Cause Of End-stage Disease Research Articles

Biomarkers for Diabetic Nephropathy with a Focus on Kidney Injury Molecule-1 (KIM-1).

Diabetic Nephropathy (DN), with an increasing rate of mortality and morbidity, is considered the main cause of End-Stage Renal Disease (ESRD). A wide spectrum of biomarkers exist for early detection of DN, but they suffer from low specificity and sensitivity, indicating the urgent demand for finding more effective biomarkers. Also, the pathophysiology of tubular damage and its relation to DN are not yet completely understood. Kidney Injury Molecule-1 (KIM-1) is a protein that is expressed at substantially low contents in the kidney under physiological conditions. A number of reports have demonstrated the close relationship between urine and tissue KIM-1 levels and kidney disorders. KIM-1 is known as a biomarker for diabetic nephropathy and renal injury. In this study, we aim to review the potential clinical and pathological roles of KIM-1 in diabetic nephropathy.

Study the effect of urokinase-type plasminogen activator (UPA) and some biochemical parameters in Iraqi hemodialysis patients with type 2 diabetes

Abstract The most common cause of end-stage renal disease (ESRD) and leading ultimately to hemodialysis (HD) is type 2 diabetes mellitus (T2DM). The current study aims to assess the role of serum urokinase plasminogen activator (UPA) levels among Iraqi hemodialysis patients with ESRD with type 2 diabetes. The study encompassed 50 patients aged 40–74 years (35 males and 15 females), admitted to the Iraqi dialysis center at Baghdad Teaching Hospital, Al-Hayat Center at Al-Karama Teaching Hospital, and Hamida Al-Misfah Dialysis Center in Imam Al-Kadhimin Medical City for the period from October 2022 to February 2023. Were diagnosed based on previous medical reports, and laboratory tests by a consultant nephrologist. UPA, Blood. Urea, Creatinine, fasting serum glucose (FSG), HbA1c, Insulin, HOMA-IR, and lipid profile levels were determined. The present study showed a significant increase in serum UPA levels in HD patients in ESRD with T2DM compared to control. In addition, there was an important negative correlation between UPA and Hb1AC, FSG, and a positive correlation with VLDL-C and TG in HD patients in ESRD with T2DM patients. This study demonstrates increased UPA serum levels in HD in ESRD with T2DM patients and associated with FSG, Hb1AC, TG, and VLDL this shows that it can be considered a good marker for the development of diabetes complications, the most important of which is diabetic kidney disease (DKD).

MicroRNA-29b Plays a Vital Role in Podocyte Injury and Glomerular Diseases through Inducing Mitochondrial Dysfunction.

Diabetic kidney disease (DKD) is becoming the most leading cause of end-stage renal disease (ESRD). Podocyte injury plays a critical role in DKD progression. Notably, mitochondrial dysfunction is crucial for podocyte injury. MicroRNAs (miRNAs) involves in various kidney diseases. Herein, we discovered miR-29b was induced in the urine of 126 patients with DKD (stage I and II), and negatively correlated with kidney function and podocyte homeostasis. Mechanically, miR-29b targeted peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a co-activator of transcription factors regulating mitochondrial biogenesis and energy metabolism. In vitro, ectopic miR-29b downregulated PGC-1α and promoted podocyte injury, while inhibition of miR-29b alleviated podocyte injury. Consistently, inhibition of miR-29b mitigated podocyte injury and preserved kidney function in ADR nephropathy and db/db mice, and overexpression of miR-29b accelerated disease. Knockout miR-29b specifically in podocyte inhibited mitochondrial dysfunction and podocyte injury. These results revealed miR-29b plays a crucial role in mitochondrial dysfunction through targeted inhibition on PGC-1α, leading to podocyte injury and DKD progression. Importantly, miR-29b could serve as a novel biomarker of podocyte injury and assists to early diagnose DKD.

Evaluation of Effect of Montelukast in the Model of Streptozotocin Induced Diabetic Nephropathy in Rats.

