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Chronic kidney disease (CKD) is a progressive condition that affects more than 10% of the world's population. Monitoring urine albumin-to-creatinine ratio (uACR) has become the gold standard for nephropathy diagnosis and control. The objective of the present study was to develop a simple, accurate, sensitive, and rapid point-of-care test (PoCT) device, MyACR, for uACR measurement, intended for use in community healthcare to screen for the risk and monitor the progress of CKD. Albumin and creatinine concentrations in urine samples were determined using spectrophotometric dye (tetrabromophenol blue)-binding and colorimetric Jaffe assay, respectively. Urine samples were diluted with distilled water (1:80) and mixed separately with albumin and creatinine reaction mixture. The creatinine reaction was incubated at room temperature (25 °C) for 30 min before analysis. Optical density (OD) was measured at the wavelengths of 625 nm (albumin) and 515 nm (creatinine). All calibration curves (0–60 mg/L and 0–2 mg/dL for albumin and creatinine) yielded linear relationships with correlation coefficients (R2) of >0.997. Good accuracy (% deviation of mean value (DMV) ≤ 5.42%) and precision (% coefficients of variation (CV) ≤ 12.69%) were observed from both the intra- and inter-day assays for the determination of albumin and creatinine using MyACR. The limit of quantification (LOQ) of albumin and creatinine in urine samples determined using MyACR and a laboratory spectrophotometer were 5 mg/L and 0.25 mg/dL, respectively, using 37.5 μL urine spiked samples (n = 5). The device was well-applied with clinical samples from 20 CKD patients. The median (range) of %DMV of the central (hospital) laboratory method (immune-based assay) was 3.48 (−17.05 to 21.64)%, with a high correlation coefficient (R2 > 0.98). In conclusion, MyACR showed satisfactory test performance in terms of accuracy, reproducibility, and sensitivity. Cost-effectiveness and improvement in clinical decision making need to be proven in future multisite community and home studies. [ABSTRACT FROM AUTHOR]

BackgroundThe aim of this study was to examine the prognostic significance of serum albumin-to-creatinine ratio (ACR) in critically ill patients with sepsis.MethodsThis retrospective study analyzed sepsis cases admitted to the Affiliated Hospital of Jiangsu University between January 2015 and November 2023. The patients were divided into four groups based on their ACR upon admission to the intensive care unit (ICU). Laboratory data were collected at the time of ICU admission, and the primary outcome measure was in-hospital all-cause mortality. Kaplan–Meier survival curves were generated to illustrate the differences in 30−/60-day mortality among the various groups. Multivariate Cox regression models and restricted cubic splines (RCS) were utilized to explore the association between ACR and all-cause mortality in sepsis patients. Subgroup analyses were conducted to examine the impact of other covariates on the relationship between ACR and all-cause mortality.ResultsA total of 1,123 eligible patients were included in the study, with a median ACR of 0.169. The in-hospital mortality rate was 33.7%, the ICU mortality rate was 31.9%, and the 30-day mortality rate was 28.1%. Kaplan–Meier survival analysis demonstrated that patients with higher ACR had a significantly lower risk of 30−/60-day mortality (log-rank p

Background: The inconsistent relationship between chemical exposure and estimated glomerular filtration rate (eGFR) has been examined in only a few studies. We investigated the association between paraben exposure and indicators of renal function in a total of 361 individuals recruiting from a representative study. Method: The levels of urinary parabens, including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP), were measured using UPLC-MS/MS. The association between paraben exposure and indices of renal function was assessed using multiple logistic regression and Bayesian Kernel Machine Regression (BKMR). Results: The median levels of urinary parabens in the adult group were significantly higher than those in the minor group, that is, 397 vs. 148 ng/mL for MeP, 38.8 vs. 13.6 ng/mL for EtP, 117 vs. 57.7 ng/mL for PrP, and 6.61 vs. 2.79 ng/mL for BuP (all P < 0.001). In the adult group, multivariate regression models confirmed a positive association between the albumin-to-creatinine ratio and urinary MeP (β = 0.580) and a positive association of BUN (β = 0.061) and a negative association of eGFR (β = −0.051) with urinary EtP (all P < 0.001). In the adult group, compared with the lowest tertile group, the adjusted odds ratio in the third tertile (T3) of urinary EtP levels indicated a 3.08 times increased risk of eGFR abnormalities, followed by the second tertile (T2) with a 2.63 times increased risk. The generalized additive model (GAM) and BKMR models showed a non-linear correlation between urinary EtP levels and early CKD, as well as reduced eGFR. We observed a significant positive cumulative effect of urinary paraben on eGFR, and a significant positive single exposure effect of urinary EtP with eGFR abnormality. Conclusion: We found a significant association between exposure to EtP and an increased risk of high BUN levels and decreased eGFR.

Abstract Aims About 20–40% patients with type 2 diabetes mellitus (T2DM) had an increased risk of developing diabetic nephropathy (DN). Dipeptidyl peptidase-4 inhibitors (DPP-4i) were recommended for treatment of T2DM, while the impact of DPP-4i on renal function remained unclear. This study aimed to explore the effect of DPP-4i on renal parameter of estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) in T2DM. Methods A systematic search was performed across PubMed, Embase and Cochrane Library. A fixed or random-effects model was used for quantitative synthesis according to the heterogeneity, which was assessed with I2 index. Sensitivity analysis and publication bias were performed with standard methods, respectively. Results A total of 17 randomized controlled trials were identified. Administration of DPP-4i produced no significant effect on eGFR (WMD, -0.92 mL/min/1.73m2, 95% CI, -2.04 to 0.19) in diabetic condition. DPP-4i produced a favorable effect on attenuating ACR (WMD, -2.76 mg/g, 95% CI, -5.23 to -0.29) in patients with T2DM. The pooled estimate was stable based on the sensitivity test. No publication bias was observed according to Begg’s and Egger’s tests. Conclusions Treatment with DPP-4i preserved the renal parameter of eGFR in diabetic condition. Available evidences suggested that administration of DPP-4i produced a favorable effect on attenuating ACR in patients with T2DM. International Prospective Register for Systematic Review (PROSPERO) number CRD.42020144642.

Introduction This study focuses on investigating the relationship between serum neurofilament light chain (sNfL) and urinary albumin-to-creatinine ratio (uACR) among American adults aged 25–75.Methods An analysis was conducted on information gathered from 1741 individuals aged between 25 and 75 who participated in the National Health and Nutrition Examination Survey (NHANES) during the years 2013–2014. Generalized linear models were utilized, and restricted cubic spline (RCS) analysis was conducted to assess a non-linear relationship.Results Upon adjusting for multiple variables, a non-linear inverse J-shaped relationship was observed between sNfL and uACR. Compared with individuals in quartile 1 (Q1) of sNfL (2.8–8.3), those with quartile 4 (Q4) (≥19.1) had an adjusted β for uACR of 51.57.Conclusions The study found a J-shaped curve linking sNfL and uACR in American adults, with a turning point around log(sNfL) 2.928 pg/mL.

Aims: About 20–40% patients with type 2 diabetes mellitus (T2DM) had an increased risk of developing diabetic nephropathy (DN). Dipeptidyl peptidase-4 inhibitors (DPP-4i) were recommended for treatment of T2DM, while the impact of DPP-4i on renal function remained unclear. This study aimed to explore the effect of DPP-4i on renal parameter of estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) in T2DM. Methods: A systematic search was performed across PubMed, Embase and Cochrane Library. A fixed or random-effects model was used for quantitative synthesis according to the heterogeneity, which was assessed with I2 index. Sensitivity analysis and publication bias were performed with standard methods, respectively. Results: A total of 17 randomized controlled trials were identified. Administration of DPP-4i produced no significant effect on eGFR (WMD, -0.92 mL/min/1.73m2, 95% CI, -2.04 to 0.19) in diabetic condition. DPP-4i produced a favorable effect on attenuating ACR (WMD, -2.76 mg/g, 95% CI, -5.23 to -0.29) in patients with T2DM. The pooled estimate was stable based on the sensitivity test. No publication bias was observed according to Begg's and Egger's tests. Conclusions: Treatment with DPP-4i preserved the renal parameter of eGFR in diabetic condition. Available evidences suggested that administration of DPP-4i produced a favorable effect on attenuating ACR in patients with T2DM. International Prospective Register for Systematic Review (PROSPERO) number: CRD.42020144642. [ABSTRACT FROM AUTHOR]

