The applicability of urinary creatinine as a method of specimen normalization in the cystic fibrosis population

Wagner, Brandie D.; Accurso, Frank J.; Laguna, Theresa A.

doi:10.1016/j.jcf.2010.02.004

Cited by 44 publications

(39 citation statements)

References 28 publications

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“…Unfortunately, no other markers of urine dilutions were available in the NHANES III and NHANES 1999–2006 datasets, and we were unable to evaluate our results against those where urine dilutions were adjusted using alternative means. Nevertheless, our unusual findings regarding creatinine adjustments in NHANES III has added to the growing number of studies questioning the practice of urinary creatinine adjustment (Wagner et al, 2010; Weaver et al, 2011, 2014). …”

Section: Discussionmentioning

confidence: 91%

Cadmium and Alzheimer’s disease mortality in U.S. adults: Updated evidence with a urinary biomarker and extended follow-up time

Peng

Bakulski

Nan

et al. 2017

Environmental Research

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Cadmium has been linked to impaired cognitive function in adults and may cause behavioral, physiological and molecular abnormalities characteristic of Alzheimer’s disease (AD) in animals. Evidence linking cadmium and AD in humans is limited, but supportive. In the most recent epidemiologic study, blood cadmium in U.S. adults was positively associated with elevated AD mortality 7–13 years later. The association between urinary cadmium – an arguably more appropriate biomarker for studying chronic diseases – and AD mortality has not yet been explored. Further study of cadmium and AD mortality in an independent population, with longer follow-up, and stratified by sex is also needed. We sought to answer these questions using the U.S. National Health and Nutrition Examination Survey (NHANES) (1999–2006 cycles) and NHANES III (interviews in 1988–1994) datasets, separately linked to AD mortality as of 2011. We used survey-weighted Cox regression models predicting age at AD death and adjusted for race/ethnicity, sex, smoking status, education and urinary creatinine. An interquartile range (IQR; IQR=0.51 ng/mL) increase in urinary cadmium was associated with 58% higher rate of AD mortality (hazard ratio (HR) =1.58, 95% CI: 1.20, 2.09. p-value=0.0009, mean follow-up: 7.5 years) in NHANES 1999–2006 participants. In contrast, in NHANES III participants, an IQR (IQR=0.78 ng/mL) increase in urinary cadmium was not associated with AD mortality (HR=0.85, 95% CI: 0.63, 1.17, p-value=0.31, mean follow-up: 13 years). Also in the NHANES III sample however, when the maximum follow-up time was restricted to 12.7 years (i.e. the same as NHANES 1999–2006 participants) and urinary creatinine adjustments were not made, urinary cadmium was associated with elevated AD mortality (HR=1.11, 95% CI: 1.02, 1.20, p-value=0.0086). Our study partially supported an association between cadmium and AD mortality, but the sensitivity of results to follow-up time and creatinine adjustments necessitate cautious interpretation of the association. Further studies, particularly those on toxicological mechanisms, are required to fully understand the nature of the “cadmium-AD mortality” association.

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Section: Discussionmentioning

confidence: 91%

Cadmium and Alzheimer’s disease mortality in U.S. adults: Updated evidence with a urinary biomarker and extended follow-up time

Peng

Bakulski

Nan

et al. 2017

Environmental Research

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“…One interesting possibility is to use the level of other biomolecules in body fluids such as creatinine levels in blood and urine to normalize miRNAs. The levels of creatinine have been used to “normalize” other biomolecules in urine, and it provides an interesting possibility as a normalization basis for miRNAs in plasma and urine [70,71]. …”

Section: Issues Associated With Mirna Measurementmentioning

confidence: 99%

Extracellular microRNA: A new source of biomarkers

Etheridge

Lee

Hood

et al. 2011

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

585

437

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MicroRNAs (miRNAs) are a recently discovered class of small, non-coding RNAs that regulate protein levels post-transcriptionally. miRNAs play important regulatory roles in many cellular processes, including differentiation, neoplastic transformation, and cell replication and regeneration. Because of these regulatory roles, it is not surprising that aberrant miRNA expression has been implicated in several diseases. Recent studies have reported significant levels of miRNAs in serum and other body fluids, raising the possibility that circulating miRNAs could serve as useful clinical biomarkers. Here, we provide a brief overview of miRNA biogenesis and function, the identification and potential roles of circulating extracellular miRNAs, and the prospective uses of miRNAs as clinical biomarkers. Finally, we address several issues associated with the accurate measurement of miRNAs from biological samples.

