Urinary Microalbumin Research Articles

Leading determinants of incident dementia among individuals with and without the apolipoprotein E ε4 genotype: a retrospective cohort study

BackgroundLittle is known regarding the leading risk factors for dementia/Alzheimer’s disease (AD) in individuals with and without APOE4. The identification of key risk factors for dementia/Alzheimer’s disease (AD) in individuals with and without the APOE4 gene is of significant importance in global health.MethodsOur analysis included 110,354 APOE4 carriers and 220,708 age- and sex-matched controls aged 40–73 years at baseline (between 2006–2010) from UK Biobank. Incident dementia was ascertained using hospital inpatient, or death records until January 2021. Individuals of non-European ancestry were excluded. Furthermore, individuals without medical record linkage were excluded from the analysis. Moderation analysis was tested for 134 individual factors.ResultsDuring a median follow-up of 11.9 years, 4,764 cases of incident all-cause dementia and 2065 incident AD cases were documented. Hazard ratios (95% CIs) for all-cause dementia and AD associated with APOE4 were 2.70(2.55–2.85) and 3.72(3.40–4.07), respectively. In APOE4 carriers, the leading risk factors for all-cause dementia included low self-rated overall health, low household income, high multimorbidity risk score, long-term illness, high neutrophil percentage, and high nitrogen dioxide air pollution. In non-APOE4 carriers, the leading risk factors included high multimorbidity risk score, low overall self-rated health, low household income, long-term illness, high microalbumin in urine, high neutrophil count, and low greenspace percentage. Population attributable risk for these individual risk factors combined was 65.1%, and 85.8% in APOE4 and non-APOE4 carriers, respectively. For 20 risk factors including multimorbidity risk score, unhealthy lifestyle habits, and particulate matter air pollutants, their associations with incident dementia were stronger in non-APOE4 carriers. For only 2 risk factors (mother’s history of dementia, low C-reactive protein), their associations with incident all-cause dementia were stronger in APOE4 carriers.ConclusionsOur findings provide evidence for personalized preventative approaches to dementia/AD in APOE4 and non-APOE4 carriers. A mother’s history of dementia and low levels of C-reactive protein were more important risk factors of dementia in APOE4 carriers whereas leading risk factors including unhealthy lifestyle habits, multimorbidity risk score, inflammation and immune-related markers were more predictive of dementia in non-APOE4 carriers.

Notoginsenoside Fc, a novel renoprotective agent, ameliorates glomerular endothelial cells pyroptosis and mitochondrial dysfunction in diabetic nephropathy through regulating HMGCS2 pathway

BackgroundDiabetic nephropathy (DN) is the primary cause of end-stage renal disease (ESRD), and the therapeutic strategies for DN are limited. Notoginsenoside Fc (Fc), a novel saponin isolated from Panax Notoginseng (PNG), has been reported to alleviate vascular injury in diabetic rats. However, the protective effects of Fc on DN remain unclear. PurposeTo investigate the beneficial effects and mechanisms of Fc on DN. MethodsDb/db mice were treated with 2.5, 5 and 10 mg·kg−1·d−1 of Fc for 8 weeks. High glucose (HG) induced mouse glomerular endothelial cells (GECs) were treated with 2.5, 5 and 10 μM of Fc for 24 h. ResultsOur data found that Fc ameliorated urinary microalbumin level, kidney dysfunction and histopathological damage in diabetic mice. Moreover, Fc alleviated the accumulation of oxidative stress, the collapse of mitochondrial membrane potential and the expression of mitochondrial fission proteins, such as Drp-1 and Fis1, while increased the expression of mitochondrial fusion protein Mfn2. Fc also decreased pyroptosis-related proteins levels, such as TXNIP, NLRP3, cleaved caspase-1, and GSDMD-NT, indicating that Fc ameliorated GECs pyroptosis. In addition, 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) expression was increased in diabetic group, which was partially abrogated by Fc. Our data further proved that knockdown of HMGCS2 could restrain HG-induced GECs mitochondrial dysfunction and pyroptosis. These results indicated that the inhibitory effects of Fc on mitochondrial damage and pyroptosis were associated with the suppression of HMGCS2. ConclusionTaken together, this study clearly demonstrated that Fc ameliorated GECs pyroptosis and mitochondrial dysfunction partly through regulating HMGCS2 pathway, which might provide a novel drug candidate for DN.

