to CKD onset, respectively, than normal BP. Hypertension stage 1 also had a shorter survival to CKD onset by point estimate, but all 95% CIs crossed 1 in all models. In a relatively healthy Asian population without diabetes, controlling BP to an appropriate range reduces the risk of developing CKD. [Display omitted] • Relationship between hypertension and CKD in adult Asians without diabetes was studied. • The ACC/AHA blood pressure classification was used. • Hypertension is associated with shorter survival to CKD development. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing haemodialysis are more susceptible to infectious diseases, including periodontitis. This study aimed to investigate the Correlation between periodontal disease and serum markers in Yemeni haemodialysis patients. Methods: A cross-sectional study was conducted on a sample of 70 haemodialysis patients. Patient interviews, clinical examinations, and laboratory tests were performed to collect data. Serum levels of albumin, calcium, phosphorus, haemoglobin, ferritin, and creatinine were measured, with separate measurements for cystatin C The association between categorical variables was assessed using the chi-square test and Pearson's correlation coefficient, considering a significance level of p < 0.05. Results: Significant correlations were found between serum biomarkers and periodontal clinical parameters. Phosphorus, creatinine, albumin, ferritin, and creatinine levels correlated significantly with the Plaque Index (p < 0.001, p < 0.001, p = 0.015, p = 0.018, and p = 0.03). While the Ferritin level showed significant correlations with both the Plaque Index and Miller Classes (r = 0.281, p = 0.018 and r = 0.258, p = 0.031), respectively. The Calcium level showed a significant correlation with the Gingival Index (r = 0.266, p = 0.027). Cystatin C level was statistically correlated with mobility (r = 0.258, p = 0.031). Also, the result showed a significant correlation between Creatinine levels and Periodontitis (r = 0.26, p = 0.03). Conclusion: This study provides evidence of a strong association between periodontal disease and chronic kidney disease in Yemeni haemodialysis patients. The findings emphasize the significance of maintaining good oral health in the care of haemodialysis patients. [ABSTRACT FROM AUTHOR]

Background: This investigation aims to examine the relationship between diabetes and prediabetes with chronic kidney disease (CKD) while taking into account key risk factors such as gender, age, lifestyle, smoking habits, and blood pressure. Methods: Between November 17, 2016, and November 22, 2018, 4063 subjects aged 35 to 70 years were enrolled in the first phase of the Bandare-Kong Non-Communicable Disease (BKNCD) Cohort Study, which is part of the PERSIAN (Prospective Epidemiological Research Studies in IrAN) cohort and was conducted in a coastal region of the Hormozgan province in southern Iran. CKD was calculated using the Modification of Diet in Renal Disease (MDRD) formula based on glomerular filtration rate (GFR)<60 mL/min per 1.73 m², or albumin/Cr>30 mg/g in random urine, self-reported kidney failure, or dialysis. Urine albumin and creatinine were determined by standard kits (Pars Azmoon, Tehran, Iran) and the BT1500 automatic chemistry analyzer (Biotecnica Instruments, Rome, Italy). Results: The prevalence of CKD was found to be 15.3%, with 29.6% identified in diabetic individuals and 16.5% in prediabetic patients. So, the prevalence of CKD in diabetics was higher than prediabetics and normal people. Increased age, dysglycemia (diabetes or prediabetes), hypertension, and use of angiotensin receptor blockers were markedly associated with an elevated risk of CKD in adults. Conclusion: The study emphasizes the importance of early detection and management of CKD risk factors, particularly among high-risk individuals, to mitigate CKD progression and associated complications. By addressing modifiable risk factors, proactive screening, and enhanced awareness, significant strides can be made in reducing CKD burden and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The main aim was to do a systematic review on the published studies to determine kidney disease in pre- and post-liver transplant and its determinants of liver transplantation. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (2020) guidelines were followed to conduct this study. All procedures followed the recommendations found in the Cochrane handbook. Full-text studies, acute kidney injury, and chronic kidney disease (CKD) pre- and post-liver transplantation were included in this study. We included papers from PsycINFO, Google Scholar, PubMed, Web of Science, Medline, Embase, Google, and the Cochrane Library in order to identify additional articles, even though the review ultimately covered all research. Results: A total of 884 references were removed because they were duplicates. The preliminary screening removed 201 of the 243 citations from consideration. There were 37 full-text articles considered for inclusion, but only 9 met the criteria; all the nine articles were very high quality. Totally 1846 patients were studied in this review from all the nine articles with an average age of 51.32 years. All articles were single-center prospective and retrospective observational studies. Conclusion: Kidney failure following liver transplantation is a prevalent and life-threatening complication. Complex events before and after LT cause the condition. The Model for End-Stage Liver Disease score-based organ allocation change is largely responsible for its rapid growth. The majority of studies indicated kidney function declined over time. This highlights the importance of monitoring liver transplant patients’ kidney function and CKD symptoms. Delaying or decreasing tacrolimus administration may help kidney functions.

Abstract Background Patients undergoing haemodialysis are more susceptible to infectious diseases, including periodontitis. This study aimed to investigate the Correlation between periodontal disease and serum markers in Yemeni haemodialysis patients. Methods A cross-sectional study was conducted on a sample of 70 haemodialysis patients. Patient interviews, clinical examinations, and laboratory tests were performed to collect data. Serum levels of albumin, calcium, phosphorus, haemoglobin, ferritin, and creatinine were measured, with separate measurements for cystatin C The association between categorical variables was assessed using the chi-square test and Pearson’s correlation coefficient, considering a significance level of p

Cannabinoids are a class of drugs derived from the Cannabis plant that are widely used for the treatment of various medical conditions and recreational use. Common examples include Δ9‐tetrahydrocannabinol (THC), cannabidiol (CBD), spice, and 2‐arachidonoylglycerol (2‐AG). With more than 100 cannabinoids identified, their influence on the nervous system, role in pain management, and effects due to illicit use have been extensively studied. However, their effects on peripheral organs, such as the kidneys, require further examination. With dramatic rises in use, production, and legalization, it is essential to understand the impact and mechanistic properties of these drugs as they pertain to renal and cardiovascular physiology. The goal of this review is to summarize prior literature on the expression of cannabinoid receptors and how cannabinoids influence renal function. This review first discusses the interaction of the endocannabinoid system (ECS) and renal physiology and pathophysiology. Following, we briefly discuss the role of the ECS in various kidney diseases and the potential therapeutic applications of drugs targeting the cannabinoid system. Lastly, recent studies have identified several detrimental effects of cannabinoids, not only on the kidney but also in contributing to adverse cardiovascular outcomes. Thus, the negative impact of cannabinoids on renal function and the development of various cardiovascular diseases is also discussed. [ABSTRACT FROM AUTHOR]

Renal fibrosis is a common feature of various chronic kidney diseases. However, the underlying mechanism remains poorly understood. The CXC chemokine receptor (CXCR) family plays a role in renal fibrosis; however, the detailed mechanisms have not been elucidated. In this study, we investigated the potential role of CXCR7 in mediating renal fibrosis. CXCR7 expression is decreased in unilateral ischemia–reperfusion injury (UIRI) and unilateral ureteral obstruction mouse models. Furthermore, CXCR7 was specifically expressed primarily in the Lotus Tetragonolobus Lectin-expressing segment of tubules, was slightly expressed in the peanut agglutinin-expressing segment, and was barely expressed in the Dolichos biflorus agglutinin-expressing segment. Administration of pFlag-CXCR7, an overexpression plasmid for CXCR7, significantly inhibited the activation of β-catenin signaling and protected against the progression of epithelial-to-mesenchymal transition (EMT) and renal fibrosis in a UIRI mouse model. Using cultured HKC-8 cells, we found that CXCR7 significantly downregulated the expression of active β-catenin and fibrosis-related markers, including fibronectin, Collagen I, and α-SMA. Furthermore, CXCR7 significantly attenuated TGF-β1-induced changes in β-catenin signaling, EMT and fibrosis. These results suggest that CXCR7 plays a crucial role in inhibiting the activation of β-catenin signaling and the progression of EMT and renal fibrosis. Thus, CXCR7 could be a novel therapeutic target for renal fibrosis. [ABSTRACT FROM AUTHOR]

