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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]

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]

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]

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. [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]

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]

(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]

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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]

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]

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]

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]

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]

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]

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]

Background: High-normal albuminuria is an important risk factor for incident chronic kidney disease in diabetic populations, in contrast to an uncertain association in nondiabetic populations. This study aimed to reveal the relationship between high-normal albuminuria and incident chronic kidney disease in a Japanese nondiabetic population.Methods: A 10-year follow-up retrospective cohort study was performed involving 1378 Japanese men (mean age 44 ± 5.3 years) without chronic kidney disease and diabetes mellitus. Chronic kidney disease was diagnosed as either estimated glomerular filtration rate < 60 mL/min/1.73 m2 or a urine albumin-to-creatinine ratio ≥ 30 mg/g.Results: At baseline, age, estimated glomerular filtration rate, and the presence of hematuria, hypertension, and dyslipidemia were independently associated with the albumin-to-creatinine ratio. Among the 1378 participants, 185 (13.4%) fulfilled diagnostic criteria for chronic kidney disease over the 10-year follow-up period. Median annual estimated glomerular filtration rate decline showed a deterioration with increasing quartiles of baseline albumin-to-creatinine ratio (P = 0.004). Participants who had a baseline albumin-to-creatinine ratio in the highest quartile (5.9-28.9 mg/g) were more likely to develop micro- or macroalbuminuria (odds ratio: 16.23, 95% confidence interval 6.56-54.03), chronic kidney disease (odds ratio: 2.48, 95% confidence interval 1.64-3.82), and hypertension (odds ratio 2.06, 95% confidence interval 1.30-3.31), but not diabetes mellitus compared with those who had an albumin-to-creatinine ratio in the lowest quartile (1.3-3.6 mg/g) after adjustment for potential confounders.Conclusions: High-normal albuminuria was associated with incident chronic kidney disease in this Japanese nondiabetic male population. [ABSTRACT FROM AUTHOR]

Adolescents with Type 1 diabetes mellitus (T1DM) are at risk for hyperfiltration and elevated urinary albumin-to-creatinine ratio (ACR), which are early indicators of diabetic nephropathy. Adolescents with T1DM also develop early changes in blood pressure, cardiovascular structure, and function. Our aims were to define the relationships between hyperfiltration, ACR, and 24-h ambulatory blood pressure over time in adolescents with T1DM. Normotensive, normoalbuminuric adolescents (n 98) with T1DM underwent baseline and 2-yr 24-h ambulatory blood pressure monitoring, glomerular filtration rate (eGFR) estimated by cystatin C (Larsson equation), and ACR measurements. Linear regression models adjusted for diabetes duration, sex, and HbA1c were used to determine associations. Hyperfiltration (eGFR 133 ml/min) was present in 31% at baseline and 21% at 2-yr follow-up. Hyperfiltration was associated with greater odds of rapid GFR decline (3 ml·min-1 ·yr-1 ) [OR: 5.33, 95%; CI: 1.87–15.17; P 0.002] over 2 yr. Natural log of ACR at baseline was associated with greater odds of hyperfiltration (OR: 1.71, 95% CI: 1.00 –2.92; P 0.049) and 2-yr follow-up (OR: 2.14, 95%; CI: 1.09 – 4.19; P 0.03). One SD increase in eGFR, but not ln ACR, at 2-yr follow-up conferred greater odds of nighttime nondipping pattern (OR: 1.96, 95% CI: 1.06 –3.63; P 0.03). Hyperfiltration was prevalent at baseline and at 2-yr follow-up, predicted rapid decline in GFR, and was related to ACR. Elevated GFR at 2-yr follow-up was associated with nighttime nondipping pattern. More work is needed to better understand early relationships between renal hemodynamic and systemic hemodynamic changes in adolescents with T1DM to reduce future cardiorenal complications. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Microalbuminuria is an early indicator of Diabetic nephropathy and cerebrovascular disease. Objective: To evaluate relationships between microalbuminuria and other predictors of morbidity and mortality in type 2 DM. Methods: Fifty type 2 diabetic subjects were recruited each for three groups separated by disease durations. Thirty non-diabetic subjects were recruited to control each group. Urine albumin-to-creatinine ratio (ACR) was estimated. Fasting plasma glucose (FPG), serum creatinine, urea, total cholesterol (TC), triglycerides (TG), high- and low density lipoprotein (HDL, LDL) were measured. Results: The diabetics with longest disease duration of >10 years were the oldest (65.86±1.71), had highest systolic BP (147.12±3.39mmHg) and least BMI (27.20±0.71Kg/m²); they had poorest lipid control (TC:5.54±0.26mmol/L), though with the least TG (0.97±0.09mmol/L); they also had the most severe microalbuminuria (33.63±8.03g/L) and ACR (65.85±10.38mg/gm). Patients with diabetes of 5-10 years had the poorest glycaemic control:FPG-7.82±0.47mmol/L; HbA1c-13.09±0.74%). Significant negative correlations exist between microalbuminuria, HBA1c(r=-2.28, p=0.028) and serum creatinine(r=-2.11,p=0.042) in patients with 5-10 years disease; a positive correlation between the ACR and TC(r=1.00,p<0.01) in those with >10 years disease. In multivariate analysis, independent predictors of microalbuminuria were disease duration (OR 2.2, p< 0.001); HBA1c (OR 7.3, p=0.02); LDL/HDL ratio (OR 13.4, p< 0.001). Conclusion: The severity and progression of albuminuria are associated with longer duration of diabetes and poor glycaemic control. Significant relationships exist between ACR and HBA1c, TC, HDL-C, TG, creatinine. Disease duration, ethnicity, HBA1c, TC, TG, HDL-C and LDL/HDL ratio are independent predictors of albuminuria. [ABSTRACT FROM AUTHOR]

