Assessment of serum magnesium and correlation with glycemic control and complication in type 2 diabetes mellitus – A cross-sectional study in a tertiary care hospital in eastern zone of India

Background: Diabetes mellitus (DM) is an expanding global health problem. Type 2 DM (T2DM) patients account about 90% of total DM patients. Magnesium is important for different physiological mechanism. Hypomagnesemia is common in T2DM patient. Magnitude of hypomagnesemia is related with glycemic control and is associated with complications of T2DM. Aims and Objectives: Our aim of the study was to assess the prevalence of hypomagnesemia in patients of T2DM patients and to find their correlation with glycemic control and complications of T2DM patients in rural population of eastern zone of India. Materials and Methods: The hospital-based cross-sectional study includes 99 male and female DM patients between 15 and 60 years age. Fasting blood sugar, postprandial blood sugar, HbA1c, serum total magnesium, and urine albumin creatinine ratio were measured. Data were entered into Microsoft Excel spreadsheet and then analyzed by SPSS (version 25.0; SPSS Inc.) and GraphPad Prism (version 5.0). P < 0.05 was considered statistically significant. Results: From our study, we observed that hypomagnesemia is common in T2DM patients. The magnitude of hypomagnesemia is correlated with glycemic control (P < 0.0001). Moreover, hypomagnesemia is associated with diabetic kidney diseases (P < 0.05). Conclusion: It can be concluded that serum magnesium should be monitored in all T2DM patients and should be managed appropriately because hypomagnesemia may induce complications in T2DM patients.

Self-Measured Blood Pressure and Target Organ Damage in Newly Detected Hypertension in South Gujarat, India

Introduction: Blood pressure transient spikes have been considered to be noise and only a hindrance to a proper assessment of typical blood pressure, which is defined as the actual underlying average blood pres-sure over a long period of time. The current study aimed to see if the highest Self measured Systolic blood Pressure could be utilized to forecast the occurrence of Target organ damage and evaluate the independent association between the maximum Self measured Systolic blood Pressure and Target organ damage in indi-viduals with untreated hypertension. Method: We evaluated the urine albumin/creatinine ratio (UACR) and carotid intima-media thickness (IMT) using ultrasonography in 462 hypertensive individuals who had never taken treatment for their hypertension. Residential blood pressure was recorded. Result: The maximal Self measured Systolic blood Pressure had considerably higher association coefficients with left ventricular mass index (LVMI) and carotid intima-media thickness than the mean Self measured Sys-tolic blood Pressure. Irrespective of the mean Self measured Blood pressure level, multivariate regression studies showed that the maximal Self measured Systolic blood Pressure was independently related with left ventricular mass index and carotid intima-media thickness. Conclusion: Transiently high blood pressure measurements recorded at Self measured shouldn't be dis-missed as noise but rather taken seriously as significant warning signs of hypertensive Target organ damage in the heart and arteries.

Prevalence of albuminuria and its association with cardiovascular diseases in Chinese residents aged over 35 years / 中华内科杂志

Objective:To investigate the prevalence of albuminuria in Chinese residents aged >35 years and its potential association with cardiovascular disease (CVD).Methods:A total of 34 647 Chinese subjects aged ≥35 years were selected by stratified multi-stage random sampling from 2012 to 2015. Data were collected through questionnaires, physical examinations, and laboratory tests. Albuminuria was categorized into 3 types according to urinary albumin-to- creatinine ratio: normal (<30 mg/g), microalbuminuria (MAU, 30-300 mg/g), and macroalbuminuria (≥300 mg/g). Measurement data were expressed as xˉ±s, and t-tests were used for comparisons between indicators. Qualitative data were expressed as rate or constituent ratio, and the χ2 test or Kruskal-Wallis test was used to examine differences. Logistic regression was used for multivariate analyses. SAS 9.4 software was used for statistical analyses, and P<0.05 was considered statistically significant. Results:The prevalence of abnormal albuminuria was 19.1%; the prevalence was 17.2% for MAU and lower in males (13.8%) than females (20.1%, P<0.01). The risk of CVD was higher among subjects with MAU ( OR=1.23, 95% CI 1.12-1.35) and macroalbuminuria ( OR=1.86, 95% CI 1.50-2.32). When MAU was complicated by hypertension and diabetes mellitus, the CVD risk was 1.76 times higher. Conclusions:The prevalence of MAU is high among Chinese subjects aged 35 years and over. Those with MAU have higher CVD risk, especially those with hypertension and diabetes mellitus.