Diabetic nephropathy is a progressive condition and a leading cause of end-stage renal disease. Oxidative stress and inflammation play an important role in its pathogenesis. In pre-clinical studies, Montelukast had shown renoprotective and anti-oxidant properties, hence the study was planned to evaluate the effect of Montelukast in a Streptozotocin (STZ) induced model of diabetic nephropathy. 40 Wistar rats of either sex were randomly divided into four groups viz. 1. Vehicle control group, 2. Enalapril (5 mg/kg), 3. Montelukast low-dose (10 mg/kg) and 4. High-dose (20 mg/kg) group. On day 1, diabetes was induced using a single dose of STZ (60 mg/kg) intraperitoneally. Diabetes induction was verified based on fasting blood glucose (FBG) levels on day 7 and from day 8 to day 42, rats were given study drugs. FBG, serum creatinine, blood urea nitrogen (BUN) and urine microalbumin levels were assessed pre-study and post-study. Assessments of kidney malondialdehyde (MDA), reduced glutathione (GSH) and renal histopathology were carried out at the end of the study. Montelukast 10 mg/kg group showed significantly lower urine microalbumin levels compared to the vehicle control group (p < 0.05). Montelukast 20 mg/kg group showed significantly lower levels of FBG, serum creatinine, BUN and urine microalbumin compared to the vehicle control group (p < 0.05). In addition, Montelukast 20 mg/kg group also showed better effects on kidney MDA and GSH levels (p < 0.05) and histopathological scores compared to the vehicle control group. Montelukast showed a protective effect in the model of diabetic nephropathy because of its antioxidant effect.

The Spectrum of Ocular Manifestations among Renal Transplant Recipients

Purpose: The study aims to report various ocular manifestations among renal transplant recipients. Methods: The cross-sectional study was conducted on renal transplant patients, with at least 4 months of posttransplant duration, attending a nephrology clinic. A comprehensive ophthalmic evaluation was performed to record various ocular manifestations. The statistical association between ocular findings and pretransplant as well as posttransplant duration was assessed. Results: One hundred and twenty-three eyes of 62 patients, with a mean age of 37.6 ± 8.2 years and functional graft, were included in the study. Diabetic nephropathy was found to be the most common underlying cause of end-stage renal disease (ESRD) and renal transplant. Hypertensive retinopathy (37.4%) was found to be the most frequent ophthalmic manifestation, followed by diabetic retinopathy (24.39%), dry eye (22.76%), cataract (18.69%), and change in refractive error (17.89%). The occurrence of hypertensive retinopathy and refractive power change was found to be significantly associated with pretransplant dialysis duration. In contrast, concerning the posttransplant period, the frequency of all the major ocular manifestations, except the dry eye, was observed to be statistically significant. Conclusion: Patients with ESRD and renal transplant should be advised to undergo regular comprehensive eye examinations. Many ocular manifestations are preventable and/or treatable, thus interdisciplinary partnership between nephrologists and ophthalmologists is warranted to improve vision and quality of life in transplant recipients.

Treatment of Patients with IgA Nephropathy: Evaluation of the Safety and Efficacy of Mycophenolate Mofetil.

