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Objective: The relationship between thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and diabetic kidney disease (DKD) is still controversial, and this study analyzed the correlation between TSH, FT3, FT4 and DKD in patients with type 2 diabetes mellitus (T2DM). Methods: T2DM patients (1216) were divided into five groups based on serum TSH, FT3, and FT4 levels, differences in urinary albumin excretion rate (UACR), estimated glomerular filtration rate (eGFR) were compared. Binary logistic regression verified independent correlations among TSH, FT3, FT4 and UACR, eGFR. TSH and FT3 predictive values for DKD were analyzed using receiver operating characteristic (ROC) curves. Results: The prevalence of albuminuria with decreased eGFR was higher in T2DM patients with subclinical hypothyroidism and overt hypothyroidism than that in patients with normal thyroid function. TSH positively correlated with UACR (r = 0.133, p < 0.001) and positively correlated with eGFR (r = -0.218, p < 0.001), FT3 negatively correlated with UACR (r = -0.260, p < 0.001) and positively correlated with eGFR (r = 0.324, p < 0.001). With the change from the lower normal level to the increased level of TSH and the change from the higher normal level to the reduced level of FT3, the prevalence of albuminuria gradually increased, the prevalence of decreased eGFR gradually increased in TSH groups and FT3 groups. After adjusting for age, BMI, duration of diabetes, TPOAb, TGAb, smoking, drinking, hypertension, the use of anti-diabetic medications (metformin, sodium–glucose cotransporter 2 inhibitors), HbA1c, CRP, TC, TG, LDL-C, and HDL-C, both TSH and FT3 correlated with increased UACR (TSH: OR 1.253, p = 0.001; FT3: OR 0.166, p < 0.001) and decreased eGFR (TSH: OR 1.245, p < 0.001, FT3: OR 0.579, p < 0.001), but this correlation of TSH with eGFR < 60 mL/min/1.73 m2 was not found in male. The area under the ROC curve (AUC) for FT3 was greater than that for TSH (FT3: 0.64; TSH: 0.61). Conclusions: Increased TSH and reduced FT3 levels were associated with DKD in T2DM patients, but in a sex-dependent manner. FT3 had a higher predictive value for DKD. [ABSTRACT FROM AUTHOR]

Background: Albuminuria is considered an early and sensitive marker of kidney dysfunction, but also an independent cardiovascular risk factor. Considering the possible relationship among metabolic liver disease, cardiovascular disease and chronic kidney disease, we aimed to evaluate the risk of developing albuminuria regarding the presence of epicardial adipose tissue and the steatotic liver disease status. Methods: A retrospective long-term longitudinal study including 181 patients was carried out. Epicardial adipose tissue and steatotic liver disease were assessed by computed tomography. The presence of albuminuria at follow-up was defined as the outcome. Results: After a median follow up of 11.2 years, steatotic liver disease (HR 3.15; 95% CI, 1.20–8.26; p = 0.02) and excess amount of epicardial adipose tissue (HR 6.12; 95% CI, 1.69–22.19; p = 0.006) were associated with an increased risk of albuminuria after adjustment for visceral adipose tissue, sex, age, weight status, type 2 diabetes, prediabetes, hypertriglyceridemia, hypercholesterolemia, arterial hypertension, and cardiovascular prevention treatment at baseline. The presence of both conditions was associated with a higher risk of developing albuminuria compared to having steatotic liver disease alone (HR 5.91; 95% CI 1.15–30.41, p = 0.033). Compared with the first tertile of visceral adipose tissue, the proportion of subjects with liver steatosis and abnormal epicardial adipose tissue was significantly higher in the second and third tertile. We found a significant correlation between epicardial fat and steatotic liver disease (rho = 0.43 [p < 0.001]). Conclusions: Identification and management/decrease of excess adiposity must be a target in the primary and secondary prevention of chronic kidney disease development and progression. Visceral adiposity assessment may be an adequate target in the daily clinical setting. Moreover, epicardial adipose tissue and steatotic liver disease assessment may aid in the primary prevention of renal dysfunction. [ABSTRACT FROM AUTHOR]

Background: The prevalence of metabolic syndrome (MetS) in American adults increased from 37.6% in the 2011–12 period to 41.8% in 2017–2018. Environmental exposure, particularly to common compounds such as glyphosate, has drawn increasing attention as a potential risk factor. Methods: We employed three cycles of data (2013–2018) from the National Health and Nutrition Examination Survey (NHANES) in a cross-sectional study to examine potential associations between urine glyphosate measurements and MetS incidence. We first created a MetS score using exploratory factor analysis (EFA) of the International Diabetes Federation (IDF) criteria for MetS, with data drawn from the 2013–2018 NHANES cycles, and validated this score independently on an additional associated metric, the albumin-to-creatinine (ACR) ratio. The score was validated via a machine learning approach in predicting the ACR score via binary classification and then used in multivariable regression to test the association between quartile-categorized glyphosate exposure and the MetS score. Results: In adjusted multivariable regressions, regressions between quartile-categorized glyphosate exposure and MetS score showed a significant inverted U-shaped or saturating dose‒response profile, often with the largest effect for exposures in quartile 3. Exploration of potential effect modification by sex, race, and age category revealed significant differences by race and age, with older people (aged > 65 years) and non-Hispanic African American participants showing larger effect sizes for all exposure quartiles. Conclusions: We found that urinary glyphosate concentration is significantly associated with a statistical score designed to predict MetS status and that dose–response coefficient is nonlinear, with advanced age and non-Hispanic African American, Mexican American and other Hispanic participants exhibiting greater effect sizes. [ABSTRACT FROM AUTHOR]

Background: Diabetes self-management (DSM) helps people with diabetes to become actors in their disease. Deprived populations are particularly affected by diabetes and are less likely to have access to these programmes. DSM implementation in primary care, particularly in a multi-professional primary care practice (MPCP), is a valuable strategy to promote care access for these populations. In Rennes (Western France), a DSM programme was designed by a MPCP in a socio-economically deprived area. The study objective was to compare diabetes control in people who followed or not this DSM programme. Method: The historical cohort of patients who participated in the DSM programme at the MPCP between 2017 and 2019 (n = 69) was compared with patients who did not participate in the programme, matched on sex, age, diabetes type and place of the general practitioner's practice (n = 138). The primary outcome was glycated haemoglobin (HbA1c) change between 12 months before and 12 months after the DSM programme. Secondary outcomes included modifications in diabetes treatment, body mass index, blood pressure, dyslipidaemia, presence of microalbuminuria, and diabetes retinopathy screening participation. Results: HbA1c was significantly improved in the exposed group after the programme (p < 0.01). The analysis did not find any significant between-group difference in socio-demographic data, medical history, comorbidities, and treatment adaptation. Conclusions: These results, consistent with the international literature, promote the development of DSM programmes in primary care settings in deprived areas. The results of this real-life study need to be confirmed on the long-term and in different contexts (rural area, healthcare organisation). [ABSTRACT FROM AUTHOR]

Background: Diabetic kidney disease (DKD) is a microvascular complication of diabetes mellitus, contributing to end-stage renal disease with limited treatment options. The development of DKD is attributed to podocyte injury resulting from abnormal podocyte autophagy. Consequently, the restoration of podocyte autophagy is deemed a practicable approach in the treatment of DKD. Methods: Diabetic mice were induced by streptozotocin and high-fat diet feeding. Following 8 weeks of "QN" agarwood treatment, metrics such as albuminuria, serum creatinine (Scr), and blood urea nitrogen (BUN) were evaluated. Renal histological lesions were evaluated by H&E, PAS, Masson, and Sirius red staining. Evaluation of the effects of "QN" agarwood on renal inflammation and fibrosis in DKD mice through WB, q-PCR, and IHC staining analysis. Cytoscape 3.7.1 was used to construct a PPI network. With the DAVID server, the gene ontology (GO) functional annotation and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the target enrichment were performed. Molecular docking and binding affinity calculations were conducted using AutoDock, while PyMOL software was employed for visualizing the docking results of active compounds and protein targets. Results: The results of this study show that "QN" agarwood reduced albuminuria, Scr, and BUN in DKD mice, and improved the renal pathological process. Additionally, "QN" agarwood was observed to downregulate the mRNA and protein expression levels of pro-inflammatory and pro-fibrotic factors in the kidneys of DKD mice. Network pharmacology predicts that "QN" agarwood modulates the epidermal growth factor receptor (EGFR) signaling pathway. "QN" agarwood can increase the expression of LC3B and Nphs1 in DKD mice while reducing the expression of EGFR. Conclusion: The present study demonstrated that "QN" agarwood ameliorated renal injury in DKD by targeting EGFR and restoring podocyte autophagy. [ABSTRACT FROM AUTHOR]

Background: Albuminuria, the presence of excess of protein in urine, is a well-known risk factor for early kidney damage among diabetic/prediabetic patients. There is a complex interaction between physical activity (PA) and albuminuria. However, the relationship of specific-domain PA and albuminuria remained obscure. Methods: Albuminuria was defined as urinary albumin/creatinine ratio (ACR) > 30 mg/g. PA was self-reported by participants and classified into transportation-related PA (TPA), occupation-related PA (OPA), and leisure-time PA (LTPA). Weighted logistic regression was conducted to compute the odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic spline (RCS) was used to evaluate the dose–response of PA domains with the risk of albuminuria. Results: A total of 6739 diabetic/prediabetic patients (mean age: 56.52 ± 0.29 years) were enrolled in our study, including 3181 (47.20%) females and 3558 (52.80%) males. Of them, 1578 (23.42%) were identified with albuminuria, and 5161(76.58%) were without albuminuria. Diabetic/prediabetic patients who adhered the PA guidelines for total PA had a 22% decreased risk of albuminuria (OR = 0.78, 95%CI 0.64–0.95), and those met the PA guidelines for LTPA had a 28% decreased of albuminuria (OR = 0.72, 95%CI 0.57–0.92). However, OPA and TPA were both not associated with decreased risk of albuminuria. RCS showed linear relationship between the risk of albuminuria with LTPA. Conclusions: Meeting the PA guideline for LTPA, but not OPA and TPA, was inversely related to the risk of albuminuria among diabetic/prediabetic patients. Additionally, achieving more than 300 min/week of LTPA conferred the positive effects in reducing albuminuria among diabetic/prediabetic patients. [ABSTRACT FROM AUTHOR]