Objectives: Objectives: The current study was designed to evaluate the role of MTHFR gene (rs1801133 and rs1801131) polymorphisms and investigate the serum Homocysteine level in Iraqi patients with CKD. Materials and Methods: Blood samples were collected from fifty CKD patients and fifty healthy control group aged (20 –65) years who attended Lmamain Al Kadhemain Medical Teaching Hospital and Al-Numan Hospital in Baghdad, Iraq. The genotyping study of the MTHFR gene at rs1801133 and rs1801131 was determined using HRM-PCR, and the serum level of Homocysteine was measured using ELISA kits. Results: Serum Hcy concentration was significantly (p˂0.01) increased in CKD patients compared to apparently healthy individuals (2.918Umol/L versus 1.621 Umol/L respectively). The frequencies and genotypes of alleles for the MTHFR gene at rs1801133 SNP in CKD patients versus healthy subjects revealed that the TT genotype percentage was in CKD patients significantly higher than in control groups (30% versus 14%, respectively). At the same time, the CT genotype was a considerably more significant percentage in CKD patients than in control groups (46% versus 16%, respectively). The frequency of the T allele was 53% and 22% for CKD patients and healthy individuals, respectively. In contrast, C allele frequency values were 47% and 78% for CKD patients and control groups, respectively. The frequencies of genotypes and alleles for the MTHFR gene at rs1801131 SNP showed that the percentage of CC genotype was in CKD patients significantly higher than that of control groups, 46% versus 12%, respectively, while C allele frequency values were 55% and 19% for CKD patients and control groups. Also, allele frequency values were 45% and 81% for CKD patients and healthy individuals, respectively. In this study, four haplotypes (AC, AT, CT, CC), certain variations in the MTHFR gene, specifically the CT haplotype formed by rs1801133 and rs1801131, have been related to an increased risk of chronic kidney disease. Conversely, the AC and AT haplotypes may have a protective effect against CKD, with the AC haplotype showing significant protection (OR, 0.45, 95% CI 0.06–0.5, p=0.0009). Conclusions: It was concluded from the current study that variants of the MTHFR gene have a role in the pathogenesis of CKD.

Abstract Background The Coronavirus disease 2019 (COVID-19) pandemic has significantly affected various aspects of public health. The virus poses a particular threat to individuals with kidney failure undergoing hemodialysis and their caregivers. The present study investigated the experience of family caregivers of individuals undergoing hemodialysis about caring during the COVID-19 pandemic in Iran. Methods This qualitative study was conducted with 17 family caregivers of individuals undergoing hemodialysis in Bojnurd, Iran using inductive qualitative content analysis. The participants were selected using convenience and purposive sampling method with maximum variation. Semi-structured interviews were used in data collection based on the interview guide. The data were analyzed with MAXQDA10. Results The results culminated in the identification of a main category of the COVID-19 care burden on caregivers and two generic categories including the COVID-19 Overt (financial/constraining) care burden (subcategories: Non-adherence to Health Protocols, COVID-19 Financial Costs, COVID-19 Restrictions and Hemodialysis Appointments, and Decreased Caregiver Support during the COVID-19 Era), and the COVID-19 Covert (emotional/psychological) Care Burden (subcategories: Caregiver’s Loneliness in the Care, Stress of Contracting COVID-19, Psychological Consequences of individuals undergoing hemodialysis Staying at Home, The burden of other Individuals’ Expectations of the Caregiver, and Physical and emotional pressure on the Caregiver). Conclusion Caregivers during the COVID-19 period have experienced both overt and covert care burden. The results of this study can contribute to understanding the experiences of caregivers of individuals with chronic diseases such as kidney failure, in critical conditions like the COVID-19 pandemic, by healthcare teams and devising strategies and programs to support them.

Chronic kidney diseases are described by the decreased ability of the kidney to perform its normal functions, which include removing waste products from the blood, controlling blood pressure, and producing erythropoietin. In the current molecular epidemiological study we aimed to find out the association between the ACE I/D, 4a/b of eNOS, rs1801133 of MTHFR, and T344C of CYP11B2 polymorphism and chronic kidney diseases (CKD) in the population of Jammu region of the north Indian population. Convenient-based random sampling and simple random sampling approach were utilized to draw patients and control respectively. DNA was isolated from the collected blood sample and after target sequence amplification, the PCR–RFLP genotyping method was utilized to detect polymorphism and the result was confirmed by statistical analysis. We observed that risk allele i.e., CC of T344C, 4a/b variation of eNOS and rs1801133 of MTHFR was found to be significantly associated with CKD with an association value of OR 1.33, 95% CIs [1.02–1.72] (p value = 0.007), OR 1.72, 95% CIs 1.72 [1.24–2.38] (p value = 0.001) and OR 5.98, 95% CIs [2.05–17.42] (p value = 0.0002) respectively. In conclusion, this molecular epidemiology study shows the variation in CYP11B2, eNOS, and MTHFR (T344C, 4a/b allele, and rs1801133 respectively) significantly increases the risk of CKD in the region of Jammu of the north Indian population. [ABSTRACT FROM AUTHOR]

Background: The Coronavirus disease 2019 (COVID-19) pandemic has significantly affected various aspects of public health. The virus poses a particular threat to individuals with kidney failure undergoing hemodialysis and their caregivers. The present study investigated the experience of family caregivers of individuals undergoing hemodialysis about caring during the COVID-19 pandemic in Iran. Methods: This qualitative study was conducted with 17 family caregivers of individuals undergoing hemodialysis in Bojnurd, Iran using inductive qualitative content analysis. The participants were selected using convenience and purposive sampling method with maximum variation. Semi-structured interviews were used in data collection based on the interview guide. The data were analyzed with MAXQDA10. Results: The results culminated in the identification of a main category of the COVID-19 care burden on caregivers and two generic categories including the COVID-19 Overt (financial/constraining) care burden (subcategories: Non-adherence to Health Protocols, COVID-19 Financial Costs, COVID-19 Restrictions and Hemodialysis Appointments, and Decreased Caregiver Support during the COVID-19 Era), and the COVID-19 Covert (emotional/psychological) Care Burden (subcategories: Caregiver's Loneliness in the Care, Stress of Contracting COVID-19, Psychological Consequences of individuals undergoing hemodialysis Staying at Home, The burden of other Individuals' Expectations of the Caregiver, and Physical and emotional pressure on the Caregiver). Conclusion: Caregivers during the COVID-19 period have experienced both overt and covert care burden. The results of this study can contribute to understanding the experiences of caregivers of individuals with chronic diseases such as kidney failure, in critical conditions like the COVID-19 pandemic, by healthcare teams and devising strategies and programs to support them. [ABSTRACT FROM AUTHOR]

Crocus sativus L., commonly known as saffron, is a precious spice coming from Asia, in particular from Iran, the country leader in its production. The spice is derived exclusively from dried stigmas and it is the most expensive one in the world. The areas of application of saffron are multiple, in fact ranging across the food, drinks, pharmaceuticals and cosmetics sectors. As is the case with other phytochemicals, not only the final product but also saffron by-products are considered a valuable source of bioactive natural compounds. In fact, its healthy effects, especially as antioxidants and anti-inflammatories (via reducing pro-inflammatory cytokines), are well-recognized in internal medicine. In particular, its healthy effects are related to counteracting degenerative maculopathy, depression and anxiety, neurodegenerative diseases, metabolic syndrome, cancer and chronic kidney disease, by promoting glucose metabolism. In this review, we summarize the most important papers in which saffron has turned out to be a valuable ally in the prevention and treatment of these pathologies. Moreover, we would like to promote the use of saffron by-products as part of a bio-circular economy system, aimed at reducing wastes, at maximizing the use of resources and at promoting environmental and economic sustainability. [ABSTRACT FROM AUTHOR]