Immunoglobulin A nephropathy (IgAN), characterized by aberrant IgA immune complex deposition, is the most prevalent primary glomerular disease and the main cause of end-stage renal disease, causing a significant physical and psychological burden on people worldwide. Conventional therapeutic approaches, such as renin-angiotensin-aldosterone system inhibitors and corticosteroids, may not achieve sufficient effectiveness and may produce major side events in the past. The previous data in Asian populations indicated that mycophenolate mofetil (MMF) might significantly advance the development of a new therapy strategy for IgAN. The effectiveness and safety of MMF in patients with IgAN will be investigated in this study. A literature search was conducted on June 30th, 2023, by searching the following databases: PubMed and the Cochrane Library according to predefined criteria. To investigate the renoprotective benefits and safety of MMF, statistical analyses were performed using Cochrane's Review Manager Version 5.3. The meta-analysis included nine randomized controlled studies that fulfilled the inclusion criterion. In the Asian population, the results revealed a substantial difference in remission rates between the MMF group and the control group (OR: 2.53, 95% CI: 1.02, 6.30, P = 0.05). MMF can increase the rate of decrease in proteinuria in IgAN patients when compared with controls in Asians (OR: 7.34, 95% CI: 2.69, 20.08, P = 0.0001), and MMF can reduce the urinary protein in patients with IgAN in Asians (WMD: -0.61, 95% CI: -1.15, -0.08, P = 0.02). Interestingly, these studies on Asians were conducted in China. However, the differences in remission rate, rate of decrease in proteinuria, and urinary protein reduction between the MMF group and control group were not found in overall populations and in the Caucasian population. The differences in complete remission rate, partial remission rate, serum creatinine (SCr) doubling rate, rate of 50% increase in SCr, and rate of need for renal replacement treatment between the MMF group and control group were not found in Asians, Caucasians, and overall populations. The difference in the rate of side effects between the MMF group and the control group was not found. MMF protects renal function and is a safe medication for treating Chinese IgAN patients. MMF might significantly advance the development of a new therapy strategy for IgAN in the Chinese population.

Analyzing three pedigrees in X-linked Alport syndrome with the presentation of nephrotic syndrome.

Alport syndrome (AS) is a common cause of end-stage renal disease (ESRD) with various clinical symptoms and incomplete manifestation. Patients with AS and other renal disorders are often misdiagnosed. This study reported three X-linked dominant Alport syndrome (XLAS) pedigrees with nephrotic syndrome (NS) as the predominant phenotype and analyzed COL4A5 gene alterations. Three Han Chinese XLAS pedigrees were recruited, and clinical phenotypes were obtained. The pre-certified individuals' peripheral blood DNA was taken, and whole-genome next-generation sequencing (NGS) was performed for candidate genes and mutation screening, followed by NGS or Sanger sequencing of suspected mutant types in participating family members. Both probands A and B were diagnosed with NS through biochemical tests, and X-linked Alport syndrome-associated renal injury was diagnosed by renal biopsy. The biopsy revealed focal foamy cells in the renal interstitium, tearing and delamination changes in the glomerular basement membrane, and negative α3 and α5 chains of type IV collagen. Proband C, who was earlier diagnosed with NS, has now advanced to ESRD, along with his mother and proband A's mother. Genetic sequencing of all three pedigrees identified three mutations, namely, c.5020C>T, c.4435_4445del, and c.1584_1587+6del in the X-linked dominant gene COL4A5 (NM_000495.5). These mutations lead to the production of shortened proteins, potentially impacting the function of COL4A5 and causing pathogenic effects. The novel c.4435_4445del and c.1584_1587+6del mutations not only enrich the spectrum of mutations in the COL4A5 gene but also indicate that carriers of both mutation sites and those with mutation c.5020C>T may present NS as their primary clinical manifestation.

Perspectives of clinical research on Shen-Shuai-Ning in the treatment of diabetic nephropathy.

Diabetic nephropathy (DN) is one of the most common chronic complications in patients with diabetes and remains a leading cause of end-stage renal disease. Despite current treatment strategies focusing primarily on blood glucose control and antihypertensive medications, their efficacy is often limited, failing to halt disease progression effectively. However, Shen-Shuai-Ning (SSN), a traditional Chinese medicine compound, has demonstrated significant clinical efficacy in DN treatment in recent years. SSN exerts multifaceted effects, including immunomodulation, attenuation of oxidative stress, and inhibition of fibrosis, leading to improvements in renal function indices and reductions in proteinuria levels, with favorable tolerability. Furthermore, when combined with conventional treatments, SSN exhibits enhanced therapeutic efficacy, providing a comprehensive and effective treatment strategy for DN patients. Future research endeavors should prioritize large-scale, multicenter clinical trials to validate its efficacy and safety across diverse populations, thereby further advancing its integration into clinical practice.