Cross-sectional associations between reproductive lifespan duration and urinary albumin-creatinine ratio / 中华内科杂志

Objective:To investigate the association between reproductive lifespan duration (RLD) and urinary albumin-creatinine ratio (UACR) in a Chinese postmenopausal population.Methods:This cross-sectional study included 11 055 naturally postmenopausal women from seven regions of China from May to December 2011. RLD was divided into four groups. Propensity score matching was performed to reduce bias, and logistic regressions and stratifications were conducted to investigate the association between RLD and increased UACR (≥30 mg/g). Mediation effect analysis was performed to quantify the effect of RLD on cardiovascular disease (CVD) induced by elevated UACR.Results:There were 2 373 participants with a RLD of 18-31 years, 2 888 participants with a RLD of 32-34 years, 2 472 participants with a RLD of 35-36 years, and 3 322 participants with a RLD of 37-50 years. The shortest RLD (18-31 years) group was characterized with older age ( P<0.001), a higher incidence of CVD ( P=0.025), and the highest level of UACR ( P<0.001). After adjusting for confounders, women with a longer RLD (37-50 years group) exhibited a lower risk of UACR elevation compared with those with the shortest RLD (18-31 years group) ( OR=0.72, 95% CI 0.64-0.82, P<0.001). Every 1-year extension in RLD was linked to a 2% reduction in the risk of UACR elevation ( OR=0.98, 95% CI 0.97-0.99, P<0.001). Stratified analysis revealed a more significant association between RLD and UACR in women who were a normal weight ( P=0.003) or overweight ( P=0.001), in those without CVD history ( P=0.001), and in those with impaired estimated glomerular filtration rate ( P=0.004). The mediation casual analysis showed that 3.0% of proteinuria inducing CVD events was mediated by RLD ( P=0.048). Conclusion:A longer RLD (37-50 years) is associated with a lower UACR in Chinese postmenopausal women.

Association between residual cholesterol and the risk of subclinical renal damage / 西安交通大学学报(医学版)

【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.

Serum monocyte/high-density lipoprotein cholesterol ratio and urinary albumin/creatinine ratio in evaluating osteoporosis in diabetic nephropathy patients / 中华内分泌外科杂志

Objective:To investigate the value of serum monocyte/high-density lipoprotein cholesterol ratio (MHR) and urinary albumin/creatinine ratio (ACR) in the evaluation of osteoporosis in diabetic nephropathy patients.Methods:Diabetic nephropathy patients treated in Hangzhou Ninth People’s Hospital from Jun. 2019 to Jun. 2022 were selected. Gender, age, height and weight of all patients were collected and recorded, and body mass index (BMI) was calculated. Blood calcium (Ca), blood phosphorus (P), parathyroid hormone (PTH), monocyte count (M), high density lipoprotein (HDL-C), urinary microalbumin and creatinine were measured and recorded in all patients. MHR and ACR were calculated, MHR=M/HDL-C, ACR=urinary microalbumin/creatinine. Lumbar spine bone mineral density (L1-L4) was measured by dual-energy X-ray absorptiometry, which was divided into osteoporosis group and non-osteoporosis group.Results:Among the 117 diabetic nephropathy patients, 47 cases were osteoporotic and 70 cases were non-osteoporotic. The proportion of women in osteoporosis group was significantly higher than that in non-osteoporosis group, and BMI, PTH, MHR, ACR and bone mineral density were significantly higher than those in non-osteoporosis group, with statistical significance (all P<0.05). Multivariate binary Logistic regression analysis showed that female, MHR and ACR were independent risk factors for osteoporosis in diabetic nephropathy patients (all P<0.05). Spearman correlation analysis showed that serum MHR and ACR were negatively correlated with lumbar bone density, with statistical significance ( r=0.524 and 0.497, P=0.004 and 0.009, respectively). ROC curve analysis showed that the area under the curve (AUC) of serum MHR and ACR for evaluating osteoporosis in diabetic nephropathy patients was 0.870 (0.809-0.931) and 0.849 (0.792-0.905), respectively. The AUC of serum MHR combined with ACR for osteoporosis in diabetic nephropathy patients was 0.927 (0.891-0.964) . Conclusion:Serum MHR and ACR can be used as the evaluation indexes of osteoporosis in diabetic nephropathy patients, and their combined efficacy is better.