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

Abstract Background Chronic kidney disease (CKD) is highly prevalent among Indigenous Australians, especially those in remote regions. The Tiwi population has been isolated from mainland Australia for millennia and exhibits unique genetic characteristics that distinguish them from other Indigenous and non-Indigenous populations. Notably, the rate of end-stage renal disease is up to 20 times greater in this population compared to non-Indigenous populations. Despite the identification of numerous genetic loci associated with kidney disease through GWAS, the Indigenous population such as Tiwi remains severely underrepresented and the increased prevalence of CKD in this population may be due to unique disease-causing alleles/genes. Methods We used albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) to estimate the prevalence of kidney disease in the Tiwi population (N = 492) in comparison to the UK Biobank (UKBB) (N = 134,724) database. We then performed an exploratory factor analysis to identify correlations among 10 CKD-related phenotypes and identify new multi-phenotype factors. We subsequently conducted a genome-wide association study (GWAS) on all single and multiple phenotype factors using mixed linear regression models, adjusted for age, sex, population stratification, and genetic relatedness between individuals. Results Based on ACR, 20.3% of the population was at severely increased risk of CKD progression and showed elevated levels of ACR compared to the UKBB population independent of HbA1c. A GWAS of ACR revealed novel association loci in the genes MEG3 (chr14:100812018:T:A), RAB36 (rs11704318), and TIAM2 (rs9689640). Additionally, multiple phenotypes GWAS of ACR, eGFR, urine albumin, and serum creatinine identified a novel variant that mapped to the gene MEIS2 (chr15:37218869:A:G). Most of the identified variants were found to be either absent or rare in the UKBB population. Conclusions Our study highlights the Tiwi population’s predisposition towards elevated ACR, and the collection of novel genetic variants associated with kidney function. These associations may prove valuable in the early diagnosis and treatment of renal disease in this underrepresented population. Additionally, further research is needed to comprehensively validate the functions of the identified variants/genes.

Background: Chronic kidney disease (CKD) is highly prevalent among Indigenous Australians, especially those in remote regions. The Tiwi population has been isolated from mainland Australia for millennia and exhibits unique genetic characteristics that distinguish them from other Indigenous and non-Indigenous populations. Notably, the rate of end-stage renal disease is up to 20 times greater in this population compared to non-Indigenous populations. Despite the identification of numerous genetic loci associated with kidney disease through GWAS, the Indigenous population such as Tiwi remains severely underrepresented and the increased prevalence of CKD in this population may be due to unique disease-causing alleles/genes. Methods: We used albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) to estimate the prevalence of kidney disease in the Tiwi population (N = 492) in comparison to the UK Biobank (UKBB) (N = 134,724) database. We then performed an exploratory factor analysis to identify correlations among 10 CKD-related phenotypes and identify new multi-phenotype factors. We subsequently conducted a genome-wide association study (GWAS) on all single and multiple phenotype factors using mixed linear regression models, adjusted for age, sex, population stratification, and genetic relatedness between individuals. Results: Based on ACR, 20.3% of the population was at severely increased risk of CKD progression and showed elevated levels of ACR compared to the UKBB population independent of HbA1c. A GWAS of ACR revealed novel association loci in the genes MEG3 (chr14:100812018:T:A), RAB36 (rs11704318), and TIAM2 (rs9689640). Additionally, multiple phenotypes GWAS of ACR, eGFR, urine albumin, and serum creatinine identified a novel variant that mapped to the gene MEIS2 (chr15:37218869:A:G). Most of the identified variants were found to be either absent or rare in the UKBB population. Conclusions: Our study highlights the Tiwi population’s predisposition towards elevated ACR, and the collection of novel genetic variants associated with kidney function. These associations may prove valuable in the early diagnosis and treatment of renal disease in this underrepresented population. Additionally, further research is needed to comprehensively validate the functions of the identified variants/genes. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to investigate associations between diabetic retinopathy (DR) and chronic kidney disease (CKD) in patients with type 2 diabetes (TD2). Methods: The participants of the cross-sectional, community-based Tongren Health Care Study underwent a detailed medical and ophthalmological examination. We defined TD2 by a fasting plasma glucose concentration of ≥7.0 mmol/L or a medical history. CKD was classified as either reduced estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 mm2 or presence of albuminuria. DR was assessed using color fundus photographs. Results: Out of 62,217 participants of the Tongren Health Care Study, 5,103 (8.2%) patients had TD2. The prevalence of DR was 12.8% (95% CI, 11.8%, 13.7%), CKD was 13.3% (95% CI, 12.4%, 14.3%), and the subtypes of CKD including reduced eGFR and albuminuria was 4.6% (95% CI, 4.2%, 5.1%) and 10.1% (95% CI, 9.3%, 10.9%), respectively. DR was detectable in 21.0% of the patients with CKD, while CKD was present in 20.9% of the DR patients. Higher DR prevalence was associated with higher prevalence of albuminuria and reduced eGFR (both p < 0.05). Factors independently associated with the presence of CKD instead of DR were older age (p < 0.001, OR = 1.05), a higher body mass index (p < 0.001, OR = 1.14), a higher serum concentration of triglycerides (p < 0.001, OR = 1.26), and a lower blood glucose (p < 0.001, OR = 0.93). Having hypertension was additionally associated with the presence of reduced eGFR as compared with DR (p = 0.005, OR = 4.47). Conclusions: TD2 patients of older age and with higher body mass index, hypertension, and dyslipidemia had a higher probability of being affected by CKD rather than DR, while those with a higher blood glucose level were more prone to DR than CKD. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a progressive condition that affects more than 10% of the world’s population. Monitoring urine albumin-to-creatinine ratio (uACR) has become the gold standard for nephropathy diagnosis and control. The objective of the present study was to develop a simple, accurate, sensitive, and rapid point-of-care test (PoCT) device, MyACR, for uACR measurement, intended for use in community healthcare to screen for the risk and monitor the progress of CKD. Albumin and creatinine concentrations in urine samples were determined using spectrophotometric dye (tetrabromophenol blue)-binding and colorimetric Jaffe assay, respectively. Urine samples were diluted with distilled water (1:80) and mixed separately with albumin and creatinine reaction mixture. The creatinine reaction was incubated at room temperature (25 °C) for 30 min before analysis. Optical density (OD) was measured at the wavelengths of 625 nm (albumin) and 515 nm (creatinine). All calibration curves (0–60 mg/L and 0–2 mg/dL for albumin and creatinine) yielded linear relationships with correlation coefficients (R2) of >0.997. Good accuracy (% deviation of mean value (DMV) ≤ 5.42%) and precision (% coefficients of variation (CV) ≤ 12.69%) were observed from both the intra- and inter-day assays for the determination of albumin and creatinine using MyACR. The limit of quantification (LOQ) of albumin and creatinine in urine samples determined using MyACR and a laboratory spectrophotometer were 5 mg/L and 0.25 mg/dL, respectively, using 37.5 μL urine spiked samples (n = 5). The device was well-applied with clinical samples from 20 CKD patients. The median (range) of %DMV of the central (hospital) laboratory method (immune-based assay) was 3.48 (−17.05 to 21.64)%, with a high correlation coefficient (R2 > 0.98). In conclusion, MyACR showed satisfactory test performance in terms of accuracy, reproducibility, and sensitivity. Cost-effectiveness and improvement in clinical decision making need to be proven in future multisite community and home studies.

Xiang Zheng,&ast; Dan Liu,&ast; Jing Zhu, Li Lu, Jianshu Yang Department of Health Management Center, the First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianshu Yang, Department of Health Management Center, the First Affiliated Hospital of Soochow University, No. 899, Pinghai Road, Gusu District, Suzhou, 215006, People’s Republic of China, Email dryangjianshu0427@outlook.comObjective: To evaluate the potential diagnostic value of the albumin-to-creatinine ratio (ACR) in screening for early kidney injury in a physically examined population from Southeast China.Methods: A total of 13,250 candidates were selected. Urinary ACR values < 30, 30– 300, and > 300 mg/g were utilized as positive cut-off points to denote normal proteinuria, microalbuminuria, and macroalbuminuria, respectively.Results: Age, systolic blood pressure, diastolic blood pressure, body mass index, waistline, fasting blood glucose, glycated hemoglobin, triglycerides, and high-density lipoprotein cholesterol were significantly different among the three groups. eGFR was negatively correlated with the levels of sCr, BUN, and UA in the microalbuminuria and macroalbuminuria groups. Furthermore, there was a significant difference in CKD stage between the normal and abnormal urine ACR groups. Meanwhile, for the 20– 40 years patients, the eGFR, sCr and BUN showed no significant difference between microalbuminuria group compared with the normal proteinuria group; in contrast, for the 41– 60 years and > 61 years patients, eGFR, sCr, BUN and UA were all markedly increase in microalbuminuria and macroalbuminuria group in comparison with the normal proteinuria group. Finally, for the 41– 60 males, only eGFR significantly decreased in microalbuminuria group compared with the normal proteinuria group, while for the 41– 60 females, only UA showed no significant difference between microalbuminuria group and normal proteinuria group. On the other hand, for the > 61 males, eGFR, sCr and BUN all significantly changed between microalbuminuria group and normal proteinuria group, while for the > 61 females, eGFR, sCr and BUN all showed no significant difference between microalbuminuria group and normal proteinuria group, as well as microalbuminuria group and macroalbuminuria group.Conclusion: We proposed using the urinary ACR for the screening of physically examined patients, especially among the elderly males. This approach would assist in the early diagnosis and treatment of renal damage.Keywords: albumin-to-creatinine ratio, microalbuminuria, kidney injury, physical examination population, screening