Resveratrol protects mesangial cells under high glucose by regulating the miR-1231/IGF1/ERK pathway.

Diabetic nephropathy (DN) is one of the complications of diabetes mellitus and the main cause of end-stage renal disease (ESRD), which is a serious threat to human health. In DN, mesangial cells (MCs) are a critical target cell that perform a variety of key functions, and abnormal proliferation of MCs is a common and prominent pathological change in DN. In recent years, the investigation of Chinese medicine interventions for DN has increased significantly in recent years due to the many potential adverse effects and controversies associated with the treatment of DN with Western medicines. In this study, we evaluated the protective effect of resveratrol (RES), an active ingredient known as a natural antioxidant, on HMCs under high glucose and explored its possible mechanism of action. We found that RES inhibited the proliferation of human mesangial cell (HMC) under high glucose and blocked cell cycle progression. In the high glucose environment, RES upregulated miR-1231, reduced IGF1 expression, inhibited the activity of the extracellular signal-regulated kinase (ERK) signaling pathway and reduced levels of the inflammatory factors TNF-α and IL-6. In addition, we found that miR-1231 mimics were synergistically inhibited with RES, whereas miR-1231 inhibitor attenuated the protective effect of RES on HMCs. Thus, our results suggest that the protective effect of RES on HMCs under high glucose is achieved, at least in part, through modulation of the miR-1231/IGF1/ERK pathway. The discovery of this potential mechanism may provide a new molecular therapeutic target for the prevention and treatment of DN, and may also bring new ideas for the clinical research in DN.

Evaluation of Risk Factors for Development of Pulmonary Hypertension in Patients with End Stage Renal Disease Undergoing Hemodialysis

Background: Pulmonary arterial hypertension (PAH) has recently been identified as a common complication in patients with end-stage renal disease (ESRD) who are undergoing hemodialysis (HD) or peritoneal dialysis (PD). The risk factors for the development of PAH in those patients are not well understood. Objective: To investigate the risk factors for the development of PAH in patients with ESRD on HD. Patients and Methods: This is a hospital-based cross-sectional study of 50 ESRD patients undergoing HD. The pulmonary artery systolic pressure (PASP) was measured using echocardiography. PASP ˃ 25 mmHg at rest was defined as PAH. As a result, patients were divided into two groups: those who had PAH and those who did not. Each patient's demographic, biochemical, and echographic findings were documented. Results: Out of 50 patients, 19 (38%) had PAH, while the remaining 31 (62%) had normal PASP. In multivariate analysis, HD duration &gt; 3.4 years (OR= 2.13, 95%CI=1.45-31.38, p= 0.025), hypertension as a cause of ESRD (OR=6.12, 95%CI=1.4-26.77, p=0.031), hemoglobin (Hb) ≤ 10.0 g/dl (OR= 4.35, 95%CI=1.88-9.84, p= 0.018), and left ventricular ejection fraction (LVEF)≤ 55% (OR= 6.75, 95%CI=1.87-23.74, p=0.021) were independent factors associated with PAH. PASP had a significant positive correlation with the rate of fistula flow (r= 0.295, p= 0.038) and E/A ratio (r= 0.368, p= 0.008), but a significant negative correlation with LVEF (r= -0.345, p= 0.014). PASP had a positive significant correlation with each of rate of fistula flow (r= 0.295, p= 0.038) and E/A ratio (r= 0.368, p= 0.008), while it has a negative significant correlation with LVEF (r= -0.345, p= 0.014). Conclusion: Longer duration of HD, hypertensive nephropathy as a cause of ESRD, Hb≤ 10 g/dl, and LVEF ≤55% are among the demographic, biochemical, and clinical factors associated with the development of PAH in patients with ESRD under HD. The PASP has a positive correlation with fistula flow rate and E/A ratio and a negative correlation with LVEF. Keywords: Pulmonary arterial hypertension, End stage renal disease, Hemodialysis.

