Albumin and multiple sclerosis: a prospective study from UK Biobank.

Background: Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system. While previous studies have indicated that albumin, the primary protein in human plasma, may exert influence on the inflammatory process and confer beneficial effects in neurodegenerative disorders, its role in the context of MS has been underexplored. Here, we aimed to explore the link between albumin and the risk of MS. Methods: Employing data from the UK Biobank, we investigated the association between baseline levels of serum and urine albumin and the risk of MS using Cox proportional hazards regression analysis. Results: A higher baseline level of serum albumin was associated with a lower risk of incident MS (HR=0.94, 95% CI: 0.91-0.98, P=7.66E-04). Subgroup analysis revealed a more pronounced effect in females, as well as participants with younger ages, less smoking and deficient levels of vitamin D. Conversely, no association was identified between baseline microalbuminuria level and risk of incident MS. Conclusion: Higher serum albumin level at baseline is linked to a reduced risk of MS. These results contribute to an enhanced understanding of albumin's role in MS, propose the potential use of albumin as a biomarker for MS, and have implications for the design of therapeutic interventions targeting albumin in clinical trials.

Correlation of uric acid with microalbuminuria in Type-2 diabetic patients with normal creatinine.

Objective: To find the correlation of serum uric acid with microalbuminuria in Type-2 diabetic patients with normal creatinine. Methods: This cross-sectional study was conducted in the Department of Diabetes, Endocrinology and Metabolic diseases, Hayatabad Medical Complex, Peshawar, Pakistan from 1st April, 2022 to 30th September, 2022. Total 160 diabetic patients between the age of 30 and 65 years were enrolled in the study. Type-2 diabetic patients with microalbuminuria between 2.5 and 30 mg/mmol were included. The demographic details of patients were recorded in the questionnaire after taking consent. Fasting Uric acid, lipid profile and glucose along with creatinine and HbA1C were estimated from patient's venous blood samples. Ratio of albumin to creatinine (ACR) in the random spot urine sample was used to detect microalbuminuria. Results: Out of 160 participants enrolled in the study there were 86 (54%) males and 74 (46%) females with the mean age of 50.15 ± 11.1 years and BMI of 20.93 kg/m2. Ninety six (60%) of the patients had Type-2 DM for less than five years, while remaining 64 (40%) were more than five years diabetic. Mean serum uric acid calculated was 6.85±2.06(mg/dl), while microalbuminuria was calculated as 8.02±0.78 (mg/mmol). The Pearson correlation of serum uric acid and microalbuminuria based on sex and age was statistically significant(p<0.05). Conclusion: We found that uric acid level was significantly associated with microalbuminuria in people with Type-2 diabetes with normal serum creatinine. Uric acid level can be a potential screening tool for early detection of DKD.

Urinary biomarkers in diabetic nephropathy.

Diabetic nephropathy (DN), a significant consequence of diabetes, is associated with adverse cardiovascular and renal disease as well as mortality. Although microalbuminuria is considered the best non-invasive marker for DN, better predictive markers are needed of sufficient sensitivity and specificity to detect disease in general and in early disease specifically. Even prior to appearance of microalbuminuria, urinary biomarkers increase in diabetics and can serve as accurate nephropathy biomarkers even in normoalbuminuria. In this review, a number of novel urine biomarkers including those reflecting kidney damage caused by glomerular/podocyte damage, tubular damage, oxidative stress, inflammation, and intrarenal renin-angiotensin system activation are discussed. Our review also includes emerging biomarkers such as urinary microRNAs. These short noncoding miRNAs regulate gene expression and could be utilized to identify potential novel biomarkers in DN development and progression. .

Microalbuminuria as a Predictor of Early Neurological Deterioration and Poor Functional Outcomes in Acute Ischemic Stroke.

