Cause Of End-stage Disease Research Articles

TMEM16A inhibits renal tubulointerstitial fibrosis via Wnt/β-catenin signaling during hypertension nephropathy

Background and objectiveHypertensive nephropathy is the second leading cause of end-stage renal disease, but its underlying pathogenesis remains unclear. Therefore, this study aimed to explore whether transmembrane protein 16 A (TMEM16A), the molecular basis of calcium-activated chloride channels (CaCC), is involved in the development and progression of hypertensive nephropathy. MethodsIn vivo and in vitro experiments were conducted using a hypertensive murine model and human kidney proximal tubular epithelial cells (HK-2 cells), respectively. Experimental resultsThe expression of TMEM16A was down-regulated in renal samples of hypertensive nephropathy patients and hypertensive model mice, accompanied by excessive deposition of extracellular matrix proteins (ECM) such as Fibronectin, Laminin, Collagen I and Collagen III, the up-regulation of α-smooth muscle actin (α-SMA) expression, and the decrease of E-cadherin. Overexpression of TMEM16A or knockdown of TMEM16A inhibited or promoted the expression of Wnt/β-catenin signaling pathway proteins Wnt3a, LRP5 and active β-catenin in HK-2 cells, preventing the epithelial-to-mesenchymal transition (EMT) of renal tubules, and the synthesis of ECM components. ConclusionIn angiotensin II (Ang II)-induced hypertensive nephropathy, TMEM16A was identified as a key player inhibiting the detrimental changes in renal tubules, suggesting a potential avenue for mitigating renal damage in hypertensive nephropathy.

Low Levels of Metrnl are Linked to the Deterioration of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Metrnl is a secreted protein that plays an important role in kidney disease. The aim of this study was to investigate DKD-related factors and the correlation between serum Metrnl levels and the severity of DKD. Ninety-six type 2 diabetes mellitus (T2DM) patients and 45 DKD patients were included in the study. A range of parameters were measured simultaneously, including waist-to-hip ratio (WHR), body mass index (BMI), urinary albumin/creatinine ratio (UACR), monocyte-lymphocyte ratio (MLR), albumin/globulin (A/G), liver and kidney function, blood lipid profile, islet function, and others. Subsequently, the related factors and predictive significance of DKD were identified. The correlation between the relevant factors of DKD and serum Metrnl levels with DKD was evaluated. The duration of the disease (OR: 1.12, 95% CI: 1.01-1.24, P=0.031), hypertension (OR: 4.86, 95% CI: 1.16-20.49, P=0.031), fasting blood glucose (OR: 1.23, 95% CI: 1.03-1.48, P=0.025), WHR (OR: 2.53, 95% CI: 1.03-6.22, P=0.044), and MLR (OR: 1.91, 95% CI: 1.18-3.08, P=0.008) are independent risk factors for DKD (P < 0.05). Conversely, A/G (OR: 0.13, 95% CI: 0.02-0.76, P=0.024) and Metrnl (OR: 0.99, 95% CI: 0.98-1.00, P=0.001) have been identified as protective factors against DKD. Furthermore, the level of Metrnl was negatively correlated with the severity of DKD (rs=-0.447, P<0.001). The area under receiver operating characteristic (ROC) curves for the diagnostic accuracy of Metrnl for DKD is 0.765 (95% CI: 0.686-0.844). The duration of the disease, hypertension, fasting blood glucose, WHR, and MLR are major risk factors for DKD. Metrnl and A/G are protective factors for DKD. Serum Metrnl concentrations are inversely correlated with DKD severity.