Clean Intermittent Catheterization in Children under 12 Years Does Not Have a Negative Impact on Long-Term Graft Survival following Pediatric Kidney Transplantation.

Congenital anomalies of the kidneys and urinary tract (CAKUTs) are one of the most prevalent primary causes of end-stage renal disease (ESRD) in young children, and approximately one-third of these children present with lower urinary tract dysfunction (LUTD). Many children with LUTD require therapy with clean intermittent catheterization (CIC). CIC commonly leads to bacteriuria, and considerations have arisen regarding whether CIC in immunosuppressed children is safe or whether repeated febrile urinary tract infections (UTIs) may lead to the deterioration of kidney graft function. We retrospectively reviewed all cases of primary kidney transplantation performed in our center between 2001 and 2020 in recipients aged less than twelve years. The number of episodes of febrile UTIs as well as the long-term kidney graft survival of children undergoing CIC were compared to those of children with urological causes of ESRD not undergoing CIC, as well as to those of children with nonurological causes of ESRD. Following successful kidney transplantation in 41 children, CIC was needed in 8 of these patients. These 8 children undergoing CIC had significantly more episodes of febrile UTIs than did the 18 children with a nonurological cause of ESRD (p = 0.04) but not the 15 children with a urological cause of ESRD who did not need to undergo CIC (p = 0.19). Despite being associated with a higher rate of febrile UTIs, CIC was not identified as a risk factor for long-term kidney graft survival, and long-term graft survival did not significantly differ between the three groups at a median follow-up of 124 months. Our study demonstrates that, under regular medical care, CIC following pediatric transplantation is safe and is not associated with a higher rate of long-term graft loss.

The clinical significance of the determination of urinary biomarkers of podocytic damage and fibroangiogenesis in patients with diabetes mellitus

Chronic kidney disease (CKD) in patients with diabetes mellitus (DM) remains a global medical and social problem of the 21st century and the leading cause of end-stage renal disease (ESRD). Kidney damage in diabetes is multifactorial, and diagnosis is often delayed, since structural changes in the glomeruli of the kidneys are detected before the appearance of significant albuminuria (AU) and a decrease in glomerular filtration rate. In this regard, the search for new, early informative biomarkers for the diagnosis of CKD in patients with DM is extremely relevant.Target: To establish the significance of biomarkers of podocyte dysfunction and fibro and angiogenesis excreted in the urine for early diagnosis and assessment of the risk of progression of kidney damage in patients with DM. Materials and Methods: in 74 patients with type 1 and type 2 diabetes (30 and 44, respectively), podocyte proteins and markers of fibro and angiogenesis were determined in the urine by enzyme immunoassay.Results: in patients with diabetes, compared to healthy people, there is increased urinary excretion of podocyte damage markers - nephrin, podocin, and fibroaniogenesis markers – type IV collagen, TGFβ-1, VEGF. Concentrations of nephrin in urine &gt;7.18 ng/U/Cr urine and collagen &gt;12.88 ng/U/Cr urine reliably indicate kidney damage. In patients with diabetes in the absence of traditional signs of CKD, diagnostically significant concentrations of nephrin were detected in 22% of cases, and collagen in 16.6%.Conclusion: determination of nephrin and/or type IV collagen in urine can be used both for early diagnosis and for monitoring kidney damage in diabetes.

ER Stress-Perturbed Intracellular Protein O-GlcNAcylation Aggravates Podocyte Injury in Diabetes Nephropathy.

