Stone-forming Children Research Articles

MP10-02 DIETARY INTERVENTION IN ENTERIC HYPEROXALURIA

You have accessJournal of UrologyCME1 Apr 2023MP10-02 DIETARY INTERVENTION IN ENTERIC HYPEROXALURIA William DeFoor, Joonsue Lee, Nehus Edward, Marion Schulte, Sydney Huesman, Ashleigh Libs, and Prasad Devarajan William DeFoorWilliam DeFoor More articles by this author , Joonsue LeeJoonsue Lee More articles by this author , Nehus EdwardNehus Edward More articles by this author , Marion SchulteMarion Schulte More articles by this author , Sydney HuesmanSydney Huesman More articles by this author , Ashleigh LibsAshleigh Libs More articles by this author , and Prasad DevarajanPrasad Devarajan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003225.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Medically complex, gastrostomy-fed children are particularly vulnerable to forming kidney stones. We have previously shown that there are elevated urinary oxalate levels in patients using enteral feeding formulas primarily based on soy protein, a known high oxalate food. Enteric hyperoxaluria may predispose patients to calcium oxalate stones. The objective of this study is assess if targeted dietary intervention decreases urinary oxalate excretion. METHODS: A retrospective cohort study was performed on medically complex children with cerebral palsy and severe developmental delay presenting to a high-volume Pediatric Stone Center with nephrolithiasis from 2015 to 2020. Inclusion criteria included those who underwent a dietary and urinary metabolic evaluation before and after the index visit. Diets were analyzed by a registered dietitian. Urinary metabolites including calcium, oxalate, and citrate as well as the supersaturations of calcium oxalate and calcium phosphate were analyzed via two 24-hour urine collections. Dietary oxalate load was determined by evaluating individual recipes for known high oxalate ingredients or soy-based formulas. Patients were stratified into those on a low versus high oxalate diet. Statistical analysis was performed using paired t-tests. RESULTS: A total of 13 medically complex stone-forming children met inclusion criteria. All patients were non-ambulatory. 11 of 13 (85%) were primarily fed via gastrostomy. Of the 13 patients, 4 were on a low oxalate diet and 9 were found to have a diet of high oxalate foods. The baseline urinary oxalate excretion (26 vs. 71 mg/m2/day, P = 0.001) and supersaturation of calcium oxalate (6.1 vs. 14.3, P=0.01) were lower in those with a low oxalate diet. Four patients on high oxalate diets were targeted for lowering the enteral oxalate load. A follow-up urinary metabolic evaluation was performed a mean of 6.5 months after the dietary intervention. The urinary oxalate level decreased from 71 to 33 mg/m2/day (P=0.049). Urinary excretion of calcium and citrate as well as the supersaturation of calcium phosphate were similar following dietary modifications. CONCLUSIONS: Urinary oxalate excretion and supersaturation of calcium oxalate were elevated in medically complex stone-forming children with high dietary oxalate content. Targeted dietary intervention to reduce the oxalate load in enteral formulas can lead to a substantial decrease in urinary oxalate excretion. Further investigation is required to determine if this leads to lower stone recurrence, hospitalizations, and the need for surgical interventions. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e114 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information William DeFoor More articles by this author Joonsue Lee More articles by this author Nehus Edward More articles by this author Marion Schulte More articles by this author Sydney Huesman More articles by this author Ashleigh Libs More articles by this author Prasad Devarajan More articles by this author Expand All Advertisement PDF downloadLoading ...