Background Ischemic stroke is a major health crisis with significant consequences. Microalbuminuria, a sign of endothelial dysfunction, has been linked to adverse outcomes in ischemic stroke. Early neurological deterioration (END) is a critical factor influencing the patient's prognosis. This study aimed to determine the prevalence of microalbuminuria, its predictive value in assessing END, and its prognostic implications in acute ischemic stroke (AIS). Methodology This study conducted at Pradyumna Bal Memorial Hospital, Kalinga Institute of Medical Sciences Bhubaneswar (November 2020-April 2022) included 114 AIS patients over 18 years who presented within 24 hours of stroke onset. Demographics, vascular risk factors, National Institutes of Health Stroke Scale (NIHSS) scores (admission and day three), modified Rankin scores (day 10), urinary albumin-to-creatinine ratios, and carotid artery Doppler studies were collected. Results The mean age of the patients was 61.87 years, with males constituting 72.8% of the population. Hypertension (50.9%) and diabetes mellitus (28.9%) were the most common comorbid conditions. The mean NIHSS stroke severity at presentation was 11.30. END occurred in 38.6% of patients. Overall, 43.9% of cases showed carotid stenosis, and the mean carotid intimal media thickness was 1.08 mm. Notably, the presence of microalbuminuria significantly increased the chances of both END (39.45 times higher risk) and worse functional outcomes (odds ratio = 19.147, p = 0.001). Conclusions Microalbuminuria emerges as a robust independent predictor of END and a poor prognosis in AIS. These findings highlight the importance of early microalbuminuria identification and intervention to reduce END risk and potentially improve outcomes in AIS patients.

Evaluation of microalbuminuria in type-2 diabetes mellitus under oral hypoglycemic agents: Association with age, sex, BMI, and renal clearance.

Background: Diabetes mellitus (DM) is increasing drastically and affecting the individuals globally, especially in the low- and middle-income countries like India. The poor glycaemic control results in micro-vascular and macro-vascular complications, leading to dysfunction of multiple organs. This study aimed to evaluate the association between the risk factors and microalbuminuria levels among patients with type 2 DM on oral hypoglycaemic agents. Materials and Methods: Hundred type 2 DM patients fulfilling the inclusion and exclusion criteria were selected by convenient random sampling. Demographic details, biochemical markers, and anti-diabetic medication details were collected. The findings were analyzed statistically using Chi-square test and one-way analysis of variance (ANOVA) with SPSS software 21.0. Results: Among the different combination therapies, 59% were commonly using metformin and teneligliptin. There was a significant association noted between microalbuminuria and risk factors like age, duration of disease, body mass index (BMI) (25.5 ± 2.9), fasting blood sugar (151 ± 53.2 mg/dL), post prandial blood sugar (227.01 ± 70.9 mg/dL), blood urea (24.42 ± 9.3 mg/dL), and serum creatinine (1.5 ± 0.2 mg/dL) (P < 0.001). One-way ANOVA showed statistical significance between microalbuminuria and the different treatment groups (P < 0.0001). Conclusion: Microalbuminuria was associated with age, duration of diabetes, glycaemic control, and BMI. In contrast, there was no significant difference noted between the genders and microalbuminuria. Microalbuminuria is an early indication of nephropathy in diabetes patients. The early identification of the risk factors is important, and it is always recommended to screen for microalbuminuria in all the diabetic patients for early detection and prevention of diabetic nephropathy and their associated complications.

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

Background: 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. Methods: 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. Results: 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. Conclusion: Montelukast showed a protective effect in the model of diabetic nephropathy because of its antioxidant effect.

Microalbuminuria in Rats Treated with D-Nitroarginine Methyl Ether.

Microalbuminuria is an early symptom and prognostic marker of the progression of renal pathology. The analysis of the role of anionic components of the renal glomeruli in the albumin retention and the development of a model of minimal changes in the glomerular filter leading to the appearance of microalbuminuria are relevant. The effect of organic cations D-arginine methyl esters (D-AME) and D-nitroarginine (D-NAME) on the excretion of albumin by the kidneys in rats was studied. D-AME had no effect on urinary albumin excretion in rats. D-NAME caused microalbuminuria, which persisted for more than a day and sharply increased after injection of vasopressin. The number of anionic sites labeled with polyethyleneimine decreased in the structures of the glomerular filter. D-NAME-induced microalbuminuria can later serve as a model for studying nephroprotective or damaging factors.

Serum cell division cycle 42 reflects the development and progression of diabetic nephropathy in patients with diabetes mellitus.