Background: The leading cause of advanced chronic kidney disease (CKD) in children is congenital anomalies of the kidney and urinary tract (CAKUT). However, the most appropriate parameters of biochemical urine analysis for detecting CAKUT with kidney dysfunction are not known. Methods: The present observational study analyzed data on children with CAKUT (stage 2–4 CKD) and the general pediatric population obtained from school urine screenings. The sensitivity and specificity of urine alpha 1-microglobulin-, beta 2-microglobulin-, protein-, and the albumin-to-creatinine ratios (AMCR, BMCR, PCR, ACR, respectively) in detecting CAKUT with kidney dysfunction were compared with those of the conventional urine dipstick, and the most appropriate of these four parameters were evaluated. Results: In total, 77 children with CAKUT and 1712 subjects in the general pediatric population fulfilled the eligibility criteria. Conventional dipstick urinalysis was insufficient due to its low sensitivity; even when the threshold of proteinuria was +/−, its sensitivity was only 29.7% for stage 2 and 44.1% for stage 3 CKD. Among the four parameters assessed, the AMCR and BMCR were adequate for detecting CAKUT in children with stage 3–4 CKD (the respective sensitivity and specificity of the AMCR for detecting CAKUT in stage 3 CKD was 79.4% and 97.5% while that of BMCR was 82.4% and 97.5%). These data were validated using national cohort data. Conclusion: AMCR and BMCR are superior to dipstick urinalysis, PCR, and ACR in detecting CAKUT with kidney dysfunction, particularly stage 3 CKD. However, for AMCR, external validation is required. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a toxic metal that accumulates in kidneys, especially in the proximal tubular epithelial cells, where virtually all proteins in the glomerular ultrafiltrate are reabsorbed. Here, we analyzed archived data on the estimated glomerular filtration rate (eGFR) and excretion rates of Cd (ECd), total protein (EProt), albumin (Ealb), β2-microglobulin (Eβ2M), and α1-microglobulin (Eα1M), which were recorded for residents of a Cd contamination area and a low-exposure control area of Thailand. Excretion of Cd and all proteins were normalized to creatinine clearance (Ccr) as ECd/Ccr and EProt/Ccr to correct for differences among subjects in the number of surviving nephrons. Low eGFR was defined as eGFR ≤ 60 mL/min/1.73 m2, while proteinuria was indicted by EPro/Ccr ≥ 20 mg/L of filtrate. EProt/Ccr varied directly with ECd/Ccr (β = 0.263, p < 0.001) and age (β = 0.252, p < 0.001). In contrast, eGFR values were inversely associated with ECd/Ccr (β = −0.266, p < 0.001) and age (β = −0.558, p < 0.001). At ECd/Ccr > 8.28 ng/L of filtrate, the prevalence odds ratios for proteinuria and low eGFR were increased 4.6- and 5.1-fold, respectively (p < 0.001 for both parameters). Thus, the eGFR and tubular protein retrieval were both simultaneously diminished by Cd exposure. Of interest, ECd/Ccr was more closely correlated with EProt/Ccr (r = 0.507), Eβ2M (r = 0.430), and Eα1M/Ccr (r = 0.364) than with EAlb/Ccr (r = 0.152). These data suggest that Cd may differentially reduce the ability of tubular epithelial cells to reclaim proteins, resulting in preferential reabsorption of albumin. [ABSTRACT FROM AUTHOR]

Population-based studies have suggested a protective effect of coffee against development of chronic kidney disease (CKD), possibly through coffee's anti-inflammatory and antioxidant compounds. Studies on coffee and kidney function decline in the general population are scarce. We studied associations of habitual coffee consumption with repeated assessments of estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR). We used data from 7,914 participants of the population-based Rotterdam Study. Baseline coffee consumption data (cups/day) were obtained from home interviews and validated food frequency questionnaires (1997–2008). Repeated assessments of eGFR (ml/min per 1.73 m2, 1997–2014) were calculated according to the creatinine-based CKD Epidemiology Collaboration equation of 2012. Repeated assessments of urinary albumin and creatinine were used to estimate ACR (mg/g, 2006–2014). Data were analyzed by applying linear mixed models, adjusted for sociodemographic, lifestyle and dietary factors, and cardiovascular disease risk factors. Predefined subgroup analyses were performed stratified by CKD risk factors. Participants' mean (SD) baseline age was 66 (10) years, 57% were women and median [IQR] coffee consumption was 3.0 [2.0, 5.0] cups/day. Those drinking more coffee were more likely to smoke, and to have type 2 diabetes (T2D) and obesity. Mean eGFR was 79 (15) ml/min per 1.73 m2. In the total study population, coffee was not associated with longitudinal eGFR during a median of 5.4 years of follow-up (β = 0.04 ml/min per 1.73 m2 per one cup/day [95% CI: −0.10,0.18]). However, among those aged >70 years, one additional coffee cup/day was associated with on average 0.84 (0.51,1.18) ml/min per 1.73 m2 higher longitudinal eGFR. Among obese participants this estimate was 0.32 (0.01,0.63). A protective trend was also observed among former smokers (0.17 [−0.03,0.39]) and those with T2D (0.42 [−0.05,0.88]). Coffee was not associated with longitudinal ACR (0.01 mg/ml [−0.01,0.02]). While coffee was not associated with eGFR and ACR in the total population, more coffee consumption was associated with higher longitudinal eGFR among those at higher risk for CKD, i.e., among those aged 70+ and obese participants. These findings require confirmation in other prospective cohort studies. [ABSTRACT FROM AUTHOR]

(1) Background: Preclinical and clinical studies on the anti-aging effect of α-Klotho are emerging. Urinary albumin excretion (UAE) is a well-known biomarker of kidney injury and generalized damage in the cardiovascular system. However, the potential relationship between α-Klotho and UAE is limited and controversial. This study aimed to quantify this relationship in the general middle-aged and elderly population from the National Health and Nutrition Survey (NHANES) 2007–2016. (2) Methods: Serum α-Klotho was measured by enzyme-linked immunosorbent assay. UAE was assessed by the albumin-to-creatinine ratio (ACR). After adjusting for several confounding variables, the relationship between α-Klotho and ACR was analyzed by weighted multivariable logistic regression, subgroup analysis, and interaction tests. A generalized additive model (GAM) with smooth functions using the two-piecewise linear regression model was used to examine the potential nonlinear relationship between α-Klotho and ACR. (3) Results: Among 13,584 participants aged 40–79 years, we observed an independent and significant negative correlation between α-Klotho and ACR (β = −12.22; 95% CI, −23.91, −0.53, p = 0.0448) by multivariable logistic regression analysis, especially in those with age ≥ 60 years, pulse pressure (PP) ≥ 60 mmHg, hypertension or diabetes. We further discovered the nonlinear relationship between α-Klotho and ACR by GAM, revealing the first negative and then positive correlations with an inflection point of 9.91 pg/mL between α-Klotho and ACR. (4) Conclusions: A dose-response relationship between α-Klotho and ACR was demonstrated, and the negative correlation therein indicated that α-Klotho has potential as a serum marker and prophylactic or therapeutic agent despite its metabolic and effective mechanisms needing to be further explored. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

An increased level of cadmium (Cd) in food crops, especially rice is concerning because rice is a staple food for over half of the world's population. In some regions, rice contributes to more than 50% of the total Cd intake. Low environmental exposure to Cd has been linked to an increase in albumin excretion to 30 mg/g creatinine, termed albuminuria, and a progressive reduction in the estimated glomerular filtration rate (eGFR) to below 60 mL/min/1.73 m2, termed reduced eGFR. However, research into albuminuria in high exposure conditions is limited. Here, we applied benchmark dose (BMD) analysis to the relevant data recorded for the residents of a Cd contamination area and a low-exposure control area. We normalized the excretion rates of Cd (ECd) and albumin (Ealb) to creatinine clearance (Ccr) as ECd/Ccr and Ealb/Ccr to correct for differences among subjects in the number of surviving nephrons. For the first time, we defined the excretion levels of Cd associated with clinically relevant adverse kidney health outcomes. Ealb/Ccr varied directly with ECd/Ccr (β = 0.239, p < 0.001), and age (β = 0.203, p < 0.001), while normotension was associated with lower Ealb/Ccr (β = −0.106, p = 0.009). ECd/Ccr values between 16.5 and 35.5 ng/L of the filtrate were associated with a 10% prevalence of albuminuria, while the ECd/Ccr value of 59 ng/L of the filtrate was associated with a 10% prevalence of reduced eGFR. Thus, increased albumin excretion and eGFR reduction appeared to occur at low body burdens, and they should form toxicity endpoints suitable for the calculation of health risk due to the Cd contamination of food chains. [ABSTRACT FROM AUTHOR]