Impact of Khat Chewing on Serum Uric Acid and Albuminuria Levels in Yemeni Type II Diabetes Mellitus Patients

Background: Diabetes mellitus is the major cause of end-stage renal disease and is a common endocrine illness defined by chronic hyperglycemia. In addition to diabetes, substance addiction is considered to be a cause of renal issues. The World Health Organization has classed khat (Catha edulis) as an illicit substance. Khat interferes with regular physiological activities, which may have negative health impacts on organs and systems. &#x0D; Objectives: To determine the effect of khat and uric acid on nephropathy in type II diabetes mellitus.&#x0D; Materials and Methods: This is an analytical, cross-sectional study that was conducted on 215 males aged 35 to 55 years who had previously been diagnosed with type II diabetes mellitus and were visiting AL- Thawra General Hospital in Ibb City. The diabetic person was corresponded in age and BMI by the control participant. The subjects were divided into two groups. There were 105 people with type II diabetes mellitus (59% chewing Khat and 46% not chewing Khat), 110 people were healthy and did not have type II diabetes (44% of them chewed Khat and 66% did not chew Khat). &#x0D; Results: A significant increase in albuminuria and proteinuria within the normal range in the diabetes mellitus Khat Chewer group compared to the diabetes mellitus Non-Khat Chewer group (p˂0.001). However, no significant differences were seen in the healthy control group.&#x0D; Conclusion: Khat chewing has a strong effect on those with type II diabetes and increases the progression of kidney nephropathy. There was an association between khat chewing and higher uric acid levels in both diabetic and non-diabetic patients.

Status and trends in epidemiologic characteristics of diabetic end-stage renal disease: an analysis of the 2021 Korean Renal Data System.

Korean Renal Data System (KORDS) is a nationwide end-stage renal disease (ESRD) registry database operated by the Korean Society of Nephrology (KSN). Diabetes mellitus is currently the leading cause of ESRD in Korea; this article provides an update on the trends and characteristics of diabetic ESRD patients. The KORDS Committee of KSN collects data on dialysis centers and patients through an online registry program. Here, we analyzed the status and trends in characteristics of diabetic chronic kidney disease stage 5D (CKD 5D) patients using data from 2001 to 2021. In 2021, the dialysis adequacy of hemodialysis (HD) was lower in diabetic CKD 5D patients than in nondiabetic CKD 5D patients, while that of peritoneal dialysis (PD) was similar. Diabetic CKD 5D patients had a higher proportion of cardiac and vascular diseases and were more frequently admitted to hospitals than nondiabetic CKD 5D patients, and the leading cause of death was cardiac disease. From 2001 to 2020, diabetic CKD 5D patients had a higher mortality rate than nondiabetic CKD 5D patients, but in 2021 this trend was reversed. Diabetic PD patients had the highest mortality rate over 20 years. The mortality rate of diabetic HD patients was higher than that of nondiabetic HD patients until 2019 but became lower starting in 2020. There was a decreasing trend in mortality rate in diabetic CKD 5D patients, but cardiac and vascular diseases were still prevalent in diabetic CKD 5D patients with frequent admissions to hospitals. More specialized care is needed to improve the clinical outcomes of diabetic CKD 5D patients.

Urine albumin-to-creatinine ratio diurnal variation rate predicts outcomes in idiopathic membranous nephropathy

BackgroundIdiopathic membranous nephropathy (IMN) is a leading cause of end-stage renal disease (ESRD). The purpose of this study was to evaluate whether urinary albumin-to-creatinine ratio (UACR) diurnal variation rate calculated by spot urinary protein test predicts 1-year nephrotic outcomes as a biomarker of proteinuria severity in patients with IMN.MethodsPatients’ baseline demographics, blood and urinary biomarkers, and clinical and pathological characteristics were collected retrospectively. Urine samples were collected at 7:00 (before breakfast) and 19:00 (after dinner) to calculate the UACR diurnal variation rate. A prediction model for no remission (NR) was developed statistically based on differences between prognosis groups. Receiver operating characteristic curve (ROC) analysis was performed to evaluate prediction abilities and determine optimal cut-off points of the model and UACR diurnal variation rate alone.ResultsThe formula for calculating the probability of NR was exp(L)/(1 + exp(L)), where the linear predictor L = – 22.038 + 0.134 × Age (years) + 0.457 × 24-h urinary protein + 0.511 × blood urea nitrogen (BUN) + 0.014 × serum uric acid (SUA) + 2.411 if glomerular sclerosis + 0.816 × fasting blood glucose (FBG)-0.039 × UACR diurnal variation rate (%). Optimal cut-off points for NR prediction by the final model and UACR diurnal variation rate alone were 0.331 and 58.5%, respectively. Sensitivity and specificity were 0.889 and 0.859 for the final model, and 0.926 and 0.676 for UACR diurnal variation rate alone.ConclusionUACR diurnal variation using spot urinary protein is a simpler way to predict nephrotic outcomes and is a highly sensitive screening tool for identifying patients who should undergo further comprehensive risk assessment.