Additive antiproteinuric effect of pentoxifylline in patients with diabetic nephropathy under angiotensin receptor blockade: A short-term, randomized, and controlled trial

Background: The ever-increasing prevalence of diabetes has led to a higher incidence of progression into complications including nephropathy. Diabetic kidney disease (DKD) is a chronic condition that is managed with renin-angiotensin-aldosterone system blockers which retard its progression. Pentoxifylline as an add-on therapy has been tried for reducing DKD. Aims and Objectives: The aims of this study were to study the safety and efficacy of pentoxifylline added on to an angiotensin II receptor blocker (ARB) to reduce the progression of the disease condition in diabetic nephropathy (DN) patients over 1 year. Materials and Methods: It is a randomized open-label study conducted in the Department of Nephrology, of a tertiary care center for 1 year. Type 2 diabetes patients with DN who satisfied the eligibility criteria were randomized into pentoxifylline added on to ARB or ARB alone and followed up for urine albumin-creatinine ratio (ACR) and serum tumor necrosis factor (TNF)-alpha. Results: Twenty-six patients were recruited and completed the study. Urine ACR was significantly low in the pentoxifylline group compared to the ARB alone group (P = 0.021). Serum TNF-? was decreased in the pentoxifylline group in comparison to the ARB alone group (P = 0.06). Conclusion: Pentoxifylline caused significant lowering of urinary ACR and urine TNF-? for 4 months.

Evaluation of Microalbuminuria in Patients with Urinary Tract Infection

Background: Urinary tract infection is a collective term for infections that involve any part of the urinary tract. It is one of the most common infections in local primary care. There are wide range of factors identified that can increase susceptibility to UTI, like sexual intercourse, congenital abnormalities, urinary obstruction, prior history of UTI, diabetes, urogenital surgery, estrogen deficiency. Diabetes mellitus has been a significant risk factor for complicated UTI. Presence of microalbumin in urine in patients of urinary tract infection may be a predictor of intrinsic renal pathology and its presence is a predictor of ongoing progressive damage to kidneys. Microalbuminuria is also associated with cardiovascular events and diabetic nephropathy. Early diagnosis of microalbuminuria will decrease the incidence of end stage renal disease and cardiovascular events. The present study was thus conducted to evaluate prevalence of microalbuminuria in patients diagnosed with urinary tract infections.Material & Methods:The present hospital based case control study was conducted on 60 patients visiting the outpatient clinic (OPD) of Department of Urology, Government Medical College and Rajindra Hospital, Patiala and diagnosed with UTI and the control group consisted of 20 age and gender matched individuals. Estimation of urine microalbumin was done by Enyme linked immunoassay(ELISA) kit method in Department of Biochemistry, GMC Patiala.Results:Out of 60 cases of UTI included in the present study, prevalence of microalbuminuria was observed in 43.3% among cases of UTI . A total of 85% of the cases with positive urine culture had microalbuminuria (p<0.01).Conclusions:Microalbuminuria and ACR can be recommended for predicting ESRD at an early stage of kidney disease.

Correlation between serum concentration of angiogenic suppressor protein 1 and urinary albumin creatinine ratio in patients with type 2 diabetes mellitus and diabetic nephropathy / 中国综合临床