Diabetes nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide, and podocyte injury is the central contributor to the progression of DN. Despite the emerging evidence that has established the importance of podocyte endoplasmic reticulum (ER) stress in the pathogenesis of DN, abnormal protein O-GlcNAcylation is also augmented. Currently, the mechanism associating these two hyperglycemia-induced disorders remains poorly understood. This study intended to elucidate whether ER stress drives hyper-protein O-GlcNAcylation to cause podocyte injury in DN. We used both type 1 and type 2 DN models to confirm the occurrence of ER stress and excessive protein O-GlcNAcylation, and then podocyte purification was also conducted for further investigation. Nephroseq V5 data were mined and in vitro studies were applied to reveal the involvement of ER stress and hyper-O-GlcNAcylation in podocyte injury. Our results indicated that ER stress was induced in both type 1 and type 2 DN, and the human RNA-seq data from Nephroseq V5 showed that O-GlcNAcylation-related genes were significantly upregulated in the DN patients. We further demonstrated that ER stress occurred prior to hyper-O-GlcNAc modification and that pharmacologically inhibited protein O-GlcNAcylation can help decrease the podocyte apoptosis induced by hyperglycemia. Together, these discoveries will aid in uncovering the activation of the ER stress-O-GlcNAcylation axis in podocyte injury under DN, which will help open up new therapeutic approaches for preventing DN progression.

Causes of Original Kidney Disease among Libyan Kidney Transplant Recipients

Abstract Introduction End-stage renal disease (ESRD) has become a significant problem in the North African region. There are few references about the primary causes of ESRD in kidney transplant (KT) recipients. The aim of this study was to determine the causes of the original kidney disease in KT recipients in Tripoli Central Hospital, Tripoli, Libya. Methods This is a hospital-based, retrospective descriptive study. It includes all KT recipients who were followed up in the outpatient clinic, at the Libyan National General Authority for Organ, Tissue, and Cell Transplantation and nephrology clinic in Tripoli Central Hospital during 2021, Tripoli, Libya. Results Data on 360 KT recipients were retrieved. Sixty-eight percent of the of the patients were males: 31.1% of all enrolled individuals were between 31 and 40 years. Patient mean age was 36.66 ± 11.86 years. The most common validated cause for ESRD was unknown (55.3%), followed by chronic glomerulonephritis (CGN; 15%), diabetes mellitus and systemic hypertension each equally (10.3%), congenital abnormalities (3.6%), polycystic kidney disease (3.3%), and nephrolithiasis (1.9%). Conclusion Original cause of kidney disease in most recipients was undetermined, possibly due to limited diagnostic tools or delayed presentation. However, CGN is a main known cause.

Childhood Obesity: Insight into Kidney Involvement.

This review examines the impact of childhood obesity on the kidney from an epidemiological, pathogenetic, clinical, and pathological perspective, with the aim of providing pediatricians and nephrologists with the most current data on this topic. The prevalence of childhood obesity and chronic kidney disease (CKD) is steadily increasing worldwide, reaching epidemic proportions. While the impact of obesity in children with CKD is less pronounced than in adults, recent studies suggest a similar trend in the child population. This is likely due to the significant association between obesity and the two leading causes of end-stage renal disease (ESRD): diabetes mellitus (DM) and hypertension. Obesity is a complex, systemic disease that reflects interactions between environmental and genetic factors. A key mechanism of kidney damage is related to metabolic syndrome and insulin resistance. Therefore, we can speculate about an adipose tissue-kidney axis in which neurohormonal and immunological mechanisms exacerbate complications resulting from obesity. Adipose tissue, now recognized as an endocrine organ, secretes cytokines called adipokines that may induce adaptive or maladaptive responses in renal cells, leading to kidney fibrosis. The impact of obesity on kidney transplant-related outcomes for both donors and recipients is also significant, making stringent preventive measures critical in the pre- and post-transplant phases. The challenge lies in identifying renal involvement as early as possible, as it is often completely asymptomatic and not detectable through common markers of kidney function. Ongoing research into innovative technologies, such as proteomics and metabolomics, aims to identify new biomarkers and is constantly evolving. Many aspects of pediatric disease progression in the population of children with obesity still require clarification. However, the latest scientific evidence in the field of nephrology offers glimpses into various new perspectives, such as genetic factors, comorbidities, and novel biomarkers. Investigating these aspects early could potentially improve the prognosis of these young patients through new diagnostic and therapeutic strategies. Hence, the aim of this review is to provide a comprehensive exploration of the pathogenetic mechanisms and prevalent pathological patterns of kidney damage observed in children with obesity.