Association between polyunsaturated fatty acids and progression among patients with diabetic kidney disease

AimsDiabetic kidney disease (DKD) is the major complication of diabetes mellitus (DM) and one of the leading causes of end-stage renal disease. Early detection and treatment are contributing to delay the progression of DKD. Dietary management has potential benefits for DKD, especially the intake of polyunsaturated fatty acids (PUFAs). However, there is a lack of sufficient evidence, so we aimed to explore the association between PUFAs intake and DKD progression. MethodsIn the National Heath and Nutrition Examination Survey (NHANES) between 2011–2018, a cross-sectional study was conducted among adults with T2DM. DKD was diagnosed with urine albumin to creatinine ratio (ACR) ≥ 30 mg/g or estimated glomerular filtration rate (eGFR) ＜60 ml/min/1.73 m2. Using Survey package of R to arrange the collected PUFAs intake data in order from small to large and divide them into four equal parts, which were expressed as Q1, Q2, Q3 and Q4 respectively. To investigate the association between PUFAs intake and DKD, a weighted univariate logistic regression analysis was performed and the odds ratio (OR) and 95% confidence interval (CI) were calculated for the association with DKD and PUFAs quartiles. ResultsThe study involved 3287 participants with T2DM, including 2043 non-DKD and 1244 DKD patients. The results showed that the intake of PUFAs was a protective factor for DKD (p = 0.022), and with the increase of the PUFAs, renal function improved in DKD patients, the adjusted mean of eGFR and Scr changing from 57 (41, 86) in Q1 to 71 (55, 101) ml/min in Q4 (p 0.001), 103 (73, 131) in Q1 to 90 (68, 117) in Q4 (p = 0.031), respectively. ConclusionOur study indicated that intake of more PUFAs may contribute to delay DKD progression, while different n-6/n-3 ratios need to be explored to protect the kidney.

Prevalence and associated factors of sexual dysfunction in female hemodialysis patients: first report from Somalia

BackgroundSexual dysfunction is frequent in female hemodialysis patients and is related to poorer quality of life. It is often a neglected topic associated with marked distress and interpersonal difficulties.ObjectiveFew studies are reported from Sub-Saharan African Countries (SSA) regarding female sexual dysfunction (FSD) in (HD) patients. The study aims to explore the prevalence and associated factors of FSD in female HD at a sole dialysis centre in Somalia.MethodOver a one-month period, a cross-sectional study was conducted among women with end-stage renal disease aged 18–50 years who were undergoing a dialysis program for at least three months at the dialysis center of our hospital. The participants were married, and they were living with their partners. Data regarding the sociodemographic features, clinical characteristics, frequency of sexual intercourse per week, and the Female Sexual Function Index (FSFI) scores were collected using a standard face-to-face interview questionnaire.ResultsDuring the study period, a total of 115 participants were eligible for the study’s inclusion criteria. The mean patient age was 38.5 ± 9.3 years. The most common cause of ESRD was diabetes, which accounted for 53%, followed by hypertension (26.1%) and glomerulonephritis (9.6%). The mean duration of dialysis was 2.9 ± 1.4 years, and approximately two-thirds of the participants (62.5%) were in the program for more than three years. Regarding the frequency of sexual intercourse, 61.7% of female participants performed sexual intercourse less than once time/a week. The prevalence of FSD was 92.2% (n = 106) of all participants. The mean FSFI score of the participants was 16.05 ± 4.48. Longer duration of dialysis program (i.e., more than four years), increasing age (i.e., > 35 years), those with diabetes had scored lower overall FSFI scores.ConclusionThe prevalence of female sexual dysfunction among Somali female hemodialysis patients was very high, representing a significant problem in end-stage renal disease (ESRD). Our study findings revealed that increasing age, diabetes, and duration of dialysis negatively impact female sexual function and are significantly associated with FSD.

