Variability of Urinary Creatinine in Healthy Individuals
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ABSTRACT:
SUBMITTER: Sallsten G
PROVIDER: S-EPMC8003281 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
| S-EPMC10993191 | biostudies-literature
Project description:In rodents and older patients with elevated blood pressure (BP), high dietary sodium increases excretion of biomarkers of kidney injury, but it is unclear whether this effect occurs in healthy young adults. The purpose of this study was to determine whether short-term high dietary salt increases urinary excretion of the kidney injury biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in healthy young adults. Twenty participants participated in a double-blind, placebo-controlled, randomized crossover study. For 10 days each, participants were asked to consume salt (3,900 mg sodium) or placebo capsules. We measured BP during each visit, obtained 24-h urine samples for measurements of electrolytes, NGAL, and KIM-1, and assessed creatinine clearance. Compared with placebo, salt loading increased daily urinary sodium excretion (placebo: 130.3 ± 62.4 mmol/24 h vs. salt: 287.2 ± 72.0 mmol/24 h, P < 0.01). There was no difference in mean arterial BP (placebo: 77 ± 7 mmHg vs. salt: 77 ± 6 mmHg, P = 0.83) between conditions. However, salt loading increased the urinary NGAL excretion rate (placebo: 59.8 ± 44.4 ng/min vs. salt: 80.8 ± 49.5 ng/min, P < 0.01) and increased creatinine clearance (placebo: 110.5 ± 32.9 mL/min vs. salt: 145.0 ± 24.9 mL/min, P < 0.01). Urinary KIM-1 excretion was not different between conditions. In conclusion, in healthy young adults 10 days of dietary salt loading increased creatinine clearance and increased urinary excretion of the kidney injury biomarker marker NGAL but not KIM-1.NEW & NOTEWORTHY In healthy young adults, 10 days of dietary salt loading increased creatinine clearance and increased urinary excretion of the kidney injury biomarker marker neutrophil gelatinase-associated lipocalin despite no change in resting blood pressure.
| S-EPMC8934673 | biostudies-literature
Project description:Exposure of humans to pesticides is widespread. Measurement of urinary levels of pesticides and their metabolites is often used in the assessment of body burdens and exposure doses to these chemicals. An understanding of temporal variability in urinary levels of pesticides within individuals is critical for accurate exposure assessment. We examined within- and between-individual variability in concentrations of nine organophosphate and pyrethroid insecticides as well as two phenoxy herbicides in urine collected consecutively for up to 44 days from 19 individuals. Seven oxidative stress biomarkers also were measured in urine samples to elucidate their relationship with pesticide exposure. Intraclass correlation coefficients (ICCs) were calculated to assess reproducibility in urinary pesticide concentrations from repeated measures. Sensitivity and specificity analyses were performed to evaluate the suitability of spot urine to characterize average exposures. Data analysis was further limited to seven pesticides and their metabolites, which had a detection frequency of >60%. Poor reproducibility was found for the seven pesticides and their metabolites in both spot (ICCs ≤0.24) and first-morning-void (FMV) samples (ICCs <0.38) collected during the 44-day study period. Use of single-spot or FMV sample to classify high (top 33%) concentrations showed high specificities (0.73-0.85) but low sensitivities (0.45-0.70). The minimum number of samples (k) required per individual to estimate participant-specific mean value for pesticides (within 20% of the "true" values) were 28-140 and 18-119 for spot and FMV samples, respectively. Repeated longitudinal measurements of these pesticides and their metabolites in urine showed considerable within-individual variability in both spot and FMV samples. Urinary concentrations of seven pesticides and their metabolites were significantly correlated with oxidative damage to lipids, proteins, and DNA.
| S-EPMC6682452 | biostudies-literature
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.