The effect of periodic resistance training on obese patients with type 2 diabetic nephropathy

Resistance training is an exercise against resistance designed to train the endurance and strength of muscle. To observe the effect of intervention of periodic resistance training on obese patients with type 2 diabetic nephropathy. A total of 60 obese patients with type 2 diabetic nephropathy were randomized into resistance training group and aerobic exercise group (30 patients each group) for observing the changes of blood glucose, body weight, blood lipid, insulin resistance, serum creatinine (Scr), urinary microalbumin, urinary albumin excretion rate (UAER) calculated by urinary creatinine, and glomerular filtration rate (GFR) after 12 weeks of intervention, and relevant significance as well. The number of patients with hypoglycemia during the intervention was also recorded. After 12 weeks of intervention, the weight, Body mass index (BMI), Waist, Triglyceride (TG), Cholesterol (TC), Low-density lipoprotein cholesterol (LDL), Fasting glucose (FBG), Fasting insulin (FINS), Glycosylated hemoglobin (HbA1c) and urine Albumin–Creatinine Ratio (uACR) were decreased and GFR was increased in both groups (P < 0.05), but the effect was more significant in the resistance training group. GFR was increased from 92.21 ± 10.67 mL/(min·1.73 m2) to 100.13 ± 12.99 mL/(min·1.73 m2) in resistance training group (P < 0.05). In the aerobic exercise group, GFR was increased from 89.98 ± 9.48 mL/(min·1.73 m2) to 92.51 ± 11.35 mL/(min·1.73 m2) (P > 0.05). Periodic resistance training can not only control the weight, blood sugar and blood lipid of obese patients with type 2 diabetic nephropathy, but also improve the urinary albumin excretion rate and glomerular filtration rate of early obese patients with type 2 diabetic nephropathy, and delay the progression of diabetic nephropathy. It is an effective non-drug intervention.

THE DICHOTOMY BETWEEN HEAT SHOCK PROTEIN-27 AND MICROALBUMIN: COVARIATE OF EARLY DIABETIC NEPHROPATHY.

Heat shock protein-27 is the microprotein released from renal parenchyma during diabetic oxidative stress, while microalbumin is the plasma protein that appears in urine in diabetic nephropathy. This case-control study was conducted from Jan to Sep 2021 in the Physiology department, BMC, BMCH, Quetta. The current study included 105 patients with an age range from 30-50 years and was divided into three groups: i) a control group of healthy participants, ii) a diabetic risk group: participants without signs of diabetic nephropathy and diabetic duration from 1-5 years, iii) diabetic nephropathy group: participants having >30 mg/dl of v microalbumin in urine and diabetic duration from 5-10 years. There were significant mean differences between all groups concerning anthropometric measurements except in height amongst all groups. Statistically significant mean differences were seen in the risk and nephropathy group concerning serum FBG, RBG, and HbA1c. Elevated microalbumin levels in the diabetic nephropathy group (50.9±8.2) compared with the diabetic risk group (15.4±2.9). Similarly, higher levels of HSP-27 were seen in the diabetic nephropathy group (230.46±23.75) as compared with the diabetic risk group (117.60±14.50). HSP-27 is a better biomarker than microalbumin and may show early glomerular injury in the early diabetic stage of diabetic nephropathy.

Improving care practices of the patient with type 2 diabetes in community health centers.

Diabetes ranks seventh in morbidity and mortality in the United States. In addition, more than 25 million Americans living with diabetes depend on community health centers (CHCs) for primary care. Preimplementation data in a group of CHCs indicated poor adherence to standards of care practices as recommended by the American Diabetes Association (ADA) with quarterly A1c (33.1%), annual serum laboratory tests (66.6%), and annual urine microalbumin (26.5%). Using a pre- and postimplementation comparison method, a NP-led practice improvement project was conducted in a group of CHCs, which sought to (1) identify adherence to ADA care standards; (2) determine whether an intervention could affect adherence to ADA standards; and (3) compare pre- and postimplementation occurrences of hemoglobin A1c greater than 7.1% and greater than 9%. Intervention composed of an educational component, standing orders to facilitate care practice changes, and electronic health record utilization changes. Postimplementation data reveal statistically significant improvements in quarterly hemoglobin A1c (93.6%), annual serum laboratory tests (96.5%), and annual urine microalbumin screening (85.5%). Improvements in translation to care for standardized guidelines facilitate improvements in health outcomes for patients. This project demonstrated improvements that can decrease the morbidity and mortality experienced by persons living with diabetes and being seen within a CHC. In addition, this project demonstrated that advanced practice nurses have the training and occupy a unique position within health care to spearhead initiatives for translation of evidence into care practices.