Urinary exosomal microRNA-145-5p and microRNA-27a-3p act as noninvasive diagnostic biomarkers for diabetic kidney disease.

Diabetic kidney disease (DKD), characterized by increased urinary microalbumin levels and decreased renal function, is the primary cause of end-stage renal disease. Its pathological mechanisms are complicated and multifactorial; Therefore, sensitive and specific biomarkers are needed. Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney. The microRNAs (miRNAs) in urinary exosome are remarkably stable and highly tissue-specific for the kidney. To determine if urinary exosomal miRNAs from diabetic patients can serve as noninvasive biomarkers for early DKD diagnosis. Type 2 diabetic mellitus (T2DM) patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups: DM, diabetic patients without albuminuria [urinary albumin to creatinine ratio (UACR) < 30 mg/g] and DKD, diabetic patients with albuminuria (UACR ≥ 30 mg/g). Healthy subjects were the normal control (NC) group. Urinary exosomal miR-145-5p, miR-27a-3p, and miR-29c-3p, were detected using real-time quantitative polymerase chain reaction. The correlation between exosomal miRNAs and the clinical indexes was evaluated. The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic (ROC) analysis. Biological functions of miR-145-5p were investigated by performing Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group (miR-145-5p: 4.54 ± 1.45 vs 1.95 ± 0.93, P < 0.001; miR-27a-3p: 2.33 ± 0.79 vs 1.71 ± 0.76, P < 0.05) and the NC group (miR-145-5p: 4.54 ± 1.45 vs 1.55 ± 0.83, P < 0.001; miR-27a-3p: 2.33 ± 0.79 vs 1.10 ± 0.51, P < 0.001). The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate. miR-27a-3p was also closely related to blood glucose, glycosylated hemoglobin A1c, and low-density lipoprotein cholesterol. ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88 [95% confidence interval (CI): 0.784-0.985, P < 0.0001] in diagnosing DKD than miR-27a-3p with 0.71 (95%CI: 0.547-0.871, P = 0.0239). Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament, cytoskeleton, and extracellular exosome and were involved in the pathological processes of DKD, including apoptosis, inflammation, and fibrosis. Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.

Puerarin alleviates diabetic nephropathy by inhibiting Caspase-1-mediated pyroptosis.

Diabetic nephropathy (DN) is an important cause of end-stage renal disease, with podocyte injury as the main feature. Pyroptosis plays a non-negligible role in the process of diabetic nephropathy. Puerarin (PR) treatment of diabetic nephropathy has great potential, but the mechanism is not very clear. This article aims to study the protective effect and mechanism of puerarin on DN. Streptozotocin (STZ)-induced C57 BL/6J mouse model of DN was given PR, Necrosulfomide (NSA), Nigericin for 12 weeks; A 60 mM high glucose(HG) induced MPC5 cell injury model was administered to PR, NSA, and Nigericin interventions for 24 h. After 12 weeks of administration, PR reduced fasting blood glucose levels in DN mice, alleviated glomerular lesions, reduced podocyte damage, and protected renal function. Meanwhile, PR also inhibits the expression of pyroptosis-related proteins. In addition, PR alleviated the release of Interleukin 18 (IL-18), Interleukin 1beta (IL-1β), and lactate dehydrogenase (LDH) in MPC5 cells under HG conditions, downregulated the expression of pyrozozois-related proteins, and improved Caspase-1-mediated pyroptosis in MPC5 cells. Our study suggests that the beneficial effects of PR in diabetic nephropathy may be associated with inhibition of Caspase-1-mediated pyroptosis.

GRK5 promoted renal fibrosis via HDAC5/Smad3 signaling pathway.

