<p><strong>BACKGROUND &amp; AIMS: </strong>It is not clear what factors affect risk of chronic kidney disease (CKD) in patients with inflammatory bowel disease (IBD); increased risk has been inconsistently associated with use of 5-aminosalicylates (5-ASAs). We aimed to calculate the relative hazard of CKD among patients with IBD, adjusted for CKD risk factors, and to determine whether IBD medications are associated with change in estimated glomerular filtration rate (eGFR).</p>

<p><strong>METHODS: </strong>We performed a retrospective cohort study of data from The Health Improvement Network. Patients with IBD (n=17,807) were matched for age, sex, and practice to individuals without IBD (n=63,466). The relative hazard of CKD, stages 3 through 5D, in patients with IBD was calculated using a Cox proportional hazards model adjusted for common CKD risk factors. We also evaluated the association of 5-ASAs, azathioprine, and methotrexate with change in eGFR using a longitudinal model.</p>

<p><strong>RESULTS: </strong>After we controlled for risk factors associated with CKD, we found IBD to be associated with development of CKD in patients 16-77 years old. As patient age increased, the adjusted hazard ratio for CKD decreased monotonically, from 7.88 (95% CI, 2.56-24.19) at age 16 to 1.13 (95% CI, 1.01-1.25) at age 77. In the longitudinal analysis, exposure to 5-ASAs or methotrexate was not associated with change in eGFR, whereas azathioprine was associated with a slightly higher eGFR (0.32 mL/min/1.73 m; 95% CI, 0.16-0.48).</p>

<p><strong>CONCLUSIONS: </strong>In a retrospective study of more than 80,000 persons, we found that IBD is associated with increased risk of CKD, and the hazard ratio is highest among younger patients. Commonly used non-biologic therapeutic agents were not associated with lower eGFR.</p>

<p>Though previous studies have demonstrated an increased fracture risk in females with anorexia nervosa (AN), fracture risk in males is not well characterized. The objective of this study was to examine sex differences in fracture risk and site-specific fracture incidence in AN. We performed a population-based retrospective cohort study using The Health Improvement Network (THIN; a large database of anonymized electronic medical records collected at primary care clinics throughout the United Kingdom). The median calendar year for the start of the observation period was 2004-2005. We identified 9239 females and 556 males &lt;60 years of age with AN, and 97,889 randomly selected sex-, age-, and practice-matched participants without eating disorders (92,329 females and 5560 males). Multivariable Cox regression was used to estimate the hazard ratio (HR) for incident fracture. Median age at start of observation was 29.8 years in females and 30.2 years in males. The HR for fracture associated with AN differed by sex and age (interaction p = 0.002). Females with AN had an increased fracture risk at all ages (HR, 1.59; 95% confidence interval [CI], 1.45 to 1.75). AN was associated with a higher risk of fracture among males &gt;40 years of age (HR, 2.54; 95% CI, 1.32 to 4.90; p = 0.005) but not among males ≤40 years. Females with AN had a higher risk of fracture at nearly all anatomic sites. The greatest excess fracture risk was noted at the hip/femur (HR, 5.59; 95% CI, 3.44 to 9.09) and pelvis (HR, 4.54; 95% CI, 2.42 to 8.50) in females and at the vertebrae (HR, 7.25; 95% CI, 1.21 to 43.45) for males with AN. AN was associated with higher incident fracture risk in females across all age groups and in males &gt;40 years old. Sites of highest fracture risk include the hip/femur and pelvis in females and vertebrae in males with AN. © 2016 American Society for Bone and Mineral Research.</p>

<p>This population-based retrospective cohort study sought to determine if anorexia nervosa (AN) is associated with a higher risk of urolithiasis. Nine thousand three hundred two females with AN were compared to 92 959 randomly selected age-matched and practice-matched females. Cox regression was used to estimate the hazard ratio (HR) for urolithiasis and evaluate effect modification by age. Twenty-three participants with AN (0.25%) developed urolithiasis compared with 154 unexposed participants (0.17%) over a median of 4&nbsp;years of observation. The risk of urolithiasis varied significantly with age (interaction p = 0.02). AN was associated with a more than threefold higher risk of urolithiasis in females ≤25&nbsp;years of age (HR 3.49, 95% CI: 1.56-7.81; p = 0.002), but not in females over 25&nbsp;years (HR 1.18, 95% CI: 0.69-2.02; p = 0.54). The distribution of diagnosis codes for urolithiasis differed between groups (p = 0.04), with a higher proportion of codes for uric acid urolithiasis in the AN (16.2%) versus unexposed group (5.0%). Copyright © 2017 John Wiley &amp; Sons, Ltd and Eating Disorders Association.</p>

<p><strong>BACKGROUND: </strong>Variability in measures of mineral metabolism has not been studied in pediatric end stage kidney disease. We sought to determine the intra-individual variability in measures of mineral metabolism in children on hemodialysis (HD) and its impact on clinical decision-making.</p>