Predictors of High Cardiovascular Risk Among Nonobese Patients with Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease in a Chinese Population.

This study aims to investigate cardiovascular risk factors in nonobese patients with type 2 diabetes (T2DM) and non-alcoholic fatty liver disease (NAFLD) and to determine whether they might be used to predict high-risk individuals effectively. This cross-sectional study included 245 nonobese patients with T2DM who underwent FibroTouch in the National Metabolic Management Center of the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from January 2021 to December 2022. All individuals were divided into NAFLD and non-NAFLD groups. Patients with NAFLD were further grouped by UAP tertiles (T1, T2 and T3). We created a Cardiovascular Score (total scale: 0-5 points; ≥3 points was defined as high-risk individual) based on baPWV, carotid ultrasound, and urinary microalbumin creatinine ratio (UA/CR) to assess the risk of cardiovascular disease in non-obese T2DM patients with NAFLD. Risk factors were evaluated using univariate and multivariate analysis. The performance of risk factors was compared according to the area under the receiver operating characteristic (ROC) curve. Atherogenic index of plasma (AIP), atherosclerosis index (AI), prevalence of hypertension, body mass index (BMI) and homeostatic model assessment of insulin resistance (HOMA-IR) were higher in the NAFLD group compared to the non-NAFLD group. In T3 group, AIP, AI, BMI and HOMA-IR were higher than those of T1 group. Multivariate logistic regression showed that age, systolic blood pressure, low-density lipoprotein-cholesterol (LDL-C) and AIP were risk factors for cardiovascular disease among nonobese patients with T2DM and NAFLD. The area under the ROC curve for age, systolic blood pressure, LDL-C and AIP were 0.705, 0.688, 0.738 and 0.642, respectively. The area under the ROC curve was 0.895 when combining them. Age, systolic blood pressure, AIP and LDL-C are all independent risk factors for cardiovascular disease in non-obese individuals with T2DM and NAFLD, which can be combined to identify high-risk populations and carry out intervention.

VISUALIZING HETEROGENEOUS TRAJECTORIES OF SUBJECTS WITH SURGICAL RELAPSE IN INFLAMMATORY BOWEL DISEASE FROM UK BIOBANK GENERAL PRACTICE DATA

Abstract BACKGROUND AND AIMS The United Kingdom (UK) Biobank (UKBB) is a large-scale biomedical database and research resource, containing in-depth health information from half a million participants in UK that have been used for detailed analyses of IBD. Using the UKBB, we examined the lab findings and prescription medication use in IBD subjects to identify trajectory patterns of disease with respect to surgical relapse. METHODS Of the 363 subjects in the UKBB with an established IBD diagnosis (UC, CD, or both) and an initial GI surgery, 116 had a subsequent surgery within 5 years of initial surgery and had follow up lab values of urine and serum creatinine, plasma and serum C-reactive protein, urine and serum albumin, urine albumin-creatinine ratio, total white blood count, urine microalbumin, total white cell count, hemoglobin estimation, and erythrocyte sedimentation rate. Additionally, data for the 9 most used IBD prescription medications: budesonide, sulfasalazine, methotrexate, hydrocortisone, balsalazide, olsalazine, prednisolone, azathioprine, and mesalamine was analyzed as well. Hidden Markov Models (HMM) using these variables and open-source packages were incorporated to label observations of each subject-visit until the subsequent surgery. Interactive visualizations using DPVis open-source package were then applied to identify individual trajectories and explore clinical characteristics. RESULTS Five hidden states were observed from HMM. The five states observed are based on differing prescription medication usage for the treatment of IBD and were assigned a color to allow for comparison (Figure 1). The majority of patients fell within the states labeled “blue” (azathioprine, sulfasalazine, and prednisone) “red” (mesalamine only) or “purple” (azathioprine, balsalazide, and prednisolone). The visualizer showed that while some transitions among states were observed, most patients fell into one of three major trajectory patterns as a factor of time to surgical relapse and were largely segregated by state. Based on the trajectories, a comparison of subjects with prescription of mesalamine-only vs. any immunosuppressive medications (azathioprine + sulfasalazine + balsalazide) in combination with prednisolone showed a significant difference in time to surgical relapse (P &amp;lt; 0.005) (Figure 2), with a shorter time to surgical relapse identified in patients who took mesalamine only. CONCLUSIONS We identified three distinct trajectories leading up to surgical relapse. These trajectories show distinctive medication prescription patterns (5-ASA vs. Azathioprine with steroid use), as well as significantly different times to surgical relapse. Furthermore, heterogeneity is shown within each trajectory pattern in terms of progression time and warrant further investigation. Figure 1 Three Trajectories of time to surgical relapse generated from 5-State HMM using lab values and prescription medications. Note that a patient can traverse multiple states so the summation of the observed subjects of those states exceeds the cohort size (N=116). Figure 2 Kaplan-Meier curves for the UC/CD subgroup with surgical relapse considering events from the first documented lab values and/or planned prescription at most 2 years prior to the baseline surgery up to the subsequent 5 years.