Background and aims: To investigate if urine albumin-to-creatinine ratio (UACR) is associated with the presence of glomerular filtration rate (GFR) <60 mL/min, severity of liver disease and survival in patients with stable decompensated cirrhosis. Methods: We evaluated prospectively 220 patients (73 % male, age 52.8 ± 12 years). In each patient, assessment of GFR was based on chromium-EDTA. Random urine samples were obtained for measurement of UACR. Results: Thirty-eight patients (17 %, group 1) had UACR ≥30 mg/g and 182 (83 %, group 2) had UACR <30 mg/g. Group 1, compared to group 2 patients, had significantly lower levels of 'true' GFR (61 vs. 71 ml/min, p = 0.035). Patients with 'true' GFR <60 mL/min ( n = 93), compared to those with 'true' GFR ≥60 mL/min ( n = 127), had higher levels of UACR (16 vs. 11.3 mg/g, p = 0.023). In multivariate analysis, serum creatinine and UACR (ΟR 0.98, 95 % CI 0.95-0.99, p = 0.04) were independently associated with the presence of GFR <60 mL/min. Based on the area under the ROC curves, the best cut-off point for UACR was >16.51 mg/g giving a sensitivity 70 %, specificity 49 %, PPV 68 % and NPV 51 %. During the follow-up period [17 (6-52) months], the patients who died or underwent LT ( n = 158), compared to those who remained alive ( n = 62), had higher levels of UACR (41 vs. 13 mg/g, p = 0.025). Patients with UACR ≥30 mg/g had worse outcome, compared to those with UACR <30 mg/g (log rank p = 0.053). Conclusions: We showed for the first time that UACR ≥30 mg/g was associated with more severe liver disease, lower GFR and worse LT-free survival in patients with decompensated cirrhosis. However, further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