Objective:To investigate the correlation between serum concentration of vasohibin-1 (VASH-1) and urinary albumin creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy.Methods:The clinical data of 196 patients with T2DM from February 2017 to December 2020 were analyzed retrospectively. According to whether diabetic nephropathy (DN) was combined, 33 patients without DN of T2DM were divided into the control group,and 163 patients with DN of T2DM were divided into the case group, and the case group was divided into four groups:normal albuminuria group (groupⅠ, UACR <30 mg/g, 21 cases),microalbuminuria group (groupⅡ, UACR ≥30-≤300 mg/g, 50 cases), clinical albuminuria group (group Ⅲ, UACR>300 mg/g, 43 cases), and clinical albuminuria hypertensive group (groupⅣ, UACR >300 mg/g with hypertension, 49 cases). Serum levels of VASH-1,C-reactive protein(CRP), erythrocyte sedimentation rate (ESR) and transforming growth factor β1 (TGF-β1) with other biochemical indicators were measured. T-test was used for comparison between measurement data groups in accordance with normal distribution, one-way ANOVA was used for comparison between multiple groups, q-test was used for pairwise comparison, and χ2 test was used for comparison between counting data groups. The influencing factors were analyzed by multivariate Logistic regression.Pearson correlation analysis was used to analyze the correlation between vash-1 and UACR. Results:UACR((1 175.9±120.4) mg/g), CRP((9.80±2.01) mg/L), ESR((20.61±2.20) mm/h),TGF-β1((16.75±2.05) μg/L), VASH-1((645.3±183.5) ng/L) in case group were higher than that in the control group((11.5±2.0) mg/g, (4.77±1.34) mg/L, (8.33±1.56) mm/h, (10.63±1.97) μg/L, (416.3±162.1) ng/L), and there were significant differences between the two groups ( t=123.39,13.76,30.54,15.75,6.66; all P<0.001). Multivariate logistic regression analysis showed that VASH-1 ( OR=1.881,95% CI 1.146-3.089), UACR( OR=1.511,95% CI 1.064-2.146), TGF-β1( OR=1.846,95% CI 1.135-3.001)were all risk factors for DN of T2DM ( P values were 0.009, 0.022 and 0.012). Serum VASH-1 ((693.5±201.4), (709.8±214.7) ng/L] in group Ⅲ and group Ⅳ were higher than those in group Ⅰ and group Ⅱ ((585.3±162.1), (632.9±165.5) ng/L). There was significant difference between the two groups ( F=129.46, P<0.001). The CRP ((7.08±1.36), (8.99±3.72), (10.58±3.48), (11.64±3.50) mg/L), ESR ((17.36±1.76), (19.05±4.12), (21.45±5.74), (22.69±9.13) mm/h) and TGF- β1 ((14.75±1.97), (16.50±1.90), (17.06±1.23), (18.39±1.46) μg/L) of groupⅠ, groupⅡ, groupⅢ and groupⅣ increased gradually, and there were significant differences between the four groups ( F values were 73.48, 156.61, 25.83; all P<0.001). Pearson correlation analysis showed that there was a significant positive correlation between VASH-1 and UACR ( r=0.532, P=0.008). Conclusion:The concentration of VASH-1 in serum of patients with T2DM complicated with DN increased with the increase of UACR. VASH-1 may become a new marker for predicting early DN of T2DM.

Effect of urinary albumin/creatinine ratio on type 2 diabetic retinopathy and its cut-off value for early diabetic retinopathy diagnosis / 中华内分泌代谢杂志

Objective:To evaluate the effect of urinary albumin creatinine ratio (UACR) on diabetic retinopathy (DR) in patients with type 2 diabetes. Receiver operating characteristic (ROC) curve was applied to find the cut-off value of UACR for diagnosing DR.Methods:A prospective cohort study of 2 490 patients with type 2 diabetes was conducted with a mean follow-up of 7 years ranging from 3 to 10 years. Dilated fundus examination was performed once a year, and patient history and clinical data were collected and analyzed. Patients were divided into three groups according to the UACR: Q1, normal urinary albumin group (UACR<30 mg/g), Q2, microalbuminuria group (30 mg/g≤UACR≤299 mg/g), and Q3, macroalbuminuria group (UACR>300 mg/g), respectively. Cox regression analysis was used to explore the influence of UACR and other factors on DR, and ROC curve was drawn to evaluate the value of UACR in diagnosis of DR.Results:Cox regression analysis showed that UACR was the risk factor of DR( HR=1.108, 95% CI 1.023-1.241, P<0.001). It showed that the patients in Q3 group had the highest risk of proliferative DR ( HR=3.128, 95% CI 2.025-4.831, P<0.001), the patients in Q2 group followed( HR=1.918, 95% CI 1.355-2.714, P<0.001), and the patients in Q1 group were the lowest. ROC curve analysis showed that area under UACR curve was 0.746(95% CI 0.681-0.812, P<0.001), and the cut-off value, sensitivity, and specificity for the diagnosis of PDR were 54.12mg/g, 0.769, and 0.653, respectively. Conclusion:The UACR can predict the progression of PDR in type 2 diabetes patients, therefore it may be used as a preliminary predictor for the progression of DR.