Enteral nutrition and the risk of nephrolithiasis in complex pediatric patients

Medically complex, non-ambulatory children can often suffer from nephrolithiasis. The purpose of this study is to determine risk factors which are predictive for recurrent stone formation in this patient population. A retrospective cohort study was performed on non-ambulatory patients with cerebral palsy and/or severe developmental delay presenting to a high-volume Pediatric Stone Center from 2015 to 2019. Two 24-hour urine collections were performed as a baseline prior to pharmacotherapeutic and/or dietary intervention. Healthy stone-forming children served as a control group. 28 non-ambulatory subjects and 38 healthy controls were evaluated. The study group had a higher rate of bilateral nephrolithiasis but a similar history of previous surgical procedures. 89% of the non-ambulatory children were fed via a gastrostomy. The median calcium excretion was the same in both groups (3.0mg/kg/day). The median 24-hour excretion of oxalate was significantly increased in the study group (54 vs 31mg/1.73m2/day, p=0.0001). Urinary citrate and phosphorus excretions, and the supersaturations of calcium oxalate and calcium phosphate were similar between study subjects and controls. Calcium oxalate stones were noted in 57% of those with known stone composition in the study group. Enteral feeding formulas were primarily based on soy protein, a known high oxalate food. Urinary oxalate excretion is significantly increased in a cohort of medically complex, non-ambulatory stone-forming children. Urinary calcium excretion was not elevated between study subjects and healthy controls. Further analysis is needed to assess if dietary intervention to limit oxalate excretion results in decreased stone formation.

Dietary risk factors for urinary stones in children.

As the incidence of urinary stone disease in children is increasing, identifying dietary risk factors becomes vitally important, especially in the context of targeting interventions to reduce risk for stone formation. Indiscriminant dietary restrictions are not appropriate for paediatric patients. Although large, prospective studies are still needed to better quantify dietary risk factors for paediatric stone formers, a number of smaller studies provide data to identify common risk factors to help prevent stone formation, while minimizing inappropriate dietary restrictions. Interpretation of 24-h urine samples to identify individualized dietary risk factors is crucial for implementing a strategy for prevention of further urinary stone formation in children. Clinicians should avoid generalized dietary restrictions in stone-forming children uninformed by laboratory data.

Analysis of urine composition from split 24-h samples: use of 12-h overnight samples to evaluate risk factors for calcium stones in healthy and stone-forming children

The analysis of 24-h urine is the gold standard to diagnose metabolic abnormalities in the stone-forming patient. However, urinary composition changes throughout the dayand analyzing the whole 24-h urine may mask peaks of increased risk of crystallization. To examine variations of stone-promoting and stone-inhibiting factors in urine using split 24-h samples from healthy and stone-forming children. Urine was collected from 87 healthy and 26 stone-forming children using a split collection procedure (12-h daytime urine and 12-h overnight urine). Urine volume, pH, calcium (Ca), magnesium (Mg), phosphate (P), citrate (Cit), uric acid (Ur), and oxalate (Ox) were determined, and the Ca/Cit ratio was calculated. The overnight urine samples in both groups had higher levels of P and Mg, lower volume, lower pH, and less citrate and uric acid. As can be seen in the table, higher percentages of healthy and stone-forming children had altered 12-h night urine than 24-h urine with regards to Ca/Cr, Cit/Cr and Ca/Cit ratios. All healthy subjects and all stone-forming children (except one) with altered Cit/Cr ratios or Ca/Cit ratios in the 24-h sample also had altered ratios in the 12-h overnight sample. This study indicates that urine composition changes throughout the day, and that there is daily variability in most of the parameters related to kidney stone formation. Furthermore, 12-h overnight samples seem to be more sensitive than 24-h samples in detecting the most common urinary abnormalities. The main limitation of this study is the relative low sample size of stone-forming children, owing to the low prevalence of nephrolithiasis in childhood. We observed a higher excretion of stone-promoting substances and a lower citrate in urine at night. However, the study results do not provide enough evidence to conclude that the use of a 12-h overnight sample collection can replace 24h urine analysis in the metabolic evaluation of children with lithiasis.