Renal fibrosis is a common pathological feature of chronic kidney diseases (CKD), poses a significant burden in the aging population, and is a major cause of end-stage renal disease (ESRD). In this study, we investigated the role of G protein-coupled receptor kinases (GRKs) 5 in the pathogenesis of renal fibrosis. GRK5 is a serine/threonine kinase that regulates G protein-coupled receptor (GPCR) signaling. GRK5 has been shown to play a role in various diseases including cardiac disorders and cancer. However, the role of GRK5 in renal fibrosis remains largely unknown. Our finding revealed that GRK5 was significantly overexpressed in renal fibrosis. Specifically, GRK5 was transferred into the nucleus via its nuclear localization sequence to regulate histone deacetylases (HDAC) 5 expression under renal fibrosis. GRK5 acted as an upstream regulator of HDAC5/Smad3 signaling pathway. HDAC5 regulated and prevented the transcriptional activity of myocyte enhancer factor 2A (MEF2A) to repress the transcription of Smad7 which leading to the activation of Smad3. These findings first revealed that GRK5 may be a potential therapeutic target for the treatment of renal fibrosis. Inhibition of GRK5 activity may be a promising strategy to attenuate the progression of renal fibrosis.

Potential of Modulating Aldosterone Signaling and Mineralocorticoid Receptor with microRNAs to Attenuate Diabetic Kidney Disease.

Diabetic Kidney Disease (DKD) is a significant complication of diabetes and primary cause of end-stage renal disease globally. The exact mechanisms underlying DKD remain poorly understood, but multiple factors, including the renin-angiotensin-aldosterone system (RAAS), play a key role in its progression. Aldosterone, a mineralocorticoid steroid hormone, is one of the key components of RAAS and a potential mediator of renal damage and inflammation in DKD. miRNAs, small noncoding RNA molecules, have attracted interest due to their regulatory roles in numerous biological processes. These processes include aldosterone signaling and mineralocorticoid receptor (MR) expression. Numerous miRNAs have been recognized as crucial regulators of aldosterone signaling and MR expression. These miRNAs affect different aspects of the RAAS pathway and subsequent molecular processes, which impact sodium balance, ion transport, and fibrosis regulation. This review investigates the regulatory roles of particular miRNAs in modulating aldosterone signaling and MR activation, focusing on their impact on kidney injury, inflammation, and fibrosis. Understanding the complex interaction between miRNAs and the RAAS could lead to a new strategy to target aldosterone signaling and MR activation using miRNAs. This highlights the potential of miRNA-based interventions for DKD, with the aim of enhancing kidney outcomes in individuals with diabetes.

Novel ferroptosis gene biomarkers and immune infiltration profiles in diabetic kidney disease via bioinformatics.

Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease, exhibiting high disability and mortality rates. Ferroptosis is vital for the progression of DKD, but the exact mechanism remains unclear. This study aimed to explore the potential mechanism of ferroptosis-related genes in DKD and their relationship with the immune and to identify new diagnostic biomarkers to help treat and diagnose DKD. GSE30122 and GSE47185 were obtained from the Gene Expression Omnibus database and were integrated into a merged dataset, followed by functional enrichment analysis. Then potential differentially expressed genes were screened. Ferroptosis-related differentially-expressed genes were identified, followed by gene ontology analysis. Protein-protein interaction networks were constructed and hub genes were screened. The immune cell-infiltrating state in the dataset was assessed using appropriate algorithms. Immune signature subtypes were constructed using the consensus clustering analysis. Hub gene expression was validated using qRT-PCR and immunohistochemistry. A total of Eleven screened ferroptosis-related differentially expressed genes were screened. Six potentially diagnostically favorable ferroptosis-related hub genes were identified. Significantly increased expression of γδT cells, resting mast cells, and macrophages infiltration was observed in the DKD group. Additionally, two distinct immune signature subgroups were identified. Ferroptosis-related hub genes were significantly correlated with differentially infiltrated immune cells. Six hub genes were significantly upregulated in HK-2 cells following high glucose treatment and in human kidney tissues of patients with DKD. Six ferroptosis-related hub genes were identified as potential biomarkers of diabetic kidney disease, but further validation is needed.

Coexistence of Type I Diabetes and Lupus Nephritis in a Young Child

ABSTRACT Systemic lupus erythematosus (SLE) and type I diabetes (T1D) are autoimmune diseases that rarely occur together in the same patient. Both SLE and T1D are frequent causes of end-stage renal diseases if not treated adequately. The rate of progression of chronic kidney disease will be higher if T1D and SLE coexist in the same patient. We present a case of a 13-year-old female child with T1D and SLE. Only a few case reports of coexisting T1D and SLE are mentioned in the literature. Our case probably is one such rare case in a child with both T1D and SLE.

