Proposed Imprecision Quality Goals for Urinary Albumin/Creatinine Ratio.
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ABSTRACT: The urinary albumin/creatinine ratio (ACR) is an important indicator of albuminuria. We aimed to estimate ACR uncertainty and its impact on test results and proposed imprecision quality goals based on the estimated uncertainty.The combined ACR uncertainty was calculated using the individual uncertainties of urinary albumin and creatinine. ACR confidence intervals (CIs) were estimated based on the expanded uncertainty. When the CI contained the ACR category boundary (30 or 300 mg/g), the cases were considered ambiguous. Quality goals for ACR were suggested using the number of ambiguous cases among actual patient results.The number of ambiguous cases resulting from the combined ACR uncertainty was higher than expected based on biological variation (BV) quality goals. When the ACR met BV quality specifications, we estimated that 4.8-15.5% of the results may have been misclassified. To minimize the number of ambiguous results, the minimum, desirable, and optimum quality goals were set at 34.0%, 18.0%, and 4.5%, respectively.We expressed ACR uncertainty using the uncertainties of urinary albumin and creatinine and assessed the impact of this combined uncertainty on the test results. Subsequently, we proposed imprecision quality goals for ACR based on ambiguous results.
Project description:BackgroundThe longitudinal relationship of albuminuria with incident frailty remains unknown. Therefore we aimed to evaluate the relation of albuminuria with the risk of incident frailty in older adults.MethodsA total of 1115 participants ≥65 years of age (average age 80.3 years) who were free of frailty in the Chinese Longitudinal Healthy Longevity Survey were included. The outcome was incident frailty, defined as a frailty index ≥0.25 during follow-up. Cox proportional hazards models were used to assess the association of the urinary albumin:creatinine ratio (UACR) with frailty.ResultsDuring a median follow-up duration of 5.3 years, 295 (26.5%) participants developed incident frailty. Overall, the UACR was significantly positively associated with the risk of incident frailty (P for trend = 0.005), with a significantly higher risk of incident frailty in participants in the quartile 4 of UACR {≥13.43 mg/g; hazard ratio [HR] 1.64 [95% confidence interval (CI) 1.13-2.37]} compared with those in quartile 1 (<0.73 mg/g). Consistently, when UACRs were assessed as clinical categories, compared with participants with UACR <10 mg/g, those with UACR ≥30 mg/g had a higher HR of incident frailty [HR 1.61 (95% CI 1.17-2.20)]. Accounting for the competing risk of death also did not substantially change the results. In addition, a stronger positive association between UACR and incident frailty was found in those with a higher high-sensitivity C-reactive protein level (hs-CRP) (P for interaction = 0.045).ConclusionAlbuminuria was positively associated with the risk of incident frailty, particularly in those with higher hs-CRP, emphasizing the importance of managing both albuminuria and inflammation for primary prevention of frailty.
Project description:An increased urinary albumin excretion rate is an important early risk factor for chronic kidney disease and other major outcomes and is usually measured using the urinary albumin-creatinine ratio (ACR). Obesity is highly prevalent in the general and chronic kidney disease populations and is an independent risk factor for moderately increased albuminuria (henceforth, moderate albuminuria). In this review, we describe how the ACR was developed and used to define moderate albuminuria. We then investigate how biases related to urinary creatinine excretion are introduced into the ACR measurement and how the use of the 30-mg/g threshold decreases the performance of the test in populations with higher muscle mass, with a primary focus on why and how this occurs in the obese population. The discussion then raises several strategies that can be used to mitigate such bias. This review provides a comprehensive overview of the medical literature on the uses and limitations of ACR in individuals with obesity and critically assesses related issues. It also raises into question the widely accepted 30-mg/g threshold as universally adequate for the diagnosis of moderate albuminuria. The implications of our review are relevant for clinicians, epidemiologists, and clinical trialists.