Objectives: The current study was designed to evaluate the role of MTHFR gene (rs1801133 and rs1801131) polymorphisms and investigate the serum Homocysteine level in Iraqi patients with CKD. Materials and Methods: Blood samples were collected from fifty CKD patients and fifty healthy control group aged (20 –65) years who attended Lmamain Al Kadhemain Medical Teaching Hospital and Al-Numan Hospital in Baghdad, Iraq. The genotyping study of the MTHFR gene at rs1801133 and rs1801131 was determined using HRM-PCR, and the serum level of Homocysteine was measured using ELISA kits. Results: Serum Hcy concentration was significantly (p˂0.01) increased in CKD patients compared to apparently healthy individuals (2.918Umol/L versus 1.621 Umol/L respectively). The frequencies and genotypes of alleles for the MTHFR gene at rs1801133 SNP in CKD patients versus healthy subjects revealed that the TT genotype percentage was in CKD patients significantly higher than in control groups (30% versus 14%, respectively). At the same time, the CT genotype was a considerably more significant percentage in CKD patients than in control groups (46% versus 16%, respectively). The frequency of the T allele was 53% and 22% for CKD patients and healthy individuals, respectively. In contrast, C allele frequency values were 47% and 78% for CKD patients and control groups, respectively. The frequencies of genotypes and alleles for the MTHFR gene at rs1801131 SNP showed that the percentage of CC genotype was in CKD patients significantly higher than that of control groups, 46% versus 12%, respectively, while C allele frequency values were 55% and 19% for CKD patients and control groups. Also, allele frequency values were 45% and 81% for CKD patients and healthy individuals, respectively. In this study, four haplotypes (AC, AT, CT, CC), certain variations in the MTHFR gene, specifically the CT haplotype formed by rs1801133 and rs1801131, have been related to an increased risk of chronic kidney disease. Conversely, the AC and AT haplotypes may have a protective effect against CKD, with the AC haplotype showing significant protection (OR, 0.45, 95% CI 0.06–0.5, p=0.0009). Conclusions: It was concluded from the current study that variants of the MTHFR gene have a role in the pathogenesis of CKD [ABSTRACT FROM AUTHOR]

Introduction and Objective. Chronic kidney disease (CKD) is a major health issue worldwide affecting 10-14% of the globe's population, with a climbing trend. CKD is associated with a variety of factors, including obesity, which has grown increasingly prevalent and adds to the pathogenesis of the disease. The aim of the review is to summarise pathomechanism and current treatment methods of chronic kidney disease. Additionally, using this knowledge, treatment suggestions are provided for different patient groups. Review Methods. A literature search was conducted in the PubMed database with inclusion criteria 'English language' and 'free full texts', and publications date between 2018 - 2023. A total of 1,172 results were found; 28 publications were ultimately included in the review. Brief description of the state of knowledge. The pathomechanisms include haemodynamic changes, oxidative stress, adipokine dysregulation, and correlations to insulin resistance and diabetes. Weight loss by proper nutrition and exercise is a beneficial approach to manage CKD in obese patients. Bariatric surgery has proven a realistic alternative due to improvements in kidney function and obesity-related comorbidities. There are several options for pharmacotherapy in CKD and obesity, including SGLT2 inhibitors, GLP-1 analogues, agents targeting the renin-angiotensin-aldosterone system and bardoxolone methyl. Addressing obesity plays an essential role in alleviating CKD risk and progression. Conclusions. Early intervention involving lifestyle changes, weight reduction strategies, surgical procedures, and medication provides a holistic approach to addressing CKD in obese people. Recognizing the complex interplay of variables that contribute to CKD enables targeted therapy approaches and better patient outcomes. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a significant risk factor for both ischaemic and haemorrhagic stroke, affecting up to a third of individuals with cerebrovascular diseases. Beyond being a risk factor for stroke, diabetes and hyperglycaemia have a negative impact on outcomes after ischaemic and haemorrhagic stroke. Hyperglycaemia during the acute ischaemic stroke phase is associated with a higher risk of haemorrhagic transformation and poor functional outcome, with evidence in favour of early intervention to limit and manage severe hyperglycaemia. Similarly, intensive glucose control nested in a broader bundle of care, including blood pressure, coagulation and temperature control, can provide substantial benefit for clinical outcomes after haemorrhagic stroke. As micro- and macrovascular complications are frequent in people with diabetes, cardiovascular prevention strategies also need to consider tailored treatment. In this regard, the broader availability of sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists can allow tailored treatments, particularly for those with heart failure and chronic kidney disease as comorbidities. Here, we review the main concepts of hyperacute stroke management and CVD prevention among people with diabetes, capitalising on results from large studies and RCTs to inform clinicians on preferred treatments. [ABSTRACT FROM AUTHOR]

Pro-B amino-terminal natriuretic peptide (NT-proBNP) is a diagnostic marker for heart failure (HF), a severe complication of chronic kidney disease (CKD). However, its significance in CKD is not clear, as other factors, such as renal function, may also have an impact. Recent studies have shown that ghrelin treatment is effective in HF in the general population, but the impact of ghrelin on cardiac function in CKD patients is still unknown. Our study aimed to investigate the factors associated with NT-proBNP in pre-dialysis CKD patients and to evaluate the correlation between NT-proBNP and ghrelin and acyl-ghrelin, molecules determined using ELISA methods. In a cross-sectional observational study, we included 80 patients with pre-dialysis CKD, with a mean age of 68 years and 50% men. The median values for NT-proBNP were 351.8 pg/mL, for acyl ghrelin 16.39 pg/mL, and for ghrelin 543.32 pg/mL. NT-proBNP was correlated with ghrelin (p = 0.034, r = 0.24), acyl-ghrelin (p = 0.033, r = −0.24), estimated glomerular filtration rate (p = 0.027, r = −0.25), serum urea (p = 0.006, r = 0.31), and ferritin (p = 0.041, r = 0.28). In multivariate analysis, ghrelin (p = 0.040) and blood urea (p = 0.040) remained significant predictors for NT-proBNP levels. NT-proBNP was a significant predictor for acyl-ghrelin (p = 0.036). In conclusion, in pre-dialysis CKD patients, a high value of NT-proBNP was associated with a high value of total ghrelin and a low value of acyl-ghrelin. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the impact of menopause on stone composition in women with urolithiasis. Study design: A cross-sectional study was conducted from March 2013 to March 2018. Women with urolithiasis patients were divided into two groups according to their menopause status. Main outcome measures: The clinical demographic characteristics, stone removal, stone composition, and urine chemistry were investigated. Univariate and multivariate survival analyses were performed to identify risk factors for the risk of uric acid stones. Results: Our study enrolled 1221 female patients with stone diseases, 783 (64.1 %) of whom were postmenopausal (66 patients surgically menopause and 717 patients naturally menopause). Postmenopausal women had higher rates of diabetes and hyperuricemia, a higher serum uric acid level, a higher urinary specific gravity, and a lower estimated glomerular filtration rate. Stone analysis revealed calcium oxalate stones in 66.2 % of the patients, apatite stones in 19.4 %, calcium oxalate and calcium phosphate stones in 7.7 %, uric acid stones in 4.4 %, struvite stones in 2.0 %, and brushite stones in 0.2 %. Postmenopausal women had a higher rate of uric acid stones. Multivariate analysis confirmed that postmenopausal status and hyperuricemia were independent risk factors of uric acid stones. Postmenopausal women required more invasive procedures to remove the stones, and they had lower self-voiding rates. Conclusions: Postmenopausal women had higher rates of stone episodes, specifically related to uric acid stones. Given the prevalence and impact of chronic kidney diseases, factors that impede optimal renal function management in women must be identified to provide tailored treatment recommendations.