Effect of sample time on urinary lithogenic risk indexes in healthy and stone-forming adults and children

BackgroundThe diagnosis and follow-up of stone forming patients is usually performed by analysis of 24-h urine samples. However, crystallization risk varies throughout the day, being higher at night. The main objective of this study is to evaluate the urinary crystallization risk in adults and children by calculating risk indexes based on different collection periods.MethodsThe study included 149 adults (82 healthy and 67 stone-formers) and 108 children (87 healthy and 21 stone-formers). 24-h urine was collected, divided into 12-h daytime sample (8 am to 8 pm), and 12-h overnight sample (8 pm to 8 am next morning). Solute concentrations, the calcium to citrate ratio (Ca/Cit), and the ion activity product of calcium oxalate (AP[CaOx]) and calcium phosphate (AP[CaP]) were calculated in each 12-h sample and in overall 24-h urine. Assessments were also related to stone type.ResultsCa/Cit and AP(CaOx) were significantly higher in stone forming patients than in healthy subjects. The 12-h overnight samples had the highest values for both risk indexes, confirming a greater risk for crystallization at night. The AP(CaP) index was significantly higher in patients with pure hydroxyapatite stones than healthy controls, but was not significantly different between stone-formers overall and healthy controls.ConclusionsThe calculation of risk indexes is a simple method that clinicians can use to estimate crystallization risk. For this purpose, the use of 12-h overnight urine may be a reliable alternative to 24-h collections.

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

Approximately half of adult stone formers submit specimens that are either under or over collections as determined by 24-hcreatinine/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. The objective of this study is to determine risk factors for inadequate 24-hurinary specimen collection in the pediatric population. 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-hurinary 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 10-15mg/kg/24h. 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. 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-hurinary 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). Any parental or child factors associated with the collection of inadequate 24-hurine 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. 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.

Do Overweight and Obese Pediatric Stone Formers Have Differences in Metabolic Abnormalities Compared With Normal-weight Stone Formers?

To determine if 24-hour urinary parameters in children with nephrolithiasis across 4 institutions were influenced by body mass index (BMI). The 24-hour urinary parameters obtained from children with nephrolithiasis between 2000 and 2013 were stratified by BMI percentile ≥85th and <85th (overweight and obese patients vs healthy weight, respectively). A total of 206 children were included in the study. Exclusion criteria included patients with a history of spina bifida, neurogenic bladder, and cerebral palsy, and patients on medical treatment before the first 24-hour urine collection. Overweight and obese patients consisted of 35.4% of the cohort (n = 73). Metabolic abnormalities were present in 130 children (63.1%). The most common abnormality present in the <85th percentile was hypercalciuria (32.3%), and in the ≥85th percentile, hyperoxaluria (37.0%). Univariable and multivariable analyses revealed that overweight and obese children were more likely to have low urinary volume and elevated uric acid compared to normal-weight children. Although there is a link between stone formation and BMI in adults, no definitive conclusions have been proven in the pediatric literature. Our study indicates that stone-forming children who are overweight or obese have low urinary volume and elevated uric acid compared to normal-weight stone-forming children.

Correspondence between Ca2+ and calciuria, citrate level and pH of urine in pediatric urolithiasis

BackgroundHypercalciuria and hypocitraturia are considered the most important risk factors for urolithiasis. Citrate binds to urinary calcium to form a soluble complex which decreases the availability of ionized calcium (Ca2+) necessary for calcium oxalate formation and phosphate crystallization. The aims of this study were to assess the Ca2+ fraction in relation to total calciuria, citraturia and urinary pH and to determine whether urinary Ca2+ concentration is a helpful biomarker in metabolic evaluation of children with urolithiasis.MethodsWe collected 24-h urine samples from 123 stone-forming children and adolescents with hypocitraturia and from 424 healthy controls. Total calciuria (total calcium, Catotal), Ca2+, pH, citrate, oxalate and Bonn Risk Index (BRI) were assessed and compared between the two groups.ResultsTotal calciuria and Ca2+ content were higher in stone-formers than in the healthy children. In both stone-formers and controls, Ca2+ content was inversely related to citraturia and urinary pH, whereas the Ca2+/Catotal ratio differed slightly between the groups. A large variability in Ca2+ level was found across individuals in both groups. The BRI increased with increasing calciuria and urine acidity.ConclusionsCompared to controls, stone-formers with hypocitraturia demonstrated a higher urinary Ca2+ concentration, but this was proportional to calciuria. The large individual variability in urinary Ca2+ content limits its practical use in metabolic evaluation of children with urolithiasis. However, the Ca/Citrate ratio may be a useful clinical tool in evaluating children with urolithiasis.