The inconsistent relationship between chemical exposure and estimated glomerular filtration rate (eGFR) has been examined in only a few studies. We investigated the association between paraben exposure and indicators of renal function in a total of 361 individuals recruiting from a representative study. The levels of urinary parabens, including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP), were measured using UPLC-MS/MS. The association between paraben exposure and indices of renal function was assessed using multiple logistic regression and Bayesian Kernel Machine Regression (BKMR). The median levels of urinary parabens in the adult group were significantly higher than those in the minor group, that is, 397 vs. 148 ng/mL for MeP, 38.8 vs. 13.6 ng/mL for EtP, 117 vs. 57.7 ng/mL for PrP, and 6.61 vs. 2.79 ng/mL for BuP (all P < 0.001). In the adult group, multivariate regression models confirmed a positive association between the albumin-to-creatinine ratio and urinary MeP (β = 0.580) and a positive association of BUN (β = 0.061) and a negative association of eGFR (β = −0.051) with urinary EtP (all P < 0.001). In the adult group, compared with the lowest tertile group, the adjusted odds ratio in the third tertile (T 3) of urinary EtP levels indicated a 3.08 times increased risk of eGFR abnormalities, followed by the second tertile (T 2) with a 2.63 times increased risk. The generalized additive model (GAM) and BKMR models showed a non-linear correlation between urinary EtP levels and early CKD, as well as reduced eGFR. We observed a significant positive cumulative effect of urinary paraben on eGFR, and a significant positive single exposure effect of urinary EtP with eGFR abnormality. We found a significant association between exposure to EtP and an increased risk of high BUN levels and decreased eGFR. [Display omitted] • The findings revealed a positive correlation between exposure to MeP and elevated ACR levels. • Our findings demonstrate that EtP is a significant risk factor for elevated BUN and reduced eGFR. • A non-linear correlation was identified between EtP exposure and the onset of early CKD. • We observed significant positive overall effects of four parabens on eGFR abnormality [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to examine the prognostic significance of serum albumin-to-creatinine ratio (ACR) in critically ill patients with sepsis., Methods: This retrospective study analyzed sepsis cases admitted to the Affiliated Hospital of Jiangsu University between January 2015 and November 2023. The patients were divided into four groups based on their ACR upon admission to the intensive care unit (ICU). Laboratory data were collected at the time of ICU admission, and the primary outcome measure was in-hospital all-cause mortality. Kaplan-Meier survival curves were generated to illustrate the differences in 30-/60-day mortality among the various groups. Multivariate Cox regression models and restricted cubic splines (RCS) were utilized to explore the association between ACR and all-cause mortality in sepsis patients. Subgroup analyses were conducted to examine the impact of other covariates on the relationship between ACR and all-cause mortality., Results: A total of 1,123 eligible patients were included in the study, with a median ACR of 0.169. The in-hospital mortality rate was 33.7%, the ICU mortality rate was 31.9%, and the 30-day mortality rate was 28.1%. Kaplan-Meier survival analysis demonstrated that patients with higher ACR had a significantly lower risk of 30-/60-day mortality (log-rank p < 0.001). Multivariable Cox proportional hazards analyses revealed that ACR was an independent predictor of in-hospital death (HR: 0.454, 95% CI 0.271-0.761, p = 0.003), ICU death (HR: 0.498, 95% CI 0.293-0.847, p = 0.010), and 30-day death (HR: 0.399, 95% CI 0.218-0.730, p = 0.003). For each 1-unit increase in ACR, there was a 1.203-fold decrease in the risk of death during the hospital stay. The RCS curve illustrated a non-linear negative correlation between ACR and in-hospital mortality (p for non-linear =0.018), ICU mortality ( p for non-linear =0.005), and 30-day mortality ( p for non-linear =0.006). Sensitivity analysis indicated consistent effect sizes and directions in different subgroups, confirming the stability of the results., Conclusion: Low ACR levels were identified as independent risk factors associated with increased in-hospital, ICU, and 30-day mortality in sepsis patients. ACR can serve as a significant predictor of the clinical outcome of sepsis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hu, Song and Zhang.)

Aims: The objective of this meta‐analysis was to examine the impact of the GLP‐1 RA on renal function parameters in randomized controlled trials. Methods: A systematic search was performed in PubMed‐MEDLINE, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases. Meta‐analysis was performed using a random‐effects model and sensitivity analysis. Results: Data from 18 randomized controlled trials involving 12 192 subjects, showed that treatment with GLP‐1 RA had no effect on serum creatinine levels (weighted mean difference [WMD]: 0.00 mg/mL, 95% confidence interval [CI]: −0.01, 0.01, P =.83, I2 = 0%) and glomerular filtration rate (WMD: 1.01 mL/min/1.73 m2, 95% CI: −1.61, 3.63, P =.45, I2 = 75%). On the other hand, a significant reduction in urinary albumin excretion (WMD: −18.01 mg/day, 95% CI: −31.20, −4.82, P =.007, I2 = 23%) and albumin‐to‐creatinine ratio (WMD: −6.74 mg/g, 95% CI: −12.64, −0.85, P =.03, I2 = 68%) was detected after GLP‐1 RA therapy. Conclusion: Results of our meta‐analysis revealed that GLP‐1 RA treatment decreases urinary albumin excretion and albumin‐to‐creatinine ratio but it did not cause significant changes in creatinine levels and glomerular filtration rate. [ABSTRACT FROM AUTHOR]

Abstract Background Most studies of chronic kidney disease (CKD) in Sub-Saharan Africa (SSA) have been conducted in urban settings. They relied on GFR estimated from serum creatinine alone and on the inexpensive, convenient urinary dipstick to assess proteinuria. The dipstick for proteinuria has not been directly compared with the gold standard albumin-to-creatinine ratio (ACR) in a large-sized study in SSA. We hereby assessed the influence of rural versus urban location on the level, interpretation, and diagnostic performance of proteinuria dipstick versus ACR. Methods In a cross-sectional population-based study of CKD in both urban (n = 587) and rural (n = 730) settings in South-Kivu, Democratic Republic of Congo (DRC), we assessed the prevalence, performance (sensitivity, specificity, positive predictive value and negative predictive value) and determinants of a positive dipstick proteinuria as compared with albuminuria (ACR). Albuminuria was subdivided into: A1 (

Introduction: This study focuses on investigating the relationship between serum neurofilament light chain (sNfL) and urinary albumin-to-creatinine ratio (uACR) among American adults aged 25-75., Methods: An analysis was conducted on information gathered from 1741 individuals aged between 25 and 75 who participated in the National Health and Nutrition Examination Survey (NHANES) during the years 2013-2014. Generalized linear models were utilized, and restricted cubic spline (RCS) analysis was conducted to assess a non-linear relationship., Results: Upon adjusting for multiple variables, a non-linear inverse J-shaped relationship was observed between sNfL and uACR. Compared with individuals in quartile 1 (Q1) of sNfL (2.8-8.3), those with quartile 4 (Q4) (≥19.1) had an adjusted β for uACR of 51.57., Conclusions: The study found a J-shaped curve linking sNfL and uACR in American adults, with a turning point around log(sNfL) 2.928 pg/mL.