Risk Factors of the Progression of Renal Function Deterioration Among Patients with Diabetic Nephropathy

Objective: To explore the risk factors for the progression of renal function deterioration in patients with diabetic nephropathy (DN). Methods: The clinical data and biochemical indexes of 100 diabetic patients admitted to our hospital from October 2021 to October 2022 were retrospectively analyzed. The patients were divided into a DN group, which consisted of 55 cases, and a nondiabetic nephropathy group (NDN), which consisted of 45 cases. The urinary microalbumin to creatinine ratio, the clinical data (gender, age, duration of the disease, and BMI), and the biochemical indexes (triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], glycated hemoglobin A1c [HbA1c], systolic blood pressure [SBP], diastolic blood pressure [DBP]) of the two groups were compared. Subsequently, the risk factors related to the progression of renal function deterioration in DN were analyzed through multifactorial logistic regression analysis. Results: No statistically significant difference was observed in the comparison of gender, age, BMI, LDL-C, and DBP between the two groups (P &gt; 0.05). The DN group demonstrated a longer disease duration and higher SBP, TC, HDL-C, HbA1c, and TG compared to the NDN group (P &lt; 0.05). Through multifactorial logistic regression analysis, it was found that the duration of the disease, the TC, the HDL-C, the HbA1c, the TG, and the SBP were independent risk factors of the deterioration of renal function in DN patients. Conclusion: Other than conventional indicators, TC, HDL-C, HbA1c, TG, and SBP are also crucial indicators in determining the progression of renal function deterioration in DN patients.

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.

The effect and mechanism of Fushen Granule on gut microbiome in the prevention and treatment of chronic renal failure.

Fushen Granule is an improved granule based on the classic formula Fushen Formula, which is used for the treatment of peritoneal dialysis-related intestinal dysfunction in patients with end-stage renal disease. However, the effect and mechanism of this granule on the prevention and treatment of chronic renal failure have not been fully elucidated. A 5/6 nephrectomy model of CRF was induced and Fushen Granule was administered at low and high doses to observe its effects on renal function, D-lactate, serum endotoxin, and intestinal-derived metabolic toxins. The 16SrRNA sequencing method was used to analyze the abundance and structure of the intestinal flora of CRF rats. A FMT assay was also used to evaluate the effects of transplantation of Fushen Granule fecal bacteria on renal-related functional parameters and metabolic toxins in CRF rats. Gavage administration of Fushen Granule at low and high doses down-regulated creatinine, urea nitrogen, 24-h urine microalbumin, D-lactate, endotoxin, and the intestinal-derived toxins indophenol sulphateand p-cresol sulphate in CRF rats. Compared with the sham-operated group in the same period, CRF rats had a decreased abundance of the firmicutes phylum and an increased abundance of the bacteroidetes phylum at the phylum level, and a decreasing trend of the lactobacillus genus at the genus level. Fushen Granule intervention increased the abundance of the firmicutes phylum, decreased the abundance of the bacteroidetes phylum, and increased the abundance of the lactobacillus genus. The transplantation of Fushen Granule fecal bacteria significantly reduced creatinine(Cr), blood urea nitrogen(Bun), uric acid(UA), 24-h urinary microalbumin, D-lactate, serum endotoxin, and enterogenic metabolic toxins in CRF rats. Compared with the sham-operated group, the transplantation of Fushen Granule fecal bacteria modulated the Firmicutes and Bacteroidetes phyla and the Lactobacillus genus. Fushen Granule improved renal function and intestinal barrier function by regulating intestinal flora, inhibiting renal fibrosis, and delaying the progression of chronic renal failure.