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“…The underlying assumption to this approach is that the UCr excretion rate is constant within an individual over time and also across individuals, which may not be the case, especially in a sick CF population receiving nephrotoxic IV medications,25, 27, 29 We chose to report both unadjusted and a novel, SG‐adjusted UDes concentration given our finding that UCr concentration significantly decreased during hospitalization, making the use of a UCr normalization ratio inappropriate in this population 27. Knowing that a method of normalization is imperative to urinary biomarker measurements, we chose to normalize UDes concentration using a regression model incorporating SG as a covariate, as opposed to using a simple ratio with UCr 27, 28. Our finding of a significant decrease in UDes held true in the analysis of both unadjusted UDes concentration and UDes concentration incorporating SG as a normalization factor into a statistical model 27.…”

Section: Discussionmentioning

confidence: 99%

“…Knowing that a method of normalization is imperative to urinary biomarker measurements, we chose to normalize UDes concentration using a regression model incorporating SG as a covariate, as opposed to using a simple ratio with UCr 27, 28. Our finding of a significant decrease in UDes held true in the analysis of both unadjusted UDes concentration and UDes concentration incorporating SG as a normalization factor into a statistical model 27. SG has been previously utilized as a normalization factor for urinary biomarker measurement and may be a more appropriate measure of urinary concentration in the CF population during exacerbation 46…”

Section: Discussionmentioning

confidence: 99%

“…The marker variables were log transformed (base 10) and anchored at 1 to satisfy normality assumptions of the statistical tests. The UDes measurements were investigated using both unadjusted values and values adjusted for either SG or Cr given our previous finding that UCr decreases significantly during treatment for pulmonary exacerbation and the findings of others 25, 27–29. It was determined the SG‐adjusted UDes was the optimal way to express UDes concentration, so further analysis and correlations were performed with this measure.…”

Section: Methodsmentioning

confidence: 99%

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Urinary desmosine: A biomarker of structural lung injury during CF pulmonary exacerbation

Laguna

Wagner

Starcher

et al. 2012

Pediatric Pulmonology

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Summary Rationale Cystic fibrosis (CF) lung disease is characterized by structural changes and remodeling in airway architecture and lung parenchyma. Neutrophilic inflammation and infection lead to injury and breakdown of airway matrix constituents, including elastin. The non-invasive measurement of urinary desmosine (UDes), a breakdown product of elastin, may be reflective of ongoing lung injury and may serve as a biomarker of active short-term damage during pulmonary exacerbation. Our objectives were to measure desmosine in the urine of CF patients hospitalized for treatment of a pulmonary exacerbation and to explore the correlation between desmosine concentration and other markers of clinical improvement, including lung function and inflammatory mediators. Methods Urine and blood samples plus lung function measurements were collected at up to three points during hospitalization for treatment of a CF pulmonary exacerbation. We used a repeated measures model, adjusted for age and time between measurements, to compare log transformed urine desmosine concentrations across multiple time points and to correlate those concentrations with related clinical variables. Change in UDes concentration was investigated using a statistical model that incorporated normalization factors to account for variations in urinary concentration. Results Desmosine was measured by radioimmunoassay in 155 spot urine samples from 53 CF patients hospitalized for 63 pulmonary exacerbations (range of results: 0–235 pmol Des/mL). Specific gravity adjusted UDes concentration decreased significantly during admission for CF pulmonary exacerbation, p<0.01 (average length of stay = 11 days). No correlation was observed between UDes concentration and lung function or inflammatory markers. Conclusions Urinary desmosine decreased significantly following treatment for an acute pulmonary exacerbation and may be a useful biomarker of short-term injury to the CF lung. Further investigation is needed to evaluate the utility of UDes concentration in the long-term progression of CF lung disease.

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The applicability of urinary creatinine as a method of specimen normalization in the cystic fibrosis population

Cited by 44 publications

References 28 publications

Cadmium and Alzheimer’s disease mortality in U.S. adults: Updated evidence with a urinary biomarker and extended follow-up time

Cadmium and Alzheimer’s disease mortality in U.S. adults: Updated evidence with a urinary biomarker and extended follow-up time

Extracellular microRNA: A new source of biomarkers

Urinary desmosine: A biomarker of structural lung injury during CF pulmonary exacerbation

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