Association of serum chemerin level with early renal insufficiency in patients with type 2 diabetes / 中华内分泌代谢杂志

Objective:To assess the correlation between circulating chemerin and two indicators of renal function, estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR), in individuals with type 2 diabetes and to determine whether chemerin is an independent marker of early renal insufficiency.Methods:A total of 742 patients with type 2 diabetes were recruited into the cross-sectional community study. Basic information, anthropometric parameters, and biochemical parameters of these individuals were determined and collected, and serum chemerin level was measured using enzyme-linked immunosorbent assay.Results:Chemerin levels were significantly higher in the eGFR-impaired group compared with eGFR-normal group, and macroalbuminuria group compared to the normal or microalbuminuria groups. Spearman′ rank correlation analysis showed serum chemerin level was correlated with eGFR ( r=-0.25, P<0.001), UACR ( r=0.23, P<0.001) and some other biochemical indicators such as triglyceride. And univariate and multivariate logistic regression analyses revealed circulating chemerin was an independent risk factor for eGFR impairment or proteinuria after adjusting corresponding covariates. Receiver operating characteristic (ROC) curve analysis showed that the area under curve (AUC) of circulating chemerin for predicting early impaired eGFR in type 2 diabetes was 0.747, while the AUC of circulating chemerin for predicting macroalbuminuria in type 2 diabetes was 0.748. Conclusion:Circulating chemerin is associated with eGFR or UACR and may be a potential diagnostic marker for early renal insufficiency in type 2 diabetes.

Research on the clinical diagnostic value of joint test of RBP, CYSC, and urinary ALB/Cr in early diabetes nephropathy / 中华内分泌外科杂志

Objective:To investigate the clinical diagnostic value of joint test of retinol-binding protein (RBP), cystatin C (CYSC) and urinary (albumin/creatinine ratio, ALB/Cr) ALB/Cr in early diabetes nephropathy.Methods:Data of 50 early diabetic nephropathy patients (EDN group) from Jan. 2020 to Jun. 2021 in our hospital, another 50 pure type 2 diabetic patients (T2DM group), and 50 healthy subjects (control group) were compared and analysed. RBP, CYSC and urinary ALB/Cr were tested for the 3 groups. Then the clinical diagnostic value between single index test and joint test for the early diabetes nephropathy were compared.Results:Group EDN had higher RBP, CYSC and urinary ALB/Cr [ (114.66±0.56) mg/L, (2.64±0.33) mg/L, (351.81±15.48) ] mg/g than group T2DM [ (83.58±0.83) mg/L, (1.41±0.29) mg/L, (113.65±12.55) mg/g] and control group[ (38.61±0.66) mg/L, (0.53±0.26) mg/L, (16.36±5.61) mg/g]. The difference was statistically significant ( P<0.05). The specificity and sensitivity of early diabetes nephropathy were 95.38% and 96.21%, both higher than single index test. Conclusion:The combined detection of serum RBP, CYSC and urine ALB/Cr has certain reference value for the clinical diagnosis of early diabetic nephropathy.

Assessment of chronic kidney disease in patients with non-alcoholic fatty liver disease (NAFLD); A single center experience

Background: Non-alcoholic fatty liver disease (NAFLD) represents a considerable percentage of chronic liver diseases worldwide. The liver is not the only organ affected by NAFLD but also affects other organs such as the cardiovascular system and the kidney. In recent decades, there has been a growing body of evidence linking NAFLD to kidney function. So, the current study aims to assess the percentage of chronic kidney disease (CKD) in NAFLD patients and its link to different stages of hepatic fibrosis. Patients and Methods: A case-control study evaluated 62 non-alcoholic fatty liver disease patients and a control group of 38 volunteers with apparently healthy livers (normal echo pattern by ultrasound). All participants underwent serum creatinine measurement, albumin creatinine ratio in urine, calculation of estimated glomerular filtration rate (eGFR), abdominal ultrasound, and fibroScan examination. Results: The authors showed that the percentage of patients with chronic kidney diseases (patients with GFR less than 60 ml or micro-albuminuria) were significantly higher among NAFLD groups than in healthy controls. There was a significant positive correlation between the albumin creatinine ratio and subcutaneous fat thickness, BMI, and steatosis degrees. The estimated glomerular filtration rate (eGFR) and the age of the patients had a significant negative correlation. In comparison, the eGFR and AST levels had a significant positive correlation. Conclusions: Our results showed that NAFLD substantially raises the risk of getting CKD

Hypoadiponectinemia as a marker of increased cardiovascular risk in patients with non-alcoholic fatty liver disease: correlation with albumin/creatinine ratio