Clinical value of retinol binding protein, C-reactive protein and urine microalbumin in patients with chronic renal disease and ischemic cerebrovascular disease.

To explore the diagnostic value of retinol binding protein (RBP), C-reactive protein (CRP) and urine microalbumin (UMA) for ischemic cerebrovascular disease (ICD) in patients with chronic kidney disease (CKD). In this study, a total of 118 patients with CKD were selected and grouped into two groups: a group of patients who were complicated with ICD (CKD+ICD group, n=58), and a group of patients with CKD only (CKD group, n=60). Then, the patients in the CKD+ICD group were further classified into a good prognosis group and a bad prognosis group according their modified Rankin scale score at sixth months after discharge. Serum RBP, CRP and urine UMA levels were compared between the CKD group and CKD+ICD group. The diagnostic efficiency of serum RBP, CRP and urine UMA levels for ICD in patients with CKD was analyzed. The receiver operating characteristic (ROC) curve was used to assess their prognostic performance. Logistic regression analysis was used to evaluate the risk factors for poor prognosis of patients with CKD and ICD. The levels of RBP, CRP, and UMA in the CKD+ICD group were significantly higher than those in the CKD group (all P<0.05). RBP demonstrated the highest diagnostic accuracy and sensitivity for ICD in CKD patients, while CRP and UMA exhibited equivalent specificity, surpassing that of RBP. ROC curves showed that the areas under the curve (AUCs) of RBP and CRP were significantly greater than that of UMA (P<0.05) and there was no significant difference for AUCs between RBP and CRP. In addition, the levels of RBP, CRP and UMA in the poor prognosis group were significantly higher than those in the good prognosis group (all P<0.05). Logistic regression analysis showed that RBP, CRP and UMA were independent risk factors for the poor prognosis of patients with CKD and ICD (Odds ratios =2.507, 3.677 and 1.919, respectively; all P<0.05). The assessment of RBP, CRP and UMA is recommended for diagnosis of ICD in CKD patients. RBP, CRP and UMA are independent risk factors for poor prognosis of CKD patients with ICD.

Prevalence of Anaemia in Individuals with Type 2 Diabetes: A Cross- sectional Study from a Tertiary Care Centre, Chennai, India

Introduction: Anaemia is frequently observed in diabetes, affecting the quality of life and also contributing to the pathogenesis of microvascular complications. However, according to the literature, there have been no previous studies on the prevalence of Anaemia in Type 2 Diabetes (T2D) without Diabetic Kidney Disease (DKD) in the south Indian population. Aim: To estimate the prevalence of anaemia in T2D and study its association with glycaemic control and diabetes-related microvascular complications. Materials and Methods: The present study was a cross- sectional study that included 100 patients with T2D visiting the Department of Endocrinology at Sri Ramachandra Hospital, Chennai between June and September 2019. After obtaining informed consent, samples for complete blood count, Fasting Plasma Glucose (FPG), glycosylated haemoglobin (HbA1c), renal function tests, lipid profile, and urine microalbumin were collected from participants. Gestational diabetes, Type 1 Diabetes (T1D), and DKD on erythropoietin were excluded from this study. The test of Proportions was performed using the Chi- square test. Results: The mean age of the study population was 57.91±9.50 years. The overall prevalence of anaemia in the present study was 60%, and it was higher among women (p=0.023). Anaemia was also observed to be more common in those with poor glycaemic control (p=0.340) and in cases where at least one microvascular complication had occurred (p=0.796). Conclusion: Anaemia was observed in almost two-thirds of patients with T2D in this study. The prevalence of anaemia was higher in individuals with poor glycaemic control and diabetes- related microvascular complications.

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.