| S-EPMC2584193 | biostudies-literature
Project description:Background and objectiveMidazolam is the preferred clinical probe drug for assessing CYP3A activity. We have previously shown substantial intraindividual variability in midazolam absolute bioavailability and clearance in patients with obesity before and after weight loss induced by gastric bypass or a strict diet. The objective was to describe intraindividual variability in absolute bioavailability and clearance of midazolam in healthy individuals without obesity.MethodsThis study included 33 healthy volunteers [28 ± 8 years, 21% males, body mass index (BMI) 23 ± 2.5 kg/m2] subjected to four pharmacokinetic investigations over a 2-month period (weeks 0, 2, 4, and 8). Semi-simultaneous oral (0 h) and intravenous (2 h later) midazolam dosing was used to assess absolute bioavailability and clearance of midazolam.ResultsAt baseline, mean absolute bioavailability and clearance were 46 ± 18% and 31 ± 10 L/h, respectively. The mean coefficient of variation (CV, %) for absolute bioavailability and clearance of midazolam was 26 ± 15% and 20 ± 10%, respectively. Approximately one-third had a CV > 30% for absolute bioavailability, while 13% had a CV > 30% for clearance.ConclusionsOn average, intraindividual variability in absolute bioavailability and clearance of midazolam was low to moderate; however, especially absolute bioavailability showed considerable variability in a relatively large proportion of the individuals.
| S-EPMC10338616 | biostudies-literature
Project description:Estimated 24-hour urinary creatinine excretion (24?hrUCr) may be useful for converting spot urine analyte/creatinine ratio into estimated 24-hour urinary excretion of the evaluated analyte, and for verifying completeness of 24-hour urinary collections. We compared various published 24?hrUCr-estimating equations against measured 24?hrUCr in hospitalized hypertensive patients. 24?hrUCr was measured in 293 patients and estimated using eight formulas (CKD-EPI, Cockcroft-Gault, Walser, Goldwasser, Rule, Gerber-Mann, Kawasaki, Tanaka). We used the Pearson correlation coefficient, the Bland-Altman method, and the percentage of estimated 24?hrUCr within 15%, 30% (P30), and 50% of measured 24hUCr to compare estimated and measured 24?hrUCr. Differences between the mean bias by eight formulas were evaluated using the Friedman rank sum test. Overall, the best formulas were CKD-EPI (mean bias 0.002?g/d, P30 86%) and Rule (mean bias 0.022?g/d, P30 89%), although both tended to underestimate 24?hrUCr with higher excretion values. The Gerber-Mann formula and the Asian formulas (Tanaka, Kawasaki) were less precise in our study population but superior in an analysis restricted to subjects with highest measured 24?hrUCr per body weight. We found significant differences between 24?hrUCr-estimating equations in hypertensive patients. In addition, formula performance was critically affected by inclusion criteria based on measured 24?hrUCr per body weight.
| S-EPMC6401114 | biostudies-literature
Project description:Rationale & objectiveUrinary biomarker concentrations are frequently indexed to urinary creatinine (Ucr) concentration in spot samples to account for urine dilution; however, this may introduce biases. We evaluated whether indexing versus adjusting urinary biomarker concentrations for Ucr concentration altered their associations with outcomes.Study designObservational cohort.Setting & participantsWe analyzed data from 2,360 Systolic Blood Pressure Intervention Trial (SPRINT) participants with estimated glomerular filtration rates < 60 mL/min/1.73 m2 and urinary albumin (UAlb) and 8 urinary kidney tubule biomarkers measured at baseline.OutcomesThe primary outcome was a composite of cardiovascular disease events; secondary outcomes were all-cause mortality and a composite of kidney outcomes (50% estimated glomerular filtration rate decline, end-stage kidney disease, or transplantation).Analytical approachWe used Cox proportional hazards regression to examine the associations of 1/Ucr with outcomes and compared the associations of UAlb and 8 individual urinary tubule biomarkers with outcomes, analyzed by indexing to Ucr, adjusting for 1/Ucr or the biomarker alone (without Ucr concentration).ResultsDuring a median follow-up of 3.3 years, 307 composite cardiovascular events, 166 deaths, and 34 composite kidney outcomes occurred. After multivariable adjustment, 1/Ucr was significantly associated with cardiovascular events (HR, 1.27 per 2-fold higher; 95% CI, 1.11-1.45), not associated with either mortality (HR, 1.06; 95% CI, 0.87-1.28) or kidney events (HR, 1.49; 95% CI, 0.95-2.35). For UAlb and urinary tubule biomarker concentrations, most risk estimates were not significantly different when indexed to Ucr concentration versus adjusted for 1/Ucr.LimitationsCohort excluded patients with diabetes and overall had low levels of albuminuria.Conclusions1/Ucr is independently associated with cardiovascular events in trial participants with chronic kidney disease. Indexing versus adjusting for 1/Ucr does not significantly change the associations of most urinary biomarkers with clinical outcomes.