The relationship between the renal renin-angiotensin aldosterone system (RAAS) and cardiorenal pathophysiology is unclear. Our aims were to assess 1) levels of urinary RAAS components and 2) the association between RAAS components and HbA1c, the urine albumin/creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and blood pressure (BP) in otherwise healthy adolescents with type 1 diabetes mellitus (TID) vs. healthy controls (HC). Urinary angiotensinogen and angtionsin-converting enzyme (ACE) 2 levels, activity of ACE and ACE2, BP, HbA1c, ACR, and eGFR were measured in 65 HC and 194 T1D from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT). Urinary levels of all RAAS components were higher in T1D vs. HC (P 0.0001). Higher HbA1c was associated with higher urinary angiotensinogen, ACE2, and higher activity of ACE and ACE2 (P 0.0001, P 0.0003, P 0.003, and P 0.007 respectively) in T1D. Higher ACR (within the normal range) was associated with higher urinary angiotensinogen (P 0.0001) and ACE activity (P 0.007), but not with urinary ACE2 activity or ACE2 levels. These observations were absent in HC. Urinary RAAS components were not associated with BP or eGFR in T1D or HC. Otherwise healthy adolescents with T1D exhibit higher levels of urinary RAAS components compared with HC. While levels of all urinary RAAS components correlate with HbA1c in T1D, only urinary angiotensinogen and ACE activity correlate with ACR, suggesting that these factors reflect an intermediary pathogenic link between hyperglycemia and albuminuria within the normal range. [ABSTRACT FROM AUTHOR]

Background: Albuminuria is generally known as a sensitive marker of renal and cardiovascular dysfunction. It can be used to help predict the occurrence of nephropathy and cardiovascular disorders in diabetes. Individuals with prediabetes have a tendency to develop macrovascular and microvascular pathology, resulting in an increased risk of retinopathy, cardiovascular diseases, and chronic renal diseases. We evaluated the clinical value of a strip test for measuring the urinary albumin-to-creatinine ratio (ACR) in prediabetes and diabetes. Methods: Spot urine samples were obtained from 226 prediabetic and 275 diabetic subjects during regular health checkups. Urinary ACR was measured by using strip and laboratory quantitative tests. Results: The positive rates of albuminuria measured by using the ACR strip test were 15.5% (microalbuminuria, 14.6%; macroalbuminuria, 0.9%) and 30.5% (microalbuminuria, 25.1%; macroalbuminuria, 5.5%) in prediabetes and diabetes, respectively. In the prediabetic population, the sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the ACR strip method were 92.0%, 94.0%, 65.7%, 99.0%, and 93.8%, respectively; the corresponding values in the diabetic population were 80.0%, 91.6%, 81.0%, 91.1%, and 88.0%, respectively. The median [interquartile range] ACR values in the strip tests for measurement ranges of <30, 30-300, and >300 mg/g were 9.4 [6.3-15.4], 46.9 [26.5-87.7], and 368.8 [296.2-575.2] mg/g, respectively, using the laboratory method. Conclusions: The ACR strip test showed high sensitivity, specificity, and negative predictive value, suggesting that the test can be used to screen for albuminuria in cases of prediabetes and diabetes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Anatomic and hemodynamic similarities between renal and cerebral vessels suggest a tight link between kidney disease and brain disease. Although several distinct markers are used to identify subclinical kidney and brain disease, a comprehensive assessment of how these markers link damage at both end organs is lacking. Aim To investigate whether measures of kidney function were associated with cerebral small vessel disease on MRI. Methods In 2526 participants of the population-based Rotterdam Study, we measured urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate based on serum creatinine and cystatin C. All participants underwent brain magnetic resonance imaging. We assessed presence of cerebral small vessel disease by calculating white matter lesion volumes and rating the presence of lacunes and cerebral microbleeds. We used multivariable linear and logistic regression to investigate the association between kidney function and cerebral small vessel disease. Results Worse kidney function was consistently associated with a larger white matter lesion volume (mean difference per standard deviation increase in albumin-to-creatinine ratio: 0·09, 95% confidence interval 0·05; 0·12; per standard deviation decrease in creatinine-based estimated glomerular filtration rate: −0·04, 95% confidence interval −0·08;−0·01, and per standard deviation decrease in cystatin C-based estimated glomerular filtration rate: −0·09, 95% confidence interval −0·13;−0·05). Persons with higher albumin-to-creatinine ratio or lower cystatin C-based estimated glomerular filtration rate levels had a higher prevalence of lacunes (odds ratio per standard deviation increase in albumin-to-creatinine ratio: 1·24, 95% confidence interval 1·07; 1·43). Only participants in the highest quartile of albumin-to-creatinine ratio had a higher frequency of microbleeds compared to the lowest quartile. Conclusions Worse kidney function is associated with cerebral small vessel disease. Of all measures of kidney function, in particular albumin-to-creatinine ratio is related to cerebral small vessel disease. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Quantification of proteinuria (albuminuria) in renal transplant recipients is important for diagnostic and prognostic purposes. Recent guidelines have recommended quantification of proteinuria by spot protein-to-creatinine ratio (PCR) or spot albumin-to-creatinine ratio (ACR). Validity of spot measurements remains unclear in renal transplant recipients. Methods Systematic review of adult kidney transplant recipients. Studies that reported the diagnostic accuracy of PCR or ACR as compared with 24-h urine protein or albumin excretion in renal transplant recipients were included. Results The search identified 8 studies involving 1871 renal transplant recipients. The correlation of the PCR to 24-h protein ranged from 0.772 to 0.998 with a median value of 0.92. PCR sensitivity ranged from 63 to 99 (50% of sensitivities were >90%); PCR specificity varied from 73 to 99 (50% of specificities were >90%). Only one study reported the bias; percent bias ranged from 12 to 21% and accuracy (within 30% of 24 h urine protein) ranged from 47 to 56% depending on the degree of proteinuria. For the ACR, percent bias ranged from 9 to 21%, and the accuracy (within 30%) ranged from 38 to 80%. Conclusions The data regarding diagnostic accuracy of PCR and ACR is limited. Only one report studied the absolute measures of agreement (bias and accuracy). We recommend verifying PCR and ACR measurements with a 24-h protein before making any major diagnostic (e.g. biopsy) or therapeutic (e.g. change in immunosuppressive agents) decisions in this population. [ABSTRACT FROM AUTHOR]