MAPK1 Mediates MAM Disruption and Mitochondrial Dysfunction in Diabetic Kidney Disease via the PACS-2-Dependent Mechanism.

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Mitochondrial dysfunction in renal tubules, occurring early in the disease, is linked to the development of DKD, although the underlying pathways remain unclear. Here, we examine diabetic human and mouse kidneys, and HK-2 cells exposed to high glucose, to show that high glucose disrupts mitochondria-associated endoplasmic reticulum membrane (MAM) and causes mitochondrial fragmentation. We find that high glucose conditions increase mitogen-activated protein kinase 1(MAPK1), a member of the MAP kinase signal transduction pathway, which in turn lowers the level of phosphofurin acidic cluster sorting protein 2 (PACS-2), a key component of MAM that tethers mitochondria to the ER. MAPK1-induced disruption of MAM leads to mitochondrial fragmentation but this can be rescued in HK-2 cells by increasing PACS-2 levels. Functional studies in diabetic mice show that inhibition of MAPK1 increases PACS-2 and protects against the loss of MAM and the mitochondrial fragmentation. Taken together, these results identify the MAPK1-PACS-2 axis as a key pathway to therapeutically target as well as provide new insights into the pathogenesis of DKD.

Combined Genetic Association and Differed Expression Analysis of UBE2L3 Uncovers a Genetic Regulatory Role of (Immuno)proteasome in IgA Nephropathy

Introduction: IgA nephropathy (IgAN) is a leading cause of end-stage renal disease. The exact pathogenesis of IgAN is not well defined, but some genetic studies have led to a novel discovery that the (immuno)proteasome probably plays an important role in IgAN. Methods: We firstly analyzed the association of variants in the UBE2L3 region with susceptibility to IgAN in 3,495 patients and 9,101 controls, and then analyzed the association between lead variant and clinical phenotypes in 1,803 patients with regular follow-up data. The blood mRNA levels of members of the ubiquitin-proteasome system including UBE2L3 were analyzed in peripheral blood mononuclear cells from 53 patients and 28 healthy controls. The associations between UBE2L3 and the expression levels of genes involved in Gd-IgA1 production were also explored. Results: The rs131654 showed the most significant association signal in UBE2L3 region (OR: 1.10, 95% CI: 1.04–1.16, p = 2.29 × 10−3), whose genotypes were also associated with the levels of Gd-IgA1 (p = 0.04). The rs131654 was observed to exert cis-eQTL effects on UBE2L3 in various tissues and cell types, particularly in immune cell types in multiple databases. The UBE2L3, LUBAC, and proteasome subunits were highly expressed in patients compared with healthy controls. High expression levels of UBE2L3 were not only associated with higher proteinuria (r = 0.34, p = 0.01) and lower eGFR (r = −0.28, p = 0.04), but also positively correlated with the gene expression of LUBAC and other proteasome subunits. Additionally, mRNA expression levels of UBE2L3 were also positively correlated with IL-6 and RELA, but negatively correlated with the expression levels of the key enzyme in the process of glycosylation including C1GALT1 and C1GALT1C1. Conclusion: In conclusion, by combined genetic association and differed expression analysis of UBE2L3, our data support a role of genetically conferred dysregulation of the (immuno)proteasome in regulating galactose-deficient IgA1 in the development of IgAN.

Pathological Characteristics of Ferroptosis in Kidney Tissues in Type 2 Diabetic Patients with Diabetic Kidney Disease.