Background: In Tunisia, the prevalence of diabetes mellitus increased from 15.5% on 2016 to 23% by 2023. While Chronic Kidney Disease (CKD) stills the most dreaded complications of diabetes, studies on the prevalence of chronic kidney disease non-dialysis diet are scarce. The aim of this study was to assess the prevalence of chronic kidney disease among the Tunisian diabetic population based on investigators' specialty, demographic criteria (gender, age, duration of diabetes and geographic distribution) and diagnosis criteria (albuminuria and/or eGFR). Methods: This observational, multicentric, and cross-sectional study enrolled all diabetic subjects from all regions of Tunisia with at least 3 months of follow-up before the inclusion date, from 09 January to 08 February 2023. CKD diagnosis was established based on the KDIGO guidelines. The study was carried out at medical departments and ambulatory clinics of different healthcare providers. Baseline data were collected by investigators using an electronic case report form (eCRF). Continuous variables were described by means, median, standard deviation, and quartiles. Categorical data were tabulated in frequencies and percentages. Results: The overall prevalence of CKD among the 10,145 enrolled patients with diabetes mellitus was 38.7% with a 95%CI [37.8-39.6%]. 50.9% were male, with a mean age of 67.5 (± 11.3) years. The mean diabetes duration was 16.1 years (± 8.9). The highest CKD prevalence was noted among nephrologists (82.2%), while it was similar between the cardiologists and the primary care physicians (30.0%). CKD prevalence was highest among males (43.0% versus 35.1%) and increased proportionally with patients' age and diabetes duration. CKD was more frequent in the Mid-East Area when compared to other regions (49.9% versus 25.3 to 40.1% in other regions). Albuminuria was present within 6.6% of subjects with CKD, and it was found an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² within 13.3% of subjects wit h CKD. 18.9% had both criteria. Conclusions: In Tunisia, CKD among diabetics had a prevalence of 38.7%, approaching European prevalence. The prevalence discrepancy worldwide of CKD can be improved with a larger population size and by implementing standardized practices. [ABSTRACT FROM AUTHOR]

Background: Hypertension is an important public health priority with a high prevalence in Africa. It is also an independent risk factor for kidney outcomes. We aimed to identify potential proteins and pathways involved in hypertension-associated albuminuria by assessing urinary proteomic profiles in black South African participants with combined hypertension and albuminuria compared to those who have neither condition. Methods: The study included 24 South African cases with both hypertension and albuminuria and 49 control participants who had neither condition. Protein was extracted from urine samples and analysed using ultra-high-performance liquid chromatography coupled with mass spectrometry. Data were generated using data-independent acquisition (DIA) and processed using Spectronaut™ 15. Statistical and functional data annotation were performed on Perseus and Cytoscape to identify and annotate differentially abundant proteins. Machine learning was applied to the dataset using the OmicLearn platform. Results: Overall, a mean of 1,225 and 915 proteins were quantified in the control and case groups, respectively. Three hundred and thirty-two differentially abundant proteins were constructed into a network. Pathways associated with these differentially abundant proteins included the immune system (q-value [false discovery rate] = 1.4 × 10− 45), innate immune system (q = 1.1 × 10− 32), extracellular matrix (ECM) organisation (q = 0.03) and activation of matrix metalloproteinases (q = 0.04). Proteins with high disease scores (76–100% confidence) for both hypertension and chronic kidney disease included angiotensinogen (AGT), albumin (ALB), apolipoprotein L1 (APOL1), and uromodulin (UMOD). A machine learning approach was able to identify a set of 20 proteins, differentiating between cases and controls. Conclusions: The urinary proteomic data combined with the machine learning approach was able to classify disease status and identify proteins and pathways associated with hypertension-associated albuminuria. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the correlation between serum methylmalonic acid (MMA) levels and cognition function in patients with chronic kidney disease (CKD). Methods: In this cross-sectional study, we included 537 CKD individuals aged ≥ 60-year-old with albuminuria from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. Four cognitive tests including the Digit Symbol Substitution Test (DSST), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Delayed Recall and Word Learning tests, and the Animal Fluency test (AF) were performed. Associations between MMA and cognition scores were assessed with linear regression models. Results: MMA level was negatively associated with residual renal function and nutrition status. After multivariate adjustment, elevated serum MMA levels were independently correlated with decline of cognition in CKD patients with albuminuria. Conclusion: Our study showed that higher serum MMA levels were independently associated with the presence of cognition dysfunction in CKD patients. The exact pathogenesis of MMA and cognition needs further research. [ABSTRACT FROM AUTHOR]

Aims: We aimed to explore the associations between urine albumin-to-creatinine ratio (uACR) and cardia-cerebrovascular disease (CVD) in Chinese population with type 2 diabetes(T2D). Methods: We included 8975 participants with T2D but free of prevalent CVD (including myocardial infarction, ischemic and hemorrhagic stroke) at baseline from Kailuan study who were assessed with uACR between 2014 and 2016. The participants were divided into three groups based on their baseline uACR: normal (< 3 mg/mmol), microalbuminuria (3–30 mg/mmol), and macroalbuminuria (≥ 30 mg/mmol). Cox regression models and restricted cubic spline were used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident CVD. The area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to see if incorporating uACR into existing models could improve performance. Results: During a median follow-up of 4.05 years, 560 participants developed first CVD event (6.24%). After adjustment for potential confounders, participants with microalbuminuria had higher risks of CVD compared with normal uACR, with HRs of 1.57(95% CI 1.04–2.37) for myocardial infarction, 1.24(95% CI 1.00–1.54) for ischemic stroke,1.62(95% CI 0.73–3.61) for hemorrhagic stroke, and 1.30(95% CI 1.07–1.57) for total CVD. The risks gradually attenuated with uACR increase, with HRs of 2.86(95% CI 1.63–5.00) for myocardial infarction, 2.46(95% CI 1.83–3.30) for ischemic stroke, 4.69(95% CI 1.72–12.78) for hemorrhagic stroke, and 2.42(95% CI 1.85–3.15) for total CVD in macroalbuminuria. The addition of uACR to established CVD risk models improved the CVD risk prediction efficacy. Conclusions: Increasing uACR, even below the normal range, is an independent risk factor for new-onset CVD in T2D population. Furthermore, uACR could improve the risk prediction for CVD among community based T2D patients. [ABSTRACT FROM AUTHOR]

1 in 7 American adults have chronic kidney disease (CKD); a disease that increases risk for CKD progression, cardiovascular events, and mortality. Currently, the US Preventative Services Task Force does not have a screening recommendation, though evidence suggests that screening can prevent progression and is cost-effective. Populations at risk for CKD, such as those with hypertension, diabetes, and age greater than 50 years should be targeted for screening. CKD is diagnosed and risk stratified with estimated glomerular filtration rate utilizing serum creatinine and measuring urine albumin-to-creatinine ratio. Once identified, CKD is staged according to C-G-A classification, and managed with lifestyle modification, interdisciplinary care and the recently expanding repertoire of pharmacotherapy which includes angiotensin converting enzyme inhibitors or angiotensin-II receptor blockers, sodium-glucose-cotransporter-2 inhibitors, and mineralocorticorticoid receptor antagonists. In this paper, we present the why, who, when, how, and what of CKD screening. [ABSTRACT FROM AUTHOR]

Background: Plasma proenkephalin A (PENK-A) is a precursor of active enkephalins. Higher blood concentrations have been associated with estimated glomerular filtration rate (eGFR) decline in European populations. Due to the significant disparity in incident chronic kidney disease (CKD) between White and Black people, we evaluated the association of PENK-A with incident CKD and other kidney outcomes among a biracial cohort in the U.S. Methods: In a nested cohort of 4,400 participants among the REasons for Geographic And Racial Differences in Stroke, we determined the association between baseline PENK-A concentration and incident CKD using the creatinine-cystatin C CKD-EPI 2021 equation without race coefficient, significant eGFR decline, and incident albuminuria between baseline and a follow-up visit 9.4 years later. We tested for race and sex interactions. We used inverse probability sampling weights to account for the sampling design. Results: At baseline, mean (SD) age was 64 (8) years, 49% were women, and 52% were Black participants. 8.5% developed CKD, 21% experienced ≥ 30% decline in eGFR and 18% developed albuminuria. There was no association between PENK-A and incident CKD and no difference by race or sex. However, higher PENK-A was associated with increased odds of progressive eGFR decline (OR: 1.12; 95% CI 1.00, 1.25). Higher PENK-A concentration was strongly associated with incident albuminuria among patients without diabetes mellitus (OR: 1.29; 95% CI 1.09, 1.53). Conclusion: While PENK-A was not associated with incident CKD, its associations with progression of CKD and incident albuminuria, among patients without diabetes, suggest that it might be a useful tool in the evaluation of kidney disease among White and Black patients. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia is frequently exhibited in individuals with chronic kidney disease (CKD). Remnant cholesterol (RC), an emerging novel lipid marker, plays an elusive role in CKD progression. This study sought to investigate the association of RC with decreased kidney function or albuminuria in the general population of U.S. Method: Data were retrieved from the continuous 2001 to 2018 cycle of the National Health and Nutrition Examination Survey (NHANES). Individuals aged between 18 and 70 years were included. RC was divided into quartiles. Albuminuria was defined by albumin-to-creatinine ratio (ACR) ≥30 mg/g, while reduced kidney function was described as an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2. Using a multivariable regression model, the association of RC with decreased eGFR or albuminuria was examined. The dose‒response relationship between RC and eGFR or ACR was also investigated using a restricted cubic spline (RCS) model. Results: A total of 1551 (10.98%) participants with impaired renal function or albuminuria were identified. After multivariate adjustment, RC was not significantly associated with kidney function decline or albuminuria (odds ratio (OR) 1.24, 95% confidence interval (95% CI): 0.95, 1.61). However, a significantly inverse correlation was observed between RC and eGFR in a dose‒response manner (β -2.12, 95% CI: -3.04, -1.21). This association remained consistent when stratifying data by gender, age, race, hypertension, diabetes and body mass index (BMI). Conclusion: A higher RC was significantly correlated with a lower eGFR in the general population. The role of RC in predicting kidney outcomes needed further investigation in prospective studies. [ABSTRACT FROM AUTHOR]