Project description:ImportanceAlthough cumulative evidence suggests that elevated urinary albumin-to-creatinine ratio (UACR) in the normal range (<30 mg/g) may be associated with an increased risk of mortality, few studies have investigated whether cardiovascular health (CVH) modifies the harmful outcomes of high-normal UACR.ObjectiveTo investigate associations of traditionally normal UACR and CVH with all-cause mortality.Design, setting, and participantsThis cohort study used National Health and Nutrition Examination Survey data from 2005 through 2018 and linked mortality information until 2019. Data were analyzed from March 1 through October 31, 2023. The study included adult participants aged 20 to 79 years with a normal UACR (<30 mg/g) based on Kidney Disease: Improving Global Outcomes criteria.ExposuresThe UACR was treated as a continuous variable and categorized into tertiles delineated as low (<4.67 mg/g), medium (4.67-7.67 mg/g), and high (7.68 to <30 mg/g). Cardiovascular health was assessed using Life's Essential 8 scores and grouped as poor (0-49 points), moderate (50-79 points), and ideal (80-100 points).Main outcomes and measuresMultivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of UACR with all-cause mortality in total participants and as stratified by CVH groups.ResultsThe study included 23 697 participants (mean [SD] age, 45.58 [15.44] years; 11 806 women [49.7%] and 11 891 men [50.3%]). During the median 7.8 years (range, 4.5-11.1 years) of follow-up, 1403 deaths were recorded. Near-linear associations were observed for continuous UACR and CVH with all-cause mortality. Compared with the low UACR group, high UACR in the normal range showed an increased mortality risk in the moderate and poor CVH groups (CVH [50-79]: HR, 1.54 [95% CI, 1.26-1.89]; CVH [0-49]: HR, 1.56 [95% CI, 1.10-2.20]), with a significant multiplicative interaction of UACR and CVH (P < .001).Conclusions and relevanceThe findings suggest that high UACR within the normal range is associated with a significantly increased risk of all-cause mortality, with the association more pronounced in adults with poor CVH status. These findings highlight the importance of risk management for early kidney dysfunction, particularly among individuals with poor CVH.
Project description:Raised albumin-creatinine ratio (ACR) is an indicator of microvascular damage and renal disease. We aimed to identify genetic variants associated with raised ACR and study the implications of carrying multiple ACR-raising alleles with metabolic and vascular-related disease. We performed a genome-wide association study of ACR using 437 027 individuals from the UK Biobank in the discovery phase, 54 527 more than previous studies, and followed up our findings in independent studies. We identified 62 independent associations with ACR across 56 loci (P < 5 × 10-8), of which 20 were not previously reported. Pathway analyses and the identification of 20 of the 62 variants (at r2 > 0.8) coinciding with signals for at least 16 related metabolic and vascular traits, suggested multiple pathways leading to raised ACR levels. After excluding variants at the CUBN locus, known to alter ACR via effects on renal absorption, an ACR genetic risk score was associated with a higher risk of hypertension, and less strongly, type 2 diabetes and stroke. For some rare genotype combinations at the CUBN locus, most individuals had ACR levels above the microalbuminuria clinical threshold. Contrary to our hypothesis, individuals carrying more CUBN ACR-raising alleles, and above the clinical threshold, had a higher frequency of vascular disease. The CUBN allele effects on ACR were twice as strong in people with diabetes-a result robust to an optimization-algorithm approach to simulating interactions, validating previously reported gene-diabetes interactions (P ≤ 4 × 10-5). In conclusion, a variety of genetic mechanisms and traits contribute to variation in ACR.
Project description:BackgroundChronic kidney disease is one of the most common complications of type 2 diabetes mellitus (T2DM), causing an increased risk of cardiovascular morbidity and mortality. Matrix metalloproteinase (MMP) activity has been proposed as useful biomarker for diabetic renal and vascular complications.MethodsA cross-sectional study was conducted among T2DM patients who attended a public secondary hospital in Mexico. We performed clinical, biochemical, and microbiological assessments, as well chronic kidney disease diagnosis according to the KDIGO guideline. Urinary MMP-9 was quantified by ELISA and adjusted using urinary creatinine (UCr).ResultsA total of 111 patients were included. Most participants were women (66%). Mean age was 61 ± 10 years and median T2DM duration was estimated at 11 years. Through multivariate analysis, MMP-9/UCr was found to be associated with albumin concentration and albumin to creatinine ratio.DiscussionValidation of non-invasive biomarkers of chronic kidney disease among T2DM patients is necessary. Here, we demonstrate MMP-9/UCr as a potential biomarker of albumin concentration and albumin to creatinine ratio in Mexican patients with T2DM.