Urine risk factors in children with calcium kidney stones and their siblings

Calcium nephrolithiasis in children is increasing in prevalence and tends to be recurrent. Although children have a lower incidence of nephrolithiasis than adults, its etiology in children is less well understood; hence treatments targeted for adults may not be optimal in children. To better understand metabolic abnormalities in stone forming children, we compared chemical measurements and the crystallization properties of 24-hour urine collections from 129 stone formers matched to 105 non-stone forming siblings and 183 normal, healthy children with no family history of stones; all aged 6 to 17 years. The principal risk factor for calcium stone formation was hypercalciuria. Stone formers have strikingly higher calcium excretion along with high supersaturation for calcium oxalate and calcium phosphate, and a reduced distance between the upper limit of metastability and supersaturation for calcium phosphate, indicating increased risk of calcium phosphate crystallization. Other differences in urine chemistry that exist between adult stone formers and normal individuals such as hyperoxaluria, hypocitraturia, abnormal urine pH and low urine volume were not found in these children. Hence, hypercalciuria and a reduction in the gap between calcium phosphate upper limit of metastability and supersaturation are crucial determinants of stone risk. This highlights the importance of managing hypercalciuria in children with calcium stones.

Urine risk factors in children with calcium kidney stones and their siblings

Calcium nephrolithiasis in children is increasing in prevalence and tends to be recurrent. Although children have a lower incidence of nephrolithiasis than adults, its etiology in children is less well understood; hence, treatments targeted for adults may not be optimal in children. To better understand metabolic abnormalities in stone-forming children, we compared chemical measurements and the crystallization properties of 24-h urine collections from 129 stone formers matched to 105 non-stone-forming siblings and 183 normal, healthy children with no family history of stones, all aged 6 to 17 years. The principal risk factor for calcium stone formation was hypercalciuria. Stone formers have strikingly higher calcium excretion along with high supersaturation for calcium oxalate and calcium phosphate, and a reduced distance between the upper limit of metastability and supersaturation for calcium phosphate, indicating increased risk of calcium phosphate crystallization. Other differences in urine chemistry that exist between adult stone formers and normal individuals such as hyperoxaluria, hypocitraturia, abnormal urine pH, and low urine volume were not found in these children. Hence, hypercalciuria and a reduction in the gap between calcium phosphate upper limit of metastability and supersaturation are crucial determinants of stone risk. This highlights the importance of managing hypercalciuria in children with calcium stones.

Does citrate prevent nephrocalcinosis in preterm neonates?

Nephrocalcinosis (NC) occurs frequently in preterm neonates. A high U-calcium/citrate is one of the contributing factors to the development of NC. In stone-forming children and adults citrate supplementation is a successful preventive therapy. In this randomized controlled trial the effect of citrate therapy was studied on the development of NC in preterm neonates with a gestational age <32 weeks. Thirty-eight preterm neonates (mean gestational age 29.8 weeks (SD 1.6), mean birth weight 1,300 g (SD 351) were treated with sodium citrate (0.52 mmol/kg/day in four doses) from day 8 of life until at term and 36 preterm neonates (mean gestational age 29.6 weeks (SD 1.6), mean birth weight 1,282 g (SD 256) were not treated. U-calcium, U-creatinine, U-citrate and U-pH were measured at day 7, 14, 21, 28 of life and at term. Renal ultrasonography (US) was performed at term. U-citrate/creatinine and U-pH were significantly higher and U-calcium/citrate was significantly lower in the citrate group at day 14, 21 and 28 compared with the control group (P<0.05). Complications of citrate administration were not encountered, however the incidence of NC was not significantly different in the treated (34%) compared with the control group (44%), P=0.37. Preterm neonates treated with citrate in the first months of life have higher U-citrate/creatinine and lower U-calcium/citrate compared with controls. Sodium citrate therapy in a dosage of 0.52 mmol/kg/day is safe but does not prevent NC. Whether a higher dose or potassium citrate decreases the incidence of NC should be evaluated in further studies.