Background: There is debate as to whether using the urinary albumin- or protein-to-creatinine ratio (ACR or PCR) should be the primary test for proteinuria. Whilst albuminuria (increased ACR) in the absence of proteinuria (increased PCR) may be expected in some patients, the converse (i.e., proteinuria in the absence of albuminuria) is more unusual and its cause and significance are unclear. We investigated the nature of such apparent non-albuminuric proteinuria in a primary care population of patients. Methods: ACR and PCR were measured in 569 urine samples from patients who either had chronic kidney disease or were at increased risk of the condition. Samples with apparent proteinuria (PCR ≥23 mg/mmol/≥200 mg/g) but no albuminuria (ACR <3.4 mg/mmol/<30 mg/g) were classified as 'discrepant' (37% of proteinuric samples, 6% of all samples); 27 of these samples were available for further analyses. The further analyses included electrophoresis, repeat measurement, immunoassays for markers of tubular proteinuria and use of alternative albumin and total protein methods. Results: Electrophoresis did not identify significant proteinuria in the discrepant samples. The only evidence of tubular proteinuria following measurement of three urinary markers of the condition was a mildly increased α1-microglobulin-to-creatinine ratio in 10 of the 27 discrepant samples analysed, four of which also had a raised β-trace protein-to-creatinine ratio. Use of an alternative urinary total protein method resulted in significantly lower PCRs and 17 of the 27 samples were no longer classified as proteinuric. Conclusions: We were unable to confirm the cause of a raised PCR without albuminuria in these patients and suspect that in most cases it is artefactual. [ABSTRACT FROM AUTHOR]