Cell division cycle 42 (CDC42) regulates podocyte apoptosis to take part in the development and progression of diabetic nephropathy (DN), but currently the clinical evidence is limited. The aim of the present study was to investigate the capability of serum CDC42 expression level to estimate the development and progression of DN in patients with diabetes mellitus (DM). Patients with type 2 DM (n=306) were enrolled and divided into normoalbuminuria (n=185), microalbuminuria (n=72) and macroalbuminuria (n=49) groups based on the urinary albumin-to-creatinine ratio. Serum CDC42 was measured in all subjects using enzyme-linked immunosorbent assay. The median (interquartile range) CDC42 in patients with DM was 0.461 (0.314-0.690) ng/ml (range, 0.087-1.728 ng/ml). CDC42 was positively associated with the estimated glomerular filtration rate (P<0.001), but negatively correlated with body mass index, systolic blood pressure, hemoglobin A1c, serum creatine, serum uric acid and C reactive protein (all P<0.050). CDC42 levels were lowest in the macroalbuminuria group, followed by the microalbuminuria group, and were highest in the normoalbuminuria group (P<0.001). CDC42 indicated that it was a favorable estimator for the presence of albuminuria [area under the curve (AUC), 0.792; 95% confidence interval (CI), 0.736-0.848] and macroalbuminuria (AUC, 0.845; 95% CI, 0.775-0.915). By analyses in four different multivariate logistic regression models, increased CDC42 was independently associated with the presence of microalbuminuria (all P<0.001), macroalbuminuria (most P<0.001) and microalbuminuria + macroalbuminuria (all P<0.001). Serum CDC42 level negatively correlated with microalbuminuria and macroalbuminuria in patients with DM, suggesting its ability for estimating the development and progression of DN.

Effects of allisartan-isoproxil-based combination antihypertensive regimen in hypertensive patients with microalbuminuria or hyperuricemia.

Microalbuminuria and hyperuricemia management are crucial for the integrated management of hypertensive patients. This retrospective post hoc analysis aims to evaluate the optimal allisartan-isoproxil-based combination regimen for hypertensive patients with microalbuminuria or hyperuricemia. A total of 460 hypertensive patients with microalbuminuria and 486 hypertensive patients with hyperuricemia were included in this study. All patients were initially treated with allisartan-isoproxil for 4 weeks. Thereafter, patients with blood pressure (BP) < 140/90 mmHg continued the monotherapy for 8 weeks; patients with BP ≥140/90 mmHg were randomly assigned in a 1:1 ratio to receive allisartan-isoproxil + amlodipine (Group A + C) or allisartan-isoproxil + indapamide (Group A + D) for 8 weeks. The changes of BP, urinary albumin and serum uric acid (UA) were measured. In patients with microalbuminuria, the urinary albumin/creatinine ratio (UACR) significantly decreased by 10.4 mg/g in Group A + C (vs. baseline p = .0035) and 24.2 mg/g in Group A + D (vs baseline p < .0001), intergroup p = NS. In patients with hyperuricemia, serum UA level decreased by 44.5 µmol/L in Group A + C (vs. baseline p = .0003), but increased by 27.2 µmol/L in Group A + D (vs. baseline p = .0167), intergroup p < .0001. The results suggest that for hypertensive patients with microalbuminuria, angiotensin receptor blocker (ARB) + calcium channel blocker (CCB) or ARB+ diuretic both are good choices based on their improvement of microalbuminuria and BP. But for patients with hyperuricemia, ARB + diuretic may further increase the level of UA.

Microalbuminuria and Functional Iron Deficiency are Risk Factors for Hearing Loss in Adolescents.

OBJECTIVES: Renal impairment and some systemic diseases are associated with hearing loss (HL) in adults. However, studies of these relationship in adolescents are rare. The objective of this study was to determine the association between HL and renal or systemic disease in adolescents. METHODS: Subjects were extracted from the 5th Korea National Health and Nutrition Examination Survey from 2011 to 2012. We included adolescents aged 10-19 years old with normal tympanic membrane and those who underwent a physical and laboratory examination and pure tone audiometry. HL, high-frequency hearing loss (HFHL), albuminuria, impaired glomerular filtration rate, hypertension, diabetes, and obesity were evaluated based on the data. RESULTS: Individuals with microalbuminruia (MIA) exhibited higher prevalence of HL (p = 0.003) and HFHL (p = 0.012) than those without MIA. The prevalence of HL and HFHL appeared to increase according to the severity of albuminuria. Additionally, individuals with HL or HFHL showed lower transferrin saturation (TSAT) than individuals without HL (p = 0.002) or HFHL (p = 0.001). And, HFHL was associated with lower ferritin levels (p = 0.017). HL and HFHL were related to MIA (p = 0.004 and p = 0.022, respectively) and TSAT (p = 0.005 and p = 0.011, respectively) after controlling other factors. CONCLUSION: MIA and TSAT level were independently associated with the HL and HFHL. Since MIA can be easily detected by dipstick test and urine analysis, hearing evaluations for individuals with MIA might be helpful to identify hearing impairments earlier in adolescents. LEVEL OF EVIDENCE: 3 (individual cross-sectional study) Laryngoscope, 134:3329-3334, 2024.