BackgroundChronic kidney diseases (CKD) is a severe public health problem. This study aimed to explore the field of inflammation-related research in CKD from a bibliometric perspective.MethodsRelevant literature published between 2004 and 2023 were searched from the Web of Science database. The bibliometric analysis were performed to summarize countries, institutions, authors, journals and keywords using VOSviewer and CiteSpace.ResultsA total of 9,287 publications on CKD and inflammation were included. Publications were mainly from the United States, China, Italy, Germany, and Japan. The findings revealed that the United States had the highest number of publications in this field, followed by China. There is strong collaboration between the two countries. The most productive institutions included the University of California system and the US Department of Veterans Affairs. Research hotspots primarily focused on inflammation mechanisms, biomarkers, and interventions.ConclusionThis study revealed the basic knowledge structure and provided a comprehensive insight into the research field of CKD and inflammation through bibliometric methods. Future studies should focus on early diagnosis, prevention, and treatment strategies of CKD, and explore more inflammation associated biomarkers and therapeutic targets for CKD.

Tetrahydrocurcumin (THC), a principal metabolite of curcumin, was tested in a rat model of type 2 diabetes mellitus. THC was administered via daily oral gavage with the lipid carrier polyenylphosphatidylcholine (PPC) as add-on therapy to losartan (angiotensin receptor blocker) to examine effects on kidney oxidative stress and fibrosis. A combination of unilateral nephrectomy, high-fat diet and low-dose streptozotocin was used to induce diabetic nephropathy in male Sprague-Dawley rats. Animals with fasting blood glucose >200 mg/dL were randomized to PPC, losartan, THC + PPC or THC + PPC + losartan. Untreated chronic kidney disease (CKD) animals had proteinuria, decreased creatinine clearance, and evidence of kidney fibrosis on histology. THC + PPC + losartan treatment significantly lowered blood pressure concurrent with increased messenger RNA levels of antioxidant copper-zinc-superoxide dismutase and decreased protein kinase C-α, kidney injury molecule-1 and type I collagen in the kidneys; there was decreased albuminuria and a trend for increased creatinine clearance compared to untreated CKD rats. There was decreased fibrosis on kidney histology in PPC-only and THC-treated CKD rats. Plasma levels of kidney injury molecule-1 were decreased in THC + PPC + losartan animals. In summary, add-on THC to losartan therapy improved antioxidant levels and decreased fibrosis in the kidneys, and lowered blood pressure in diabetic CKD rats.

Background: The urinary biomarker response precedes the appearance of any renal structural or functional derangement. Transforming growth factor-β1 (TGF-β1), neutrophil gelatinase associated lipocalin (NGAL), and Cystatin C (CysC) can act as the early prognostic markers in posterior urethral valve (PUV) patients. Aim: To compare the urinary levels of TGF-β1, NGAL, and CysC between PUV cases and age matched controls and to correlate these with renal structural and functional parameters. Materials and Methods: This prospective study included children with PUV diagnosed using the standard investigations and an equal number of age-matched controls with nonurological problems. For the study subjects, the urinary samples were collected at three different time points (pre- and postoperatively at 3 and 6 months), whereas for controls, only single-voided samples were studied. The urinary levels of TGF-β1, NGAL, and CysC were estimated by the standardized techniques using the ELISA kits. Statistical methods were used to drive the comparisons between cases and controls. Results: Fifteen children with a median age of 10 (5–48) months were enrolled in each of the two groups. The mean uTGF-β1 in the case group was significantly higher at all three time points (43.20 ± 6.13 pg/ml, 43.33 ± 11.89 pg/ml and 40.71 ± 9.01 pg/ml) as compared to the control group (29.12 ± 8.31 pg/ml) (P ≤ 0.001). The median uNGAL in the case group was also higher (17.78 ng/ml, 2.35 ng/ml and 2.536 ng/ml) as compared to the control group (1.31 ng/ml). However, the difference was significant only preoperatively (P = 0.02). The median uCysC in case group was similarly higher (0.347 μg/ml, 0.439 μg/ml, and 0.382 μg/ml) than the control group (0.243 μg/ml) (P > 0.05). Serum creatinine in the case group (0.49 mg/dl) showed no significant rise above that of control (0.24 mg/dl). A cutoff value of uTGF-β1 = 36.55 pg/ml (P < 0.001), uNGAL = 0.879 ng/ml (P = 0.02), and uCysC = 0.25 μg/ml (P = 0.22) was found to be associated with renal damage in PUV. A significant correlation was found between uNGAL and S. creatinine at 3 months (r = 0.43, P = 0.017) and 6 months (r = 0.47, P = 0.08). Conclusion: The elevated uTGF-β1, a decline in uNGAL and an increase in uCysC suggests ongoing inflammation, improvement in hydronephrosis and a prolonged proximal tubular dysfunction in PUV patients, respectively.

In Japan, pediatric urinary screening in schools for asymptomatic hematuria and proteinuria began in 1974 and has been very successful in detecting asymptomatic kidney diseases at an early stage. While the American Academy of Pediatrics recommended discontinuing urinalysis as a public health service in 2007, urinary screening in Japan has proven extremely successful in reducing the incidence of kidney failure with replacement therapy in children and young adults, especially through the early treatment of glomerulonephritis, such as immunoglobulin A nephropathy. Furthermore, the positivity rate on urinary screening in Japan is significantly lower than in the United States where the rate of false positive results is typically very high. Japan’s seamless and efficient pediatric urinary screening may be a helpful example for other countries as well. However, the present investigation revealed several, unresolved problems with the system. For example, the methods used varied in terms of their cutoff point, additional examinations, and types of detailed testing. In Japan, various urinary screening methods are being tested to optimize the system for national use. Recently, the authors also recommended a system of detailed examinations, including beta-2 microglobulin testing and ultrasonography, to detect congenital anomalies of the kidney and urinary tract, the most common, underlying disease in kidney failure with replacement therapy, which is often overlooked until the symptoms have become grave. While school urinary screening has been ongoing for about 50 years and should be continued, improvements should also be made to it as needed.

Yumei Liao,1,&ast; Aihong Wang,1,&ast; Wenjuan Sui,2 Abbas Khan,3 Zibo Xiong,1,4,5 Guang Yang1,4,5 1Division of Renal Medicine, Peking University Shenzhen Hospital, Peking University, Shenzhen, Guangdong, 518036, People’s Republic of China; 2Institute of City Strategy Studies, Guangdong University of Foreign Studies, Guangzhou, Guangdong, 510006, People’s Republic of China; 3Department of Nutrition and Health Promotion, University of Home Economics Lahore Pakistan, Lahore, 54000, Pakistan; 4Institute of Nephrology, Shenzhen Peking University-Hong Kong University of Science and Technology (PKU-HKUST) Medical Center, Shenzhen, Guangdong, 518036, People’s Republic of China; 5Shenzhen Clinical Research Centre for Urology and Nephrology, Shenzhen, Guangdong, 518036, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zibo Xiong; Guang Yang, Email xiong0301@163.com; guang.yang@pkuszh.comBackground: Nephrology nursing faces an inevitable challenge when it comes to falls. This study aims to review existing literature on falls in chronic kidney disease (CKD) patients and to discuss potential solutions.Methods: This review explores the characteristics and causes of falls in CKD patients, elucidate the underlying mechanisms, shares better nursing practices, and discusses both current prevention strategies as well as potential future interventions.Results: CKD patients often experience consciousness impairment and motor dysfunction due to factors such as muscle atrophy, nerve damage, malnutrition, anemia, fluid-electrolyte imbalances, hormonal disorders, and dialysis. Additionally, this study not only shares insights from nursing experience with these patients, but also reviews current evidence-based fall prevention strategies and proposes potential new interventions that could be tested in future research.Conclusion: CKD may increase the risk of involuntary falls in patients due to consciousness impairment and motor dysfunction. Advocating for a standardized expert consensus on fall risk assessment and comprehensive care for CKD patients would enhance the nursing framework in nephrology wards and help patients decrease their fall risk and elevate their quality of life.Keywords: falls, chronic kidney diseases, dialysis, nephrology nursing, anemia

Due to various causes, chronic kidney disease（CKD） is characterized by chronic irreversible changes in the structure and function of kidney. The most common pathological manifestation is renal fibrosis. Many studies have demonstrated that injured renal tubular epithelial cells could release a large variety of cytokines to cause extracellular matrix deposition and promote the development of renal fibrosis during CKD. This review summarized the latest studies on the roles of renal tubular epithelial cell injury-related cytokines in CKD. It provided new concepts for clarifying the mechanism and exploring new treatments of CKD.