Background: This study aimed to identify the factors relating to moderately increased albuminuria among middle-aged and older individuals in Japan. Methods: We conducted specific health examinations in which we measured albuminuria levels, and administered a questionnaire survey to record participants' lifestyles in western Tokushima Prefecture, Japan. A total of 1,660 people whose albuminuria was less than 300 mg/g creatinine (Cr) were analyzed. We divided participants into two groups—those with normal albuminuria (< 30 mg/gCr) and those with moderately increased albuminuria (≥ 30 mg/gCr, > 300 mg/gCr)—and compared their characteristics. To investigate all relevant factors, we conducted a multivariate logistic regression analysis. Results: The moderately increased albuminuria group were significantly older and had, among them, significantly higher percentages of a body mass index (BMI) ≥ 25 kg/m2, diabetes, hypertension, and mild liver disorder (aspartate transaminase ≥ 31 U/L or alanine aminotransferase ≥ 31 U/L or gamma-glutamyl transferase ≥ 51 U/L). (p < 0.01) In a multivariate logistic regression analysis that used microalbuminuria as an independent variable, we found the adjusted odds ratio (AOR) and 95% confidence interval (CI) to be significantly higher among individuals with diabetes (AOR: 2.04, 95% CI: 1.40–2.99); hypertension (AOR: 1.90, 95% CI: 1.36–2.65); BMI ≥ 25 kg/m2 (AOR: 1.76, 95% CI: 1.27–2.44); and mild liver disorder (AOR: 1.54, 95% CI: 1.10–2.18). Conclusions: In addition to diabetes, hypertension, and BMI ≥ 25 kg/m2, this study found that among the middle-aged and older general population living in western Tokushima Prefecture, there were cases of mild liver disorder (elevated serum transaminase), which independently associated with moderately increased albuminuria. Therefore, in health checkups targeting the general population, there is a need to consider measuring albuminuria, even in those who have only mild liver dysfunction (health guidance level). Trial registration: N/A. [ABSTRACT FROM AUTHOR]

Background: Podocyte apoptosis is one of the important pathological mechanisms of diabetic kidney disease (DKD). Acteoside (Act), a major active component of Rehmannia glutinosa leaves total glycoside, has a strong renoprotective action. Our study aims to demonstrate Act's renoprotective actions in db/db mice. Methods: We adopted C57BLKS/J db/db mice as DKD animal models. After 8 weeks of Act administration, the 24-hour urine albumin, renal function index, and blood lipid levels were quantified using matching kits. Renal pathology was evaluated by HE and PAS staining. The podocyte damage and apoptosis-related signaling pathway were observed by using immunohistochemistry, western blot, and TUNEL staining. Results: The albuminuria of db/db mice was reduced from 391 ug/24 h to 152 ug/24 h, and renal pathology changes were alleviated after Act administration. The western blot and immunohistochemistry showed that Act treatment upregulated the synaptopodin and podocin expression compared with db/db mice, while the TUNEL staining indicated podocyte apoptosis was inhibited. The B-cell lymphoma-2 (Bcl-2) level was upregulated in the Act group, but cleaved caspase-3 and Bcl-2 associated X protein (Bax) expression declined, while the protein kinase B/glycogen synthase kinase-3β (AKT/GSK-3β) signaling pathway was repressed. Conclusions: By inhibiting the AKT/GSK-3β signaling pathway, Act protected podocytes from apoptosis, decreasing the urine albumin of db/db mice and delaying the course of DKD. [ABSTRACT FROM AUTHOR]

Objective: To study the development of microalbuminuria (MAU) in essential hypertension (EHT), we investigated the association of MAU with central blood pressure (CBP), direct renin concentration (DRC), plasma aldosterone (PA), and uric acid (UA). Method: We determined 24 h-urinary albumin excretion (24 h-UAE) in patients with EHT who were hospitalized at TEDA International Cardiovascular Hospital from June 2020 to May 2022. We defined MAU as 24 h-UAE in the range of 30 mg/24 h to 300 mg/24 h. Univariate and multivariate analyses were conducted to determine the associations of MAU with CBP, DRC, PA, and UA in EHT, considering demographic and clinical information. We also plotted receiver operating characteristic curves (ROCs) for predicting MAU using these results. Results: More than a quarter of patients (26.5%, 107/404, 95% CI: 22.2–31.1%) were diagnosed with MAU in EHT. A higher body mass index (BMI), longer duration of hypertension, and higher severity were associated with MAU. Also, nearly 10% more creatinine levels were recorded in the MAU group than in the control group (69.5 ± 18.7 µmol/L vs. 64.8 ± 12.5 µmol/L, P = 0.004). The increase was also observed for PA (15.5, 9.7–20.6 ng/dL vs. 12.3, 9.0–17.3 ng/dL, P = 0.024) and UA (419.8 ± 105.6 µmol/L vs. 375.1 ± 89.5 µmol/L, P < 0.001) in the MAU group compared to that in the control group. Several variables were associated with MAU, including central diastolic blood pressure (CDBP) (OR = 1.017, 95% CI: 1.002–1.032, P = 0.027), PA (OR = 1.043, 95% CI: 1.009–1.078, P = 0.012) and UA (OR = 1.005, 95% CI: 1.002–1.008, P < 0.001). For MAU prediction, the area under the curve (AUC) was 0.709 (95% CI: 0.662–0.753; P < 0.001) when CDBP, PA, and UA were used in combination, and the optimal probability of the cut-off value was 0.337. Conclusion: We found that CDBP, PA, and UA, used for MAU prediction, might be associated with its development during EHT. [ABSTRACT FROM AUTHOR]

Aims: We aimed to investigate the potential association between weight-adjusted-waist index (WWI) and chronic kidney disease (CKD). Design and methods: This research examined data collected from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2020. CKD was defined as the low estimated glomerular filtration rate (eGFR) or the existence of albuminuria (urinary albumin-to-creatinine ratio (ACR) ≥ 30mg/g). Low-eGFR was described as eGFR < 60 mL/min/1.73m2. The associations between WWI with CKD, albuminuria, and low-eGFR were examined using generalized additive models and weighted multivariable logistic regression models. We also analyzed the associations of other obesity indicators with CKD, albuminuria, and low-eGFR, including body mass index (BMI), waist-to-height ratio (WHtR), waist circumference(WC), height, and weight. The receiver operating characteristic (ROC) curves were used to assess and compare their diagnostic abilities. Results: Males made up 48.26% of the total 40,421 individuals that were recruited. The prevalences of CKD, albuminuria, and low-eGFR were 16.71%, 10.97%, and 7.63%, respectively. WWI was found to be positively linked with CKD (OR = 1.42; 95% CI: 1.26, 1.60). A nonlinear connection between WWI and CKD was found using smooth curve fitting. Additionally, a higher prevalence of albuminuria is linked to a higher level of WWI (OR = 1.60; 95% CI: 1.40, 1.82). Different stratifications did not substantially influence the connection between WWI and CKD, albuminuria, and low-eGFR, according to subgroup analysis and interaction tests. We observed higher height was related to higher low-eGFR prevalence (OR = 1.05; 95% CI: 1.03, 1.06). ROC analysis revealed that WWI had the best discrimination and accuracy for predicting CKD and albuminuria compared to other obesity indicators (BMI, WHTR, WC, height and weight). In addition, height had the highest area under the curve (AUC) value for predicting low-eGFR. Conclusion: WWI is the best obesity indicator to predict CKD and albuminuria compared to other obesity indicators (BMI, WHTR, WC, height, and weight). WWI and CKD and albuminuria were found to be positively correlated. Furthermore, height had the strongest ability to predict low-eGFR. Therefore, the importance of WWI and height in assessing kidney health in US adults should be emphasized. [ABSTRACT FROM AUTHOR]

Objective: The objective was to analyze the relationship between serum 25-hydroxy-vitamin D (25(OH)D) level and albuminuiria in middle-aged and older patients with type 2 diabetes of Gansu Province. Methods: Data pertaining to 380 in-patients with type 2 diabetes were collected. Subjects were classified groups based on gender,age,25(OH)D,BMI and UACR.Serum 25(OH)D and other clinical characteristics among various UACR groups were compared.The relationship between albuminuiria and 25(OH)D was analyzed. Results: Out of the 380 subjects, 83.4%were classified as vitamin D deficiency, 14.5%were classified as vitamin D insufficiency, while 2.1% were classified as vitamin D sufficiency. Among the participants,41% had albuminuria (microalbuminuria,28.7%;macroalbuminuria,12.3%).The prevalence of 25(OH)D deficiency in the albuminuria group(84.6%) was significantly higher than that in the normoalbuminuria group(82.6%)(Mann–Whitney U test:Z = -3.86,P = 0.000); patients with macroalbuminuria had the highest prevalence of 25(OH)D deficiency (91.5%; P < 0.01 versus normoalbuminuria).A binary logistic analysis demonstrated that 25(OH)D were protective factors for albuminuria. Conclusions: The prevalence of vitamin D deficiency in patients with albuminuria was overtly higher than that in patients without albuminuria among middle-aged and older adults with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Associations between kidney function and dementia risk are inconclusive. Chronic kidney disease (CKD) severity is determined by levels of both estimated glomerular filtration rate (eGFR) and the urine albumin to creatinine ratio (ACR). However, whether there is a graded increase in dementia risk for worse eGFR in each ACR category is unclear. Also, whether genetic risk for dementia impacts the associations is unknown. The current study aims to investigate the associations between eGFR and albuminuria with dementia risk both individually and jointly, whether the associations vary by different follow-up periods, and whether genetic factors modified the associations. Methods: In 202,702 participants aged ≥ 60 years from the UK Biobank, Cox proportional-hazards models were used to examine the associations between eGFR and urine albumin creatinine ratio (ACR) with risk of incident dementia. GFR was estimated based on serum creatinine, cystatin C, or both. The models were restricted to different follow-up periods (< 5 years, 5–10 years, and ≥ 10 years) to investigate potential reverse causation. Results: Over 15 years of follow-up, 6,042 participants developed dementia. Decreased kidney function (eGFR < 60 ml/min/1.73m2) was associated with an increased risk of dementia (Hazard Ratio [HR] = 1.42, 95% Confidence Interval [CI] 1.28–1.58), compared to normal kidney function (≥ 90 ml/min/1.73m2). The strength of the association remained consistent when the models were restricted to different periods of follow-up. The HRs for incident dementia were 1.16 (95% CI 1.07–1.26) and 2.24 (95% CI 1.79–2.80) for moderate (3-30 mg/mmol) and severely increased ACR (≥ 30 mg/mmol) compared to normal ACR (< 3 mg/mmol). Dose–response associations were observed when combining eGFR and ACR, with those in the severest eGFR and ACR group having the greatest risk of dementia (HR = 4.70, 95% CI 2.34–9.43). APOE status significantly modified the association (p = 0.04), with stronger associations observed among participants with a lower genetic risk of dementia. There was no evidence of an interaction between kidney function and non-APOE polygenic risk of dementia with dementia risk (p = 0.42). Conclusions: Kidney dysfunction and albuminuria were individually and jointly associated with higher dementia risk. The associations were greater amongst participants with a lower genetic risk of dementia based on APOE, but not non-APOE polygenic risk. [ABSTRACT FROM AUTHOR]