Correlation of serum uric acid levels with certain anthropometric parameters in prediabetic and drug-naive diabetic subjects.

Introduction: Uric acid is produced during the metabolism of nucleotide and adenosine triphosphate and contains the final product of human purine metabolism. It acts both as an antioxidant and pro-inflammatory marker and has a positive association with visceral fat in overweight subjects. The aim of the present study is to find an association of uric acid level with certain anthropometric parameters in subjects having type 2 diabetes. Materials and Methods: The study included 124 urban drug-naive diabetic Indian subjects above 18 years of age from the general population of the city of North India. Uric acid concentrations were estimated by the uricase method. Fasting plasma glucose (FPG) concentrations were estimated by the glucose oxidase-peroxidase method. Anthropometric measurements and information on lifestyle factors and disease history were collected through in-person meeting. Results: All participants of the study subjects had a body mass index (BMI) of more than 23.5. BMI, waist-to-hip ratio (WHR), waist-to-height ratio, waist circumference, neck circumference, weight, age, sagittal abdominal diameter (SAD), skinfold thickness, and body roundness index were positively correlated with the serum uric acid level. The correlation of weight, BMI, SAD, and WHR was statistically significant. Conclusion: We found that serum uric acid level increases as body fat content increases. Statistical data show remarkable results for a significant correlation of uric acid level with BMI, WHR, SAD, and FPG. Hypertrophy occurs as a result of inflammatory processes and oxidative stress when the supply of energy starts to exceed the storage capacity of adipocytes, as a result, adipokines such as interleukin (IL)-1, IL-6, and tumor-necrosis factor-alpha are released more frequently which lead to low-grade chronic inflammation. Uric acid levels are much lean toward visceral obesity than overall body fat content.

Résumé Introduction: L'acide urique est produit lors du métabolisme des nucléotides et de l'adénosine triphosphate, et il représente le produit final du métabolisme des purines chez l'homme. Il agit à la fois comme un antioxydant et un marqueur pro-inflammatoire, et il est positivement associé à la graisse viscérale chez les sujets en surpoids. L'objectif de la présente étude est de rechercher une association entre le taux d'acide urique et certains paramètres anthropométriques chez des sujets atteints de diabète de type 2. Matériels et méthodes: L'étude a inclus 124 sujets diabétiques urbains indiens, naïfs aux médicaments, âgés de plus de 18 ans, issus de la population générale de la ville du nord de l'Inde. Les concentrations d'acide urique ont été estimées par la méthode de l'uricase. Les concentrations de glucose plasmatique à jeun (FPG) ont été estimées par la méthode glucose oxydase-peroxydase. Les mesures anthropométriques et les informations sur les facteurs de mode de vie et les antécédents médicaux ont été recueillies lors de rencontres en personne. Résultats: Tous les participants de l'étude présentaient un indice de masse corporelle (IMC) supérieur à 23,5. L'IMC, le rapport taille-hanche (WHR), le rapport taille-hauteur, la circonférence de taille, la circonférence du cou, le poids, l'âge, le diamètre abdominal sagittal (SAD), l'épaisseur des plis cutanés et l'indice de rondeur corporelle étaient corrélés positivement avec le taux d'acide urique sérique. La corrélation du poids, de l'IMC, du SAD et du WHR était statistiquement significative. Conclusion: Nous avons constaté que le taux d'acide urique sérique augmente avec l'augmentation de la teneur en graisse corporelle. Les données statistiques montrent des résultats remarquables pour une corrélation significative du taux d'acide urique avec l'IMC, le WHR, le SAD et le FPG. L'hypertrophie se produit en raison de processus inflammatoires et de stress oxydatif lorsque l'apport d'énergie dépasse la capacité de stockage des adipocytes. Par conséquent, des adipokines telles que l'interleukine (IL)-1, l'IL-6 et le facteur alpha de nécrose tumorale sont libérées plus fréquemment, ce qui entraîne une inflammation chronique de bas grade. Les niveaux d'acide urique sont davantage associés à l'obésité viscérale qu'à la teneur globale en graisse corporelle. Mots-clés: Anthropométrique, syndrome métabolique, microalbuminurie, acide urique sérique.