Clinical metabolomics of Zicuiyin in treatment of diabetic kidney disease

This study aimed to analyze the therapeutic effect of Zicuiyin on diabetic kidney disease(DKD) and explore the possible targets of this formula. Eighteen DKD patients treated in the endocrine department or nephrology department of Second Affilia-ted Hospital of Tianjin University of Traditional Chinese Medicine from January to December in 2019 were enrolled and assigned into a test group(n=10) and a control group(n=8). Both groups received routine chemical medicine treatment. In addition, the test group was treated with Zicuiyin and the control group with Huangkui Capsules for 8 weeks. The clinical trial was approved by the Ethics Committee of Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, with the ethical approval No. 2017-023-01, and all the patients signed the informed consent form. The results showed that the 8-week treatment with Zicuiyin lowered the level of glycosylated hemoglobin(HbA1c) and recovered the 24 h urinary protein(24hUP), 24 h urinary microalbumin(24hmAlb), urine albumin-to-creatinine ratio(UACR), and estimated glomerular filtration rate(eGFR) of the patients with 24hUP&lt;3.5 g. According to the different levels in 24hUP, all the patients were divided into two subgroups(subgroup A with 24hUP&lt;3.5 g and subgroup B with 24hUP≥3.5 g). The ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS)-based non-targeted metabolomics analysis was conducted on the baseline serum samples from diffe-rent subgroups of patients. Nineteen biomarker candidates were identified to distinguish the metabolic differences between the two subgroups, and their correlations with clinical indicators were analyzed. Zicuiyin lowered the levels of phenylalanine, pseudouridine, and adenosine [fold change(FC)&lt;0.5, P&lt;0.05] in subgroup A. The results indicated that Zicuiyin was more effective on the DKD patients with low urinary protein levels, and its targets were involved in phenylalanine metabolism and nucleoside metabolism.

Efficacy of atorvastatin calcium on clinical manifestations and serum inflammatory markers in elderly patients with hypertension.

To evaluate the effects of atorvastatin calcium on clinical manifestations and serum inflammatory markers in elderly patients with hypertension. This retrospective cohort study included 68 elderly patients with hypertension admitted to the Chongming Branch of Shanghai Tenth People's Hospital between March 2022 and June 2023. Patients were matched into two groups, each comprising 34 participants: a control group receiving amlodipine besylate and an experimental group receiving additional atorvastatin calcium. The study compared blood pressure, lipid profiles, and serum inflammatory markers before and after treatment between the groups. Biomarkers measured included tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6). Indices of target organ function measured were urinary microalbumin (mAlb), endogenous creatinine clearance (Ccr), and various cardiac structural indices, including left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and left ventricular posterior wall thickness (LVPW). Adverse reactions post-treatment were also recorded. Post-treatment assessments indicated significant reductions in both diastolic and systolic blood pressure (DBP and SBP), as well as improvements in lipid profiles (total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) in both groups. The experimental group exhibited greater improvements in 24-hour mean diastolic and systolic blood pressures after 4, 8, and 12 weeks of treatment compared to the control group (all P < 0.05). Additionally, serum inflammatory markers, including TNF-α, hs-CRP, and IL-6, were significantly lower in the experimental group than in the control group (all P < 0.05). The experimental group also showed superior improvements in mAlb and Ccr levels (both P < 0.05). Cardiac function indicators improved, with the experimental group showing greater increases in LVEF and more pronounced reductions in LVEDD and LVPW (both P < 0.05) compared to the control group. The incidence of adverse reactions was slightly lower in the experimental group (11.76%) than that in the control group (14.71%), although this difference was not statistically significant (P > 0.05). Adding atorvastatin calcium to amlodipine therapy significantly improves clinical outcomes and reduces serum inflammatory marker levels in elderly patients with hypertension. This combination therapy is considered safe and may be recommended for broader clinical application.

Use of Transcriptome Sequencing to Analyze the Effects of Different Doses of an Astragalus-Rhubarb-Saffron Mixture in Mice with Diabetic Kidney Disease.

