Initial collection of an inadequate 24-hour urine sample in children does not predict subsequent inadequate collections.

INTRODUCTION: Approximately half of adult stone formers submit specimens that are either under or over collections as determined by 24-h creatinine/kg. Previously identified predictors of inadequate collection in adults include female sex, older age, higher body mass index (BMI), vitamin D supplementation, and weekday collection. OBJECTIVE: The objective of this study is to determine risk factors for inadequate 24-h urinary specimen collection in the pediatric population. STUDY DESIGN: A retrospective analysis of all children (<18 years of age) with renal and/or ureteral calculi evaluated at the study tertiary care pediatric center from 2005 to 2015 was performed. Those who had at least one 24-h urinary metabolic profile after a clinical visit for kidney and/or ureteral stones were included; children with bladder stones were excluded. Adequate collections had a urine creatinine of 10-15 mg/kg/24 h. A bivariate analysis of potential factors associated with inadequate collection of the initial urinary metabolic profile, including child demographics, parental socio-economic factors, history of stone surgery, and weekday vs. weekend urine collection, was performed. A mixed-effects logistic regression, controlling for correlation of specimens from the same patient, was also performed to determine whether an initial inadequate collection predicted a subsequent inadequate collection. RESULTS: Of 367 patients, 80 had an adequate collection (21.9%): median age, 13 years (interquartile range, 8-16); 61.1% female; 93.5% white; 19.5% obese; and 13.0% overweight. No parental or child factors were associated with inadequate collection (Summary Table). Of inadequate collections, more than 80% were over collections. In the 175 patients with more than one 24-h urinary specimen collection, the effect of an initial inadequate collection on subsequent inadequate collections was not significant after controlling for the correlation of samples from the same patient (p = 0.8). DISCUSSION: Any parental or child factors associated with the collection of inadequate 24-h urine specimens in children were not found. An initial inadequate collection does not predict subsequent inadequate collections. It was surprising that >80% of the inadequate collections were over collections rather than under collections. Possible explanations are that children collected urine samples for longer than the 24-h period or that stone-forming children produce more creatinine per 24-h period than healthy children due to hyperfiltration. CONCLUSION: Inadequate collections are very common, and the risk factors for them are unclear. A repeat collection would be suggested if the first is inadequate. Further studies must be planned to explore barriers to accurate specimen collection using qualitative research methodology.

Urinary antimicrobial peptides: Potential novel biomarkers of obstructive uropathy.

INTRODUCTION: Antimicrobial peptides (AMPs) have historically been evaluated for their role in protecting against uropathogens. However, there is mounting evidence to support their expression in noninfectious injury, with unclear meaning as to their function. It is possible that AMPs represent urothelial injury. Urinary tract obstruction is known to alter the urothelium; however, AMPs have not been evaluated for expression in this noninfectious injury. OBJECTIVE: A pilot study to compare urinary AMP expression in children undergoing surgical intervention for ureteropelvic junction obstruction (UPJO) with nonobstructed controls. STUDY DESIGN: Bladder urine was collected from consenting/assenting pediatric patients with UPJO at intervention. Control bladder urines were obtained from age-matched and sex-matched healthy children without known obstruction or infection. Enzyme-linked immunosorbent assays were run for the following AMPs: ß defense 1 (BD-1), neutrophil gelatinase-associated lipocalin (NGAL), cathelicidin (LL-37), hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), and human α defensin 5 (HD-5); and normalized to urine creatinine. Results were analyzed with Student's t-test or Mann-Whitney U test, when appropriate, and receiver operating characteristic curves. A P-value of <0.05 was considered significant. RESULTS: Thirty bladder urine samples were obtained from children with UPJO at the time of decompressive intervention. Mean patient age was 4.7 years (range 0.3-18.4); 20 (67%) patients were male. Fifteen bladder urine samples were obtained from age-matched and sex-matched controls. Urinary AMP levels were significantly higher in UPJO patients than controls for BD-1 (P = 0.015), NGAL (P < 0.001), LL-37 (P < 0.001), and HIP/PAP (P = 0.046). Optimal threshold values of these AMPs were determined, with each demonstrating significant odds ratios of predicting urinary obstruction. DISCUSSION: Certain urinary AMPs are altered even in noninfectious urinary tract pathology. This represents a novel induction of AMP expression, as the current study is the first to report elevations in BD-1 and HIP/PAP in urinary tract obstruction. This suggests other roles for these AMPs outside of their antimicrobial properties, and likely is a reflection of the urothelial and tubular stress resulting from obstructive uropathy. CONCLUSIONS: Induction of AMPs BD-1, NGAL, LL-37, and HIP/PAP was found to occur in urinary tract obstruction. Further evaluation of AMP expression as a biomarker of uroepithelial injury outside of infection is indicated.

Dietary modifications alone do not improve bone mineral density in children with idiopathic hypercalciuria.

Prior cross-sectional studies have demonstrated an association between hypercalciuria and low bone mineral density (BMD) in children and adults. However, the natural history of BMD in children with hypercalciuria and its response to therapy has not been evaluated. The objective of this retrospective study was to determine the change over time in lumbar (L1 - L4) BMD Z-score measured on sequential DXA scans in 19 children with hypercalciuria treated with dietary recommendations without (n = 12, Group A) and with citrate (n = 7, Group B). The mean lumbar bone density Z-score/year decreased in Group A (-0.11 ±/0.41) indicating that children with hypercalciuria lose L1 - L4 BMD over time. In contrast, the L1 - L4 BMD Zscore/ year increased in Group B (0.19 ± 0.38) suggesting that pharmacologic therapy may reverse this trend. Similarly 75% of patients in Group A, but only 29% patients in Group B had a decrease in L1 - L4 BMD. There was a definite, although not significant, trend towards improved mean bone mineral density Z-score per year and a lower percentage of patients with a decreased Z-score in hypercalciuric children treated with potassium citrate. Our findings suggest the possibility that dietary recommendations alone is not adequate as the bone mineral density of children with hypercalciuria will decrease over time, potentially increasing the risk for osteoporosis as an adult.