Background: Kidney disease is an important comorbidity in people living with HIV(PLWH), and is associated with poor outcomes. However, data on renal function of PLWH are limited in China so far. In this study we assessed the prevalence of kidney disease in patients either on antiretroviral therapy (ART) or not respectively in a single center in China and explored the possible risk factors associated. Methods: In the cross-sectional study, we recruited hospitalized adult PLWH. Demographic characteristics, clinical information and laboratory variables were collected. Kidney disease was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and/or isolated hematuria, proteinuria, microalbuminuria. We calculated the prevalence of kidney disease and used logistic regression to assess its associated risk factors. Results: A total of 501 adult PLWH were enrolled, 446 (89.0%) males and 55 (11.0%) females. The median age was 39 (IQR 30–50) years old. The prevalence of kidney disease was 19.0%, 22 (4.4%) patients with eGFR < 60 mL/min/1.73 m2, 53 (10.6%) patients with hematuria, 11 (2.2%) patients with proteinuria, and 40 (8.0%) patients with microalbuminuria. 297 (59.3%) patients were receiving ART. The patients on ART had a higher prevalence of renal disease than those had not been administrated with ART (22.6% vs. 13.7%, P = 0.013). On the multivariate logistic regression analysis among patients not on ART, lower haemoglobin (OR 0.994, 95%CI: 0.902–0.988, P = 0.013) were significantly associated with kidney disease. While among those on ART, older age (OR 1.034, 95%CI: 1.003–1.066, P = 0.032), lower haemoglobin (OR 0.968, 95%CI: 0.948–0.988, P = 0.002) and lower albumin (OR 0.912, 95%CI: 0.834–0.997, P = 0.044) were significantly associated with kidney disease. Conclusions: The prevalence of kidney disease among hospitalized PLWH in China is high, especially in patients on ART. A larger scale study on Chinese outpatient PLWH should be conducted, so as to precisely assess prevalence of kidney disease in general Chinese PLWH. [ABSTRACT FROM AUTHOR]

Background: Impaired kidney function and albuminuria are associated with increased risk of heart failure (HF) in patients with type 2 diabetes (T2D). We investigated whether rapid kidney function decline over time is an additional determinant of increased HF risk in patients with T2D, independent of baseline kidney function, albuminuria, and other HF predictors. Methods: Included in the study were 7,539 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with baseline urinary albumin-to-creatinine ratio (UACR) data, who had completed 4 years of follow-up and had ≥ 3 eGFR measurements during that period (median eGFR/year = 1.9, IQR 1.7–3.2). The association between rapid kidney function decline (eGFR loss ≥ 5 ml/min/1.73 m2/year) and odds of HF hospitalization or HF death during the first 4 years of follow-up was estimated by logistic regression. The improvement in risk discrimination provided by adding rapid kidney function decline to other HF risk factors was evaluated as the increment in the area under the Receiving Operating Characteristics curve (ROC AUC) and integrated discrimination improvement (IDI). Results: Over 4 years of follow-up, 1,573 participants (20.9%) experienced rapid kidney function decline and 255 (3.4%) experienced a HF event. Rapid kidney function decline was associated with a ~ 3.2-fold increase in HF odds (3.23, 95% CI, 2.51–4.16, p < 0.0001), independent of baseline CVD history. This estimate was not attenuated by adjustment for potential confounders, including eGFR and UACR at baseline as well as at censoring (3.74; 95% CI 2.63–5.31). Adding rapid kidney function decline during follow-up to other clinical predictors (WATCH-DM score, eGFR, and UACR at study entry and end of follow-up) improved HF risk classification (ROC AUC = + 0.02, p = 0.027; relative IDI = + 38%, p < 0.0001). Conclusions: In patients with T2D, rapid kidney function decline is associated with a marked increase in HF risk, independent of starting kidney function and/or albuminuria. These findings highlight the importance of serial eGFR measurements over time to improve HF risk estimation in T2D. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular mortality and the impact of cardiac risk factors in advanced chronic kidney disease (CKD) remain poorly investigated. We examined the risk of cardiovascular mortality in patients with advanced CKD with and without diabetes as well as the impact of albuminuria, plasma hemoglobin, and plasma low-density lipoprotein (LDL) cholesterol levels. Methods: In a Danish nationwide registry-based cohort study, we identified persons aged ≥ 18 years with an estimated glomerular filtration rate < 30 mL/min/1.73m2 between 2002 and 2018. Patients with advanced CKD were age- and sex-matched with four individuals from the general Danish population. Cause-specific Cox regression models were used to estimate the 1-year risk of cardiovascular mortality standardized to the distribution of risk factors in the cohort. Results: We included 138,583 patients with advanced CKD of whom 32,698 had diabetes. The standardized 1-year risk of cardiovascular mortality was 9.8% (95% CI 9.6–10.0) and 7.4% (95% CI 7.3–7.5) for patients with and without diabetes, respectively, versus 3.1% (95% CI 3.1–3.1) in the matched cohort. 1-year cardiovascular mortality risks were 1.1- to 2.8-fold higher for patients with diabetes compared with those without diabetes across the range of advanced CKD stages and age groups. Albuminuria and anemia were associated with increased cardiovascular mortality risk regardless of diabetes status. LDL-cholesterol was inversely associated with cardiovascular mortality risk in patients without diabetes, while there was no clear association in patients with diabetes. Conclusions: Diabetes, albuminuria, and anemia remained important risk factors of cardiovascular mortality whereas our data suggest a limitation of LDL-cholesterol as a predictor of cardiovascular mortality in advanced CKD. [ABSTRACT FROM AUTHOR]

Background: In clinical trials enrolling patients with type 2 diabetes (T2D) at high cardiovascular risk, many glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improved albuminuria status and possibly mitigated kidney function loss. However, limited data are available regarding the effects of GLP-1 RAs on albuminuria status and kidney function in real-world settings, including populations with a lower baseline cardiovascular and kidney risk. We assessed the association of GLP-1 RAs initiation with long-term kidney outcomes in the Maccabi Healthcare Services database, Israel. Methods: Adults with T2D treated with ≥ 2 glucose-lowering agents who initiated GLP-1 RAs or basal insulin from 2010 to 2019 were propensity-score matched (1:1) and followed until October 2021 (intention-to-treat [ITT]). In an as-treated (AT) analysis, follow-up was also censored at study-drug discontinuation or comparator-initiation. We assessed the risk of a composite kidney outcome, including confirmed ≥ 40% eGFR loss or end-stage kidney disease, and the risk of new macroalbuminuria. Treatment-effect on eGFR slopes was assessed by fitting a linear regression model per patient, followed by a t-test to compare the slopes between the groups. Results: Each propensity-score matched group constituted 3424 patients, 45% women, 21% had a history of cardiovascular disease, and 13.9% were treated with sodium-glucose cotransporter-2 inhibitors at baseline. Mean eGFR was 90.6 mL/min/1.73 m2 (SD 19.3) and median UACR was 14.6 mg/g [IQR 0.0–54.7]. Medians follow-up were 81.1 months (ITT) and 22.3 months (AT). The hazard-ratios [95% CI] of the composite kidney outcome with GLP-1 RAs versus basal insulin were 0.96 [0.82–1.11] (p = 0.566) and 0.71 [0.54–0.95] (p = 0.020) in the ITT and AT analyses, respectively. The respective HRs for first new macroalbuminuria were 0.87 [0.75–0.997] and 0.80 [0.64–0.995]. The use of GLP-1 RA was associated with a less steep eGFR slope compared with basal insulin in the AT analysis (mean annual between-group difference of 0.42 mL/min/1.73 m2/year [95%CI 0.11–0.73]; p = 0.008). Conclusion: Initiation of GLP-1 RAs in a real-world setting is associated with a reduced risk of albuminuria progression and possible mitigation of kidney function loss in patients with T2D and mostly preserved kidney function. [ABSTRACT FROM AUTHOR]

Background: The potential effects of time factor and albuminuria on the morbid alterations in patients with type 2 diabetes (T2D) and COVID-19 are still unclear. We aimed to address the morbid alterations and the potential effects of time factor and albuminuria on the patients' characteristics before, during, and 1 year after COVID-19 recovery. Methods: 83 patients with T2D were included, at Mansoura University Hospital, Egypt (July 2021-December 2021). Data of detailed history, physical examination, laboratory tests were recruited from files of the patients. Diagnosis and resolution of COVID-19 were established by Real time polymerase chain reaction (RT-PCR) test of SARS-CoV2. Complete blood count (CBC), renal and hepatic function tests, multiple measures of morning spot urine albumin to creatinine ratio (urine ACR), glycosylated hemoglobin (HBA1c), lipid profile, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Ferritin, neutrophil to lymphocyte ratio (NLR), vitamin D3, intact parathyroid hormone (intact PTH), serum calcium were applied to all participants. Results: Our participants had a mean age of 45 years, 60.2% male, 56.6% were hospitalized, and 25.3% were admitted to ICU for severe COVID-19. Albuminuria was prevalent in 71.1% before, 98.8% during, and 92.8% after COVID-19 recovery. Patients with albuminuria showed older age, longer duration of T2D, more frequent severe COVID-19 and hospitalization (p = 0.03, p < 0.001, p = 0.023& p = 0.025) respectively. Body mass index (BMI), mean arterial blood pressure, ESR, CRP, ferritin, NLR, HBA1c, triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio, vitamin D3, serum calcium, alkaline phosphatase (ALP), hepatic aminotransferases, and urine ACR showed significant alterations throughout the study (p < 0.001 for all). Although the interaction between time and albuminuria showed non-significant effect on all studied parameters, we noticed relevant main effects of time factor on Body mass index (BMI), HBA1c, glomerular filtration rate (eGFR), TG/HDL ratio, NLR, vitamin D3, (p < 0.001 for all). Moreover, albuminuria showed main effects on BMI, serum creatinine, and intact PTH (p = 0.019, 0.005 & <0.001), respectively. Conclusion: The characteristics of patients with T2D significantly altered throughout the study. Time factor and albuminuria exerted relevant main effects on the patients' characteristics without significant effect of their interaction. [ABSTRACT FROM AUTHOR]