ABSTRACT Objective: We assessed plasma adiponectin and its correlation with carotid intima-media-thickness (CIMT), as a marker of atherosclerosis, and urine albumin/creatinine ratio (ACR) in patients with non-alcoholic fatty liver disease (NAFLD). Subjects and methods: The study included 100 Egyptian subjects (50 patients with NAFLD with no history of diabetes or hypertension and 50 age and sex-matched normal healthy control subjects). Urine albumin/creatinine ratio (ACR) was assessed in all participants and fasting plasma adiponectin was measured using ELISA technique. Ultrasonography was used to diagnose NAFLD. CIMT was assessed using high-resolution Doppler ultrasonography. Results: Mild albuminuria was detected in patients with NAFLD (mean urine ACR = 42 ± 30 mg/g). Plasma adiponectin was significantly lower and urine ACR and CIMT significantly higher in patients with NAFLD as compared with the control group (P < 0.001 for all). A significant negative correlation was found between plasma adiponectin and both urine ACR and CIMT in patients with NAFLD (P < 0.001 and < 0.05 respectively). A significant positive correlation was also found between CIMT and urine ACR in those patients (P < 0.05). Plasma adiponectin and urine ACR were independent determinants of CIMT in patients with NAFLD (P < 0.01 and < 0.05 respectively). Conclusion: Patients with NAFLD, without diabetes, have an increased risk of atherosclerosis and cardiovascular disease. Hypoadiponectinemia and low-grade albuminuria are important markers of that risk.

VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses

Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses

The relationship between heart rate variability and urine albumin/creatinine ratio in patients with type 2 diabetes / 中华内分泌代谢杂志

Objective:To explore the relationship between heart rate variability (HRV) and urine albumin/creatinine ratio (ACR) in patients with type 2 diabetes.Methods:A total of 1 543 patients with type 2 diabetes were selected from the Department of Endocrinology of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, and all the participants received 24-hour Holter monitoring and ACR measurement. HRV parameters include the standard deviation of all normal to normal intervals (SDNN), root mean square differences of successive RR intervals (rMSSD), the percent of adjacent RR intervals with a difference greater than 50 ms (PNN50), low frequency (LF), high frequency (HF), the ratio of LF to HF (LF/HF). Multivariate linear regression was used to analyze the relationship between HRV and ACR. Logistic regression was performed to further analyze the relationship between HRV and albuminuria while HRV parameter was divided into ≤25% (Q1) and ≥25% (Q2-Q4).Results:Multivariate linear regression results showed that the decrease of HRV parameters [ln(SDNN), ln(PNN50), ln(LF), ln(HF), ln(LF/HF)] was closely related to the increase of ln(ACR) (all P<0.05). Logistic regression analysis results showed that SDNN( OR=1.669, 95% CI 1.290-2.159), PNN50( OR=1.372, 95% CI 1.063-1.770), LF( OR=1.918, 95% CI 1.441-2.551), and LF/HF ( OR=1.623, 95% CI 1.220-2.183) were independent risk factors for albuminuria (all P<0.05); Furthermore, logistic regression analysis stratified by the median duration of diabetes (10 years) and cardiovascular disease found that in patients with diabetes≤10 years or without cardiovascular disease, the risk of albuminuria in the SDNN and LF Q1 group were higher than that in the Q2-Q4 group; while in patients with diabetes>10 years or with cardiovascular disease, the risk of albuminuria in the SDNN, PNN50, LF, and LF/HF Q1 group were higher than that in the Q2-Q4 group. Conclusion:The reduction of HRV parameters in patients with type 2 diabetes is closely related to the increase of ACR. With the progress of diabetes, more HRV parameters demonstrated predictive effect for risk of albuminuria.