| S-EPMC8350828 | biostudies-literature
Project description:BACKGROUNDThe 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.METHODSThe 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.RESULTSThe 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.CONCLUSIONSWe 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.
| S-EPMC5973915 | biostudies-literature
Project description:Oxidative stress in humans is affected by the health and nutritional status as well as exposure to external environmental factors. To evaluate the effects of external factors, an assessment of baseline levels as well as diurnal variations in oxidative stress status of healthy individuals is needed. In this study, we examined intra- and inter-individual variability of oxidative stress biomarkers (OSBs) of lipids (malondialdehyde [MDA] and four F2-isoprostane isomers, namely, 8-isoprostaglandinF2? [8-PGF2?], 11?-prostaglandinF2? [11-PGF2?], 15(R)-prostaglandinF2? [15-PGF2?], and 8-iso,15(R)-prostaglandinF2? [8,15-PGF2?]); proteins (o,o'-dityrosine [diY]); and DNA (8-hydroxy-2'-deoxyguanosine [8-OHdG]) in urine from healthy individuals. The significance of creatinine correction, which is typically used to account for urinary dilution, on OSB concentrations was evaluated. Analysis of 515 urine samples, collected longitudinally from 19 healthy individuals daily for over a month, showed inter-individual coefficient of variation (CV) in concentrations from 112% for MDA to 272% for 15-PGF2?. Intra-individual CV in concentrations ranged from 29% for 8-OHdG to 149% for 15-PGF2?. MDA was the most abundant OSB found in urine. The intra- and inter-individual variability in F2-isoprostane concentrations were higher than the values calculated for diY, 8-OHdG, and MDA. All seven OSB concentrations were significantly correlated with each other and with creatinine. Creatinine normalization of OSB concentrations improved predictability in OSB concentrations over time. Our results suggest that 8-OHdG, showing the highest ICC (0.96), yielded more reproducible measurements with a low CV, and is the most suitable biomarker of OSB in spot urine samples. The measured concentrations and diurnal variability in urinary OSB levels in healthy individuals reported in this study are useful as a benchmark for future toxicological and epidemiological studies.
| S-EPMC6396322 | biostudies-literature
Project description:BackgroundDifferent immunotherapy approaches for the treatment of cancer and autoimmune diseases are being developed and tested in clinical studies worldwide. Their resulting complex experimental data should be properly evaluated, therefore reliable normal healthy control baseline values are indispensable.Methodology/principal findingsTo assess intra- and inter-individual variability of various biomarkers, peripheral blood of 16 age and gender equilibrated healthy volunteers was sampled on 3 different days within a period of one month. Complex "crossomics" analyses of plasma metabolite profiles, antibody concentrations and lymphocyte subset counts as well as whole genome expression profiling in CD4+T and NK cells were performed. Some of the observed age, gender and BMI dependences are in agreement with the existing knowledge, like negative correlation between sex hormone levels and age or BMI related increase in lipids and soluble sugars. Thus we can assume that the distribution of all 39.743 analysed markers is well representing the normal Caucasoid population. All lymphocyte subsets, 20% of metabolites and less than 10% of genes, were identified as highly variable in our dataset.Conclusions/significanceOur study shows that the intra-individual variability was at least two-fold lower compared to the inter-individual one at all investigated levels, showing the importance of personalised medicine approach from yet another perspective.
| S-EPMC3257221 | biostudies-literature