Prevalence and the factors associated with microalbuminuria among patients with type 2 diabetes mellitus and/or hypertension in the urban areas of Puducherry district: a cross-sectional study.

BACKGROUND: Microalbuminuria is an early indicator for renal and cardiovascular diseases, especially among patients with diabetes mellitus (DM) and hypertension (HTN). We determined the prevalence and the factors associated with microalbuminuria among patients with type 2 DM and/or HTN in the urban areas of the Puducherry district in India. METHODS: We included 225 patients aged 40-69 years with DM and/or HTN from a non-communicable diseases (NCDs) survey conducted during 2019-2020 in the urban areas of Puducherry district. The prevalence of microalbuminuria and various biological risk factors of NCDs were assessed as per the WHO STEPS methodology. The prevalence of microalbuminuria was presented as proportions (95% CI), and the adjusted prevalence ratio (aPR) was estimated using weighted forward stepwise generalized linear modelling. P-value ≤0.05 was considered statistically significant. RESULTS: The mean (SD) age of the patients was 54 (11) years. Over one-third (38.2%) (95% CI: 31.6-44.4) of patients with DM and/or HTN had microalbuminuria. The prevalence was highest among those having both DM and HTN 48% (95% CI: 37-59), followed by those having only DM 40.6% (95% CI: 29-52.2) and only HTN 27.7% (95% CI: 18.1-38.6). The prevalence of microalbuminuria was twice (aPR = 2.1, 95% CI: 1.1-3.9) higher among women and 2.4 times (95% CI: 1.12-5.1) higher among those having both DM and HTN as compared to those with only HTN. CONCLUSION: The prevalence of microalbuminuria among patients with DM and/or HTN is concerningly high. Population-based screening for microalbuminuria, especially among women and those having both DM and HTN, needs to be undertaken in the urban areas of Puducherry district.

Microalbuminuria serves as an early indicator for kidney and cardiovascular diseases, especially among patients with diabetes mellitus (DM) and hypertension (HTN). Our study focussed on determining the prevalence of microalbuminuria among individuals with type 2 DM and/or HTN in the urban areas of the Puducherry district in India. We included 225 patients aged 40­69 years with DM and/or HTN who participated in a non-communicable diseases (NCDs) survey conducted during 2019­2020 in urban Puducherry. We found that over one-third (38.2%) of patients with DM and/or HTN had microalbuminuria. The prevalence was highest among those having both DM and HTN (48%), followed by those having only DM (40.6%) and only HTN (27.7%). The prevalence of microalbuminuria was 2.1 times higher among women than men and 2.4 times higher among individuals with both DM and HTN compared to those with only HTN. These findings highlight the concerningly high prevalence of microalbuminuria among patients with DM and/or HTN in the urban areas of Puducherry district. To address this issue, it is crucial that the public health authorities of Puducherry district implement population-based screening initiatives for microalbuminuria, particularly targeting women and individuals with both DM and HTN in the urban areas of the Puducherry district.

Association of Normal and Mutated APOL1 G2 Rs60910145 alleles with SCD, Body Mass Index, and Renal Function Biomarkers and Indices.

PURPOSE OF THE STUDY: The current study aimed to detect the frequency of normal and mutated APOL1 alleles in sickle cell disease (SCD) patients and test their relation with Microalbuminuria, Creatinine, Urea, Glomerular Filtration Rate (GFR), and Body Mass Index (BMI). PATIENTS AND METHODS: The study included 156 SCD subjects. Serum Creatinine (mg/dl) and Urea (mg/dl) as well as Microalbuminuria (mg/l) level were measured by using Biosystems kit (Biosystems, Barcelona, Spain) and Mindary BA88A semi-automated biochemistry analyzer. Glomerular filtration rate and body mass index were calculated by equations. Blood DNA extraction was achieved by using the modified G-DEX™IIb Genomic DNA Extraction Kit protocol. The PCR was done for the detection of the APOL1 G2 rs60910145 alleles by using allele-specific PCR and primers. RESULTS: The CC allele was more frequent in study cases (66.7%) than TT allele. The frequency of a mutated allele (CC) was insignificantly higher in males (67.8%) than in females (65.2%) and in rural (70.9%) than urban areas. It is also higher in Shankhab compared to other tribes and subjects 26-37 years compared to other, P˃0.05. Interstingly, the subjects who carry the CC allele showed a significantly higher level of Microalbuminuria, Creatinine, BMI, and Urea compared to those carry TT allele. Moreover, GFR is also higher in subjects who carry CC than TT allele but it is not significant. CONCULSION: Altogether, the study findings highlighted the link of normal and mutated APOL1 G2 rs60910145 alleles with SCD and displayed the significant value of mutated APOL1 allele in the prediction of early nephropathy in SCD patients.