Project description:BackgroundThe prevalence of obese and overweight patients has increased dramatically worldwide. Both are common risk factors for chronic kidney disease (CKD) as indicated by a diminished estimated glomerular filtration rate (eGFR) or microalbuminuria. This study aimed to investigate whether anthropometric parameters [waist circumference (WC), waist-to-height ratio (WHtR) and body mass index (BMI)] are associated with renal function in a population-based study of Caucasian subjects.MethodsData from 3749 subjects (1825 women) aged 20 to 81 years from the Study of Health in Pomerania (SHIP) were analysed. Renal indices, including the urinary albumin-to-creatinine ratio (uACR), microalbuminuria, eGFR and CKD, were studied. Parameters of anthropometry (WC, WHtR and BMI) were categorised into sex-specific quintiles.ResultsAnalysis of variance (ANOVA) models, adjusting for age, sex, type 2 diabetes mellitus and hypertension, revealed that a high and low WC or WHtR and low BMI were independently related to a higher uACR. Logistic regression models confirmed these results with respect to uACR and showed that subjects with a high or low WC or a high WHtR had increased odds of microalbuminuria. The ANOVA models revealed no relations of the investigated anthropometric parameters with eGFR. However, subjects with high values for these parameters had increased odds of CKD.ConclusionsOur results demonstrate U-shaped associations between markers of central fat distribution and uACR or microalbuminuria in the general population, suggesting that both obese and very thin subjects have a higher risk of renal impairment.
Project description:ObjectiveThe albumin-to-creatinine ratio (ACR) reflects urinary albumin excretion and is increasingly being accepted as an important clinical outcome predictor. Because of the great public health need for a simple and inexpensive test to identify individuals at high risk for developing type 2 diabetes, it has been suggested that the ACR might serve this purpose. We therefore determined whether the ACR could predict incident diabetes in a well-characterized cohort of pre-diabetic Americans.Research design and methodsA total of 3,188 Diabetes Prevention Program (DPP) participants with a mean BMI of 34 kg/m(2) and elevated fasting glucose, impaired glucose tolerance, and baseline urinary albumin excretion measurements were followed for incident diabetes over a mean of 3.2 years.ResultsOf the participants, 94% manifested ACR levels below the microalbuminuria range and 21% ultimately developed diabetes during follow-up. Quartiles of ACR (median [range] within quartiles: 1, 3.0 [0.7-3.7]; 2, 4.6 [3.7-5.5]; 3, 7.1 [5.5-9.7]; and 4, 16.5 [9.7-1,578]) were positively associated with age, markers of adiposity and insulin secretion and resistance, blood pressure, and use of antihypertensive agents with antiproteinuric effects and inversely related to male sex and serum creatinine. An elevated hazard rate for developing diabetes with doubling of ACR disappeared after adjustment for covariates. Within the DPP intervention groups (placebo, lifestyle, and metformin), we found no consistent trend in incident diabetes by quartile or decile of ACR.ConclusionsAn ACR at levels below the microalbuminuria range does not independently predict incident diabetes in adults at high risk of developing type 2 diabetes.
Project description:BackgroundUrine albumin-to-creatinine ratio (ACR) and protein-to-creatinine ratio (PCR) are used to measure urine protein. Recent guidelines endorse ACR use, and equations have been developed incorporating ACR to predict risk of kidney failure. For situations in which PCR only is available, having a method to estimate ACR from PCR as accurately as possible would be useful.MethodsWe used data from a population-based cohort of 47,714 adults in Alberta, Canada, who had simultaneous assessments of urine ACR and PCR. After log-transforming ACR and PCR, we used cubic splines and quantile regression to estimate the median ACR from a PCR, allowing for modification by specified covariates. On the basis of the cubic splines, we created models using linear splines to develop equations to estimate ACR from PCR. In a subcohort with eGFR<60 ml/min per 1.73 m2, we then used the kidney failure risk equation to compare kidney failure risk using measured ACR as well as estimated ACR that had been derived from PCR.ResultsWe found a nonlinear association between log(ACR) and log(PCR), with the implied albumin-to-protein ratio increasing from <30% in normal to mild proteinuria to about 70% in severe proteinuria, and with wider prediction intervals at lower levels. Sex was the most important modifier of the relationship between ACR and PCR, with men generally having a higher albumin-to-protein ratio. Estimates of kidney failure risk were similar using measured ACR and ACR estimated from PCR.ConclusionsWe developed equations to estimate the median ACR from a PCR, optionally including specified covariates. These equations may prove useful in certain retrospective clinical or research applications where only PCR is available.