Introduction: IgA nephropathy (IgAN) is the most common glomerulonephritis globally. Because of the heterogeneity of the disease prognostic biomarkers are highly needed. Aim: To investigate associations between galactose-deficient IgA1 (Gd-IgA1) concentrations in plasma and urine and disease activity and progression in patients with IgAN. Methods: Serum and urine samples were collected at the time of kidney biopsy (baseline) in patients with IgAN (n = 40) and analysed for Gd-IgA1. Patients with chronic kidney disease (CKD) without IgAN (n = 21) and healthy controls (n = 19) were examined as controls. In 19 patients with IgAN, analyses of Gd-IgA1 were repeated after a median follow up time of approximately 10 years. Results: Serum Gd-IgA1 and Gd-IgA1:IgA were significantly elevated at the time of kidney biopsy in patients with IgAN compared to patients with non-IgAN CKD and healthy controls (p < 0.001). Urinary Gd-IgA1:creatinine was significantly elevated in patients with IgAN compared to patients with non-IgAN CKD. Neither serum Gd-IgA1, nor serum Gd-IgA1:IgA, correlated significantly to estimated GFR, urine albumin:creatinine (UACR), or blood pressure, at baseline. Serum Gd-IgA1 and Gd-IgA1:IgA at time of biopsy did not correlate significantly to annual changes in eGFR or UACR during follow up. In patients with IgAN, serum Gd-IgA1 decreased significantly over time during approximately 10 years of follow up (Δ-20 ± 85%, p = 0.027). Urinary Gd-IgA1:creatinine showed a strong positive correlation to UACR in patients with IgAN and likely reflected unspecific glomerular barrier injury. Conclusion: Although serum Gd-IgA1 and the Gd-IgA1:IgA ratio were significantly elevated in patients with IgAN at the time of kidney biopsy they were not related to disease activity or progression in this patient cohort. [ABSTRACT FROM AUTHOR]

Purpose: Diabetes is the leading cause of kidney disease. Up to 40% of the population with diabetes experience diabetic kidney disease (DKD). The correlation of DKD with insulin resistance (IR) indices has been shown in previous studies. In this study, the objective was to evaluate surrogate IR indices, including the Triglyceride-Glucose (TyG) index, Visceral Adiposity Index (VAI), Lipid Accumulation Product (LAP), and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) to find the most valuable index for the correlation between albuminuria and IR in the type 2 diabetes (T2D) population. Albuminuria is defined as urine albumin excretion of > 30 mg/day. Methods: In this cross-sectional study, 2934 participants were enrolled and evaluated for urinary albumin excretion, and albuminuria was detected in 526 of the entries. The logistic regression models and Receiver Operating Characteristic (ROC) curve analysis were performed to assess the relationship of TyG index, VAI, LAP, and HOMA-IR's with albuminuria in patients with T2D. Results: The TyG index had the highest association (OR 1.67) with the presence of albuminuria in patients with T2D, followed by HOMA-IR (OR 1.127), VAI (OR 1.028), and LAP (OR 1.004). These four indices remained independent after adjustment for multiple confounders. Based on the ROC curve, TyG revealed the best area under the curve (AUC) for revealing albuminuria with sufficient accuracy (AUC: 0.62) in comparison with other measured indices. The calculated TyG index cut-off point for the presence of albuminuria was 9.39. Conclusion: Among the indices, TyG index had the most significant correlation with albuminuria in patients with T2D. [ABSTRACT FROM AUTHOR]

Background: The FIDELIO-DKD and FIGARO-DKD randomized clinical trials (RCTs) showed finerenone, a novel non-steroidal mineralocorticoid receptor antagonist (MRA), reduced the risk of renal and cardiovascular events in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Using RCT inclusion and exclusion criteria, we analyzed the RCT coverage for patients with T2DM and CKD in routine clinical practice in Germany. Methods: German patients from the DPV/DIVE registries who were ≥ 18 years, had T2DM and CKD (an estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2OR eGFR ≥ 60 mL/min/1.73m2 and albuminuria [≥ 30 mg/g]) were included. RCT inclusion and exclusion criteria were then applied, and the characteristics of the two populations compared. Results: Overall, 65,168 patients with T2DM and CKD were identified from DPV/DIVE. Key findings were (1) Registry patients with CKD were older, less often male, and had a lower eGFR, but more were normoalbuminuric vs the RCTs. Cardiovascular disease burden was higher in the RCTs; diabetic neuropathy, lipid metabolism disorders, and peripheral arterial disease were more frequent in the registry. CKD-specific drugs (e.g., angiotensin-converting enzyme inhibitors [ACEi] and angiotensin receptor blocker [ARBs]) were used less often in clinical practice; (2) Due to the RCT's albuminuric G1/2 to G4 CKD focus, they did not cover 28,147 (43.2%) normoalbuminuric registry patients, 4,519 (6.9%) albuminuric patients with eGFR < 25, and 6,565 (10.1%) patients with microalbuminuria but normal GFR (≥ 90 ml/min); 3) As RCTs required baseline ACEi or ARB treatment, the number of comparable registry patients was reduced to 28,359. Of these, only 12,322 (43.5%) registry patients fulfilled all trial inclusion and exclusion criteria. Registry patients that would have been eligible for the RCTs were more often male, had higher eGFR values, higher rates of albuminuria, more received metformin, and more SGLT-2 inhibitors than patients that would not be eligible. Conclusions: Certain patient subgroups, especially non-albuminuric CKD-patients, were not included in the RCTs. Although recommended by guidelines, there was an undertreatment of CKD-patients with renin-angiotensin system (RAS) blockers. Further research into patients with normoalbuminuric CKD and a wider prescription of RAS blocking agents for CKD patients in clinical practice appears warranted. [ABSTRACT FROM AUTHOR]

Background and objectives: Albuminuria is recognized as being a predictor of cardiovascular and renal disease. We aimed to identify the impact of the long-term burden and trends of systolic blood pressure on albuminuria in midlife, as well as to explore sex differences concerning this relationship. Methods: This longitudinal study consisted of 1,683 adults who had been examined 4 or more times for blood pressure starting in childhood, with a follow-up time period of 30 years. The cumulative effect and longitudinal trend of blood pressure were identified by using the area under the curve (AUC) of individual systolic blood pressure measurement with a growth curve random effects model. Results: Over 30 years of follow-up, 190 people developed albuminuria, including 53.2% males and 46.8% females (aged 43.39 ± 3.13 years in the latest follow-up). The urine albumin-to-creatinine ratio (uACR) values increased as the total and incremental AUC values increased. Additionally, women had a higher albuminuria incidence in the higher SBP AUC groups than men do (13.3% for men vs. 33.7% for women). Logistic regression showed that the ORs of albuminuria for males and females in the high total AUC group were 1.34 (0.70–2.60) and 2.94 (1.50–5.74), respectively. Similar associations were found in the incremental AUC groups. Conclusions: Higher cumulative SBP was correlated with higher uACR levels and a risk of albuminuria in middle age, especially in women. The identification and control of cumulative SBP levels from an early age may assist in reducing the incidences of renal and cardiovascular disease for individuals in later life. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial dysfunction is considered to be an important contributor in podocyte injury under diabetic conditions. The BaoShenTongLuo (BSTL) formula has been shown to reduce podocyte damage and postpone the progression of diabetic kidney disease (DKD). The potential mechanisms underlying the effects of BSTL, however, have yet to be elucidated. In this study, we aimed to investigate whether the effects of BSTL are related to the regulation of mitochondrial biogenesis via the adenosine monophosphate-activated protein kinase (AMPK) pathway. Methods: High-Performance Liquid Chromatography Electrospray Ionization Mass Spectrometer (HPLC–ESI–MS) analysis was performed to investigate the characteristics of pure compounds in BSTL. db/db mice and mouse podocyte clone-5 (MPC5) cells were exposed to high glucose (HG) to induce DKD and podocyte damage. Body weight, random blood glucose, urinary albumin/creatinine ratio (UACR), indicators of renal function and renal histological lesions were measured. Markers of podocyte injury, mitochondrial morphology, mitochondrial deoxyribonucleic acid (mtDNA) content, mitochondrial respiratory chain complexes activities, reactive oxygen species (ROS) production, and mitochondrial membrane potential (MMP) levels were assessed. Protein expressions of AMPK, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), transcription factor A (TFAM), mitochondrial fusion protein 2 (MFN2) and dynamin-related protein 1 (DRP1) were also detected. MPC5 cells were transfected with AMPKα small interfering RNA (AMPKα siRNA) to determine the underlying mechanisms of BSTL improvement of mitochondrial function under diabetic conditions. Results: In vivo, treatment with BSTL reduced the UACR levels, reversed the histopathological changes in renal tissues, and alleviated the podocyte injury observed in db/db mice. After BSTL treatment, the decreased mtDNA content and mitochondrial respiratory chain complex I, III, and IV activities were significantly improved, and these effects were accompanied by maintenance of the protein expression of p-AMPKαT172, PGC-1α, TFAM and MFN2. The in vitro experiments also showed that BSTL reduced podocyte apoptosis, suppressed excessive cellular ROS production, and reversed the decreased in MMP that were observed under HG conditions. More importantly, the effects of BSTL in enhancing mitochondrial biogenesis and reducing podocyte apoptosis were inhibited in AMPKα siRNA-treated podocytes. Conclusion: BSTL plays a crucial role in protecting against podocyte injury by regulating the AMPK-mediated mitochondrial biogenesis in DKD. [ABSTRACT FROM AUTHOR]