Kaming Xue,1 Bobin Mi2 1Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of ChinaCorrespondence: Bobin Mi, Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email mibobin@hust.edu.cnAbstract: Chronic kidney diseases (CKD) present a formidable global health challenge, characterized by a deficiency of effective treatment options. Extracellular vesicles (EVs), recognized as multifunctional drug delivery systems in biomedicine, have gained accumulative interest. Specifically, engineered EVs have emerged as a promising therapeutic approach for targeted drug delivery, potentially addressing the complexities of CKD management. In this review, we systematically dissect EVs, elucidating their classification, biogenesis, composition, and cargo molecules. Furthermore, we explore techniques for EV engineering and strategies for their precise renal delivery, focusing on cargo loading and transportation, providing a comprehensive perspective. Moreover, this review also discusses and summarizes the diverse therapeutic applications of engineered EVs in CKD, emphasizing their anti-inflammatory, immunomodulatory, renoprotective, and tissue-regenerating effects. It critically evaluates the challenges and limitations in translating EV therapies from laboratory settings to clinical applications, while outlining future prospects and emerging trends.Keywords: extracellular vesicles, nanomaterials, chronic kidney diseases, drug delivery systems, application

Chronic kidney diseases (CKDs) are a significant public health issue with potential for severe complications such as hypertension, anemia, and renal failure. Timely diagnosis is crucial for effective management. Leveraging machine learning within healthcare offers promising advancements in predictive diagnostics. In this paper, we developed a machine learning-based kidney diseases prediction (ML‐CKDP) model with dual objectives: to enhance dataset preprocessing for CKD classification and to develop a web-based application for CKD prediction. The proposed model involves a comprehensive data preprocessing protocol, converting categorical variables to numerical values, imputing missing data, and normalizing via Min-Max scaling. Feature selection is executed using a variety of techniques including Correlation, Chi-Square, Variance Threshold, Recursive Feature Elimination, Sequential Forward Selection, Lasso Regression, and Ridge Regression to refine the datasets. The model employs seven classifiers: Random Forest (RF), AdaBoost (AdaB), Gradient Boosting (GB), XgBoost (XgB), Naive Bayes (NB), Support Vector Machine (SVM), and Decision Tree (DT), to predict CKDs. The effectiveness of the models is assessed by measuring their accuracy, analyzing confusion matrix statistics, and calculating the Area Under the Curve (AUC) specifically for the classification of positive cases. Random Forest (RF) and AdaBoost (AdaB) achieve a 100% accuracy rate, evident across various validation methods including data splits of 70:30, 80:20, and K-Fold set to 10 and 15. RF and AdaB consistently reach perfect AUC scores of 100% across multiple datasets, under different splitting ratios. Moreover, Naive Bayes (NB) stands out for its efficiency, recording the lowest training and testing times across all datasets and split ratios. Additionally, we present a real-time web-based application to operationalize the model, enhancing accessibility for healthcare practitioners and stakeholders.Web app link: https://rajib-research-kedney-diseases-prediction.onrender.com/

Renal fibrosis is a common feature of various chronic kidney diseases. However, the underlying mechanism remains poorly understood. The CXC chemokine receptor (CXCR) family plays a role in renal fibrosis; however, the detailed mechanisms have not been elucidated. In this study, we investigated the potential role of CXCR7 in mediating renal fibrosis. CXCR7 expression is decreased in unilateral ischemia–reperfusion injury (UIRI) and unilateral ureteral obstruction mouse models. Furthermore, CXCR7 was specifically expressed primarily in the Lotus Tetragonolobus Lectin-expressing segment of tubules, was slightly expressed in the peanut agglutinin-expressing segment, and was barely expressed in the Dolichos biflorus agglutinin-expressing segment. Administration of pFlag-CXCR7, an overexpression plasmid for CXCR7, significantly inhibited the activation of β-catenin signaling and protected against the progression of epithelial-to-mesenchymal transition (EMT) and renal fibrosis in a UIRI mouse model. Using cultured HKC-8 cells, we found that CXCR7 significantly downregulated the expression of active β-catenin and fibrosis-related markers, including fibronectin, Collagen I, and α-SMA. Furthermore, CXCR7 significantly attenuated TGF-β1-induced changes in β-catenin signaling, EMT and fibrosis. These results suggest that CXCR7 plays a crucial role in inhibiting the activation of β-catenin signaling and the progression of EMT and renal fibrosis. Thus, CXCR7 could be a novel therapeutic target for renal fibrosis.

Background: The urinary biomarker response precedes the appearance of any renal structural or functional derangement. Transforming growth factor-Pi (TGF-P1), neutrophil gelatinase associated lipocalin (NGAL), and Cystatin C (CysC) can act as the early prognostic markers in posterior urethral valve (PUV) patients. Aim: To compare the urinary levels of TGF-β1, NGAL, and CysC between PUV cases and age matched controls and to correlate these with renal structural and functional parameters. Materials and Methods: This prospective study included children with PUV diagnosed using the standard investigations and an equal number of age-matched controls with nonurological problems. For the study subjects, the urinary samples were collected at three different time points (pre- and postoperatively at 3 and 6 months), whereas for controls, only single-voided samples were studied. The urinary levels of TGF-β1, NGAL, and CysC were estimated by the standardized techniques using the ELISA kits. Statistical methods were used to drive the comparisons between cases and controls. Results: Fifteen children with a median age of 10 (5-48) months were enrolled in each of the two groups. The mean uTGF-β1 in the case group was significantly higher at all three time points (43.20 ± 6.13 pg/ml, 43.33 ± 11.89 pg/ml and 40.71 ± 9.01 pg/ml) as compared to the control group (29.12 ± 8.31 pg/ml) (P ≤ 0.001). The median uNGAL in the case group was also higher (17.78 ng/ml, 2.35 ng/ml and 2.536 ng/ml) as compared to the control group (1.31 ng/ml). However, the difference was significant only preoperatively (P = 0.02). The median uCysC in case group was similarly higher (0.347 µ.g/ml, 0.439 µ.g/ml, and 0.382 µ.g/ml) than the control group (0.243 µ.g/ml) (P > 0.05). Serum creatinine in the case group (0.49 mg/dl) showed no significant rise above that of control (0.24 mg/dl). A cutoff value of uTGF-β1 = 36.55 pg/ml (P < 0.001), uNGAL = 0.879 ng/ml (P = 0.02), and uCysC = 0.25 µg/ml (P = 0.22) was found to be associated with renal damage in PUV. A significant correlation was found between uNGAL and S. creatinine at 3 months (r = 0.43, P = 0.017) and 6 months (r = 0.47, P = 0.08). Conclusion: The elevated uTGF-β1, a decline in uNGAL and an increase in uCysC suggests ongoing inflammation, improvement in hydronephrosis and a prolonged proximal tubular dysfunction in PUV patients, respectively. [ABSTRACT FROM AUTHOR]