RESULTS OF A PROSPECTIVE TRIAL TO COMPARE NORMAL URINE SUPERSATURATION IN CHILDREN AND ADULTS

Urinary stone disease is relatively rare in children but is often due to metabolic abnormalities. Urinary supersaturation (SS) indices have been suggested as more precise predictors of stone recurrence. We previously reported urinary metabolic evaluations in stone-forming children using adult references. We now assess normal SS values in children. A prospective trial was performed to assess urinary metabolic profiles in children with no personal or family history of urinary calculi. The 24-hour urine collections were performed and evaluated at an outside central laboratory. Urine chemistries were adjusted for urine creatinine. Urine pH and SS for calcium oxalate, calcium phosphate and uric acid were also assessed. The data were compared to a cohort of normal adults. A total of 168 samples from 168 adults (58% males) and 51 samples from 30 children (59% males) were evaluated. The mean age of the children was 8.8 years (range 5 to 18). Calcium oxalate SS was similar between children and adults, and urine pH was the major cause of differences seen in the calcium phosphate and uric acid SS indices. Children had a much higher excretion of calcium, oxalate and citrate when adjusted for creatinine. There are significant differences in the normal ranges of urine chemistries in children and adults. An understanding of normal supersaturation values may allow metabolic abnormalities in stone-forming children to be more precisely diagnosed and treated.

Urinary glycosaminoglycan excretion in healthy and stone-forming children.

Both in vivo and in vitro studies suggest that macromolecules excreted in the urine, e.g. glycosaminoglycans (GAGs) may be inhibitors of kidney stone formation. We evaluated urinary GAG excretion in 22 children with calcium oxalate stones [8 with absorptive hypercalciuria, 6 with renal hypercalciuria (RH), 8 with normocalciuria], and in 20 age-matched controls. There was no significant difference between the two groups in the total urinary GAG level. In terms of the various GAG fractions, patients with RH excreted considerably less keratan sulphate and considerably more dermatan sulphate than the other patients and healthy controls. There was no difference between the two groups in condroitin sulphate, heparan sulphate and hyaluronic acid excretion. We conclude that there is no significant correlation between the formation of calcium oxalate stones and urinary GAG excretion.

The aetiological and clinical pattern of childhood urolithiasis in Saudi Arabia.

The clinical and aetiological pattern in 85 stone-forming children presenting to an integrated nephrourological service in Riyadh is reviewed. All patients were below the age of 15 years, the male to female ratio being 2:1. Only 2 children presented with bladder calculi. The remaining all had upper tract stones and, in 12 cases, these were bilateral. Of 34 calculi recovered for analysis, one-third was predominantly calcium oxalate and a further third was composed of uric acid or urate. Four patients had cysteine stones and the remaining 7 presented mixed calcium stones, 6 (17.6%) being struvite and infection-related. Of the 85 patients 55 were treated successfully with extracorporeal shock wave lithotripsy, 16 underwent surgery and 7 had their stones removed by endourological procedures. In the remaining 7 children, stones dissolved or were passed spontaneously during medical therapy. Nine children (10.6%) showed a primary metabolic defect leading to their stone formation, 10 (11.8%) had a predisposing anatomical anomaly and 15 (17.6%) presented with urinary tract infection. Of the remaining 51 patients (60%) with idiopathic disease, 6 showed hypercalciuria on investigation and 2 children may have formed their stones due to prolonged recumbency.

Urologic Manifestations of Hyperparathyroidism in Childhood

Among renal stone-forming children 6 per cent suffer from primary hyperparathyroidism. Urologic complications were noted in 7 of 9 children (78 per cent) with surgically proved hyperparathyroidism seen in a 24-year period. These included nephrolithiasis and nephrocalcinosis (6), defective urinary concentration or acidification (5) and mild impairment of renal function (3). All children responded favorably to parathyroidectomy, which should be performed before treatment of stone disease is undertaken. The nature of urologic manifestations of hyperparathyroidism and their management are discussed.