Introduction: The association between the changes in albuminuria levels and the clinical prognosis of stroke is unknown. The present study aimed to explore the relationships between changes in albuminuria and the risk of adverse stroke outcomes. Methods: The patients with ischemic stroke or transient ischemic attack from the Third China National Stroke Registry (CNSR-III) who had the urinary albumin-to-creatinine ratio (ACR) detected at baseline and 3-month were recruited. They were classified into 4 groups according to baseline and 3-month ACR and followed up for 1 year. Results: A total of 5,311 patients were finally included in the study. There were 3,738 (70.4%), 483 (9.1%), 451 (8.5%), and 639 (12.0%) patients with no albuminuria, baseline albuminuria, 3-month albuminuria, and persistent albuminuria, respectively. After adjustment for confounding variables, persistent albuminuria was independently associated with all-cause death (hazard ratio [HR], 2.23; 95% CI, 1.17–4.25; p = 0.02), stroke recurrence (HR, 1.55; 95% CI, 1.02–2.36; p = 0.04), and poor functional outcome (OR, 2.22; 95% CI, 1.66–2.96; p < 0.001). Baseline albuminuria was independently associated with poor functional outcome (OR, 1.65; 95% CI, 1.19–2.28; p = 0.003), while 3-month albuminuria was independently associated with stroke recurrence (HR, 1.68; 95% CI, 1.06–2.65; p = 0.03). Conclusions: Changes in albuminuria can predict adverse 1-year outcomes in Chinese ischemic stroke patients. In particular, persistent albuminuria was independently associated with 1-year all-cause death, stroke recurrence, and poor functional outcome. [ABSTRACT FROM AUTHOR]

Background: The present study was conducted to assess the correlation of urinary albumin-to-creatinine ratio (ACR), high-sensitive C-reactive protein, and lipid profile in diabetic subjects. Methodology: The present study included 120 diabetic subjects divided into three groups of 40 subjects each where the group I included diabetics having a diagnosis of diabetes for less than 5 years, group II included diabetics diagnosed with diabetes between 5-10 years, and group III subjects having diabetes diagnosed for more than 10 years. For these subjects, albumin-to-creatinine ratio (ACR), high-sensitive C-reactive protein, and lipid profiles were assessed. Results: A correlation was seen between triglycerides, albumin-to-creatinine ratio, and highsensitive C-reactive protein in group I subjects. In group II, a significant correlation was seen between the albumin-to-creatinine ratio and high-sensitive C-reactive protein. A significant correlation was seen in LDL, cholesterol, and albumin-to-creatinine ratio. Conclusion: The present study concludes that ACR and levels of high-sensitive C-reactive protein are higher in subjects having diabetes for a longer duration. [ABSTRACT FROM AUTHOR]

Abstract Background Renal function is a key factor of cardiovascular disease. Carotid intima-media thickness (IMT) has been widely used as a marker of early subclinical atherosclerosis. The determinants of cystatin C, a novel marker of renal function, have not been extensively studied in the Asian population. This study aimed to assess the determinants of cystatin C and explore whether carotid thickening was associated with urinary albumin-creatinine ratio and cystatin C in community-living Taiwanese adults. Methods A cross-sectional study was conducted on participants from Taichung City, Taiwan. All the participants underwent carotid ultrasonography. Carotid IMT-mean and IMT-maximum were derived. Kidney biomarkers were measured on the basis of urinary albumin-to-creatinine ratio (ACR) and cystatin C. Multiple linear regression analysis was used. Results A total of 1032 individuals were recruited, and 469 (45.44%) of them were men. An increased cystatin C level was significantly associated with older age, male gender, lack of physical activity, low HDL cholesterol, abdominal obesity, high hs-CRP, and high ACR. The multivariate-adjusted mean carotid IMT-mean and IMT-maximum values significantly increased by 80.49 and 195.23 μm for every one unit of increase in cystatin C level and by 0.07 and 0.14 μm for every one unit of increase in ACR, respectively (all p

Cadmium (Cd) is a toxic metal that accumulates in kidneys, especially in the proximal tubular epithelial cells, where virtually all proteins in the glomerular ultrafiltrate are reabsorbed. Here, we analyzed archived data on the estimated glomerular filtration rate (eGFR) and excretion rates of Cd (ECd), total protein (EProt), albumin (Ealb), β2-microglobulin (Eβ2M), and α1-microglobulin (Eα1M), which were recorded for residents of a Cd contamination area and a low-exposure control area of Thailand. Excretion of Cd and all proteins were normalized to creatinine clearance (Ccr) as ECd/Ccr and EProt/Ccr to correct for differences among subjects in the number of surviving nephrons. Low eGFR was defined as eGFR ≤ 60 mL/min/1.73 m2, while proteinuria was indicted by EPro/Ccr ≥ 20 mg/L of filtrate. EProt/Ccr varied directly with ECd/Ccr (β = 0.263, p < 0.001) and age (β = 0.252, p < 0.001). In contrast, eGFR values were inversely associated with ECd/Ccr (β = −0.266, p < 0.001) and age (β = −0.558, p < 0.001). At ECd/Ccr > 8.28 ng/L of filtrate, the prevalence odds ratios for proteinuria and low eGFR were increased 4.6- and 5.1-fold, respectively (p < 0.001 for both parameters). Thus, the eGFR and tubular protein retrieval were both simultaneously diminished by Cd exposure. Of interest, ECd/Ccr was more closely correlated with EProt/Ccr (r = 0.507), Eβ2M (r = 0.430), and Eα1M/Ccr (r = 0.364) than with EAlb/Ccr (r = 0.152). These data suggest that Cd may differentially reduce the ability of tubular epithelial cells to reclaim proteins, resulting in preferential reabsorption of albumin.

An increased level of cadmium (Cd) in food crops, especially rice is concerning because rice is a staple food for over half of the world’s population. In some regions, rice contributes to more than 50% of the total Cd intake. Low environmental exposure to Cd has been linked to an increase in albumin excretion to 30 mg/g creatinine, termed albuminuria, and a progressive reduction in the estimated glomerular filtration rate (eGFR) to below 60 mL/min/1.73 m2, termed reduced eGFR. However, research into albuminuria in high exposure conditions is limited. Here, we applied benchmark dose (BMD) analysis to the relevant data recorded for the residents of a Cd contamination area and a low-exposure control area. We normalized the excretion rates of Cd (ECd) and albumin (Ealb) to creatinine clearance (Ccr) as ECd/Ccr and Ealb/Ccr to correct for differences among subjects in the number of surviving nephrons. For the first time, we defined the excretion levels of Cd associated with clinically relevant adverse kidney health outcomes. Ealb/Ccr varied directly with ECd/Ccr (β = 0.239, p < 0.001), and age (β = 0.203, p < 0.001), while normotension was associated with lower Ealb/Ccr (β = −0.106, p = 0.009). ECd/Ccr values between 16.5 and 35.5 ng/L of the filtrate were associated with a 10% prevalence of albuminuria, while the ECd/Ccr value of 59 ng/L of the filtrate was associated with a 10% prevalence of reduced eGFR. Thus, increased albumin excretion and eGFR reduction appeared to occur at low body burdens, and they should form toxicity endpoints suitable for the calculation of health risk due to the Cd contamination of food chains.

Preeclampsia (PE), a serious medical condition with substantial maternal and perinatal implications, poses a significant challenge, particularly in high-incidence countries like Indonesia. Red blood cell (RBC) indices, neutrophil-to-lymphocyte ratio (NLR), and microalbuminuria (albumin-to-creatinine ratio (ACR)) may signal systemic inflammation and endothelial dysfunction, recently recognized as potential indicators for diagnosing and predicting disease severity. The aim of this study was to analyze RBC indices, NLR, and ACR changes in women with PE and their potential for predicting disease severity. A cross-sectional study was conducted at multi-center hospitals across Medan, Indonesia, from June 2022 to June 2023. The patients were grouped into PE cases with and without severe features. Demographic characteristics and complications were recorded while blood and urine were tested. The Chi-squared test, Fisher's exact test and Mann-Whitney test were used to determine biomarkers associated with severe PE. A total of 208 PE patients were included in the study (104 patients for each PE with and without severe features). Our data indicated that PE patients with severe features had higher red cell distribution width (18.5% vs 13.7%; p <0.001), NLR (5.66% vs 4.1%; p <0.001), and ACR (755.97 mg/dL vs 468.63 mg/dL; p <0.001) compared to those without severe features. In contrast, the platelet count was lower in severe features than those without (21.9 × 106/μL vs 27.0 × 106/μL; p =0.002). This study highlighted that PE patients with severe features predominantly had higher levels of RDW, NLR, and ACR and lower platelet counts compared to those without severe features. Therefore, basic tests such as complete blood count and urinalysis, which are inexpensive and feasible in primary care settings with limited resources, offer hope as valuable diagnostic biomarkers for pregnant women diagnosed with PE in a low resource setting., Competing Interests: All authors affirm that they have no conflicts of interest., (© 2024 The Author(s).)