The progression of chronic kidney diseases (CKD) is complex, influenced by a myriad of factors including gut microbiota. While emerging evidence suggests that gut microbiota can have beneficial effects in managing CKD, it is also recognized that dysbiosis may contribute to the progression of CKD and associated uremic complications. Our previous research has demonstrated the efficacy of lanthanum hydroxide in delaying kidney failure and preserving renal function. However, the role of lanthanum hydroxide in modulating gut microbiota in this context remains unclear. In our study, we induced CKD in rats using adenine, leading to gut microbial dysbiosis, kidney pathology, and disturbances in amino acid metabolism. In this adenine‐induced CKD model with hyperphosphatemia, treatment with lanthanum hydroxide improved renal function. This improvement was associated with the restoration of gut microbial balance and an increase in urine ammonium metabolism. These results suggest that the therapeutic potential of lanthanum hydroxide in CKD may be partly due to its ability to reshape gut microbiota composition. This study underscores the significance of lanthanum hydroxide in kidney protection, attributing its benefits to the modulation of gut microbiota in a rat model of CKD. [ABSTRACT FROM AUTHOR]

Background: The relationship between the use of multiple medications and the risk of chronic kidney disease (CKD) warrants investigation. The aim of this study was to examine the association between polypharmacy and CKD. Methods: A population-based case-control study was conducted using data from the Taiwanese National Health Insurance Research Database. Medication use was assessed from 2002 to 2003, and newly diagnosed CKD using the International Classification of Disease, 9th revision, Clinical Modification (ICD-9 CM) from 2004 to 2011 was analyzed. Propensity score analysis was used to recruit 3,249 cases and 3,249 controls through random selection. The risk of CKD was compared among individuals who used less than five medicines per day and those who used more than five medicines per day. Results: A dose-response relationship was observed between the number of medications used and the risk of CKD. Propensity score analysis showed an increased risk of CKD among patients who used five to nine medicines per day (odds ratio (OR), 1.90; 95% CI, 1.69--2.14) and those who used more than ten medicines per day (OR, 3.06; 95% Cl, 3.61--2.60). Nevertheless, the use of ICD codes to identify CKD may result in misclassification bias. The severity of renal impairment was not assessed. Non-adherence and over-the-counter drugs were not accounted for. Conclusion: In a nationwide study, polypharmacy was found to be associated with CKD in the older population, and this trend persisted after propensity score matching. There was a positive correlation between the number of medications used and the incidence of CKD. [ABSTRACT FROM AUTHOR]

Purpose: The development of roxadustat is a standard treatment for renal anemia, and multiple clinical trials have proved its safety and efficacy. However, less information is available from trials of the population with diabetic nephropathy (DN). This study aimed to determine whether roxadustat is effective for treating DN. Methods: This was a single-center, retrospective, institutional review board-approved cohort study. The patients with DN were chosen and given roxadustat or erythropoietin (EPO) for 8 weeks. The mean hemoglobin (Hb) level after 8 weeks of treatment served as the primary outcome. Alterations in the iron index and lipid levels were considered secondary objectives. Sub-group analysis was performed to observe the impact of inflammation and glycemic status on Hb. Results: A total of 80 patients were enrolled, 40 in each group. After 8 weeks of treatment, the Hb levels in the roxadustat group were higher than those in the control group. The number of patients who achieved Hb response was higher in the roxadustat group than in the control group (77.5% versus 27.5%; P < 0.001). In addition to lowering total cholesterol and low-density lipoprotein cholesterol, roxadustat decreased ferritin and elevated total iron-binding capacity. Compared to the control group, roxadustat was more beneficial for patients with an inflammatory condition and poor glycemic control. Conclusions: Roxadustat treatment remarkably corrected anemia in patients with DN, and its effectiveness was unaffected by inflammation or glycemic control levels. In addition, roxadustat can also reduce a patient's blood lipid level and enhance the body's use of iron. Clinical trial registration: ChiCTR2200057232. [ABSTRACT FROM AUTHOR]

Abstract Background Tubulointerstitial kidney disease associated microenvironmental dysregulation, like acidification, inflammation and fibrosis, affects tubule cells and fibroblasts. Micromilieu homeostasis influences intracellular signaling and intercellular crosstalk. Cell–cell communication in turn modulates the interstitial microenvironment. We assessed the impact of acidosis on inflammatory and fibrotic responses in proximal tubule cells and fibroblasts as a function of cellular crosstalk. Furthermore, cellular signaling pathways involved were identified. Methods HK-2 (human proximal tubule) and CCD-1092Sk (human fibroblasts), in mono and coculture, were exposed to acidic or control media for 3 or 48 h. Protein expression of inflammation markers (TNF, TGF-ß and COX-2), dedifferentiation markers (N-cadherin, vinculin, ß-catenin and vimentin), fibrosis markers (collagen III and fibronectin) and phospho- as well as total MAPK levels were determined by western blot. Secreted collagen III and fibronectin were measured by ELISA. The impact of MAPK activation was assessed by pharmacological intervention. In addition, necrosis, apoptosis and epithelial permeability were determined. Results Independent of culture conditions, acidosis caused a decrease of COX-2, vimentin and fibronectin expression in proximal tubule cells. Only in monoculture, ß-Catenin expression decreased and collagen III expression increased in tubule cells during acidosis. By contrast, in coculture collagen III protein expression of tubule cells was reduced. In fibroblasts acidosis led to an increase of TNF, COX-2, vimentin, vinculin, N-cadherin protein expression and a decrease of TGF-ß expression exclusively in coculture. In monoculture, expression of COX-2 and fibronectin was reduced. Collagen III expression of fibroblasts was reduced by acidosis independent of culture conditions. In coculture, acidosis enhanced phosphorylation of ERK1/2, JNK1/2 and p38 transiently in proximal tubule cells. In fibroblasts, acidosis enhanced phosphorylation of p38 in a sustained and very strong manner. ERK1/2 and JNK1/2 were not affected in fibroblasts. Inhibition of JNK1/2 and p38 under coculture conditions reduced acidosis-induced changes in fibroblasts significantly. Conclusions Our data show that the crosstalk between proximal tubule cells and fibroblasts is crucial for acidosis-induced dedifferentiation of fibroblasts into an inflammatory phenotype. This dedifferentiation is at least in part mediated by p38 and JNK1/2. Thus, cell–cell communication is essential for the pathophysiological impact of tubulointerstitial acidosis.

Background The pathophysiological mechanism of cardiovascular disease in patients with chronic kidney disease (CKD) is complicated. Mediation analysis is an important statistical tool for gaining insight into the complex mechanisms of exposure-outcome effects. We investigated the potential mediating role of the left ventricular mass index (LVMI) on the association between fluid balance (overhydration/extracellular water, OH/ECW) and left ventricular diastolic function (E/e´ ratio) in patients with CKD not yet on dialysis. Methods Bioimpedance spectroscopy, echocardiography, and laboratory evaluations were performed on 425 consecutive patients on the same day. The patients were classified into two groups according to the estimated glomerular filtration rate corresponding to CKD stages 3 and 5. Mediation analysis was performed using the PROCESS macro and bootstrapping methods. Results OH/ECW and LVMI were positively correlated with the E/e´ ratio in both the CKD stages 3 and five groups. In CKD stage 5, there was a statistically significant association between OH/ECW and LVMI, whereas no correlation was observed in CKD stage 3. In the mediation analysis, LVMI positively mediated the relationship between OH/ECW and E/e´ ratio when controlling for confounders in patients with CKD stage 5 (B = 2.602; Boot 95% confidence interval, 1.313–4.076). Conclusion In our analysis, the indirect effect of mediators was significant in patients with advanced CKD. Therefore, our study suggests that further research on several other risk factors may be needed to determine the underlying mechanisms of association between the associated factors in all CKD stages.