A Prospective, Multicentered, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Keluoxin Capsules in the Treatment of Microalbuminuria in Patients with Type 2 Early Diabetic Kidney Disease.

Background: To evaluate the efficacy and safety of Keluoxin (KLX) capsules and provide validated evidence for the application of KLX in the treatment of diabetic kidney disease (DKD). Methods: A multicenter, randomized, double-blind, placebo-controlled trial design was used to screen 129 patients with DKD (urinary albumin-to-creatinine ratio [UACR]: male, 2.5-30 mg/mmol; female, 3.5-30 mg/mmol) and with Qi and Yin deficiency and blood stasis symptoms. Written informed consent was obtained from all patients. The patients were randomly divided into KLX and control groups. The KLX group was orally administered KLX (6 g/day) and irbesartan tablets (150 mg/day), whereas the control group was administered KLX placebo (6 g/day) and irbesartan tablets (150 mg/day). Patients were observed for 24 weeks to evaluate the natural logarithm of the UACR (log-UACR), the odds ratio (OR) for a sustained increase in the UACR of at least 30% and 40%, estimated glomerular filtration rate (eGFR), changes in symptoms and quality-of-life scores, and adverse events. Results: The changes of the natural log-UACR during the 24 weeks compared with baseline in the KLX group were better than those in the control group (LS mean ± standard error, -0.26 ± 0.10 vs. 0.01 ± 0.09, p = 0.0292). The incidence of a sustained increase in the UACR of at least 30% and 40% was found to be significantly lower in the KLX group (OR, 0.26; 95% confidence interval [CI], 0.09-0.75; OR, 0.29; 95% CI, 0.10-0.82). Changes in symptoms and quality-of-life scores in the KLX group were better than those in the control group. There was no statistically significant difference in eGFR or the incidence of adverse events between the groups. Conclusions: Overall, these results suggest that KLX capsules combined with irbesartan can reduce microalbuminuria, relieve the symptoms, and improve the quality of life for patients with type 2 early DKD compared with the use of irbesartan alone. Trial registration: Chinese Clinical Trial Registry, registration number: ChiCTR2100052764.

Sympathetic skin response for early detection of type 2 diabetic peripheral neuropathy and nephropathy.

BACKGROUND: Diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) are common complications of type 2 diabetes mellitus (T2DM). Although nerve conduction studies (NCS) and sympathetic skin response (SSR) can detect DPN, the more sensitive method for early diagnosis remains unclear. Furthermore, whether DPN can be used as a predictor for diabetic nephropathy needs clarification. METHODS: We evaluated nerve conduction studies, sympathetic skin response, and the diabetic nephropathy indicator microalbuminuria (MAU) in 192 patients with type 2 diabetes mellitus and 50 healthy controls. RESULTS: Patients with type 2 diabetes mellitus showed a lower sensory nerve conduction velocity (SCV), sensory active nerve potential (SNAP), motor nerve conduction velocity (MCV), and compound motor action potential (CMAP) than the controls on NCS. Abnormal rates for nerve conduction studies and sympathetic skin response were 75.0% and 83.3%, respectively, in patients with type 2 diabetes mellitus. Interestingly, 54.2% of patients with normal nerve conduction studies had an abnormal sympathetic skin response. Moreover, we found a positive correlation between sympathetic skin response and microalbuminuria for the first time. The abnormal rate of microalbuminuria was 53.8%, lower than that of abnormal nerve conduction studies or sympathetic skin response patients. CONCLUSION: Sympathetic skin response is a more sensitive method than nerve conduction studies for the early diagnosis of diabetic peripheral neuropathy. Abnormal sympathetic skin response might serve as an indicator for early diabetic nephropathy. Additionally, diabetic peripheral neuropathy may occur earlier than diabetic nephropathy in the development of type 2 diabetes mellitus.

Positive association between circulating Caveolin-1 and microalbuminuria in overt diabetes mellitus in pregnancy.

