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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.

(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.

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&reg, and the albumin-specific immunochromatographic assay Micral-Test&reg, 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 (&ge, 30 mg/g) was detected in 12.7% (95% CI 85.6&ndash, 96.3%) with the ACR. Sensitivity was 82.9% (95% CI 75.1&ndash, 89.1%) and 91.9% (95% CI 88.7&ndash, 96.9%) and specificity 71.5% (95% CI 68.4&ndash, 74.6%) and 17.5% (95% CI 15.0&ndash, 20.2%) for the Combur9-Test&reg, and Micral-Test&reg, respectively. Correct classification to KDIGO albuminuria stages A2/A3 with the Combur9-Test&reg, was 15.4%, 51.4%, and 87.9% at cut-offs of 30, 100, and &ge, 300 mg/dL, and with the Micral-Test&reg, 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&reg, 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&reg, respectively. Conclusion: Compared to the Combur9-Test&reg, the utility of the Micral-Test&reg, is limited, because the fraction of correctly ruled out patients is small and a large proportion with a positive Micral-Test&reg, require a subsequent ACR conformation test.

Objective: To understand the relationship between nativity and measures of kidney function including estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). Methods: 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. Results: 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 = 30mg/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). Conclusions: 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.

High levels of albuminuria have been demonstrated to associate with hearing loss in non-diabetic people, while the clinical impact of low-grade albuminuria has attracted less attention. This cross-sectional population-based study aimed to examine whether hearing loss in non-diabetic United States (US) adults is independently associated with low-grade albuminuria or reduced estimated glomeruli filtration rate (eGFR). A total of 2518 participants aged 20 to 69 years were selected from the US National Health and Nutritional Examination Survey database. Participants with diabetes or high-grade albuminuria were excluded. Hearing loss was assessed using low-frequency pure-tone average (LFPTA) thresholds (0.5, 1.0, 2.0 kHz) and high-frequency pure-tone average (HFPTA) thresholds (3.0, 4.0, 6.0, 8.0 kHz). Logistic and linear regression analyses were used to evaluate associations between renal function indicators and hearing loss. The median age of included participants was 37.4 years, and 55% of them were female. Multivariate analysis revealed that participants with urinary albumin-to-creatinine ratio (UACR) in the highest tertile had a significantly higher risk of hearing loss (OR, 1.79; 95% CI, 1.01–3.19) and higher HFPTA thresholds (β: 2.23; SE: 0.77). Participants with eGFR

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. Electronic supplementary material The online version of this article (10.1186/s40885-018-0095-3) contains supplementary material, which is available to authorized users.

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.

The prognostic significance of blood pressure (BP) variability has lately enjoyed considerable attention. The need for early markers of cardiovascular dysfunction is imperative in black South Africans who have a significant risk for cardiovascular disease. We therefore compared 24-h BP variability with various traditional and advanced BP measurements, regarding their association with sub-clinical organ damage in black and white South Africans. The study included 409 African and Caucasian teachers aged 25–60 yrs. We measured office BP, 1-min continuous (finger) BP, ambulatory BP, BP reactivity and determined weighted 24-h BP variability. Albumin-to-creatinine ratio, Cornell product and carotid cross-sectional wall area (CSWA) were measures of organ damage. Africans had higher 24-h BP, BP variability, BP reactivity and sub-clinical organ damage (P

Albuminuria has been associated with increased risk of multiple adverse outcomes, including ESRD, acute kidney injury, cardiovascular disease, and death. Some clinicians advocate for population-based screening of this condition, as a means of identifying individuals at high risk for morbidity and mortality. Several factors influence the potential implementation of screening for albuminuria in the general population, including the type of test used, the threshold for albuminuria, the validity and prognostic value of testing, frequency of follow-up testing, and associated costs of screening. This review discusses the available literature addressing these issues, and suggests an approach to screening patients for albuminuria. (C) 2011 by the National Kidney Foundation, Inc. All rights reserved.

Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: The Insulin Resistance Atherosclerosis Study.BackgroundMicroalbuminuria is a risk factor for cardiovascular disease, but the underlying pathomechanisms are still poorly understood. A relationship between C-reactive protein (CRP), a sensitive marker of inflammation, and atherosclerotic disease has been reported recently.MethodsWe hypothesized that microalbuminuria might be associated with chronic inflammation and investigated the relationship of urinary albumin excretion, as assessed from the albumin-to-creatinine ratio (ACR), in an untimed morning urine specimen, and two inflammatory markers (CRP and fibrinogen) in the large, triethnic population of the Insulin Resistance Atherosclerosis Study (IRAS). After exclusion of subjects with macroalbuminuria, 1481 subjects were studied.ResultsBoth inflammatory markers were related to urinary ACR (r = 0.17 for CRP and r = 0.14 for fibrinogen, both P = 0.0001), an association that remained significant after adjustment for demographic variables, diabetic status, smoking, and use of angiotensin-converting enzyme inhibitors (P < 0.01). Mean levels of CRP and fibrinogen were elevated in microalbuminuric (N = 262) versus normoalbuminuric (N = 1219) subjects (5.37 ± 0.47 vs. 3.80 ± 0.15 mg/L and 295.7 ± 4.0 vs. 278.2 ± 1.6 mg/dL, both P < 0.0001). The associations were consistent among nondiabetic and type 2 diabetic subjects and among the three ethnic groups of the IRAS (non-Hispanic whites, blacks, Hispanics). In a logistic regression model, fibrinogen was independently associated with microalbuminuria (P = 0.047), along with hypertension, female gender, waist circumference, and fasting blood glucose, while CRP was not independently related to microalbuminuria in this model (P = 0.26).ConclusionWe have shown an association of CRP and fibrinogen with urinary albumin excretion in the microalbuminuric range in type 2 diabetic and nondiabetic individuals. Chronic inflammation therefore emerges as a potential mediator between microalbuminuria and macrovascular disease.

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.