Diabetes kidney disease (DKD) is a common complication of diabetes and is currently considered the primary cause of end-stage renal disease. Ferroptosis has been found to participate in the development of DKD. However, no ferroptosis-related markers have been evaluated in human DKD samples. This study aimed to examine the ferroptosis-related pathological alterations in DKD samples. This study enrolled patients with DKD at the Third Hospital of Hebei Medical University between January 2018 and December 2022, of whom 30 were diagnosed with DKD and 10 with non-DKD (CON). Clinical data of patients were collected, and hematoxylin-eosinstaining (H&E), PASM, and immunohistochemical staining were performed to evaluate pathological changes and the expression of ferroptosis-related proteins, including GPX4, ACSL4, Nrf2, TfR1, FTH, and FTL. Compared with the CON group, patients with DKD exhibited significantly elevated serum creatinine levels and reduced eGFR (P < 0.05). Iron content and the expression of the ferroptosis-related protein ACSL4 were significantly increased, while the expression of Nrf2 was significantly decreased in the renal tissues of patients with DKD (P all < 0.05). There were no differences in the expression of GPX4, TfR1, FTH, or FTL between the two groups. Nrf2 and ACSL4 expression were influential factors in the occurrence of DKD and both exhibited diagnostic value for DKD. Nrf2 was a protective factor (OR, < 1), whereas ACSL4 was a risk factor (OR, > 1). Ferroptosis-promoting gene profile was identified in DKD renal samples, indicating that ferroptosis may participate in the pathogenesis of DKD. The expression levels of Nrf2 and ASCL4 in the kidneys are related to the severity and progression of DKD.

Atherogenic Index of Plasma as an Early Marker of Chronic Kidney Disease and Liver Injury in Type 2 Diabetes.

Diabetic kidney disease (DKD) is the main cause of end-stage renal disease and has a high mortality rate. Currently, no effective treatments are available to reduce the progression of kidney damage associated with diabetes. To explore the influence and predictive value of the atherogenic index of plasma (AIP) on early chronic kidney disease and liver injury in patients with type 2 diabetes mellitus (T2DM). Medical records of 1057 hospitalized adult patients with T2DM between January 2021 and December 2022 were collected. The predictive value of AIP, renal function, and liver injury in patients with T2DM were analyzed using Pearson's correlation, multiple logistic regression, and receiver operating characteristic (ROC) curve analyses. AIP was a sensitive indicator of early liver and kidney injury in patients with T2DM. Patients in the DKD group showed increased AIP that positively correlated with serum creatinine, uric acid, and β2-microglobulin levels. Increased AIP negatively correlated with estimated glomerular filtration rate (eGFR). AIP significantly correlated with alanine aminotransferase and aspartate aminotransferase levels and glutamyl transpeptidase-to-platelet ratio (GPR). An eGFR of 60-100 mL/min/1.73 m2 significantly increased the risk of DKD as the AIP increased. At lower GPR levels, the risk of DKD significantly increased with increasing AIP. However, no significant difference was found between the 2 groups when the GPR was >0.1407. The ROC curve analysis showed that AIP could predict early liver injury. AIP is directly involved in early liver and kidney injury in T2DM and may be a sensitive indicator for early detection.

Diabetic microvascular complications and associated factors in patients with type 2 diabetes in Southern Ethiopia.

Microvascular complications are long-term complications that affect small blood vessels, usually developed in diabetes, and are primary causes of end-stage renal disease, several painful neuropathies, and blindness. Thus, this study aimed to determine diabetic microvascular complications and factors associated with them among patients with type 2 diabetes. An institution-based cross-sectional study was conducted among 378 type 2 diabetes patients. The presence of at least one diabetic microvascular complications diagnosed by physicians and found on the record was considered to have microvascular complications. The data was collected by reviewing the medical records of T2DM patients who were on follow-up from January 1, 2012, to December 31, 2021. The collected data was entered into EpiData version 3.1 and analyzed by Stata version 14. Bivariate and multivariable logistic regression were used to identify statistically significant risk factors for diabetic microvascular complications at p-value < 0.05. Patients with type 2 diabetes mellitus had a prevalence of diabetic microvascular complications of 26.5% (95% CI: 22.0%, 30.9%). Diabetic neuropathy was the highest (13.2%), followed by diabetic nephropathy (12.4%), and diabetic retinopathy (6.4%). Increasing age, poor glycemic control, hypertension comorbidity, anemia, positive proteinuria, a longer duration of type 2 diabetes mellitus, and hypercholesterolemia were significantly associated factors with diabetic microvascular complications. Diabetic microvascular complications were highly prevalent. Therefore, the study suggests that interventional strategies should be taken for poor glycemic control, hypertension comorbidity, anemia, positive proteinuria, and hypercholesterolemia to control the development of diabetic microvascular complications in patients with type 2 diabetes.