Downregulating lncRNA MIAT attenuates apoptosis of podocytes exposed to high glucose.

Diabetic nephropathy (DN), a destructive complication of diabetes mellitus (DM), is one of the leading causes of end-stage renal disease (ESRD). This study aimed to investigate the role of long non-coding RNA (lncRNA) MIAT in high-glucose (HG)-induced podocyte injury associated with DN. Three human kidney podocyte (HKP) cultures were treated with HG to mimic DN. Expression of lncRNA MIAT, podocyte-specific and injury-related proteins, and apoptosis were assessed before and after MIAT knockdown using MIAT shRNAs. MIAT expression was upregulated in HKPs in response to glucose stress. HG treatment resulted in a significant increase in the apoptotic rate, Bax level, and levels of injury-related proteins desmin, fibroblast-specific protein 1 (FSP-1), and smooth muscleα-actin (α-SMA), and a significant reduction in Bcl-2 levels and the levels of podocyte-specific proteins synaptopodin and podocin. Transfection of HKPs with shRNAs significantly reduced MIAT levels (p < 0.05) and attenuated apoptosis in HG-medium. Correspondingly, the levels of synaptopodin and podocin were upregulated, and desmin, FSP-1, and α-SMA were reduced (p < 0.05). Western blot analysis also showed that anti-apoptotic active caspase-3 and Bax and proapoptotic Bcl-2 were elevated and decreased, respectively, after MIAT knockdown, suggesting that apoptosis pathways are deactivated after MIAT downregulation. High glucose upregulates MIAT level in HKPs and induces cellular injury. Knockdown of MIAT alleviates the injury likely via deactivating apoptosis pathways.

Ethnicity and IgA nephropathy: worldwide differences in epidemiology, timing of diagnosis, clinical manifestations, management and prognosis.

Immunoglobulin A nephropathy (IgAN), the most common primary glomerulonephritis, is one of the major causes of end-stage renal disease. Significant variances in epidemiology, clinical manifestation, timing of diagnosis, management and renal prognosis of IgAN have been reported worldwide. The incidence of IgAN is the most frequent in Asia, followed by Europe, and lower in Africa. Moreover, Asian patients show more frequent acute lesions in renal histology and present poorer renal outcomes compared with Caucasians. The comorbidities also show the difference between Asians and Caucasians. Although the frequency of gross hematuria with upper respiratory tract infection is not different, comorbidities with gastrointestinal diseases are reported to be higher in Europe. Recently, genetic studies for variant ethnic patients revealed widely ranging genetic risks in each ethnicity. A genetic risk score is most elevated in Asians, intermediate in Europeans and lowest in Africans, consistent with the disease prevalence of IgAN globally. Ethnic variance might be highly affected by the difference in genetic background. However, it is also essential to mention that the different timing of diagnosis due to variant urinary screening systems and the indication for renal biopsy in different countries may also contribute to these variances. The management of IgAN also varies internationally. Currently, several novel therapies based on the pathogenesis of IgAN are being assessed and are expected to become available soon. Further understanding the ethnic variance of IgAN might help establish individualized care for this disease. Here, we review the issues of ethnic heterogeneities of IgAN.

Unveiling FOS as a Potential Diagnostic Biomarker and Emetine as a Prospective Therapeutic Agent for Diabetic Nephropathy.