Background: Although albuminuria has been linked to heart failure in the general population, the relationship between urine albumin-to-creatinine ratio (uACR) and heart failure in type 2 diabetes patients is not well understood. We aimed to investigate the relationship between uACR and new-onset heart failure (HF) in type 2 diabetics. Methods: We included 9287 Chinese participants with type 2 diabetes (T2D) but no heart failure (HF) who were assessed with uACR between 2014 and 2016. The participants were divided into three groups based on their baseline uACR: normal (< 3 mg/mmol), microalbuminuria (3–30 mg/mmol), and macroalbuminuria (≥ 30 mg/mmol). The relationship between uACR and new-onset HF was studied using Cox proportional hazard models and restricted cubic spline. The area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to see if incorporating uACR into existing models could improve performance. Results: 216 new-onset HF cases (2.33%) were recorded after a median follow-up of 4.05 years. When compared to normal uACR, elevated uACR was associated with a progressively increased risk of new-onset HF, ranging from microalbuminuria (adjusted HR, 2.21; 95% CI 1.59–3.06) to macroalbuminuria (adjusted HR, 6.02; 95% CI 4.11–8.80), and 1 standard deviation (SD) in ln (uACR) (adjusted HR, 1.89; 95% CI 1.68–2.13). The results were consistent across sex, estimated glomerular filtration rate, systolic blood pressure, and glycosylated hemoglobin subgroups. The addition of uACR to established HF risk models improved the HF risk prediction efficacy. Conclusions: Increasing uACR, even below the normal range, is an independent risk factor for new-onset HF in a type 2 diabetic population. Furthermore, uACR may improve HF risk prediction in community-based T2D patients. [ABSTRACT FROM AUTHOR]

Background: Microvascular dysfunction (MVD) is an important contributor to major clinical disease such as stroke, dementia, depression, retinopathy, and chronic kidney disease. Alcohol consumption may be a determinant of MVD. Objective: Main objectives were (1) to study whether alcohol consumption was associated with MVD as assessed in the brain, retina, skin, kidney and in the blood; and (2) to investigate whether associations differed by history of cardiovascular disease or sex. Design: We used cross-sectional data from The Maastricht Study (N = 3,120 participants, 50.9% men, mean age 60 years, and 27.5% with type 2 diabetes [the latter oversampled by design]). We used regression analyses to study the association between total alcohol (per unit and in the categories, i.e. none, light, moderate, high) and MVD, where all measures of MVD were combined into a total MVD composite score (expressed in SD). We adjusted all associations for potential confounders; and tested for interaction by sex, and history of cardiovascular disease. Additionally we tested for interaction with glucose metabolism status. Results: The association between total alcohol consumption and MVD was non-linear, i.e. J-shaped. Moderate versus light total alcohol consumption was significantly associated with less MVD, after full adjustment (beta [95% confidence interval], -0.10 [-0.19; -0.01]). The shape of the curve differed with sex (Pinteraction = 0.03), history of cardiovascular disease (Pinteraction < 0.001), and glucose metabolism status (Pinteraction = 0.02). Conclusions: The present cross-sectional, population-based study found evidence that alcohol consumption may have an effect on MVD. Hence, although increasing alcohol consumption cannot be recommended as a policy, this study suggests that prevention of MVD may be possible through dietary interventions. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a globally significant non-communicable disorder. CKD prevalence varies between countries and within a country. We compared the prevalence rates of CKD in South Africa with sub-Saharan Africa, Africa, and globally. Methods: We registered a systematic review with the International Prospective Register of Systematic Reviews for prevalence studies reporting CKD stages III-V from 2013 to 2021. The analysis sought to explain any significant differences in prevalence rates. The R statistical package was used for data analysis. Comparisons included measures of effect size due to the large sample sizes analysed. We also compared sex differences in prevalence rates, common aetiologies, and type of study methodologies employed. Results: Eight studies were analysed, with two from each region. The matched prevalence rates of CKD between the various regions and South Africa showed significant differences, except for one comparison between South Africa and an African study [p = 0.09 (95% CI − 0.04–0.01)]. Both sub-Saharan African studies had a higher prevalence than South Africa. One study in Africa had a higher prevalence, while the other had a lower prevalence, whilst one Global study had a higher prevalence, and the other had a lower prevalence compared to South Africa. The statistical differences analysed using the Cramer's V test were substantially less than 0.1. Thus, differences in comparisons were largely due to differences in sample sizes rather than actual differences. Conclusion: Variable prevalence rates between regions included disparities in sample size, definitions of CKD, lack of chronicity testing and heterogeneous laboratory estimations of eGFR. Improved consistency and enhanced methods for diagnosing and comparing CKD prevalence are essential. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to investigate the association between estimated glucose disposal rate (eGDR), a proxy for insulin resistance, and retinopathy or kidney disease, i.e. micro-, or macroalbuminuria, in young individuals with type 1 diabetes (T1D). Material and Methods: Using data from the Swedish pediatric registry for diabetes (SweDiabKids) and the registry for adults (NDR), all individuals with T1D with a duration of diabetes of less than 10 years between 1998 and 2017 were included. We calculated the crude incidence rates with 95% confidence intervals (CIs) and used multivariable Cox regression to estimate crude and adjusted hazard ratios (HRs) for two cohorts: retinopathy cohort or kidney disease cohort, stratified by eGDR categories: < 4, 4 to 5.99, 6 to 7.99, and ≥ 8 mg/kg/min (reference). Results: A total of 22 146 (10 289 retinopathy cohort, and 11 857 kidney disease cohort with an overlapping of 9575) children and adults with T1D (median age 21 years, female 42% and diabetes duration of 6 and 7 years, respectively for the cohorts) were studied. During a median follow-up of 4.8 years (IQR 2.6–7.7) there were 5040 (24.7%), 1909 (48.1%), 504 (52.3%) and 179 (57.6%) events for retinopathy in individuals with an eGDR ≥ 8, 7.99 to 6, 5.99 to 4, and < 4 mg/kg/min, respectively. Corresponding numbers for kidney disease was 1321 (6.5%), 526 (13.3%), 255 (26.8%) and 145 (46.6%). After multiple adjustments for different covariates, individuals with an eGDR 7.99 to 6, 5.99 to 4 and < 4 mg/kg/min, had an increased risk of retinopathy compared to those with an eGDR ≥ 8 mg/kg/min (adjusted HRs, 95% CIs) 1.29 (1.20 to 1.40); 1.50 (1.31 to 1.71) and 1.74 (1.41 to 2.14). Corresponding numbers for kidney disease was (adjusted HRs, 95% CIs) 1.30 (1.11 to 1.52); 1.58 (1.25 to 1.99) and 1.33 (0.95 to 1.86), respectively. Conclusions: eGDR, a proxy for insulin resistance, is associated with retinopathy and kidney disease in young adults with T1D. The risk of retinopathy increased with lower eGDR. The risk of kidney disease also increased with lower eGDR; however results show no association between the lowest eGDR and kidney disease. eGDR can be helpful to identify young T1D individuals at risk. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1–7) [Ang-(1–7)] might have beneficial effects on the cardiovascular system. We investigated the effects of olmesartan on the changes in serum ACE2 and Ang-(1–7) levels as well as kidney and vascular function in patients with type 2 diabetes and hypertension. Methods: This was a prospective, randomized, active comparator-controlled trial. Eighty participants with type 2 diabetes and hypertension were randomized to receive 20 mg of olmesartan (N = 40) or 5 mg of amlodipine (N = 40) once daily. The primary endpoint was changes of serum Ang-(1–7) from baseline to week 24. Results: Both olmesartan and amlodipine treatment for 24 weeks decreased systolic and diastolic blood pressures significantly by > 18 mmHg and > 8 mmHg, respectively. Serum Ang-(1–7) levels were more significantly increased by olmesartan treatment (25.8 ± 34.5 pg/mL → 46.2 ± 59.4 pg/mL) than by amlodipine treatment (29.2 ± 38.9 pg/mL → 31.7 ± 26.0 pg/mL), resulting in significant between-group differences (P = 0.01). Serum ACE2 levels showed a similar pattern (6.31 ± 0.42 ng/mL → 6.74 ± 0.39 ng/mL by olmesartan treatment vs. 6.43 ± 0.23 ng/mL → 6.61 ± 0.42 ng/mL by amlodipine treatment; P < 0.05). The reduction in albuminuria was significantly associated with the increases in ACE2 and Ang-(1–7) levels (r = − 0.252 and r = − 0.299, respectively). The change in Ang-(1–7) levels was positively associated with improved microvascular function (r = 0.241, P < 0.05). Multivariate regression analyses showed that increases in serum Ang-(1–7) levels were an independent predictor of a reduction in albuminuria. Conclusions: These findings suggest that the beneficial effects of olmesartan on albuminuria may be mediated by increased ACE2 and Ang-(1–7) levels. These novel biomarkers may be therapeutic targets for the prevention and treatment of diabetic kidney disease. Trial registration: ClinicalTrials.gov NCT05189015. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction is a major determinant in the progression of fatty liver disease. It is pivotal to evaluate the metabolic status and subsequent transition in fatty liver population and to identify the risk of subclinical atherosclerosis. Methods: The prospective cohort study included 6260 Chinese community residents during 2010–2015. Fatty liver was determined as hepatic steatosis (HS) by ultrasonography. Metabolic unhealthy (MU) status was defined as having diabetes and/or ≥ 2 metabolic risk factors. Participants were categorized into 4 groups according to the combination of metabolic healthy (MH)/MU and fatty liver status (MHNHS, MUNHS, MHHS and MUHS). Subclinical atherosclerosis was assessed by elevated brachial-ankle pulse wave velocity, pulse pressure and/or albuminuria. Results: 31.3% of the participants had fatty liver disease and 76.9% were in MU status. During a 4.3-year follow-up, 24.2% of participants developed composite subclinical atherosclerosis. Multivariable adjusted odds ratios for composite subclinical atherosclerosis risk were (1.66 [1.30–2.13]) in MUNHS group and (2.57 [1.90–3.48]) in MUHS group. It seemed that participants with fatty liver disease were more prone to be remained in MU status (90.7% vs.50.8%) and less likely to regress to MH status (4.0% vs. 8.9%). Fatty liver participants progressed to (3.11 [1.23–7.92]) or maintained MU status (4.87 [3.25–7.31]) significantly impelled the development of the composite risk, while regressing to MH status (0.15 [0.04–0.64]) were more intended to mitigate the risk. Conclusions: The current study emphasized the importance of assessing metabolic status and its dynamic changes, especially in the fatty liver population. Regressing from MU to MH status not only benefited the systematic metabolic profile but also ameliorated future cardiometabolic complications. [ABSTRACT FROM AUTHOR]