Incidence and Predictors of Diabetic Nephropathy among Type 2 Diabetes Mellitus Patients, Southern Ethiopia.

Diabetic nephropathy is the most common cause of end-stage renal disease, and it brings high morbidity and mortality. Globally, the predominant rise in type II diabetes prevalence significantly increases the incidence of diabetic nephropathy. Therefore, timely diagnosis and prompt management of diabetic nephropathy and early identification of predictors are essential. Thus, this study aimed to determine the incidence and predictors of diabetic nephropathy among type II diabetes mellitus patients. A retrospective follow-up study was conducted among 532 type II diabetes patients who enrolled at Hawassa University Comprehensive Specialized Hospital from January 1, 2012, to December 31, 2021. A simple random sampling technique was used to select the study participants. The extracted data were entered into EpiData version 3.1 and analyzed by Stata version 14. A bivariate and multivariable Cox proportional hazard regression analysis was fitted to identify predictors of diabetic nephropathy. The Cox proportional hazards assumption was checked using the Schoenfeld residual test, and the goodness of fit of the model was checked using the Cox-Snell residual test. An adjusted hazard ratio with a 95% confidence interval and P values were used to identify statistically significant predictors. The overall incidence rate of diabetic nephropathy was 2.71 cases (95% CI: 2.12, 3.47) per 1,000 person-months of observation. Age (AHR = 1.027; 95% CI = 1.005, 1.049), fasting blood sugar (AHR = 1.010; 95% CI = 1.007, 1.013), and systolic blood pressure (AHR = 1.050; 95% CI = 1.031,1.069) were significant positive predictors of diabetic nephropathy, whereas the duration of diabetes longer than five years (AHR = 0.20; 95% CI = 0.09, 0.44) was a protective predictor for the development of diabetic nephropathy. The incidence rate of diabetic nephropathy was high. Age, fasting blood sugar, systolic blood pressure, and duration of diabetes were found to be independent predictors of diabetic nephropathy. To overcome this public health problem, prompt and effective strategies should be designed based on identified predictors to prevent the development of diabetic nephropathy.

Crocin protects against endoplasmic reticulum stress-related tubular injury in diabetic nephropathy via the activation of the PI3K/AKT/Nrf2 pathway.

Diabetic nephropathy (DN) is the main cause of end-stage renal disease, but the current treatment is not satisfactory. Crocin is a major bioactive compound of saffron with antioxidant and anti-endoplasmic reticulum stress (ERS) abilities used to treat diabetes. This study specifically investigated whether crocin has a regulatory role in renal injury in DN. The experiment was divided into control, (db/m mice), model (db/db mice), and experimental groups (db/db mice were intraperitoneally injected with 40 mg/kg crocin). Renal function-related indicators (Scr, BUN, FBG, UP, TG, TC, ALT, and AST) and oxidative stress-related indicators (ROS, MDA, GSH, SOD, and CAT) were assessed. The pathological changes of renal tissues were confirmed by HE, Masson, PAS, and TUNEL staining. The levels of ERS-related proteins (GRP78 and CHOP), apoptosis-related proteins, and PI3K/AKT and Nrf2 pathways-related proteins in renal tissue were detected. In db/db mice, renal function-related indicators, apoptotic cells of renal tissues, the contents of ROS and MDA as well as the expressions of CHOP, GRP78, and Bax were increased, the degree of renal tissue damage was aggravated, while the contents of GSH, SOD, and CAT, as well as the protein levels of Nrf2, PARP, anti-apoptotic proteins (Mcl-1, Bcl-2, Bcl-xl) were decreased compared to the db/m mice. However, crocin treatment reversed the above-mentioned situation. The expressions of the PI3K/AKT and Nrf2 pathways-related proteins were also activated by crocin. Crocin inhibited oxidative stress and ERS-induced kidney injury in db/db mice by activating the PI3K/AKT and Nrf2 pathways.