Correlation between markers of early renal injury in urine and serum homocysteine elevation / 中华健康管理学杂志

Objective:To investigate the correlation between early renal impairment markers in urine and elevated serum homocysteine.Methods:Clinical data of serum homocysteine (Hcy) and early renal injury markers in urine of the health examination population from the Physical Examination Center of Peking University Third Hospital from January 2019 to May 2020 were retrospectively analyzed (1133 cases). The previous medical history, age, sex, blood pressure, body mass index (BMI) of the subjects were collected. Early urine kidney injury markers, including urine microalbumin (U-mALB), urinary N-acetyl-β-D-glucosaminidase (NAG), urinary albumin to creatinine ratio (UACR), and serum renal function, liver function, blood lipid, myocardial enzyme and glycosylated hemoglobin (HbA 1C), etc. were also collected. Those with incomplete previous history, general information, biochemical indexes and decreased estimated glomerular filtration rate (eGFR) were excluded, and 969 cases were included. The included subjects were divided into the normal group (?15 μmol/L) and the elevated group (≥15 μmol/L) according to Hcy levels, the indexes with significant difference between the two groups were included as independent variables, and the multivariate logistic regression was used to explore the influence factors of Hcy elevation. Results:The male ratio, the incidence of increased U-mALB, NAG and UACR were significantly higher in the elevated group than those in the normal Hcy group (93.4% vs 50.6%, 16.4% vs 8.0%, 23.0% vs 14.0%, 13.9% vs 7.9%) (all P<0.05). Systolic blood pressure, diastolic blood pressure, serum uric acid, calcium, alanine aminotransferase (ALT) and lactate dehydrogenase in the elevated group were higher than those in the normal group [(127.5±15.4) vs (121.9±16.2) mmHg (1 mmHg=0.133 kPa), (78.6±9.3) vs (76.0±11.0) mmHg, (385.9±86.0) vs (335.7±88.2) μmol/L, (2.392±0.086) vs (2.366±0.092) mmol/L, (27.8±21.0) vs (23.8±20.2) U/L, (198.3±28.4) vs (192.2±31.2) U/L] (all P<0.05), while high density lipoprotein cholesterol (HDL-C), serum phosphorus were lower than those in the normal group [(1.21±0.25) vs (1.31±0.30) mmol/L, (1.107±0.154) vs (1.158±0.159) mmol/L] (all P<0.05). The increased systolic blood pressure, male, uric acid, U-mALB, NAG were independent correlative factors of Hcy elevation. Conclusion:The increase of Hcy is independently correlated with urine U-mALB and NAG, which suggests that the level of Hcy should be detected as soon as possible in patients with elevated early renal injury markers.

Evaluation of angiogenic factors (PlGF and sFlt-1) in pre-eclampsia diagnosis / Avaliação dos fatores angiogênicos (PlGF e sFlt-1) no diagnóstico de pré-eclâmpsia

Abstract Objective: Recent observations support the hypothesis that an imbalance between angiogenic factors has a fundamental role in the pathogenesis of pre-eclampsia and is responsible for the clinical manifestations of the disease. The goal of the present study was to evaluate the sensitivity, specificity, and the best accuracy level of Soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio in maternal serum and protein/creatinine ratio in urine sample to define the best cutoff point of these tests to discriminate between the patients with gestational hypertension and the patients with pre-eclampsia, to evaluate the possibility of using them as diagnostic methods. Methods: A prospective longitudinal study was performed, and blood samples were collected from 95 pregnant patients with hypertension to measure serum concentrations of biomarkers sFlt-1 and PlGF. Urine samples were collected for protein screening. Significance was set as p < 0.05. Results: The sFlt-1/PlGF ratio demonstrated a sensitivity of 57.5% and a specificity of 60% using 50.4 as a cutoff point. The test that showed the best accuracy in the diagnosis of pre-eclampsia was protein/creatinine ratio, with a sensitivity of 78.9% and a specificity of 70% using 0.4 as a cutoff point and showing an area under the receiver operating characteristic curve of 0.80 (p < 0.001). Conclusion: No studied laboratory test proved to be fairly accurate for the diagnosis of pre-eclampsia, except for the protein/creatinine ratio. The evidence is insufficient to recommend biomarkers sFlt-1 and PlGF to be used for the diagnosis of pre-eclampsia.