AbstractContext Sanziguben (SZGB) is an empirical prescription used in traditional Chinese medicine to treat diabetic nephropathy (DN). As an abundant and primarily effective component of SZGB, Sanziguben polysaccharides (SZP) can be digested by flora to generate biological activity.Objective Our study aimed to clarify the potential mechanism of SZP in improving chronic DN.Materials and methods Male db/db mice were randomized into DN, SZP (500 mg/kg) and metformin (MET, 300 mg/kg) groups. Wild-type littermates served as the normal control (NC) group. The drug was orally administered for 8 weeks. Enzyme-linked immunosorbent assay was used to detect the inflammatory factors. Proteins related to inflammation were evaluated using western blotting and immunohistochemical examination. Gut microbiota was analysed using 16S rRNA sequencing.Results SZP significantly reduced 24 h urine albumin (p

AbstractContext Salvianolic acid B (SAB) can alleviate renal fibrosis and improve the renal function.Objective To investigate the effect of SAB on renal tubulointerstitial fibrosis and explore its underlying mechanisms.Materials and methods Male C57 mice were subjected to unilateral ureteric obstruction (UUO) and aristolochic acid nephropathy (AAN) for renal fibrosis indication. Vehicle or SAB (10 mg/kg/d, i.p.) were given consecutively for 2 weeks in UUO mice while 4 weeks in AAN mice. The serum creatinine (Scr) and blood urine nitrogen (BUN) were measured. Masson’s trichrome staining and the fibrotic markers (FN and α-SMA) were used to evaluate renal fibrosis. NRK-49F cells exposed to 2.5 ng/mL TGF-β were treated with SAB in the presence or absence of 20 μM 3-DZNep, an inhibitor of EZH2. The protein expression of EZH2, H3k27me3 and PTEN/Akt signaling pathway in renal tissue and NRK-49F cells were measured by Western blots.Results SAB significantly improved the levels of Scr by 24.3% and BUN by 35.7% in AAN mice. SAB reduced renal interstitial collagen deposition by 34.7% in UUO mice and 72.8% in AAN mice. Both in vivo and in vitro studies demonstrated that SAB suppressed the expression of FN and α-SMA, increased PTEN and decreased the phosphorylation of Akt, which were correlated with the down-regulation of EZH2 and H3k27me3. The inhibition of EZH2 attenuated the anti-fibrotic effects of SAB in NRK-49Fs.Conclusion SAB might have therapeutic potential on renal fibrosis of CKD through inhibiting EZH2, which encourages further clinical trials.

Background: With societal and economic development, the annual incidence of chronic kidney disease (CKD) is increasing. Current treatments for CKD are limited, and once patients progress to the uraemic stage, it places a significant economic burden on families and society. Based on the "gut-kidney axis" theory and real-world research, this study aims to evaluate the clinical efficacy, safety, and potential mechanism of high-position colon dialysis combined with traditional Chinese medicine (TCM) retention enema in treating stage 3-5 chronic kidney disease (non-dialysis). Additionally, it seeks to identify new therapeutic targets and approaches for CKD treatment. Methods: The TCM decoction was analyzed using Ultra-Performance Liquid Chromatography-Quadrupole-Orbitrap-High Resolution Mass Spectrometry (UPLC-Q-Orbitrap-HRMS). Participants meeting the inclusion criteria were divided into a control group (n = 153) and a treatment group (n = 159) based on their preferences and physicians' recommendations. Both groups adhered to a high-quality low-protein, low-salt, low-phosphorus, and low-fat diet supplemented with essential amino acids, and were monitored for blood pressure, blood glucose, and blood lipids. The treatment group received high-position colon dialysis combined with TCM retention enemas (administered at least 12 times every other day). Results: Thirteen compounds were identified from the herbs by UPLC-QOrbitrap-HRMS. The CKD3-5 treatment group exhibited improvements in blood biochemistry and other laboratory indices, with significant enhancements in renal function-related indices for CKD4 and CKD5 stages (p < 0.05). Following treatment, indoxyl sulfate (IS), endotoxin, and D-lactic acid levels decreased to a certain extent in both groups, with a statistically significant difference observed within the treatment group (p < 0.05). The treatment group displayed a significant reduction in aerobic bacterial colonies, an increase in anaerobic bacterial colonies, a decrease in Escherichia coli colonies, and an increase in Bifidobacterium and Lactobacillus colonies (p < 0.05). No significant changes in colony numbers were observed in the control group. Conclusion: High-position colon dialysis combined with TCM retention enema may serve as an adjuvant treatment for CKD4-5 (non-dialysis), and its mechanism may be related to the reduction of uraemic toxins, improvement of intestinal mucosal barrier function, and regulation of intestinal microecology. [ABSTRACT FROM AUTHOR]

Background and Aim: Decreased kidney function is a putative risk factor for various cancers. However, few studies have investigated the association between a decreased estimated glomerular filtration rate (eGFR) and incident pancreatic cancer. We aimed to investigate the risk of incident pancreatic cancer according to eGFR categories. Methods: In this retrospective cohort study, we included 359 721 adults who underwent health checkups in 2009 or 2010 by using the Korean National Health Insurance Database. The study population was categorized into four groups by eGFR (mL/min/1.73 m2) using the Chronic Kidney Disease Epidemiology Collaboration equation: group 1 (eGFR < 45), group 2 (eGFR ≥ 45 to < 60), group 3 (eGFR ≥ 60 to < 90), and group 4 (eGFR ≥ 90). Multivariate Cox proportional hazards models were used to determine the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of pancreatic cancer until 2019 by comparing the eGFR groups. Results: During the 3 493 589.05 person‐years of follow‐up, 1702 pancreatic cancer cases were identified. Compared with group 4 (eGFR ≥ 90), HRs and 95% CIs for the incidence of pancreatic cancer were 1.39 (1.24–1.56) for group 3 (eGFR ≥ 60 to < 90), 1.79 (1.47–2.16) for group 2 (eGFR ≥ 45 to < 60), and 2.05 (1.62–2.60) for group 1 (eGFR < 45) in the multivariate adjusted model. Conclusions: Decreased eGFR was significantly associated with an increased risk of pancreatic cancer in Korean population. Further studies are needed to investigate the relationship between a decreased eGFR and the risk of pancreatic cancer in other ethnic groups. [ABSTRACT FROM AUTHOR]

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Fibrillin-1 (FBN1) is a large, cysteine-rich, calcium binding extracellular matrix glycoprotein encoded by FBN1 gene. It serves as a structural component of microfibrils and provides force-bearing mechanical support in elastic and nonelastic connective tissue. As such, mutations in the FBN1 gene can cause a wide variety of genetic diseases such as Marfan syndrome, an autosomal dominant disorder characterized by ocular, skeletal and cardiovascular abnormalities. FBN1 also interacts with numerous microfibril-associated proteins, growth factors and cell membrane receptors, thereby mediating a wide range of biological processes such as cell survival, proliferation, migration and differentiation. Dysregulation of FBN1 is involved in the pathogenesis of many human diseases, such as cancers, cardiovascular disorders and kidney diseases. Paradoxically, both depletion and overexpression of FBN1 upregulate the bioavailability and signal transduction of TGF-β via distinct mechanisms in different settings. In this review, we summarize the structure and expression of FBN1 and present our current understanding of the functional role of FBN1 in various human diseases. This knowledge will allow to develop better strategies for therapeutic intervention of FBN1 related diseases. [ABSTRACT FROM AUTHOR]