Background: Diabetic kidney disease (DKD) is a serious complication that begins with albuminuria and often leads to a rapid progressive decline in renal function. Niclosamide is a potent inhibitor of the Wnt/β-catenin pathway, which controls the expression of multiple genes of the renin–angiotensin–aldosterone system (RAAS), which in turn is influences the progression of DKD. This study was conducted to evaluate the effect of niclosamide as adjuvant therapy on DKD. Methods: Out of 127 patients screened for eligibility, 60 patients completed the study. After randomization, 30 patients in the niclosamide arm received ramipril plus niclosamide, and 30 patients in the control arm received ramipril only for 6 months. The primary outcomes were the changes in urinary albumin to creatinine ratio (UACR), serum creatinine, and estimated glomerular filtration rate (eGFR). The secondary outcomes were measurements of urinary matrix metalloproteinase-7 (MMP-7), 8-hydroxy-2ʹ-deoxyguanosine (8-OHdG), and podocalyxin (PCX). Comparisons between the two arms were done using student t-test. Correlation analysis was done using Pearson correlation. Results: Niclosamide decreased UACR by 24% (95% CI − 30 to − 18.3%) while there was a rise in UACR in the control arm by 11% (95% CI 4 to 18.2%) after 6 months (P < 0.001). Moreover, a significant reduction in MMP-7 and PCX was noticed in the niclosamide arm. Regression analysis revealed a strong association between MMP-7, which is a noninvasive biomarker predicting the activity of the Wnt/β-catenin signaling, and UACR. A 1 mg/dL decline in MMP-7 level was associated with a 25 mg/g lowering in UACR (B = 24.95, P < 0.001). Conclusion: The addition of niclosamide to patients with diabetic kidney disease receiving an angiotensin-converting enzyme inhibitor significantly reduces albumin excretion. Further larger-scale trials are needed to confirm our results. Trial registration: The study was prospectively registered on clinicaltrial.gov on March 23, 2020, with identification code NCT04317430. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a significant health care burden, with a worldwide prevalence of approximately 11%. The general population spends over 50% of the awake time sedentary activities. However, to the best of our knowledge, no study has evaluated the association between sedentary time and CKD, with a focus on both kidney damage and kidney function, in the South Korean population. Accordingly, the present study aimed to address this gap in the knowledge. Method: We used data from the 8th Korea National Health and Nutrition Examination Survey. The analysis included 9,534 participants, especially excluded those who had been diagnosed with kidney disease or who were currently undergoing treatment. Sedentary behavior was self-reported by the participants. An estimated glomerular filtration rate (eGFR) and/or albuminuria were used as measures for detection of CKD according to the guidelines of the Kidney Disease Improving Global Outcomes. We analyzed the data using multiple logistic regression. Results: Among the women, the risk of CKD was significantly greater among those who sat for ≥ 12 h/d relative to those who sat for < 6 h/d, after adjusting for physical activity and other covariates (odds ratio [OR]: 1.45, 95% confidence interval [CI]: 1.01–2.06). Similarly, among those who sat over 12 h/d, those who engaged in low levels of physical activity had a higher risk of CKD than those who engaged in high levels of activity (OR: 1.65, 95% CI: 1.04–2.61). No statistically significant results were found for men. Conclusion: Excessive sedentary behavior was associated with an increased risk of CKD, especially albuminuria, regardless of the level of physical activity, only in women. These findings emphasize the importance of avoiding excessive sitting for a long time and increasing overall physical activity levels. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the association between albuminuria and hypertensive retinopathy (HR) in hypertensive adults. Methods: This was a cross-sectional subgroup analysis of data from the China Stroke Primary Prevention Trial. We enrolled 2,964 hypertensive adults in this study. Keith-Wagener-Barker stages was used to assess HR. The urinary albumin to creatinine ratio (UACR) was calculated to evaluate albuminuria. Results: HR was found in 76.6% (n = 2, 271) of the participants, albuminuria was found in 11.1% (n = 330). The UACR levels were significantly higher in subjects with HR than in those without HR (grade 1, β = 1.42, 95% confidence intervals [CI]: -0.12, 2.95, p = 0.070; grade 2, β = 2.62, 95% CI: 0.56, 4.67, p = 0.013; grade 3, β = 5.17, 95% CI: 1.13, 9.20, p = 0.012). In the subgroup analyses, the association between HR and UACR was stronger in current smokers (p for interaction = 0.014). The correlation between HR grades 1 and 2 and UACR was stronger in subjects with higher triglyceride levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglycerides levels (< 1.7 mmol/L, p for interaction = 0.023). The odds of albuminuria were significantly higher in subjects with HR than in those without HR (grade 1, odds ratio [OR] = 1.57, 95% CI: 1.08, 2.29, p = 0.019; grade 2, OR = 2.02, 95% CI: 1.28, 3.18, p = 0.002; grade 3, OR = 2.12, 95% CI: 0.99, 4.55, p = 0.053). In the subgroup analyses, the association between HR grades 1 and 2 and albuminuria was stronger in subjects with higher triglycerides levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglyceride levels (< 1.7 mmol/L, p for interaction = 0.014). Conclusion: HR was positively correlated with albuminuria in hypertensive Chinese adults. This correlation was more remarkable when the population was stratified by triglycerides levels and smoking status. HR can be used as an indicator of early renal injury. [ABSTRACT FROM AUTHOR]

Background: In recent years, it has been reported that diabetic patients tend to have a lower zinc intake due to unbalanced diet accompanying changes in lifestyle habits. We investigated serum zinc concentration in diabetic patients according to the stage of nephropathy. Methods: We enrolled 227 diabetic patients (119 men, 108 women, average age 65.7 ± 14.7 [mean ± standard deviation]) who were hospitalized for diabetes treatment due to poor blood glucose control. We investigated the relationship between fasting serum zinc concentration and estimated glomerular filtration rate (eGFR) and albuminuria (urinary albumin-to-creatinine ratio, UACR), as well as serum zinc concentration by stage of diabetic kidney disease and chronic kidney disease. Results: The mean HbA1c value was 10.5 ± 2.1%. Serum zinc concentration was 75.5 ± 16.0 μg/dL in males and 75.7 ± 12.2 μg/dL in females, showing no gender difference and no significant relationship with diabetes type. The serum zinc concentration was negatively correlated with age (r = − 0.309, P < 0.001) and positively correlated with eGFR (r = 0.144, P = 0.030). A tendency was observed of serum zinc concentration to decrease after overt nephropathy, with values of 76.4 ± 14.1 μg/dL in pre-nephropathy (stage 1, n = 131), 78.5 ± 13.2 μg/dL in incipient nephropathy (stage 2, n = 65), 66.4 ± 14.3 μg/dL in overt nephropathy (stage 3, n = 25), and 65.7 ± 11.9 μg/dL in kidney failure (stage 4, n = 6). Serum zinc showed a negative trend with estimated GFR (P = 0.004) and significant reduction in albuminuria, with stage A3 (n = 29, 65.7 ± 13.9 μg/dL) having lower levels than A1 (n = 131, 76.4 ± 14.1 μg/dL, P = 0.001) and A2 (n = 67, 78.4 ± 13.1 μg/dL, P < 0.001). Conclusions: In diabetic patients, serum zinc concentration tended to decrease as age increased and also as renal function deteriorated. This study suggests that consideration of zinc deficiency is necessary in patients with overt albuminuria. [ABSTRACT FROM AUTHOR]

Background: Lipid accumulation product (LAP) and visceral adiposity index (VAI) are novel, non-imaging markers of visceral adiposity that are calculated by using body mass index (BMI), waist circumference (WC) and serum lipid concentrations. We hypothesized that LAP and VAI are more strongly associated with adverse kidney outcomes than BMI and WC. Methods: Using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we used multivariable logistic regression to evaluate associations of LAP, VAI, BMI and WC with incident chronic kidney disease (CKD), (incident eGFR < 60 ml/min/1.73m2 and > 25% decline). Results: Among the overall cohort of 27,550 participants, the mean baseline age was 65 years; 54% were women; and 41% were African American. After a median of 9.4 years (IQR 8.6, 9.9) of follow-up, a total of 1127 cases of incident CKD were observed. Each two-fold higher value of VAI (OR 1.12, 95% CI 1.04, 1.20), LAP (OR 1.21, 95% CI 1.13, 1.29), WC (OR 2.10, 95% CI 1.60, 2.76) and BMI (OR: 2.66, 95% CI 1.88, 3.77), was associated with greater odds of incident CKD. Conclusions: LAP and VAI as measures of visceral adiposity are associated with higher odds of incident CKD but may not provide information beyond WC and BMI. [ABSTRACT FROM AUTHOR]

Background and purpose: Diabetic kidney disease (DKD) is highly prevalent among patients with diabetes mellitus. It affects approximately 20% of diabetic patients, who are believed to be more than 400 million individuals. The objectives of the present work were to assess patterns of albuminuria and determine microalbuminuria predictors among patients living with type 2 diabetes (T2D) who attended the family medicine department of Jazan Armed Forces Hospital. Methods: A case–control design was used and included two groups (n, 202/group), one with microalbuminuria and the other with a normal urine albumin/creatinine ratio (ACR). Data regarding patient history, glycosylated hemoglobin (HbA1c), lipid profile, renal function tests, ACR, ASCVD (atherosclerotic cardiovascular disease) risk, etc., were collected. Results: The prevalence rates of microalbuminuria and macroalbuminuria were 26.4% and 3.9%, respectively. HbA1c was significantly higher in patients with microalbuminuria (9.3 ± 2.2; P˂0.001) and macroalbuminuria (10.5 ± 2.3; P˂0.001) than in those with normal ACR (8.3 ± 1.9%). The predictors of microalbuminuria were poor glycemic control with HbA1c ≥ 7% {OR, 2.5 (95% C. I, 1.5–4.2)}; hypertension {(OR, 1.8 (95% C. I, 1.2–2.8)}; estimated glomerular filtration rate (eGFR) of ˂90 mL/min/1.73 m2 {OR, 2.2 (95% C. I, 1.4–3.6}; smoking {OR, 1.3 (95% C. I, 0.7–2.6}; and body mass index {OR, 1.05 (95% C. I, 1.01–1.09}. Conclusion: Microalbuminuria is highly prevalent among patients with type 2 diabetes and is associated with poor glycemic control and hypertension, necessitating aggressive and timely screening and treatment. [ABSTRACT FROM AUTHOR]