AIMS: Mounting evidence has shown that caveolin-1 plays a pathological role in the progression of albuminuria. Our study aimed to provide clinical evidence showing whether circulating caveolin-1 levels were associated with microalbuminuria (MAU) in women with overt diabetes mellitus in pregnancy (ODMIP). METHODS: A total of 150 pregnant women were enrolled in different groups, including 40 women with ODMIP and MAU (ODMIP + MAU), 40 women with ODMIP, and 70 women without ODMIP (Non-ODMIP). Plasma caveolin-1 levels were determined by ELISA. The presence of caveolin-1 in the human umbilical vein vascular wall was evaluated by immunohistochemical and western blot analysis, respectively. Albumin transcytosis across endothelial cells was measured using an established nonradioactive in vitro approach. RESULTS: Significantly increased levels of plasma caveolin-1 were detected in ODMIP + MAU women. The Pearson's correlation analysis revealed a positive correlation between plasma caveolin-1 levels and Hemoglobin A1c (HbA1c %) as well as with MAU in the ODMIP + MAU group. Simultaneously, experimental knockdown or overexpression of caveolin-1 significantly decreased or increased the level of albumin transcytosis across both human and mouse glomerular endothelial cells (GECs), respectively. CONCLUSIONS: Our data showed a positive association between plasma caveolin-1 levels and microalbuminuria in ODMIP + MAU.

Enhanced trimethylamine metabolism and gut dysbiosis in type 2 diabetes mellitus with microalbumin.

Background: Abnormal gut microbiota and blood trimethylamine-N-oxide (TMAO) metabolome have been reported in patients with type 2 diabetes mellitus (T2DM) and advanced diabetic nephropathy. This study aimed to investigate the gut microbiota profiles and a group of targeted urine metabolic characteristics in T2DM patients with or without microalbuminuria, to determine the correlation between the gut microbiota composition, trimethylamine (TMA) metabolism, and the clinical features during progression of diabetic kidney disease (DKD). Methods: This study included 26 T2DM patients with microalbuminuria (Micro), 26 T2DM patients with normoalbuminuria (Normo), and 15 healthy controls (HC). Urine and Fecal samples were detected using ultra performance liquid chromatography tandem mass spectrometry and 16S ribosomal DNA gene sequencing, respectively. Results: The TMAO/TMA ratio decreased gradually during the HC-Normo-Micro transition. The levels of TMA, choline and betaine were significantly different between the HC group and the T2DM patients belonging to both Normo and Micro groups. At the operational taxonomic unit (OTU) level, the gut microflora diversity was significantly reduced in the Micro groups compared to the HC groups and the Normo groups. Taxonomic analyses revealed significant consumption in the relative abundances of eight bacterial genera and significant enrichment of two bacterial genera during the HC-Normo-Micro transition. Furthermore, the relative abundances of six bacterial genera, namely, Ruminococcus_1, [Eubacterium]_ruminantium_group, Roseburia, Faecalibacterium, Fusicatenibacter and Coprococcus_3 exhibited significant differences, and were associated with elevated urinary albumin creatinine ratio (UACR), TMAO/TMA, TMA and its precursors in the Micro group compared with the other groups. Conclusion: The imbalance of gut microbiota has occurred in patients with early-stage DKD, and the consumption of short-chain fatty acid-producing bacteria were associated with the accumulation of TMA and UACR.

Changes in serum tumor markers in type 2 diabetes mellitus with microalbuminuria.

Objectives: The objective of this study was to investigate changes in serum tumor markers in type 2 diabetes mellitus (T2DM) with microalbuminuria and analyze the relationship between tumor markers and microalbuminuria. Methods: A total of 956 T2DM patients aged 40-70 years hospitalized in the Department of Endocrinology, Xinhua Hospital, China, affiliated with Shanghai Jiaotong University School of Medicine, were enrolled from January 2018 to December 2020. The sample comprised 313 T2DM patients with microalbuminuria and 643 T2DM patients with normal urinary microalbumin levels. After assessing the changes in serum tumor markers in T2DM with microalbuminuria, we analyzed the risk of microalbuminuria by the serum tumor marker category using multiple logistic regression analysis. Results: Serum CEA, CA199, CA125, CA153, CA211, SCC, CA242, and CA50 levels were significantly higher in T2DM patients with microalbuminuria than in those without microalbuminuria, while serum AFP levels were lower in the microalbuminuria group (P < 0.05). Following adjustment of confounders, serum CEA, CA211, and SCC were independently associated with microalbuminuria in T2DM. An ROC curve was used to estimate the cutoff point of tumor markers for microalbuminuria. Taking the values under the cutoff points as a reference, values for CEA, CA211, and SCC above the cutoff points indicated a significantly high risk of microalbuminuria. The OR of increased CEA for microalbuminuria was 2.006 (95%CI 1.456-2.765), the OR of increased CA211 for microalbuminuria was 1.505 (95%CI 1.092-2.074), and the OR of increased SCC for microalbuminuria was 1.958 (95%CI 1.407-2.724). Conclusion: Several serum tumor markers were related to microalbuminuria in T2DM. Serum tumor markers such as CEA, SCC, and CA211 may indicate early diabetic nephropathy, particularly when elevated in combination.