Summary: The prevalence of kidney disease is increasing rapidly worldwide, reflecting rising rates of obesity, diabetes, and associated metabolic syndrome (MetS). Chronic kidney disease and related comorbidities such as obesity, diabetes, and hypertension place a significant financial burden on healthcare systems. Despite the widespread use of RAAS inhibitors, intensive blood pressure and glycemic control, and newer therapeutic options consisting of sodium/glucose cotransporter‐2 (SGLT‐2) inhibitors or glucagon‐like peptide‐1 (GLP‐1) receptor agonists, a significant risk of progression to end‐stage renal disease remains in the high‐risk obese and diabetic population. The MetS is a cluster of cardiovascular risk factors that adversely affect the development and progression of chronic kidney failure. According to the criteria of the World Health Organization, it is defined by visceral adiposity, impaired glucose tolerance or insulin resistance, atherogenic dyslipidemia, raised blood pressure, and microalbuminuria with a albumin‐to‐creatinine ratio ≥30 mg/g. At molecular level MetS is marked by a proinflammatory state and increased oxidative stress leading to various pathophysiological changes causing endothelial dysfunction and a hypercoagulable state. Because the kidney is a highly vascularized organ, it is especially susceptible for those microvascular changes. Therefore, the MetS and its individual components are associated with the premature development, acceleration, and progression of chronic kidney disease. Therefore, it is becoming increasingly important to elucidate the underlying mechanisms of MetS‐associated chronic kidney disease in order to develop new strategies for preventing and slowing the progression of renal disease. In this review, we will elucidate (i) the renal structural, hemodynamic, and metabolic changes that occur in obesity and obesity‐related kidney injury; (ii) the clinicopathological characteristics of obesity‐related kidney injury, primarily focusing on obesity‐associated glomerulopathy; (iii) the potential additional factors or predisposing factors that may turn patients more susceptible to renal structural or functional compensatory failure and subsequent injury. [ABSTRACT FROM AUTHOR]

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Background: Lead is a highly toxic metal. Multiple lead exposures produce serious poisoning and sometimes fatality because lead builds up slowly in the exposed body. Signs of repeated exposure to lead are high blood pressure, numbness or tingling of the extremities, memory loss, anemia, and kidney dysfunction. Methods: A cross-sectional study was conducted involving patients with chronic kidney disease (CKD) who attended to medical city hospital. The study was conducted from January 2 to May 31, 2022. Inclusion criteria were by involved adults ≥30 years old with CKD of both genders. Glomerular filtration rate (GFR) was measured for all patients according to the Cockcroft-Gault equation. Whole blood samples were taken to measure lead levels in the Toxicology Center of Baghdad Medical City. The collection of data was done by interview using a special questionnaire. Verbal consent was taken as an ethical issue by each participant in the study. Results: A total of 315 CKD patients were involved. The mean blood lead level was 24.62 µg/dL, the range was between 15 µg/dL, and 33 µg/dL for both genders, which is higher than the cut point of 10 µg/dL depended in this study. About 38.4%, and 30.8% of patients had GFR (15--29 mL/ min/1.73 m2), and (<15) mL/min/1.73 m2 and they were considered as stage 4 and 5 CKD patients, respectively. Conclusions: Lead level in blood and GFR had a significant association. [ABSTRACT FROM AUTHOR]

Oxidative stress (OS) is implicated in several chronic diseases. Extra-cellular superoxide dismutase (ec-SOD) catalyses the dismutation of superoxide anions with a protective role in endothelial cells. In chronic kidney disease (CKD), OS and thyroid dysfunction (low fT3 syndrome) are frequently present, but their relationship has not yet been investigated. This cohort study evaluated ec-SOD activity in CKD patients during haemodialysis, divided into "acute haemodialytic patients" (AH, 1–3 months of treatment) and "chronic haemodialytic patients" (CH, treated for a longer period). We also evaluated plasmatic total antioxidant capacity (TAC) and its relationships with thyroid hormones. Two basal samples ("basal 1", obtained 3 days after the last dialysis; and "basal 2", obtained 2 days after the last dialysis) were collected. On the same day of basal 2, a sample was collected 5 and 10 min after the standard heparin dose and at the end of the procedure. The ec-SOD values were significantly higher in CH vs. AH in all determinations. Moreover, the same patients had lower TAC values. When the CH patients were divided into two subgroups according to fT3 levels (normal or low), we found significantly lower ec-SOD values in the group with low fT3 in the basal, 5, and 10 min samples. A significant correlation was also observed between fT3 and ec-SOD in the basal 1 samples. These data, confirming OS and low fT3 syndrome in patients with CKD, suggest that low fT3 concentrations can influence ec-SOD activity and could therefore potentially contribute to endothelial oxidative damage in these patients. [ABSTRACT FROM AUTHOR]

To study the complications of ultrasound-guided radiofrequency ablation (RFA) in chronic kidney disease (CKD) patients undergoing renal replacement therapy with secondary hyperparathyroidism (SHPT). This retrospective study reviewed the clinical data, including general information, examination results, treatment times, time interval, and postoperative complications, of 103 SHPT patients who received ultrasound-guided RFA treatment from July 2017 to January 2021. Of 103 patients, 52 required two sessions of RFA within a month. The incidence of recurrent laryngeal nerve injury at the second treatment was significantly higher than that at the first treatment (first session vs. second session, 5.77% vs. 21.15%; p =.021). Of all the enrolled 103 patients, 27 suffered complications after the first session of RFA. When we separated patients into complications group and non-complication group, we detected more ablated nodules in the complications group (Z = −2.222; p =.0026). Subgroup analysis further showed that the patients in the severe hypocalcemia group were younger (p =.005), had more ablated nodules (p =.003) and higher blood phosphorus (p =.012) and alkaline phosphatase (ALP) levels (p =.002). Univariate analysis showed that age, serum phosphorus, ALP, and number of ablated nodules were associated with a higher risk of severe hypocalcemia after the first session of RFA. An interval of more than 1 month between two treatments may help to avoid recurrent laryngeal nerve injury. Age, serum phosphorus, ALP, and number of ablated nodules were associated with a higher risk of severe hypocalcemia after the first session of RFA. [ABSTRACT FROM AUTHOR]

Sanziguben (SZGB) is an empirical prescription used in traditional Chinese medicine to treat diabetic nephropathy (DN). As an abundant and primarily effective component of SZGB, Sanziguben polysaccharides (SZP) can be digested by flora to generate biological activity. Our study aimed to clarify the potential mechanism of SZP in improving chronic DN. Male db/db mice were randomized into DN, SZP (500 mg/kg) and metformin (MET, 300 mg/kg) groups. Wild-type littermates served as the normal control (NC) group. The drug was orally administered for 8 weeks. Enzyme-linked immunosorbent assay was used to detect the inflammatory factors. Proteins related to inflammation were evaluated using western blotting and immunohistochemical examination. Gut microbiota was analysed using 16S rRNA sequencing. SZP significantly reduced 24 h urine albumin (p < 0.05) of DN mice. Compared to DN group, SZP significantly decreased the homeostasis model assessment of insulin resistance index, serum creatinine and blood urea nitrogen levels (20.27 ± 3.50 vs. 33.64 ± 4.85, 19.22 ± 3.77 vs. 32.52 ± 3.05 μmol/L, 13.23 ± 1.42 vs. 16.27 ± 0.77 mmol/L, respectively), and mitigated renal damage. SZP also regulated gut microbiota and decreased the abundance of Gram-negative bacteria (Proteobacteria, Klebsiella and Escherichia-Shigella). Subsequently, SZP reduced lipopolysaccharides levels (1.06- to 1.93-fold) of DN mice. Furthermore, SZP inhibited the expression levels of TLR4, phospho-NF-κB p65, NLRP3 proteins and interleukin (IL)-18 and IL-1β. These results demonstrated that SZP improved intestinal flora disorder and inhibited the TLR4/NF-κB/NLRP3 pathway to alleviate DN. [ABSTRACT FROM AUTHOR]