Normalisation of urinary biomarkers to creatinine for clinical practice and research – when and why

Tang, Kai Wen Aaron; Toh, Qi Chun; Teo, Boon Wee

doi:10.11622/smedj.2015003

Cited by 89 publications

(72 citation statements)

References 48 publications

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“…Dichotomized uKIM-1/Cr of high and low levels based on an observed median value of 0.2417 pg/g was used in the analysis. Creatinine indexing may be inappropriate in the setting of AKI [18] due to inconsistent creatinine excretion, but in the setting of chronic disease including the ADPKD population creatinine indexing is more common [19].…”

Section: Predictorsmentioning

confidence: 99%

KIM-1 and Kidney Disease Progression in Autosomal Dominant Polycystic Kidney Disease: HALT-PKD Results

et al. 2020

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Background: Cyst compression of renal tubules plays a role in the progression of autosomal dominant polycystic kidney disease (ADPKD) and may induce expression of kidney injury molecule-1 (KIM-1). Whether urinary KIM-1 indexed for creatinine (uKIM-1/Cr) is a prognostic marker of disease progression in ADPKD is unknown. In this secondary analysis of a prospective cohort study, we sought to determine whether patients with high as opposed to low uKIM-1/CR at baseline had greater rates of eGFR loss and height-adjusted total kidney volume (HtTKV) increase. Methods: Baseline uKIM-1/ Cr values were obtained from 754 participants in Halt Progression of Polycystic Kidney Disease (HALT-PKD) studies A (early ADPKD) and B (late ADPKD). The predictor was uKIM-1/ Cr, which was dichotomized by a median value of 0.2417 pg/g, and the primary outcomes were measured longitudinally over time. Mixed-effects linear models were used in the analysis to calculate the annual slope of change in eGFR and HtTKV. Results: Patients with high uKIM-1/Cr (above the median) had an annual decline in eGFR that was 0.47 mL/min greater than that in those with low uKIM-1/Cr (p = 0.0015) after adjustment for all considered covariates. This association was seen in study B patients alone (0.45 mL/min; p = 0.009), but not in study A patients alone (0.42 mL/min; p = 0.06). High baseline uKIM-1/Cr was associated with higher HtTKV in the baseline cross-sectional analysis compared to low uKIM-1/Cr (p = 0.02), but there was no difference between the groups in the mixed-effects model annual slopes. Conclusion: Elevated baseline uKIM-1/Cr is associated with a greater decline in eGFR over time. Further research is needed to determine whether uKIM-1/Cr improves risk stratification in patients with ADPKD.

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Section: Predictorsmentioning

confidence: 99%

KIM-1 and Kidney Disease Progression in Autosomal Dominant Polycystic Kidney Disease: HALT-PKD Results

et al. 2020

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“…This is in comparison to other biofluids, such as serum, plasma, and cerebrospinal fluids, which are physiologically and homeostatically managed by the body, resulting in much more controlled metabolite concentrations. When urine is sampled, factors such as the collection time and the flow rate can cause fluctuations in the concentrations of urinary metabolites [ 4 , 8 , 9 , 10 ]. It has been reported that the total concentration of urinary metabolites, regarded as urine sample concentration, can vary by more than 15-fold between samples [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Towards Standardization of Data Normalization Strategies to Improve Urinary Metabolomics Studies by GC×GC-TOFMS

et al. 2020

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Urine is a popular biofluid for metabolomics studies due to its simple, non-invasive collection and its availability in large quantities, permitting frequent sampling, replicate analyses, and sample banking. The biggest disadvantage with using urine is that it exhibits significant variability in concentration and composition within an individual over relatively short periods of time (arising from various external factors and internal processes regulating the body’s water and solute content). In treating the data from urinary metabolomics studies, one must account for the natural variability of urine concentrations to avoid erroneous data interpretation. Amongst various proposed approaches to account for broadly varying urine sample concentrations, normalization to creatinine has been widely accepted and is most commonly used. MS total useful signal (MSTUS) is another normalization method that has been recently reported for mass spectrometry (MS)-based metabolomics studies. Herein, we explored total useful peak area (TUPA), a modification of MSTUS that is applicable to GC×GC-TOFMS (and data from other separations platforms), for sample normalization in urinary metabolomics studies. Performance of TUPA was compared to the two most common normalization approaches, creatinine adjustment and Total Peak Area (TPA) normalization. Each normalized dataset was evaluated using Principal Component Analysis (PCA). The results showed that TUPA outperformed alternative normalization methods to overcome urine concentration variability. Results also conclusively demonstrate the risks in normalizing data to creatinine.

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“…Sample preparation and measurements were carried out according to the manufacturer's protocol and have been described in detail elsewhere (Wang-Sattler et al 2008). Serotonin concentrations were normalized to creatinine levels as earlier described (Tang et al 2015).…”

Section: Laboratory Methodsmentioning

confidence: 99%

Plasma Levels of Glial Cell Marker S100B in Children With Autism

et al. 2019

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Autism spectrum disorder (ASD) is a neurodevelopmental condition with increasing incidence. Recent evidences suggest glial cells involvement in autism pathophysiology. S100B is a calcium binding protein, mainly found in astrocytes and therefore used as a marker of their activity. In our study, children with autism had higher plasma concentrations of S100B compared to non-autistic controls. No association of S100B plasma levels with behavioral symptoms (ADI-R and ADOS-2 scales) was found. Plasma S100B concentration significantly correlated with urine serotonin, suggesting their interconnection. Correlation of plasma S100B levels with stool calprotectin concentrations was found, suggesting not only brain astrocytes, but also enteric glial cells may take part in autism pathogenesis. Based on our findings, S100B seems to have a potential to be used as a biomarker of human neurodevelopmental disorders, but more investigations are needed to clarify its exact role in pathomechanism of autism.

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Normalisation of urinary biomarkers to creatinine for clinical practice and research – when and why

Cited by 89 publications

References 48 publications

KIM-1 and Kidney Disease Progression in Autosomal Dominant Polycystic Kidney Disease: HALT-PKD Results

KIM-1 and Kidney Disease Progression in Autosomal Dominant Polycystic Kidney Disease: HALT-PKD Results

Towards Standardization of Data Normalization Strategies to Improve Urinary Metabolomics Studies by GC×GC-TOFMS

Plasma Levels of Glial Cell Marker S100B in Children With Autism

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