Background
Reference values for urinary calcium (Ca) and other solutes/creatinine (Cr) ratios in infants and young children are scarce. Its variation with type of lactation administered, breastfed ...(BF) or formula (F), is incompletely known.
Methods
A total of 511 spot urine samples from 136 children, aged 6 days to < 5 years, was collected. Urine was collected no fasting in infants < 18 months and first morning fasting in children aged 2.5–4 years. Urinary osmolality, Cr, urea, Ca, phosphate (P), magnesium (Mg), and uric acid (UA) were determined. Values are expressed as solute-to-Cr ratio.
Results
Urinary values were grouped according to the child’s age: 6–17 days (G1), 1–5 months (G2), 6–12 months (G3), 13–18 months (G4), and 2.5–4 years (G5). G1 was excluded; Ca/Cr and UA/Cr (95th percentile) decreased with age (G2 vs. G5) from 1.64 to 0.39 and 2.33 to 0.83 mg/mg, respectively. The P/Cr median rises significantly with age from 0.31 (G2) to 1.66 mg/mg (G5). Mg/Cr was similar in all groups (median 0.20, 95th percentile 0.37 mg/mg). Ca/Cr (95th percentile) of BF infants was 1.80 mg/mg (< 3 months) and 1.63 mg/mg (3–5 months), much higher than F infants (0.93 and 0.90 mg/mg, respectively). P/Cr and P/Ca were lower in BF infants.
Conclusions
Values for urinary Ca/Cr, P/Cr, Mg/Cr, and UA/Cr in infants and children < 5 years were updated. BF infants < 6 months showed higher Ca/Cr and lower P/Cr than F infants. New cutoff values to diagnose hypercalciuria in infants < 6 months, according to the type of lactation, are proposed.
Graphical abstract
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Supplementary information
Urinary biomarkers, such as albumin and other markers of kidney injury, are frequently reported as a normalized ratio to urinary creatinine (UCr) concentration UCr to control for variations in urine ...flow rate. The implicit assumption is that UCr excretion is constant across and within individuals, such that changes in the ratio will reflect changes in biomarker excretion. Using computer simulations of creatinine kinetics, we found that normalized levels of a biomarker reflecting tubular injury can be influenced by dynamic changes in the UCr excretion rate when the glomerular filtration rate changes. Actual timed urine collections from hospitalized patients with changing glomerular filtration rates and/or critical illness exhibited variability in UCr excretion rates across and within individuals. Normalization by UCr may, therefore, result in an underestimation or overestimation of the biomarker excretion rate depending on the clinical context. Lower creatinine excretion in the setting of acute kidney injury or poor renal allograft function may amplify a tubular injury biomarker signal, thereby increasing its clinical utility. The variability of creatinine excretion, however, will complicate the determination of a threshold value for normalized biomarkers of acute or chronic kidney disease, including albumin. Thus, we suggest that the most accurate method to quantify biomarkers requires the collection of timed urine specimens to estimate the actual excretion rate, provided that the biomarker is stable over the period of collection. This ideal must be balanced, however, against practical considerations.
Background
The leading cause of advanced chronic kidney disease (CKD) in children is congenital anomalies of the kidney and urinary tract (CAKUT). However, the most appropriate parameters of ...biochemical urine analysis for detecting CAKUT with kidney dysfunction are not known.
Methods
The present observational study analyzed data on children with CAKUT (stage 2–4 CKD) and the general pediatric population obtained from school urine screenings. The sensitivity and specificity of urine alpha 1-microglobulin-, beta 2-microglobulin-, protein-, and the albumin-to-creatinine ratios (AMCR, BMCR, PCR, ACR, respectively) in detecting CAKUT with kidney dysfunction were compared with those of the conventional urine dipstick, and the most appropriate of these four parameters were evaluated.