Background: Most studies of chronic kidney disease (CKD) in Sub-Saharan Africa (SSA) have been conducted in urban settings. They relied on GFR estimated from serum creatinine alone and on the inexpensive, convenient urinary dipstick to assess proteinuria. The dipstick for proteinuria has not been directly compared with the gold standard albumin-to-creatinine ratio (ACR) in a large-sized study in SSA. We hereby assessed the influence of rural versus urban location on the level, interpretation, and diagnostic performance of proteinuria dipstick versus ACR.Methods: In a cross-sectional population-based study of CKD in both urban (n = 587) and rural (n = 730) settings in South-Kivu, Democratic Republic of Congo (DRC), we assessed the prevalence, performance (sensitivity, specificity, positive predictive value and negative predictive value) and determinants of a positive dipstick proteinuria as compared with albuminuria (ACR). Albuminuria was subdivided into: A1 (< 30 mg/g creatinine), A2 (30 to 299 mg/g creatinine) and A3 (≥ 300 mg/g creatinine).Results: The overall prevalence of positive dipstick proteinuria (≥ 1+) was 9.6 % (95 % CI, 7.9-11.3) and was higher in rural than in urban residents (13.1 % vs. 4.8 %, p < 0.001), whereas the prevalence of albuminuria (A2 or A3) was similar in both sites (6 % rural vs. 7.6 % urban, p = 0.31). In both sites, dipstick proteinuria ≥ 1 + had a poor sensitivity (< 50 %) and positive predictive value (< 11 %) for the detection of A2 or A3. The negative predictive value was 95 %. Diabetes [aOR 6.12 (1.52-24.53)] was a significant predictor of A3 whereas alkaline [aOR 7.45 (3.28-16.93)] and diluted urine [aOR 2.19 (1.35-3.57)] were the main predictors of positive dipstick proteinuria.Conclusions: ACR and dipstick proteinuria have similar positivity rates in the urban site whereas, in the rural site, dipstick was 2-fold more often positive than ACR. The poor sensitivity and positive predictive value of the dipstick as compared with ACR makes it unattractive as a screening tool in community studies of CKD in SSA. [ABSTRACT FROM AUTHOR]

ObjectivesHypertension guidelines recommend screening for chronic kidney disease (CKD) using serum creatinine and urine dipstick; this strategy may lead to misclassification. Persons with occult CKD [i.e. missed by creatinine but detected by cystatin C or albumin-to-creatinine ratio (ACR)] have higher risks for death, cardiovascular events, and end-stage renal disease.MethodsWe studied occult CKD prevalence among nondiabetic, hypertensive adults in National Health and Nutrition Examination Survey 1988-1994 (N = 2088) and 1999-2002 (N = 737). We defined occult CKD as estimated glomerular filtration rate by cystatin C (eGFRcys) less than 60 ml/min per 1.73 m and/or ACR at least 30 mg/g among persons with eGFRcreat more than 60 ml/min per 1.73 m. We studied occult CKD prevalence by either marker, stratified by age, race/ethnicity, and assessed clinical predictors associated with occult CKD presence.ResultsIn 1988-1994, occult CKD was prevalent among 25% of nondiabetic hypertensive persons, and it was 22% in 1999-2002. Each marker's ability to detect occult CKD varied by age and race. Cystatin C detected occult CKD among 8.9% of persons more than 65 years, and among 3.8% of whites. ACR detected occult CKD among 9.3% of persons less than 45 years, 16.6% of Blacks, and 20.6% of Mexican-Americans. In multivariate models, each decade of advancing age was associated with a higher occult CKD prevalence by cystatin C (OR 3.1, 95% CI 2.5-3.8) in 1988-1994 and 1999-2002 (OR 2.9, 1.8-4.6).ConclusionCurrent hypertension guidelines may fail to detect a large proportion of high-risk individuals with CKD who can be identified by cystatin C or ACR. Future studies are needed to evaluate targeted use of multimarker renal panels among hypertensives.

Objective This population-based cross-sectional study aimed to investigate the association between thyroid hormones and renal function in euthyroid Chinese individuals, as the relationship between thyroid hormones and renal function in this population remains unclear. Methods A total of 661 participants were included in the study after excluding individuals with thyroid diseases, incomplete clinical measurements, or those taking medications affecting thyroid function. Participants were categorized into three groups based on serum thyroid hormone and antibody levels. The study adjusted for covariates and assessed the glomerular filtration rate (GFR) and urine albumin-to-creatinine ratio (ACR) in relation to thyroid hormone levels. Results After adjusting for covariates, the study found a significant increase in GFR in the middle and highest tertiles of free triiodothyronine (FT3) and the highest tertile of total triiodothyronine (TT3). Serum FT3 and TT3 levels were significantly associated with GFR. Additionally, the study observed a significantly lower GFR in the highest tertile of thyroid-stimulating hormone (TSH) compared to the lowest tertile. However, thyroid hormone and antibody levels were not associated with the ACR. Furthermore, the highest tertiles of TT3 and total thyroxine (TT4) were associated with a decreased risk of chronic kidney disease (CKD). Conclusion In our study among euthyroid Chinese individuals, we observed a significant association between thyroid function and GFR. Specifically, lower FT3, TT3, and higher TSH were associated with reduced GFR, indicating a potential role for thyroid hormones in maintaining renal function. Furthermore, lower levels of TT3 and TT4 were associated with an increased risk of CKD. These findings suggest a direct link between thyroid and renal function, even in euthyroid individuals, emphasizing the need for further investigation to elucidate the underlying mechanisms and potential therapeutic implications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Liu et al.)

To understand the relationship between nativity and measures of kidney function including estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). Seven waves of data from the National Health and Nutrition Examination Survey (2001–2014) was analyzed. General linear regression methods were used to assess the relationship between eGFR, ACR and nativity (foreign-born vs. US-born). Models were adjusted for length of time in the US, demographic variables, comorbidities, lifestyle factors, and access to healthcare. There were 27,111 individuals representing 217,842,257 US adults included in the study. Approximately 26.1% were immigrants, with 40.4% of immigrants having resided < 15 years in the US. Among immigrants with < 15 years of residence, 51% were Hispanic, and 54.4% had high school or below education. After controlling for demographics and length of time in the US, immigrants were 26% more likely to have an ACR ≥ 30 mg/g (OR 1.26, 95% CI: 1.08–1.47); however, after controlling for demographics, length of time, comorbidities, and lifestyle factors the results were no longer significant. Immigrants were significantly less likely to have an eGFR < 60 (OR 0.42, 95% CI 0.36–0.50), which remained after adjustment (OR 0.75, 95% CI 0.61–0.93). Immigrants had significantly lower odds of having an eGFR < 60 compared to US-born adults. Additionally, immigrants with ≥ 15 years in the US had mean eGFR values that were less than immigrants < 15 years in the US, indicating that there is some decrease in kidney function as the length of US residence increases. [ABSTRACT FROM AUTHOR]

ObjectiveHIV-infected persons have substantially higher risk of kidney failure than persons without HIV, but serum creatinine levels are insensitive for detecting declining kidney function. We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women.MethodsIn the Women's Interagency HIV Study, we measured concentrations of albumin-to-creatinine ratio, interleukin-18 (IL-18), kidney injury marker-1 (KIM-1), and neutrophil gelatinase-associated lipocalin from stored urine among 908 HIV-infected and 289 HIV-uninfected participants. Primary analyses used cystatin C-based estimated glomerular filtration rate (CKD-EPI eGFRcys) as the outcome, measured at baseline and 2 follow-up visits over 8 years; secondary analyses used creatinine (CKD-EPI eGFRcr). Each urine biomarker was categorized into tertiles, and kidney decline was modeled with both continuous and dichotomized outcomes.ResultsCompared with the lowest tertiles, the highest tertiles of albumin-to-creatinine ratio (-0.15 mL/min per 1.73 m, P < 0.0001), IL-18 (-0.09 mL/min per 1.73 m, P < 0.0001) and KIM-1 (-0.06 mL/min per 1.73 m, P < 0.001) were independently associated with faster eGFRcys decline after multivariate adjustment including all 3 biomarkers among HIV-infected women. Among these biomarkers, only IL-18 was associated with each dichotomized eGFRcys outcome: ≥3% (relative risk = 1.40; 95% confidence interval: 1.04 to 1.89); ≥5% (1.88; 1.30 to 2.71); and ≥10% (2.16; 1.20 to 3.88) for the highest versus lowest tertile. In alternative models using eGFRcr, the high tertile of KIM-1 had independent associations with 5% (1.71; 1.25 to 2.33) and 10% (1.78; 1.07 to 2.96) decline, and the high IL-18 tertile with 10% decline (1.97; 1.00 to 3.87).ConclusionsAmong HIV-infected women in the Women's Interagency HIV Study cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function.

Abstract Background Data are limited with regard to the relationship of albuminuria and major adverse cardiovascular events (MACE) in Chinese elder patients with high cardiovascular risk. Methods We did a retrospective cohort study using Chinese elder patients with high cardiovascular risks (n = 1474) to identify the association of albumin-to-creatinine ratio (ACR) and the incidence of MACE and all-cause mortality. Individuals were followed up from January, 2002 to November, 2007. The all-cause mortality and MACE, composite outcome of cardiovascular death, myocardial infarction, stroke and hospitalization of congestive heart failure were defined as primary endpoint. Results During the median following up of 56 months, 213 patients developed primary endpoint and 117 patients died. Patients with higher baseline urinary ACR (> 30 mg/g) experienced a nearly 2-fold of all-cause mortality and a 3-fold of heart failure hospitalization than those with lower baseline urinary ACR (≤10 mg/g).MACE, cardiovascular death, stoke and myocardial infarction showed no difference in three grades of urinary ACR (> 30 mg/g, 10 mg/g-30 mg/g, ≤10 mg/g) in this cohort. Patients above 65 years with increased ACR tended to experience higher mortality risks, and the association of increased ACR with higher hospitalization of congestive heart failure seemed to be more prominent in patients below 65 years than above 65 years. Conclusions In this post hoc analysis of Chinese individuals with high cardiovascular risks, higher urinary ACR was associated with higher all-cause mortality and heart failure hospitalization. Further studies are needed to find out whether there is age-specific ACR cutoff point.