<p><strong>METHODS: </strong>We conducted a prospective single-center study of children (3.6-17.3 years old) on chronic HD. Serial twice weekly measures of serum calcium, phosphate and intact parathyroid hormone (PTH), as well as weekly measures of fibroblast growth factor 23 (FGF23) and vitamin D metabolites, were obtained over a 12-week period in 10 children. Samples (n = 226) were assayed in a single batch at the end of the study.</p>

<p><strong>RESULTS: </strong>The median intra-individual coefficient of variation (CV) calculated by 4-week blocks was 5.1-6.5% for calcium, 9.5-14.9% for phosphate and 32.7-33.4% for PTH. The median overall CV for FGF23 was 44.4%. Using the first value of each block as a reference, subsequent values would dictate a discrepant management decision 33-56%, 19-28%, and 30-33% of the time for calcium, phosphate, and PTH, respectively. Adjusting for sex and age, most of the variability in phosphate and PTH was attributable to within-participant variability. For calcium, 49% of the variability was attributable to day of blood collection (Monday vs. Friday). The median (range) of an individual participant's values within clinical target ranges was 55% (26-86%) for calcium, 58% (0-96%) for phosphate, and 21% (0-64%) for PTH.</p>

<p><strong>CONCLUSIONS: </strong>There is considerable intra-individual variability in measures of mineral metabolism that serve as surrogate markers for bone health in children on HD. Within a 4-week period, at least 20-30% of measures would dictate a discrepant decision from the referent measure of that month. These findings have important implications for clinical decision-making and underscore the need to base therapeutic decisions on trends rather than single measurements.</p>

<p>Although intestinal and urinary microbiome perturbations are associated with nephrolithiasis, whether antibiotics are a risk factor for this condition remains unknown. We determined the association between 12 classes of oral antibiotics and nephrolithiasis in a population-based, case-control study nested within 641 general practices providing electronic health record data for &gt;13 million children and adults from 1994 to 2015 in the United Kingdom. We used incidence density sampling to match 25,981 patients with nephrolithiasis to 259,797 controls by age, sex, and practice at date of diagnosis (index date). Conditional logistic regression models were adjusted for the rate of health care encounters, comorbidities, urinary tract infections, and use of thiazide and loop diuretics, proton-pump inhibitors, and statins. Exposure to any of five different antibiotic classes 3-12 months before index date was associated with nephrolithiasis. The adjusted odds ratio (95% confidence interval) was 2.33 (2.19 to 2.48) for sulfas, 1.88 (1.75 to 2.01) for cephalosporins, 1.67 (1.54 to 1.81) for fluoroquinolones, 1.70 (1.55 to 1.88) for nitrofurantoin/methenamine, and 1.27 (1.18 to 1.36) for broad-spectrum penicillins. In exploratory analyses, the magnitude of associations was greatest for exposure at younger ages (&lt;0.001) and 3-6 months before index date (&lt;0.001), with all but broad-spectrum penicillins remaining statistically significant 3-5 years from exposure. Oral antibiotics associated with increased odds of nephrolithiasis, with the greatest odds for recent exposure and exposure at younger age. These results have implications for disease pathogenesis and the rising incidence of nephrolithiasis, particularly among children.</p>

<p><strong>PURPOSE: </strong>To determine the association between dietary zinc intake and incident calcium kidney stones and examine the relationship between dietary zinc intake and urinary zinc excretion among adolescents.</p>

<p><strong>MATERIAL AND METHODS: </strong>This study was a nested case-control study conducted within a large pediatric healthcare system. Three 24-hour dietary recalls and spot urine chemistries were obtained for 30 participants aged 12-18 years with a first idiopathic calcium-based kidney stone and 30 healthy controls, matched on age, sex, race, and month of enrollment. Conditional logistic regression models were used to estimate the odds ratio (OR) between daily zinc intake and incident calcium kidney stones, adjusting for dietary phytate, protein, calcium, sodium, and oxalate. Multivariable linear regression was used to estimate the association between dietary and urine zinc, adjusting for urine creatinine and dietary phytate and calcium.</p>

<p><strong>RESULTS: </strong>Cases had lower daily zinc intake (8.1mg) than controls (10mg; p=0.029). Daily zinc intake of boys and girls with calcium stones was 2mg and 1.2mg lower, respectively, than the daily intake of zinc recommended by the Institute of Medicine. There was a 13% lower odds of incident stones for every 1mg higher daily zinc intake (OR, 0.87; 95% CI, 0.75-0.99). There was an estimated 4.5μg/dL increase in urine zinc per 1mg increase in dietary zinc (p=0.009), with weak evidence of a smaller increase in urine zinc in cases than in controls (interaction p=0.08).</p>

<p><strong>CONCLUSIONS: </strong>Lower dietary zinc intake was independently associated with incident calcium nephrolithiasis in this population of adolescents.</p>

<p>Pediatric stone disease is increasing in incidence and healthcare costs. With more years at-risk for stone recurrence during their lifetimes, children with nephrolithiasis constitute a high-risk patient population that requires focused intervention through both medical and surgical means. Through high-quality future studies to compare methods of stone prevention and treatment, the burden of stone disease on the youngest members of society may be ameliorated.</p>