To investigate the therapeutic effect and underlying mechanism of a traditional Chinese medicine (TCM) mixture consisting of Astragalus, rhubarb, and saffron in a mouse model of diabetic kidney disease (DKD). Forty-eight db/db mice received no TCM (DKD model), low-dose TCM, medium-dose TCM, or high-dose TCM, and an additional 12 db/m mice received no TCM (normal control). Intragastric TCM or saline (controls) was administered daily for 24 weeks. Blood glucose, body weight, serum creatinine (SCr), blood urea nitrogen (BUN), blood lipids, and urinary microalbumin were measured every four weeks, and the urinary albumin excretion rate (UAER) was calculated. After 24 weeks, kidney tissues were collected for transcriptome sequencing, and the main functions of these genes were determined via functional enrichment analysis. Compared with the DKD model group, the medium-dose and high-dose TCM groups had significantly decreased levels of SCr, BUN, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and UAER (all p<0.05). We identified 42 genes that potentially functioned in this therapeutic response, and the greatest effect on gene expression was in the high-dose TCM group. We also performed functional enrichment analysis to explore the potential mechanisms of action of these different genes. A high-dose of the Astragalus-rhubarb-saffron TCM provided the best prevention of DKD. Analysis of the kidney transcriptome suggested that this TCM mixture may prevent DKD by altering immune responses and oxygen delivery by hemoglobin.

Association of high vibration perception threshold with reduced renal function in patients with type 2 diabetes.

To investigate the correlation between vibration sensory threshold (VPT) and renal function, including glomerulus and renal tubule, in patients with type 2 diabetes mellitus (T2DM). A total of 1274 patients with T2DM who were enrolled in the Department of Endocrinology of the First Affiliated Hospital of Fujian Medical University between January 2017 and June 2020 were included. Patients were grouped according to VPT levels and divided into three groups, including the normal VPT group (VPT<15V), the mild-moderate elevated VPT group (VPT15~25V), and the severely elevated VPT group (VPT≥25 V). Linear correlation analysis was used to analyze the correlation between VPT and renal functions, including glomerulus markers urine microalbumin (MA) and urinary immunoglobulin G (U-IgG), and renal tubule marker α1-microglobulin (α1-MG). Chronic kidney disease (CKD) was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The binary logistic regression of the relation between VPT and CKD, eGFR<60 ml/min, and UACR >30 mg/g were expressed. In the mild-moderate and severely elevated VPT group, injury biomarkers of glomerulus (MA and U-IgG), renal tubule (α1-MG), and the incidence of CKD, eGFR<60 ml/min, and UACR > 30 mg/g were gradually increased compared with the normal VPT group. Furthermore, patients with diabetes and severely elevated VPT had significantly higher levels of MA (β=197.54, p=0.042) and α1-MG (β=11.69, p=0.023) compared to those with normal VPT. Also, patients with mild-moderate elevated VPT demonstrate significantly higher levels of MA (β=229.02, p=0.005). Patients in mild-moderate elevated VPT group (OR=1.463, 95% CI 1.005-2.127; OR=1.816, 95% CI 1.212-2.721) and severely elevated VPT group (OR=1.704, 95% CI 1.113-2.611; OR=2.027, 95% CI 1.248-3.294) are at a higher incidence of CKD and elevated levels of UACR>30mg/g compared to those in the VPT normal group. Moreover, the incidence of positive Upro was notably higher in the severely elevated VPT group (OR=1.738, 95% CI 1.182-2.556). However, this phenomenon was not observed in the incidence of eGFR <60 ml/min. A higher VPT is positively associated with the incidence of CKD in patients with T2DM, particularly with elevated UACR. VPT may serve as a marker for glomerulus and renal tubule injury.

A Klotho-Based Machine Learning Model for Prediction of both Kidney and Cardiovascular Outcomes in Chronic Kidney Disease

Introduction: This study aimed to develop and validate machine learning (ML) models based on serum Klotho for predicting end-stage kidney disease (ESKD) and cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Methods: Five different ML models were trained to predict the risk of ESKD and CVD at three different time points (3, 5, and 8 years) using a cohort of 400 non-dialysis CKD patients. The dataset was divided into a training set (70%) and an internal validation set (30%). These models were informed by data comprising 47 clinical features, including serum Klotho. The best-performing model was selected and used to identify risk factors for each outcome. Model performance was assessed using various metrics. Results: The findings showed that the least absolute shrinkage and selection operator regression model had the highest accuracy (C-index = 0.71) in predicting ESKD. The features mainly included in this model were estimated glomerular filtration rate, 24-h urinary microalbumin, serum albumin, phosphate, parathyroid hormone, and serum Klotho, which achieved the highest area under the curve (AUC) of 0.930 (95% CI: 0.897–0.962). In addition, for the CVD risk prediction, the random survival forest model with the highest accuracy (C-index = 0.66) was selected and achieved the highest AUC of 0.782 (95% CI: 0.633–0.930). The features mainly included in this model were age, history of primary hypertension, calcium, tumor necrosis factor-alpha, and serum Klotho. Conclusion: We successfully developed and validated Klotho-based ML risk prediction models for CVD and ESKD in CKD patients with good performance, indicating their high clinical utility.