Abstract Background Proteinuria is well recognised as a marker of chronic kidney disease (CKD), as a risk factor for progression of CKD among those with known CKD, and as a risk factor for cardiovascular events and death among both the general and CKD populations. Which measure of proteinuria is most predictive of renal events remains uncertain. Methods We conducted a prospective study with 144 proteinuric CKD and kidney transplant recipients attending an outpatient clinic of a tertiary care hospital in Australia. We concurrently collected morning spot urine protein-to-creatinine ratio (UPCR), albumin-to-creatinine ratio (UACR) and 24-h urinary protein excretion (24-UPE) from each participant at baseline. The primary outcome was a composite of death, ESKD or > 30% decline in eGFR over 5-years. Secondary outcomes were each component of the composite outcome. For each proteinuria measure, we performed a Cox Proportional Hazards model and calculated the Harrell’s C-statistic and Akaike’s Information Criterion (AIC). Results After a mean follow-up of 5 years (range 4.4–6), 85 (59%) patients met the primary composite outcome including 23 deaths (16%). The multivariable analysis showed strong evidence of an association between each log-transformed proteinuria measurement and the primary composite outcome. [Log-UPCR 1.31 (95% CI 1.18–1.63), log-UACR 1.27 (1.11–1.45) and log-24-UPE 1.43 (1.20–1.71)]. The C-Statistic were similar for all three measures of proteinuria [UPCR: 0.74 (95% CI: 0.69–0.80), UACR: 0.75 (0.69–0.81), 24-UPE: 0.75 (0.69–0.81)] as were the models’ AIC (671, 668 and 665 respectively). For secondary outcomes, no proteinuria measure was significantly associated with death alone ([log-UPCR = 1.18 (0.96–1.84), log-UACR = 1.19 (1.00–1.55), log-24-UPE = 1.19 (0.83–1.71)], whilst UACR and 24-UPE demonstrated marginally better association with ESKD and > 30% decline in eGFR respectively. [For ESKD, adj log-UACR HR = 1.33 (1.07–1.66). For > 30% decline in eGFR, log-24-UPE adj HR = 1.54 (1.13–2.09)]. Conclusion In patients with stable, non-nephrotic CKD, all three measures of proteinuria were similarly predictive of hard clinical endpoints, defined as a composite of death, ESKD and > 30% decline in eGFR. However, which measure best predicted the outcomes individually is less certain.

Myonectin is a newly discovered myokine correlated with diabetes. Diabetic nephropathy (DN), which is diagnosed according to albuminuria, is one of the most common microvascular complications of diabetes. Albuminuria predisposes to future cardiovascular diseases and mortality. The aim of this study is to assess the association between serum myonectin concentrations with DN. A total of 188 patients with type 2 diabetes (T2DM) and 66 control subjects were enrolled in this investigation. T2DM patients were divided into three groups: normoalbuminuria (n = 84), microalbuminuria (n = 70), and macroalbuminuria (n = 34) according to urine albumin-to-creatinine ratio (ACR). T2DM patients showed lower serum myonectin concentrations compared with the controls. Serum myonectin concentrations were significantly decreased in macroalbuminuria group than in normoalbuminuria and microalbuminuria groups. In addition, microalbuminuria group had decreased serum myonectin concentrations compared with normoalbuminuria group. Logistic regression analysis demonstrated a correlation between serum myonectin and a decreased risk of T2DM and DN. Simply linear regression analysis indicated serum myonectin was negatively correlated body mass index (BMI), total cholesterol, low-density lipoprotein cholesterol, blood urea nitrogen, creatinine, uric acid, and ACR, and positively correlated with glomerular filtration rate, insulin treatment. BMI, ACR, and insulin treatment were still correlated with the serum myonectin after a multiple linear regression analysis. Our investigation indicates serum myonectin is decreased in DN patients and correlated with renal function. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the prevalence of chronic kidney disease (CKD) in individuals with arterial hypertension (AH) and/or diabetes mellitus (DM) accompanied by Primary Health Care (PHC) in Brazil. The estimated glomerular filtration rate (eGFR) based on creatinine, and urinary albumin-to-creatinine ratio (ACR) were measured in 841 subjects with AH and/or DM, followed by PHC in the city of Viçosa. The CKD was diagnosed according to KDIGO criteria. Sociodemographic, clinical, and anthropometric factors related to the prevalence of CKD were investigated through multiple logistic regression. The prevalence of hidden CKD was 15.4%. Of these, 7.5% were identified by albuminuria (ACR ≥30 mg/g) with slightly decreased eGFR. Age, baseline disease, waist circumference (WC), and systolic blood pressure remained associated with CKD after multivariate analysis. The two major risk factors for hidden CKD were the presence of AH in association with DM and an increase in age. Hidden CKD was more common within people with AH and DM, and with high WC, glycosylated hemoglobin, and serum phosphorus as well as male gender and decreased serum albumin. This knowledge of risk associations can help avoid progression to CKD. [ABSTRACT FROM AUTHOR]

Objectives: Albuminuria is a significant biomarker of various kidney diseases and is associated with renal outcome. Recently, caffeine intake has shown potential renoprotective effects. However, the relationship between caffeine intake and albuminuria remains profoundly elusive., Methods: We conducted a cross-sectional study aimed to explore the association between caffeine intake and albuminuria in the American adult population using the data acquired from the National Health and Nutrition Examination Survey (NHANES) 2005-2016. Caffeine intake was assessed by 24-h dietary recalls, and albuminuria was assessed by albumin-to-creatinine ratio. Multivariate logistic regression was performed to explore the independent association between caffeine intake and albuminuria. Subgroup analysis and interaction tests were also conducted., Results: Among 23,060 participants, 11.8% of the individuals exhibited albuminuria, and the prevalence of albuminuria decreased with higher caffeine intake tertiles (Tertile 1: 13%; Tertile 2: 11.9%; Tertile 3: 10.5%; P  < 0.001). After adjusted potential confounders, the results of logistic regression indicated that a higher caffeine intake was associated with a decreased risk of albuminuria (OR = 0.903; 95% CI: 0.84, 0.97; P  = 0.007), especially in females and the participants aged <60 years and chronic kidney disease stage II., Conclusion: The present study first indicated an inverse correlation between caffeine intake and albuminuria, which further confirmed the potentially protective effects of caffeine on the kidney.

Aims: Intracranial plaque may cause stroke in the absence of luminal stenosis. Although urine albumin-to-creatinine ratio (ACR) has been proved an established risk factor for cardiovascular disease, stroke and carotid atherosclerosis, little is known on the relationship between urine ACR and intracranial plaque., Methods: Subjects with history of stroke or coronary heart disease (CHD) were excluded in the PRECISE study. The intracranial plaque was assessed by vessel wall magnetic resonance imaging (MRI). Subjects were stratified according to ACR tertiles. Logistic regression and ordinal regression were performed to analyze the association between ACR and the presence of intracranial plaque or sum of the stenosis score for each artery., Results: 2962 individuals were included with the mean age of 61.0±6.6 years. The median ACR was 11.7mg/g (interquartile range 7.0-22.0 mg/g), and the mean estimated glomerular filtration rate (eGFR) based on combination of creatinine and cystatin C was 88.5±14.8 ml/min·1.73m 2 . 495 (16.7%) participants had intracranial plaque. The highest ACR tertile with ACR ＞16.00mg/g was independently associated with the presence of intracranial plaque (OR 1.38, 95% CI: 1.05-1.82, p=0.02) and the odds of higher intracranial plaque burden (common OR 1.39, 95% CI: 1.05-1.83, p=0.02) after adjustment of confounding factors. No significant association was observed between eGFR and intracranial plaque presence or intracranial plaque burden., Conclusions: Among a low-risk community-dwelling population without prior stroke or CHD in China, ACR was independently associated with intracranial plaque presence and plaque burden measured by vessel wall MRI.

Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are associated with chronic kidney disease (CKD). Diet could play a predisposing role in the development of increased albuminuria in patients with NAFLD and MetS; however, published evidence is still limited. The aim of this cross-sectional analysis was to assess whether dietary fats are associated with changes in urinary albumin-to-creatinine ratio (UACR) in 146 patients aged 40–60-years with NAFLD and MetS. Dietary data were collected by food frequency questionnaire; UACR was measured in a single first morning void. Sources and types of dietary fats used in the analysis were total fat, fats from animal and vegetable sources, saturated, monounsaturated, polyunsaturated, and trans fats. One-way analysis of variance was performed to assess differences in dietary fats intakes across stages of UACR. The association between dietary fats and UACR was assessed by Pearson’s correlation coefficient and multivariable linear regression. Patients with increased UACR showed a worse cardiometabolic profile and higher intakes of animal fat, as compared to patients with normal levels of albuminuria. Animal fat intake was associated with mean UACR, independent of potential covariates.

Objective  To assess the effect of aspirin use in low-risk pregnancy on: (1) pregnancy-associated plasma protein-A (PAPP-A) and placental-like growth factor (PLGF); (2) urinary albumin-to-creatinine ratio (ACR) and blood pressure; (3) fetal growth parameters; and (4) placental histopathology. Study Design  This secondary analysis from the T rial of low-dose aspirin with an E arly S creening T est for preeclampsia and growth restriction randomized controlled trial was based on low-risk nulliparous women randomized at 11 weeks to (1) aspirin 75 mg; (2) no aspirin; and (3) aspirin based on the preeclampsia Fetal Medicine Foundation screening test. At baseline, women underwent assessment of blood pressure, PAPP-A, PLGF, and ACR, repeated 9 to 10 weeks postaspirin, in addition to fetal growth assessment. Gross and histopathological placental analyses were performed in line with Amsterdam criteria. Results  A total of 445 subjects were included (aspirin n  = 163 [36.6%]; no aspirin n  = 282 [63.4%]). Although the fetal-to-placental weight ratio was significantly greater in the aspirin group (7.5 [±1.3] vs. 7.3 [±1.4], p  = 0.045), as was change in ultrasound assessed estimated fetal weight from second to third trimesters (1,624.5 g [±235.1] vs. 1,606.2 [±189.4], p  = 0.042), this was invalidated by the lack of a difference in birth weight. Aspirin did not significantly impact on change in serum or urine preeclampsia biomarkers, maternal blood pressure, or placental histopathology. Conclusion  Aspirin use in low-risk pregnancy does not appear to impact on preeclampsia biomarkers, fetal growth, or placental pathology. [ABSTRACT FROM AUTHOR]

Background Gait disturbance is proposed as a mechanism for higher risk of fall in kidney disease patients. We investigated the association of kidney function with gait pattern in the general population and tested whether the association between impaired kidney function and fall is more pronounced in subjects with lower gait function. Methods We included 1430 participants (mean age: 60 years) from the Rotterdam Study. Kidney function was assessed using estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). We assessed global gait, gait velocity and seven independent gait domains: Rhythm, Phases, Variability, Pace, Tandem, Turning and Base of Support. Regression models adjusted for cardiometabolic and neurological factors were used. We evaluated whether participants with impaired kidney function and impaired gait fell more in the previous year. Results The study population had a median (interquartile range) ACR of 3.6 (2.5–6.2) mg/g and mean ± SD eGFR of 87.6 ± 15 mL/min/1.73 m2. Higher ACR and lower eGFR were associated with lower global gait score [per doubling of ACR: −0.10, 95% confidence interval (CI): −0.14 to −0.06, and per SD eGFR:−0.09, 95% CI: −0.14 to −0.03] and slower gait speed (ACR: −1.44 cm/s, CI: −2.12 to −0.76; eGFR: −1.55 cm/s, CI: −2.43 to −0.67). Worse kidney function was associated with lower scores in Variability domain. The association between impaired kidney function and history of fall was present only in participants with lower gait scores [odds ratio (95% CI): ACR: 1.34 (1.09–1.65); eGFR: 1.58 (1.07–2.33)]. Conclusions We observed a graded association between lower kidney function and impaired gait suggesting that individuals with decreased kidney function, even at an early stage, need to be evaluated for gait abnormalities and might benefit from fall prevention programmes. [ABSTRACT FROM AUTHOR]

To assess the efficacy of three lifestyle interventions on the reduction of liver fat content and metabolic syndrome (MetS), and whether such reductions would influence renal outcomes, we conducted a randomized controlled trial on 128 participants with MetS and non-alcoholic fatty liver disease (NAFLD), as well as available data on estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatine ratio (UACR). Patients were randomized in 1:1:1 ratio to either Conventional Diet, Mediterranean diet (MD)–high meal frequency, and MD–physical activity groups. Each intervention aimed at reducing caloric intake by 25%–30% of baseline intake and increase energy expenditure by 400 kcal/70 kg. Patients attended regular visits and were followed-up for 6 months. Increased albuminuria was present in 13.3% of patients, while 32.8% showed hyperfiltration. UACR reduction was associated with higher levels of UACR at baseline but not with changes in liver fat. eGFR decreased in patients presenting hyperfiltration at baseline and was associated with reduction in liver fat and insulin resistance, as well as with increase in energy expenditure (R2 = 0.248, p = 0.006). No significant differences were observed between the three treatment groups. In patients with NAFLD and MetS, energy expenditure significantly reduced hepatic fat accumulation and insulin resistance, which reduced glomerular hyperfiltration. Increased albuminuria was reduced, but it was not associated with reduced liver fat.

Background: Semiquantitative dipstick tests are utilized for albuminuria screening. Methods: In a prospective cross-sectional survey, we analyzed the diagnostic test validity of the semiquantitative colorimetric indicator-dye-based Combur9-Test® and the albumin-specific immunochromatographic assay Micral-Test® for the detection of albuminuria, the distribution of the semiquantitative measurements within the albuminuria stages according to KDIGO, and the utility for albuminuria screening compared with an albumin-to-creatinine ratio (ACR) in a walk-in population. Results: In 970 subjects, albuminuria (≥30 mg/g) was detected in 12.7% (95% CI 85.6–96.3%) with the ACR. Sensitivity was 82.9% (95% CI 75.1–89.1%) and 91.9% (95% CI 88.7–96.9%) and specificity 71.5% (95% CI 68.4–74.6%) and 17.5% (95% CI 15.0–20.2%) for the Combur9-Test® and Micral-Test®, respectively. Correct classification to KDIGO albuminuria stages A2/A3 with the Combur9-Test® was 15.4%, 51.4%, and 87.9% at cut-offs of 30, 100, and ≥300 mg/dL, and with the Micral-Test® it was 1.8%, 10.5%, and 53.6% at cut-offs of 2, 5, and 10 mg/dL, respectively. Overall, disagreement to KDIGO albuminuria was seen in 27% and 73% with the Combur9-Test® and Micral-Test®, respectively. From the total population, 62.5% and 15.3% were correctly ruled out and 2.2% and 1% were missed as false-negatives by the Combur9-Test® and Micral-Test®, respectively. Conclusion: Compared to the Combur9-Test®, the utility of the Micral-Test® is limited, because the fraction of correctly ruled out patients is small and a large proportion with a positive Micral-Test® require a subsequent ACR conformation test.

Background/Aims: Either protein-to-creatinine ratio (PCR) or albumin-to-creatinine ratio (ACR) can be adopted for estimation of proteinuria in patients with chronic kidney disease (CKD). Estimated protein excretion rate (ePER) and estimated albumin excretion rate (eAER) may be superior to ACR and PCR. Reports show that urine albumin-to-protein ratio (APR) may be useful in detecting tubular proteinuria, but should be compared with urine protein electrophoresis (PEP). Methods: Both 24-h urine and spot urine were collected from 77 stable CKD patients for measurement of albumin, protein, and creatinine, and PEP. Based on MDRD and CKD-EPI equations, ePERMDRD, ePERCKD-EPI, eAERMDRD and eAERCKD-EPI were calculated to estimate daily proteinuria and albuminuria. Glomerular CKD was defined by clinical and/or pathological evidence. Results: ACR correlated significantly with PCR. However, microalbuminuria was present in patients without pathologic proteinuria. Twenty-four-hour urine albumin correlated better with eAERMDRD and eAERCKD-EPI than ACR, and 24-h urine protein correlated better with ePERMDRD and ePERCKD-EPI than PCR. APR significantly but not well correlated with the albumin fraction in urine PEP. The albumin fraction obtained from urine PEP was significantly higher in patients with glomerulopathy than those with non-glomerular CKD, whereas there were no differences in APR between groups. In contrast with APR, the albumin fraction in urine PEP was independently associated with glomerular CKD. Conclusions: Both PCR and ACR are useful in evaluation of proteinuria. In quantifying daily proteinuria and albuminuria, ePER and eAER are superior to PCR and ACR, respectively. Compared with APR, urine PEP is more useful in diagnosing glomerular proteinuria.