Resumo Objetivo: Pesquisas recentes sustentam a hipótese de que um desequilíbrio entre fatores angiogênicos desempenhe um papel fundamental na patogênese da pré-eclâmpsia e seja responsável pelas manifestações clínicas da doença. O objetivo do presente estudo foi avaliar a sensibilidade, a especificidade e o nível de melhor acurácia do Fator semelhante a tirosina quinase 1 (sFlt-1), Fator de crescimento placentário (PlGF), e relação sFlt-1/PlGF no soro materno e relação proteína/creatinina em amostra de urina e definir o melhor ponto de corte desses testes para distinguir pacientes com hipertensão gestacional daquelas com pré-eclâmpsia, a fim de avaliar a possibilidade de utilizá-los como métodos diagnósticos. Métodos: Foi realizado um estudo prospectivo longitudinal e foram coletadas amostras de sangue de 95 gestantes com hipertensão arterial para dosar as concentrações séricas dos biomarcadores sFlt-1 e PlGF. Amostras de urina foram coletadas para pesquisa de proteinúria. Foram consideradas significativas as diferenças com p < 0,05. Resultados: A relação sFlt-1/PlGF demonstrou sensibilidade de 57,5% e especificidade de 60% utilizando 50,4 como ponto de corte. O teste que apresentou a melhor acurácia no diagnóstico de pré-eclâmpsia foi a relação proteína/creatinina, com sensibilidade de 78,9% e especificidade de 70%, utilizando 0,4 como ponto de corte e demostrando uma área sob a curva receiver operating characteristic (ROC, na sigla em inglês) de 0,80 (p < 0,001). Conclusão: Nenhum método de rastreamento isolado se mostrou com boa acurácia para o diagnóstico de pré-eclâmpsia, exceto a relação proteína/creatinina. As evidências são insuficientes para recomendar os biomarcadores sFlt-1 e PlGF como diagnóstico de pré-eclâmpsia.

A prospective post-partum evaluation of renal function in preeclampsia

Background: Hypertensive disorder comprises one of the leading causes of maternal and perinatal morbidity and mortality across the globe. Because women with preeclampsia are at risk of cardiovascular disease and end-stage renal disease, proper follow-up after delivery for resolution of proteinuria and hypertension is required and investigations should be conducted to find out and adequately treat any underlying cardiovascular or renal disease.Methods: This was a prospective study and included as participants pregnant women with preeclampsia who met the inclusion and exclusion criteria and who subsequently delivered at Government Medical College Hospital, Thrissur, Kerala, India. For each eligible participant, clinical and laboratory data were collected from third trimester of antenatal period, and six weeks and three months after delivery.Results: In this study, it is found that 26.2% and 4.23% patients had persistence of systolic blood pressure at 6 weeks and 3 months postpartum where as 19.4% and 3.38% had persistence of diastolic blood pressure at 6 weeks and 3 months post-partum. Serum creatinine was persistently high in 14.4% and 6.77% after 6 weeks and 3 months postpartum respectively. Proteinuria resolved completely in non-severe preeclampsia by 6 weeks postpartum itself. In severe preeclampsia group, 65% and 25% of patients had persisting proteinuria after 6 weeks and 3 months postpartum.Conclusions: Hypertension that persists more than 6 weeks postpartum usually represents a pathology not directly associated with pregnancy such as essential hypertension or underlying endocrine, neurological, or renal disease. Proteinuria that persists beyond 6-12 weeks postpartum may also warrant further investigation, particularly in early onset preeclampsia, the group of women most likely to have underlying renal disease.

Urinary uric acid or urinary creatinine ratio as a non-invasive marker for perinatal asphyxia

Background: Perinatal asphyxia is amongst the common problem of neonates and there exists a significant contribution to the neonatal morbidity and mortality. It is observed as a common and a vital cause of the preventable cerebral injury. The prediction of the perinatal asphyxial outcome is very important but dreadful. There is a limited role for APGAR score to predict the immediate outcome, like HIE and the long-term neurological sequelae observational error may happen in APGAR. But the biochemical parameters can truly be relied upon. This study was done to assess urinary uric acid/urinary creatinine ratio (UA/Cr) as a non-invasive marker for perinatal asphyxia and co-relate its absolute value to the degree of the perinatal asphyxia.Methods: In this prospective case control study conducted in the Pediatrics Department of Shri Ram Murti Smarak Institute of Medical Sciences between Nov 2017 to May 2019, 42 asphyxiated and 42 non-asphyxiated newborns were included. Detailed history and assessment were for all the enrolled newborns. Spot urine samples were sent for the uric acid and creatinine estimation. Results were documented, and statistical analysis was performed.Results: Urinary uric acid to creatinine ratio used as additional non-invasive, early and easy biochemical marker of the birth asphyxia that biochemically supports severity grading and clinical diagnosis of the asphyxia by APGAR score.Conclusions: The ratio of the urinary uric acid and creatinine enables rapid and early recognition of asphyxial injury and also the evaluation of its severity and potential for short-term morbidity or death.