Clinical value of noninvasive lens advanced glycation end product detection in early screening and severity evaluation of patients with diabetic kidney disease.

BACKGROUND: Advanced glycation end products (AGEs) deposited in the lens are correlated with those in the kidneys, indicating a possible value in evaluating diabetic kidney disease (DKD). This study explored the value of noninvasively measuring lens AGEs to diagnose and evaluate the severity of diabetic nephropathy in patients with type 2 diabetes mellitus (T2DM). METHODOLOGY: A total of 134 T2DM patients admitted to the Fifth People's Hospital of Shanghai from March 2020 to May 2021 were selected randomly. Patients were divided into low-, medium-and high-risk groups according to the risk assessment criteria for DKD progression and into DKD and non-DKD (non-DKD) groups according to the Guidelines for the Prevention and Treatment of Diabetic Nephropathy in China. The concentrations of noninvasive AGEs in the lens in all the groups were retrospectively analyzed. RESULTS: The concentration of noninvasive lens AGEs in the high-risk patients, according to the 2012 guidelines of the Global Organization for Improving the Prognosis of Kidney Diseases, was significantly higher than that in the remaining groups. Regression analysis suggested the value of lens AGEs in diagnosing DKD and evaluating DKD severity. Cox regression analysis indicated that the noninvasive lens AGE concentration was positive correlated with the course of disease. CONCLUSION: The receiver operating characteristic (ROC) curve suggested that using noninvasive lens AGE measurements has clinical value in the diagnosis of DKD (area under the curve 62.4%,95% confidence interval (CI) 52.4%-73.9%, p = 0.014) and in assessing the severity of DKD (area under the curve 83.2%, 95% CI 74.1%-92.3%, P < 0.001). Noninvasive lens AGE testing helps screen T2DM patients for DKD and evaluate the severity of DKD.

Impact of magnesium supplementation on clinical outcome and disease progression of patients with diabetic nephropathy: a prospective randomized trial.

Background: Magnesium (Mg) deficiency is closely linked with proteinuria. Objectives: To assess the impact of oral Mg citrate supplementation on the clinical outcome of diabetic nephropathy (DN) patients. Design: This was a prospective, randomized, controlled, open-label study. Methods: Sixty DN patients were recruited from Nephrology and Endocrinology departments, Ain Shams University Hospitals, Cairo, Egypt. Patients were assigned by stratified randomization based on their Mg status, to either Mg citrate group, (n = 30), who received the standard regimen + oral Mg citrate 2.25 g/day or Control group, (n = 30), who received the standard regimen only. The primary endpoint was a change in urinary albumin to creatinine ratio (UACR) after 12 weeks. Secondary outcomes were insulin resistance, glycemic control, lipid profile, serum osteocalcin, quality of life (QoL) and Mg tolerability. Results: Out of a total of 60 patients enrolled, only 54 patients (26 in Mg citrate group and 28 in the control group) completed the study. Groups were comparable at baseline. The UACR median percent reduction was significantly higher in the Mg citrate group (-6.87%) versus (-0.9%) in the Control group, p = 0.001. After 12 weeks, the estimated glomerular filtration rate significantly improved in the Mg citrate group versus Control group (p = 0.001). Comparable change was observed in glycemic indices. Lipid profile significantly improved in the Mg citrate group versus Control group (p = 0.001). Serum osteocalcin levels significantly declined in the Mg citrate group (p = 0.001) versus control group. Regarding QoL, the total score and all domains significantly improved in the Mg citrate group compared to control. The Mg supplement was tolerable with only mild reported side effects that required no intervention. Conclusion: Oral Mg citrate supplementation improved microalbuminuria in DN patients. It also had favorable effects on serum osteocalcin, lipid profile and QoL with no reported major side effects. Trial registration: ClinicalTrials.gov identifier: NCT03824379.