Multiple first-morning urine samples are recommended for measuring the urine albumin-to-creatinine ratio (ACR); however, this can be challenging in community-based research.The objectives of the study are to pilot-test a home urine collection protocol and examine how the average and variance of ACR varied with the number of urine collections and time to laboratory analysis. This is a prospective observational pilot study. This study was conducted in London, Ontario, Canada at the London Health Sciences Centre (2012-2013). The patients were adults with chronic kidney disease (mean estimated glomerular filtration rate, 36 mL/min/1.73 m(2)). Participants collected a first-morning 20-mL urine sample on three consecutive days. This process was repeated after 3 months. Samples were picked up by hospital courier and analyzed for ACR on the same day; additional aliquots were analyzed after a delay of 24-48 h (stored at 4 °C) and 3-9 months (stored at -80 °C). The geometric mean of the percentage change in ACR between baseline and 3 months was calculated and compared between single samples and the average of two vs. three consecutive samples.Of 31 patients enrolled, 26 (83.9 %) submitted all six urine samples. The geometric mean of ACR for three consecutive samples at baseline was 87, 83, and 80 mg/mmol, and the corresponding percentage increase from baseline to 3 months was 15 % (95 % confidence interval (CI), -9 to 46 %), 33 % (95 % CI, 10 to 59 %), and 22 % (95 % CI, -6 to 57 %). Compared with single urine collections at baseline and follow-up, averaging ACR values from two consecutive first-morning urine samples improved the sample variance and reduced the required sample size to detect a given treatment effect by approximately 30 %. No further gain in statistical efficiency was achieved with three urine samples. Results were similar when the laboratory analysis was delayed by 24-48 h, but a delay of 3-9 months resulted in systematic overestimation of the ACR. Our study's generalizability is limited by its small sample size and reliance on a clinic-based population from a single urban center.We successfully used a home urine collection protocol to obtain multiple first-morning urine samples in patients with chronic kidney disease. Statistical efficiency was improved by averaging ACR values from two consecutive first-morning urine samples at baseline and follow-up.Le prélèvement de la première urine du matin est recommandé pour procéder à l’analyse du ratio albumine/créatinine (RAC) chez les patients atteints d’insuffisance rénale chronique (IRC). Toutefois, cette procédure représente un défi dans le domaine de la recherche communautaire.Cette étude constitue un essai pilote qui visait à établir un protocole normalisé pour la collecte d’échantillons d’urine chez les patients atteints d’IRC. Cet essai pilote avait également pour objectif de caractériser les variations dans les valeurs moyennes et les valeurs d’écart à la moyenne des RAC en fonction du nombre de prélèvements effectués et du moment où ceux-ci sont analysés en laboratoire.Il s’agit d’une étude pilote prospective réalisée par observation. L’étude s’est tenue auLes participants, des adultes atteints d’IRC (débit de filtration glomérulaire moyen de 36 mL/min/1,73 mDes 31 patients inclus dans l’étude, 83,9 % (n = 26) ont fourni les six échantillons d’urine requis pour analyse. Les moyennes géométriques des RAC pour les échantillons prélevés sur trois jours consécutifs s’élevaient à 87,83 et 80 mg/mmol, et les pourcentages correspondants à la variation entre le RAC au jour 1 et le RAC après 3 mois étaient respectivement de 15 % (95 % IC : −9 % à 46 %), de 33 % (95 % IC : 10 % à 59 %), et de 22 % (95 % IC : −6 % à 57 %). En comparant les RAC des échantillons individuels au jour 1 et après 3 mois avec la moyenne des RAC de deux échantillons prélevés consécutivement, un accroissement de la variance a été observé. De plus, cette comparaison a également permis de conclure qu’il était possible de détecter un effet thérapeutique donné dans un échantillon jusqu’à 30 % moins volumineux. Aucun avantage sur le plan de l’efficacité statistique n’a été amené par l’analyse de trois prélèvements consécutifs. Enfin, les résultats d’analyse du RAC de 24 à 48 heures suivant l’arrivée des échantillons n’a offert que peu de variation en comparaison avec les valeurs obtenues au jour 1. Par contre, dans le cas des échantillons analysés après 3 à 9 mois ceux-ci ont systématiquement entraîné une surévaluation de la mesure du RAC.La possibilité de généralisation de la présente étude est limitée par son faible échantillonnage et par le fait qu’elle s’appuie sur une population clinique provenant d’une seule agglomération urbaine.L’essai pilote mené dans le but d’établir un protocole normalisé permettant aux patients atteints d’IRC de prélever des échantillons d’urine du matin à la maison a été couronné de succès. De plus, les résultats montrent que d’utiliser les moyennes de RAC de deux échantillons prélevés consécutivement permet d’accroître l’efficacité statistique tant pour les échantillons analysés au jour 1 que lors du suivi après 3 mois.

Background: Hypertension and increased blood glucose are associated with subclinical kidney damage, atherosclerosis and with low testosterone values. Low testosterone in men is often accompanied by increased levels of estradiol. Objectives and methods: In this study, the association between estradiol, subclinical kidney damage and atherosclerosis in African and white men in a South African cohort was investigated. Cardiovascular variables were studied by means of B-mode ultrasound and ambulatory blood pressure (BP) monitoring. The sex hormones and other biochemical values were measured from fasting venous blood and overnight urine samples. The ethnic groups were stratified into low and high testosterone groups by means of median split. Results: The low testosterone African group demonstrated a higher cardiovascular risk compared with the low testosterone white men with 91% being hypertensive and having increased albumin-to-creatinine ratio (ACR), left carotid intima–media thickness (L-CIMTf) and estradiol-to-testosterone ratio. In the low-testosterone African men, estradiol explained 33% of the variance in ACR, whereas the estradiol-to-testosterone ratio explained 22% of the variance in L-CIMTf, respectively. Estradiol-to-testosterone ratio was positively associated with ACR in the low testosterone whites. Conclusion: We conclude that increased levels of estradiol may play a role in the development of subclinical kidney damage in both African and white men as well as atherosclerosis in low-testosterone African men. http://dx.doi.org/10.1097/HJH.0b013e3283599bb5