Diabetic nephropathy (DN) is one of the primary causes of end-stage renal disease, yet effective therapeutic targets remain elusive. This study aims to identify novel diagnostic biomarkers and potential therapeutic candidates for DN. Differentially expressed genes (DEGs) in GSE96804 and GSE142025 were identified and functional enrichment analysis was performed. Diagnostic biomarkers were selected using machine learning algorithms and evaluated by Receiver Operating Characteristic analysis. c-Fos expression was validated in an established DN mouse model. Immune infiltration levels were assessed with Single-Sample Gene Set Enrichment Analysis. Co-expression analysis revealed regulatory relationships involving FOS. cMAP predicted potential therapeutic candidates. Transcriptome sequencing and experiments in RAW264.7 cells was performed to investigate molecular mechanisms of emetine. In both datasets, we identified 44 upregulated and 74 downregulated DEGs involved in focal adhesion, ECM-receptor interaction, and the PI3K-Akt signaling pathway. FOS emerged as a robust diagnostic marker with decreased expression in DN patients and DN mouse. Co-expression analysis revealed potential regulatory mechanisms of FOS, implicating the MAPK signaling pathway, regulation of cell proliferation and apoptotic signaling pathways. Immune dysregulation was observed in DN patients. Notably, emetine was identified as a potential therapeutic candidate. Transcriptome sequencing and experimental validation demonstrated emetine suppressed M1 macrophage polarization by inhibiting the activation of NF-κB signaling pathway, as well as reducing the expression of Il-18 and Ccl5. In conclusion, our study identified FOS as a promising diagnostic biomarker and emetine as a potential therapeutic candidate for DN. These findings enhance our understanding of DN pathogenesis and present novel prospects for therapeutic strategies.

Research Progress on Application of Inonotus obliquus in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is one of the prime causes of end-stage renal disease. At present, the treatment of DKD is mainly confined to inhibiting the renin-angiotensin-aldosterone system, but the therapeutic effects is not satisfactory. As a kind of very rare and precious medicinal fungi, Inonotus obliquus has a very high medicinal value. Due to its special hypoglycemic and pharmacological effect, researchers currently have attached great importance to it. In this paper, the biological activities, pharmacological effects and application status in the treatment of DKD-related diseases of Inonotus obliquus and the latest progress of metabolites isolated from it in DKD were summarized, thus providing detailed insights and basic understanding of the potential application prospects in DKD.

Evaluation of risk factors affecting the lifespan and efficiency of dialysis accesses installed in dialysis patients referees to Ahvaz therapeutic centers in a two-year cohort study

Introduction: It is crucial in order to provide optimal hemodialysis to patients with end-stage renal disease (ESRD) to establish venous access with the least amount of complications. Objectives: In this study, we examined the risk factors that affect the efficiency and longevity of dialysis access for patients receiving dialysis in Ahvaz medical centers. Patients and Methods: In our retrospective study, 180 hemodialysis patients were referred to the Golestan educational and medical center in Ahvaz, Iran. An arteriovenous fistula (AVF) or catheter was conducted to provide them with vascular access. Detailed demographic information about the patient was collected, including age, gender, height, weight, body mass index (BMI), cause of ESRD, duration of renal failure, duration of dialysis, and comorbidities. There were instances of access inefficiency as a result of infection, stenosis, closure, thrombosis, bleeding, and pseudoaneurysms. The data was analyzed using Mann-Whitney U, t test, and chi-square tests with SPSS version 22. Statistics were considered significant at a P value of 0.05. Results: The mean age of the patients was 50.08 ± 12.213 years, and the mean BMI was 27.90 ± 9.112 kg/m2 . Among dialysis patients, there was a significant relationship between male gender, clopidogrel administration, diabetes history, hypertension and access failure. It is estimated that 36.7% of vascular access failures are caused by thrombosis, while 32.8% are due to access stenosis or closure. Conclusion: Our study showed that male gender, clopidogrel administration, and a history of diabetes and hypertension were risk factors affecting dialysis access quality and efficiency. According to our study, it may be possible to develop a more appropriate approach for determining the type and location of dialysis access.