Background: The utility of dipstick proteinuria for predicting microalbuminuria in non-diabetic lifestyle-related diseases compared with the urine protein-to-creatinine ratio (uPCR) and the effect of dipstick proteinuria on the cut-off value (CO) and accuracy of uPCR are unclear.Methods: The subjects included Japanese patients ≥ 18 years old with lifestyle-related diseases who had an estimated glomerular filtration rate of ≥ 15 ml/min/1.73 m2 and uPCR of < 0.5 g/gCr at initiation. Urine dipstick, uPCR and urine albumin-to-creatinine ratio (uACR) were measured three times per case. Microalbuminuria was defined as uACR of 30-299 mg/gCr for at least 2 of 3 measurements. Youden's Index was used as the optimal CO. Factors associated with microalbuminuria were analyzed using a logistic regression model.Results: In 313 non-diabetic cases (median 70.8 years old), 3 dipstick proteinuria measurements were independently useful for detecting microalbuminuria, and the CO was set when a trace finding was obtained at least 1 of 3 times (sensitivity 0.56, specificity 0.80, positive predictive value [PPV] 0.73, negative predictive value [NPV] 0.65). A single uPCR measurement was more useful than 3 dipstick measurements, and was useful for detecting microalbuminuria even in cases with three consecutive negative proteinuria findings, indicating that the CO of the second uPCR with G1-3a (n = 136) was 0.06 g/gCr (sensitivity 0.76, specificity 0.84. PPV 0.68, NPV 0.89), while that with G3-b4 (n = 59) was 0.10 g/gCr (sensitivity 0.56, specificity 0.91. PPV 0.83, NPV 0.71). The sum of 3 uPCRs was useful for detecting microalbuminuria in cases with G1-3a (sensitivity 0.67, specificity 0.94, PPV 0.82, NPV 0.86) and G3b-4 (sensitivity 0.78, specificity 0.94, PPV 0.91 NPV 0.83), with both COs being 0.23 g/gCr. These COs of microalbuminuria did not change when trace or more proteinuria was included, although the sensitivity increased. A high uPCR and low urine specific gravity or creatinine level were independent factors for uACR ≥ 30 mg/gCr in cases with negative proteinuria, although the uPCR was a major predictive factor of a uACR ≥ 30 mg/gCr.Conclusions: The uPCR (preferably determined using early-morning urine), including in dipstick-negative proteinuria cases with non-diabetic lifestyle-related diseases, can aid in the early detection of microalbuminuria.Trial Registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Nephropathy in Diabetes type 2 (NID-2) study is an open-label cluster randomized clinical trial that demonstrated that multifactorial intensive treatment reduces Major Adverse Cardiac Events (MACEs) and overall mortality versus standard of care in type 2 diabetic subjects with albuminuria and no history of cardiovascular disease. Aim of the present post-hoc analysis of NID- 2 study is to evaluate whether the number of risk factors on target associates with patient outcomes. Methods: Intervention phase lasted four years and subsequent follow up for survival lasted 10 years. To the aim of this post-hoc analysis, the whole population has been divided into 3 risk groups: 0–1 risk factor (absent/low); 2–3 risk factors (intermediate); 4 risk factors (high). Primary endpoint was a composite of fatal and non-fatal MACEs, the secondary endpoint was all-cause death at the end of the follow-up phase. Results: Absent/low risk group included 166 patients (52.4%), intermediate risk group 128 (40.4%) and high-risk group 23 (7.3%). Cox model showed a significant higher risk of MACE and death in the high-risk group after adjustment for confounding variables, including treatment arm (HR 1.91, 95% CI 1.04–3.52, P = 0.038 and 1.96, 95%CI 1.02–3.8, P = 0,045, respectively, vs absent/low risk group). Conclusions: This post-hoc analysis of the NID-2 trial indicates that the increase in the number of risk factors at target correlates with better cardiovascular-free survival in patients with type 2 diabetes at high CV risk. Clinical Trial Registration: ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT00535925 [ABSTRACT FROM AUTHOR]

Objective: To analyse the correlation between urinary albumin excretion rate (UAER) and estimated glomerular filtration rate (eGFR) and the risk factors for reducing eGFR in patients with type 2 diabetes mellitus (T2DM)., Methods: A total of 431 T2DM patients admitted between January 2019 and March 2020 were selected and divided into two groups according to eGFR level. Comparing the differences between baseline data and clinical indicators, multivariate logistic regression was used to analyse the risk factors of eGFR reduction and to analyse the association between UAER and eGFR., Results: In total, 167 patients were included in the study group and 264 patients were included in the conventional group. The study group participants were older, had longer diabetes duration, and had higher fatty liver, peripheral vascular disease (PVD), hypertension prevalence, and mean body mass index (P < 0.05). The levels of various indicators were lower than those of the conventional group (P < 0. 05). Additionally, PVD, nocturnal systolic blood pressure, fatty liver, and beta-2-microglobulin (β 2-MG) were independent risk factors for eGFR decline, with high density lipoprotein (HDL) and fasting C-peptide (CP) as protective factors. There was no obvious correlation between UAER and eGFR., Conclusion: Peripheral vascular disease, systolic blood pressure, fatty liver, and beta-2-microglobulin are risk factors for decreased eGFR levels in patients with T2DM, which should be applied for control DKD. HDL and fasting CP have important effects on maintaining eGFR, and blood pressure and fasting CP can be used as new targets for subsequent diabetic kidney disease treatment., (© 2024. The Author(s).)

Background: The estimated glomerular filtration rate (eGFR) and the albumin-to-creatinine ratio (ACR) are risk factors for diabetes-related outcomes. A composite that captures information from both may provide a simpler way of assessing risk. Methods: 9115 of 9901 Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) participants with both an ACR and eGFR at baseline were included in this post hoc epidemiologic analysis. The hazard of higher baseline levels of 1/eGFR and natural log transformed ACR (calculated as ln [ACR × 100] to eliminate negative values) and their interaction for incident major adverse cardiovascular events (MACE), kidney outcomes, and deaths was estimated. The hazard of the geometric mean of these two baseline measures (the kidney disease index or KDI) was also assessed. Results: A non-linear relationship was observed between 1/eGFR and all three outcomes, and between ln [ACR × 100] and the kidney outcome. There was also a negative interaction between these two risk factors with respect to MACE and death. Conversely, a linear relationship was noted between the KDI and all three outcomes. People in the highest KDI fifth experienced the highest incidence of MACE, death, and the kidney outcome (4.43, 4.56, and 5.55/100 person-years respectively). C statistics for the KDI were similar to those for eGFR and albuminuria. Conclusions: The KDI combines the baseline eGFR and ACR into a novel composite risk factor that has a simple linear relationship with incident serious outcomes in people with diabetes and additional CV risk factors. Trial Registration clinicaltrials.gov NCT01394952. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to explore the factors associated with the fall risk in type 2 diabetes (T2D) patients with a lacunar stroke. Materials and methods: We compiled data of 146 T2D patients (mean age 68 years), including the Morse fall scale data (MFS), nutrition score, self-care scale, laboratory data, and data from continuous glucose monitoring system (CGMS) from 2019 to 2021 in Shanghai Pudong Hospital. Thereby, we evaluated the associations between MFS and other clinical parameters. Results: The analyses showed that there were significantly increased size and numbers of lacunar infarction (p < 0.05). Furthermore, the greater risk group had an older mean age (p < 0.05), and significant decreased estimated glomerular filtration rate (eGFR), total triglyceride (TG), while increased microalbuminuria, magnesium, lipoprotein A (LP(a)), anti-thyroid peroxidase antibody (TPOAb) (p < 0.05). However, the time in range (TIR) was very comparable (p > 0.05). The correlational study revealed the higher score of MFS was associated with the age (r = 0.41), number of lacunar infarction (r = 0.18), nutrition score (r = 0.20), self-care score (r = − 0.43), serum creatine level (r = 0.19), eGFR (r = − 0.26) (p < 0.05). The total numbers of lacunar infarction were associated with age (r = 0.36), eGFR (r = − 0.40), homocysteine level (r = 0.33) (p < 0.05). Conclusions: Age, nutrition, self-care ability, and renal function are all critical factors associated with the risk of fall in T2D with lacunar infarction. The age, eGFR, and homocysteine are closely associated with lacunar infarction, suggesting that in T2D, evaluation of kidney dysfunction, homocysteine level in the elderly can predict lacunar infarcts and falls. [ABSTRACT FROM AUTHOR]

Background: We investigated the effects of sodium–glucose cotransporter 2 inhibitor (SGLT2i) administration focusing on its involvement in tubulo-interstitial disorders in diabetic kidney. Methods: Enrolled patients with diabetic kidney disease received a mean dose of 52.3 mg of an SGLT2i (ipragliflozin) daily. Blood and urine were sampled at 0, 1, and 12 months (M). Results: Non-renal-dysfunction patients (NRD: baseline eGFR ≥ 60 mL/min/1.73 m2, n = 12) and renal-dysfunction patients (RD: baseline eGFR < 60 mL/min/1.73 m2, n = 9) were analyzed separately. The median urine albumin-to-Cr ratio (ACR) was significantly decreased at 1 M in both groups (NRD: 163.1 at 0 M vs 118.5 mg/g Cr at 1 M, RD: 325.2 at 0 M vs 136.0 mg/g Cr at 1 M). In the RD, but not the NRD group, reduction of urine monocyte chemotactic protein-1 (MCP-1) by SGLT2i showed a significant difference between high-responders (HR: − 25.7 ± 11.4%) and low-responders (LR: 59.2 ± 17.0%), defined by ACR reduction at 1 M. Univariate analysis showed a significant correlation between the reduction of ACR and MCP-1 (R = 0.683, p = 0.042) in RD. Conclusion: SGLT2i exerted an anti-albuminuric effect regardless of the presence/absence of renal dysfunction. However, the anti-albuminuric effect of SGLT2i in patients with renal dysfunction appears more closely associated with amelioration of tubulo-interstitial disorders compared to patients without renal dysfunction. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the presence of LGA and the relationship with the 10-year risk of a cardiovascular event in hypertensive and diabetic patients in Primary Health Care.Study Design: The study design used is cross-sectional.Methods: This study was based on the application of questionnaires, anthropometric measurements, and laboratory tests carried out from August 2017 to April 2018. Logistic regression was used to evaluate the odds ratio of the explanatory variables in relation to the highest tercile of LGA. The Framingham risk score was used to assess the 10-year risk of cardiovascular event. The comparison of this score with the LGA terciles was analyzed using ANOVA.Results: An increase in the 10-year risk of cardiovascular event score was observed with an increasing LGA tercile, and this pattern prevailed after adjusting for confounding variables.Conclusion: An association between LGA and the 10-year risk of cardiovascular event was observed in a representative sample of hypertensive and diabetic patients. [ABSTRACT FROM AUTHOR]