Immune-metabolic marker of albumin-to-fibrinogen ratio based prognostic nomogram for patients following peritoneal dialysis.

The nutritional status and coagulation function of peritoneal dialysis (PD) patients are closely associated with their prognosis. This study aims to investigate the prognostic value of the albumin-to-fibrinogen ratio (AFR) on mortality in PD patients and to establish a prognostic prediction model based on AFR. We retrospectively collected data from 148 PD patients treated at our hospital between Oct. 2011 and Dec. 2021. Using the "survminer" package in R, we determined the optimal cutoff value for AFR and divided the patients into low-AFR and high-AFR groups. The primary endpoint of this study was overall survival (OS). Univariate and multivariate Cox analyses were used to assess the impact of AFR and other factors on prognosis, and a corresponding prognostic prediction model was constructed using a nomogram, which was evaluated through ROC curves, the c-index, and calibration plots. The optimal cutoff value for AFR was 9.06. In the entire cohort, 30 patients (20.2%) were classified into the low-AFR group. Compared to the high-AFR group, patients in the low-AFR group were older, had lower total urine output over 24 h, higher blood urea nitrogen, higher total protein and urinary microalbumin levels, and longer remission times (p < 0.05). They also had a poorer OS (HR: 1.824, 95%CI: 1.282-2.594, p < 0.05). Multivariate Cox analysis indicated that AFR was an independent prognostic factor for OS (HR: 1.824, 95% CI: 1.282-2.594, p < 0.05). A prognostic prediction model based on AFR, age, and cause of ESRD was successfully validated for predicting OS in PD patients. AFR represents a potential prognostic biomarker for PD patients. The prognostic prediction model based on AFR can provide accurate OS predictions for PD patients, aiding clinicians in making better-informed decisions.

Estimation of Microalbuminuria in Children with Beta Thalassaemia Major: A Cross-sectional Study

Introduction: Improvement in the standard of care of Thalassaemia by regular blood transfusion increases life expectancy. Multiple transfusions with concurrent iron overload and chronic anaemia, leading to tissue-level hypoxemia, cause significant renal dysfunction. Microalbuminuria is a sensitive marker of glomerular damage, and studies in thalassemic children have demonstrated variable prevalence rates of microalbuminuria. Aim: To study the prevalence of microalbuminuria and its association with clinical and laboratory parameters in children with Beta Thalassaemia Major (BTM). Materials and Methods: A cross-sectional study was conducted from January 2018 to June 2019 at Indira Gandhi Institute of Child Health, Bangaluru, Karnataka,India. A total of 155 children with Beta Thalassaemia Major (BTM) aged 2-18 years, attending the Thalassaemia Day Care Centre, were included in the study. Their demographic details such as age, gender, clinical parameters like frequency of transfusions, type of chelation therapy, height, weight, Body Mass Index (BMI), organomegaly, and laboratory parameters like serum creatinine, ferritin, pretransfusion Hb%, and Urinary Microalbumin Creatinine Ratio (UMCR) were studied as per a predesigned proforma. The association between microalbuminuria with clinical and laboratory parameters was evaluated using the independent sample T-test or Mann-Whitney U test and Chi-square/Fischer’s-exact test. Results: A total of 155 children with BTM were studied. In the present study, out of a total of 155 patients, microalbuminuria was found in 66 (42.6%). A significant increase in the prevalence of microalbuminuria was observed as the age advanced, as the frequency of blood transfusions increased, with low pretranfusion haemoglobin (g%), and with elevated serum ferritin. Conclusion: In the present study, the prevalence of microalbuminuria was found to be 42.6%. Screening for microalbuminuria is recommended in all children with beta thalassaemia major for the early detection of renal dysfunction, prevention of disease progression, and improvement in the quality of their lives.