<p><strong>BACKGROUND AND OBJECTIVES: </strong>The prevalence of nephrolithiasis in the United States has increased substantially, but recent changes in incidence with respect to age, sex, and race are not well characterized. This study examined temporal trends in the annual incidence and cumulative risk of nephrolithiasis among children and adults living in South Carolina over a 16-year period.</p>

<p><strong>DESIGN, SETTING, PARTICIPANTS, &amp; MEASUREMENTS: </strong>We performed a population-based, repeated cross-sectional study using the US Census and South Carolina Medical Encounter data, which capture all emergency department visits, surgeries, and admissions in the state. The annual incidence of nephrolithiasis in South Carolina from 1997 to 2012 was estimated, and linear mixed models were used to estimate incidence rate ratios for age, sex, and racial groups. The cumulative risk of nephrolithiasis during childhood and over the lifetime was estimated for males and females in 1997 and 2012.</p>

<p><strong>RESULTS: </strong>Among an at-risk population of 4,625,364 people, 152,925 unique patients received emergency, inpatient, or surgical care for nephrolithiasis. Between 1997 and 2012, the mean annual incidence of nephrolithiasis increased 1% annually from 206 to 239 per 100,000 persons. Among age groups, the greatest increase was observed among 15-19 year olds, in whom incidence increased 26% per 5 years (incidence rate ratio, 1.26; 95% confidence interval, 1.22 to 1.29). Adjusting for age and race, incidence increased 15% per 5 years among females (incidence rate ratio, 1.15; 95% confidence interval, 1.14 to 1.16) but remained stable for males. The incidence among blacks increased 15% more per 5 years compared with whites (incidence rate ratio, 1.15; 95% confidence interval, 1.14 to 1.17). These changes in incidence resulted in doubling of the risk of nephrolithiasis during childhood and a 45% increase in the lifetime risk of nephrolithiasis for women over the study period.</p>

<p><strong>CONCLUSIONS: </strong>The incidence of kidney stones has increased among young patients, particularly women, and blacks.</p>

<p><strong>PURPOSE: </strong>We review the current literature on the diagnostic evaluation and dietary and pharmacological management of children with nephrolithiasis.</p>

<p><strong>MATERIALS AND METHODS: </strong>We searched MEDLINE(®), Embase(®) and the Cochrane Library from their inceptions to March 2014 for published articles in English on kidney stones and therapy in children 0 to 18 years old. Based on review of the&nbsp;titles and abstracts, 110 of the 1,014 articles (11%) were potentially relevant to the diagnostic evaluation and medical management of nephrolithiasis in children. We summarized this literature and drew on studies performed in adult populations to augment areas in which no studies of sufficient quality have been performed in children, and to highlight areas in need of research.</p>

<p><strong>RESULTS: </strong>During the last 25 years the incidence of nephrolithiasis in children has&nbsp;increased by approximately 6% to 10% annually and is now 50 per 100,000 adolescents. Kidney stones that form during childhood have a similar composition to those that form in adulthood. Approximately 75% to 80% of stones are&nbsp;composed of predominantly calcium oxalate, 5% to 10% are predominantly calcium phosphate, 10% to 20% are struvite and 5% are pure uric acid. The recurrence rate of nephrolithiasis in patients with stones that form during childhood is poorly defined. Ultrasound should be used as the initial imaging study to evaluate children with suspected nephrolithiasis, with noncontrast computerized tomography reserved for those in whom ultrasound is nondiagnostic and the suspicion of nephrolithiasis remains high. Current treatment strategies for children with kidney stone disease are based largely on extrapolation of studies performed in adult stone formers and single institution cohort or case series studies of children. Tamsulosin likely increases the spontaneous passage of ureteral stones in children. Increased water intake and reduction of salt consumption should be recommended for all children with a history of kidney stones. Potassium citrate is a potentially effective medication for children with calcium oxalate stones and concomitant hypocitraturia, as well as children with uric acid stones. However, long-term compliance with therapy and the effect on decreasing stone recurrence in children are unknown. Based largely on efficacy in adult populations, thiazide diuretics should be considered in the treatment of children with calcium based stones and persistent hypercalciuria refractory to reductions in salt intake.</p>

<p><strong>CONCLUSIONS: </strong>The incidence of kidney stone disease in children is increasing, yet&nbsp;few randomized clinical trials or high quality observational studies have assessed whether dietary or pharmacological interventions decrease the recurrence of kidney stones in children. Collaborative efforts and randomized clinical trials are needed to determine the efficacy and effectiveness of alternative treatments for children with nephrolithiasis, particularly those with calcium oxalate stones and concomitant hypercalciuria and hypocitraturia. Additional areas in need of study are the optimal length of time for a trial of stone passage in children, the cost-effectiveness of medical expulsive therapy vs analgesics alone, and the size and location of stones for which medical expulsive therapy is most effective.</p>