Linkage mapping in a backcross of {Brown Norway [BN/Crl (BN)] × ZUCLepr faSte (ZUC)} × ZUC identified a male-specific quantitative trait locus (QTL) for urinary albumin excretion (UAE) on rat chromosome 1. A homozygous ZUC.BN-(D1Rat42-D1Rat90)/Ste congenic was produced containing BN donor alleles from 135 to 276 Mb from chromosome 1 on the ZUC background. We observed threefold higher urinary albumin-to-creatinine ratios (ACR) in 15-wk-old Zucker background strain males than in same sex and age congenic animals when both strains are also homozygous for the ZUC leptin receptor fatty mutation (Lepr faSte) (P < 0.0001). We then linkage mapped within the donor region without confounded effects from other chromosomes. Phenotypes were collected in 248 F2 male rats in a population made by crossing parents heterozygous for both the BN donor region and ZUC Lepr faSte. Significant interactions were observed between the Lepr genotype and chromosome 1 QTL for six renal traits: urine volume, UAE at 10 and 15 wk, ACR, right kidney weight, and plasma urea nitrogen. A few traits, such as UAE and ACR, exhibit a second peak at the distal end of the chromosome. Hydronephrosis exhibited one or two QTLs contingent on adjustment for body weight. The results now demonstrate at least two sets of coincident traits with different correlations to kidney function. [ABSTRACT FROM AUTHOR]

Objective To determine the performance of screening for pre-eclampsia by maternal characteristics, urine albumin concentration and albumin-to-creatinine ratio (ACR) at 11+0 to 13+6 weeks. Design Prospective cross-sectional observational study. Setting Routine antenatal visit. Population A total of 2679 pregnant women at 11+0 to 13+6 weeks of gestation. Methods Maternal variables, urine albumin concentrations and ACR of 51 women who developed pre-eclampsia were compared with 2364 women who were unaffected by hypertensive disorders. Regression analysis was used first to determine which of the factors among the maternal characteristics were significant predictors of urine albumin concentration and ACR in the unaffected group and second to determine the contribution of urine albumin concentration and ACR in the prediction of pre-eclampsia. Main outcome measures Development of pre-eclampsia. Results In the unaffected group, log urine albumin concentration and log ACR were influenced by ethnic origin, age, body mass index (BMI), parity and smoking. In the prediction of pre-eclampsia, significant contributions were provided by log urine albumin concentration, log ACR, ethnic origin, BMI, age, family and history of pre-eclampsia. The median urine albumin concentration and the median ACR in the pre-eclampsia group were significantly higher than those in the unaffected group. However, in screening for pre-eclampsia, the area under the receiver operating characteristic curve was not significantly improved by the combined models than with maternal variables alone. The value of urine albumin concentration was not improved by correcting for the creatinine concentration. Conclusion In the prediction of pre-eclampsia, urine albumin concentration at 11+0 to 13+6 weeks does not provide additional value to maternal variables. [ABSTRACT FROM AUTHOR]

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. [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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 < 0.001 except ACR on IMT-maximum with p < 0.01). Lack of physical activity, low HDL, abdominal obesity, high hs-CRP, and high ACR were the determinants of cystatin C.Conclusion: Cystatin C and ACR were strongly and linearly associated with carotid thickening, a marker of subclinical atherosclerosis. [ABSTRACT FROM AUTHOR]

Cluster of differentiation 93 (CD93) is a glycoprotein expressed in activated endothelial cells. The extracellular portion of CD93 can be secreted as a soluble form (sCD93) under inflammatory conditions. As diabetic nephropathy (DN) is a well-known inflammatory disease, we hypothesized that sCD93 would be a new biomarker for DN. We prospectively enrolled 97 patients with type 2 diabetes and evaluated the association between serum sCD93 and DN prevalence. The association between CD93 and development of DN was investigated using human umbilical cord endothelial cells (HUVECs) in vitro and diabetic db/db mice in vivo. Subjects with higher sCD93 levels had a lower estimated glomerular filtration rate (eGFR). The sCD93 level was an independent determinant of both the albumin-to-creatinine ratio (ACR) and the eGFR. The risk of prevalent DN was higher in the high sCD93 group (adjusted odds ratio 7.212, 95% confidence interval 1.244–41.796, p = 0.028). In vitro, CD93 was highly expressed in HUVECs and both CD93 expression and secretion were upregulated after lipopolysaccharides (LPS) stimulation. In vivo, peritoneal and urine sCD93 levels and the renal glomerular expression of CD93 were significantly higher in the db/db mice than in the control db/m+ mice. These results suggest the potential of sCD93 as a candidate biomarker associated with DN. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]