Results
In total, 77 children with CAKUT and 1712 subjects in the general pediatric population fulfilled the eligibility criteria. Conventional dipstick urinalysis was insufficient due to its low sensitivity; even when the threshold of proteinuria was +/−, its sensitivity was only 29.7% for stage 2 and 44.1% for stage 3 CKD. Among the four parameters assessed, the AMCR and BMCR were adequate for detecting CAKUT in children with stage 3–4 CKD (the respective sensitivity and specificity of the AMCR for detecting CAKUT in stage 3 CKD was 79.4% and 97.5% while that of BMCR was 82.4% and 97.5%). These data were validated using national cohort data.
Conclusion
AMCR and BMCR are superior to dipstick urinalysis, PCR, and ACR in detecting CAKUT with kidney dysfunction, particularly stage 3 CKD. However, for AMCR, external validation is required.
Graphical Abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
Aim.Thе purpose of the work was to develop a new construction of enzyme biosensor based on creatinine deiminase for highly sensitive creatinine determination. Methods. A new construction of enzyme ...biosensor based on creatinine deiminase was developed for the creatinine determination. A differential pair of gold interdigitated electrodes deposited onto a ceramic substrate was used as the electrochemical transducer. Creatinine deiminase was immobilized by cross-linking with glutaraldehyde on the surface of electrodes. Results. The biosensor showed high sensitivity towards creatinine, the limit of detection was 5 µM. The biosensor was characterized by wide linear range of creatinine determination, high reproducibility of responses and showed high storage stability – after 50 days storage the biosensor retained 83% of the initial response value. Conclusions. In future the developed biosensor can be used for express evaluation of the creatinine in biological samples.
Many xenobiotics including the pharmacoenhancer cobicistat increase serum creatinine by inhibiting its renal active tubular secretion without affecting the glomerular filtration rate. This study ...aimed to define the transporters involved in creatinine secretion, applying that knowledge to establish the mechanism for xenobiotic-induced effects. The basolateral uptake transporters organic anion transporter OAT2 and organic cation transporters OCT2 and OCT3 were found to transport creatinine. At physiologic creatinine concentrations, the specific activity of OAT2 transport was over twofold higher than OCT2 or OCT3, establishing OAT2 as a likely relevant creatinine transporter and further challenging the traditional view that creatinine is solely transported by a cationic pathway. The apical multidrug and toxin extrusion transporters MATE1 and MATE2-K demonstrated low-affinity and high-capacity transport. All drugs known to affect creatinine inhibited OCT2 and MATE1. Similar to cimetidine and ritonavir, cobicistat had the greatest effect on MATE1 with a 50% inhibition constant of 0.99μM for creatinine transport. Trimethoprim potently inhibited MATE2-K, whereas dolutegravir preferentially inhibited OCT2. Cimetidine was unique, inhibiting all transporters that interact with creatinine. Thus, the clinical observation of elevated serum creatinine in patients taking cobicistat is likely a result of OCT2 transport, facilitating intracellular accumulation, and MATE1 inhibition.
A low-cost and disposable microcell was constructed with a screen-printed electrode for the non-enzymatic electrochemical determination of creatinine. The working electrode was modified with carbon ...black and maintained in contact with paper-adsorbed iron (III) ions. A small sample volume of 3 μL was required for the device operation. Then, iron (III) ions were complexed in the presence of creatinine in a chemical step, followed by an electrochemical reduction of non-complexed metallic ions in excess. Cyclic voltammetry and differential-pulse voltammetry experiments were employed for the electrochemical characterizations and analytical performance evaluation of the microcell. The working electrode modification with carbon black provided a significant increase of analytical signal. The sensor presented a linear response for creatinine concentrations ranging from 0.10 to 6.5 mmol L−1, with a limit of detection of 0.043 mmol L−1. Experiments for creatinine determination in real samples were successful performed through of standard recovery in urine.
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•Creatinine was determinate by a non-enzymatic, low-cost, and disposable microcell.•A small urine sample volume of 3 μL was required for the operation of the device.•The working electrode modification with carbon black provided a significant increase of analytical signal.
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