Navigating the microbial maze: unraveling the connection between gut microbiome and pediatric kidney and urinary tract disease.

The gut microbiome is made up of trillions of bacteria, viruses, archaea, and microbes that play a significant role in the maintenance of normal physiology in humans. Recent research has highlighted the effects of the microbiome and its dysbiosis in the pathogenesis and maintenance of kidney disease, especially chronic kidney disease (CKD) and its associated cardiovascular disease. While studies have addressed the kidney-microbiome axis in adults, how dysbiosis may uniquely impact pediatric kidney disease patients is not well-established. This narrative review highlights all relevant studies focusing on the microbiome and pediatric kidney disease that were published between 7/2015 and 7/2023. This review highlights pediatric-specific considerations including growth and bone health as well as emphasizing the need for increased pediatric research. Understanding microbiome-kidney interactions may allow for novel, less invasive interventions such as dietary changes and the use of probiotics to improve preventive care and ameliorate long-term morbidity and mortality in this vulnerable population.

Evidence of increased vascular stiffness and left ventricular hypertrophy in children with cystic kidney disease.

BACKGROUND: Cardiovascular disease (CVD) is the most common cause of mortality in chronic kidney disease (CKD). Children with early-onset CKD arguably experience the greatest lifetime CVD burden. We utilized data from the Chronic Kidney Disease in Children Cohort Study (CKiD) to evaluate two pediatric CKD cohorts: congenital anomalies of the kidney and urinary tract (CAKUT) and cystic kidney disease for CVD risks and outcomes. METHODS: CVD risk factors and outcomes including blood pressures, left ventricular hypertrophy (LVH), left ventricular mass index (LVMI), and ambulatory arterial stiffness index (AASI) scores were evaluated. RESULTS: Forty-one patients in the cystic kidney disease group were compared to 294 patients in the CAKUT group. Cystic kidney disease patients had higher cystatin-C levels, despite similar iGFR. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) indexes were higher in the CAKUT group, but a significantly higher proportion of cystic kidney disease patients was on anti-hypertensive medications. Cystic kidney disease patients had increased AASI scores and a higher incidence of LVH. CONCLUSIONS: This study provides a nuanced analysis of CVD risk factors and outcomes including AASI and LVH in two pediatric CKD cohorts. Cystic kidney disease patients had increased AASI scores, higher incidence of LVH, and higher rates of anti-hypertensive medication use which could imply a greater burden of CVD despite similar GFR. Our work suggests that additional mechanisms may contribute to vascular dysfunction in cystic kidney disease, and that these patients may need additional interventions to prevent the development of CVD. A higher resolution version of the Graphical abstract is available as Supplementary information.

A survey on nutritional management of critically ill children on continuous renal replacement therapy.

We conducted a survey of pediatric nephrologists to examine the knowledge and current practices of and identify challenges in the nutritional management of critically ill children during continuous renal replacement therapy (CRRT). Although it is known that there is a significant effect on nutrition during CRRT, there seems to be a lack of knowledge as well as variability in the practices of nutritional management in these patients, as indicated by our survey results. The heterogeneity of our survey results highlights the need to establish clinical practice guidelines and develop consensus around optimal nutritional management in pediatric patients requiring CRRT. The results as well as the known effects of CRRT on metabolism should be considered during the development of guidelines in critically ill children on CRRT. Our survey findings also highlight the need for further research in the assessment of nutrition, determination of energy needs and caloric dosing, specific nutrient needs, and management.

Pediatric Mineral and Bone Disorder of Chronic Kidney Disease and Cardiovascular Disease.

Chronic kidney disease is common and causes significant morbidity including shortened lifespans and decrease in quality of life for patients. The major cause of mortality in chronic kidney disease is cardiovascular disease. Cardiovascular disease within the chronic kidney disease population is closely tied with disordered calcium and phosphorus metabolism and driven in part by renal bone disease. The complex nature of renal, bone, and cardiovascular diseases was renamed as mineral and bone disorder of chronic kidney disease to encompass how bone disease drives vascular calcification and contributes to the development of long-term cardiovascular disease, and recent data suggest that managing bone disease well can augment and improve cardiovascular disease status. Pediatric nephrologists have additional obstacles in optimal mineral and bone disorder of chronic kidney disease management such as linear growth and skeletal maturation. In this article, we will discuss cardiovascular and bone diseases in chronic kidney disease and end-stage kidney disease patients with a focus on pediatric issues and concerns.

A Meta-Analysis of Extracorporeal Anticoagulants in Pediatric Continuous Kidney Replacement Therapy.

OBJECTIVE: Continuous kidney replacement therapy (CKRT) is the primary therapeutic modality utilized in hemodynamically unstable patients with severe acute kidney injury. As the circuit is extracorporeal, it poses an increased risk of blood clotting and circuit loss; frequent circuit losses affect the provider's ability to provide optimal treatment. The objective of this meta-analysis is to evaluate the safety and efficacy of the extracorporeal anticoagulants in the pediatric CKRT population. DATA SOURCES: We conducted a literature search on PubMed/Medline and Embase for relevant citations. STUDY SELECTION: Studies were included if they involved patients under the age of 18 years undergoing CKRT, with the use of anticoagulation (heparin, citrate, or prostacyclin) as a part of therapy. Only English articles were included in the study. DATA EXTRACTION: Initial search yielded 58 articles and a total of 24 articles were included and reviewed. A meta-analysis was performed focusing on the safety and effectiveness of regional citrate anticoagulation (RCA) vs unfractionated heparin (UFH) anticoagulants in children. DATA SYNTHESIS: RCA had statistically significantly longer circuit life of 50.65 hours vs. UFH of 42.10 hours. Two major adverse effects metabolic alkalosis and electrolyte imbalance seen more commonly in RCA compared to UFH. There was not a significant difference in the risk of systemic bleeding when comparing RCA vs. UFH. CONCLUSION: RCA is the preferred anticoagulant over UFH due to its significantly longer circuit life, although vigilant circuit monitoring is required due to the increased risk of electrolyte disturbances. Prostacyclin was not included in the meta-analysis due to the lack of data in pediatric patients. Additional studies are needed to strengthen the study results further.

Cardiovascular implications in adolescent and young adult hypertension.

Background: Hypertension is one of the most prevalent diseases in the United States, affecting an estimated 3.5% of children and adolescents. It can be adversely affect most organ systems but is particularly detrimental to the heart and vascular systems. The repercussions can be gauged through well-established measures of cardiovascular function including left ventricular mass index (LVMI), left ventricular hypertrophy (LVH), carotid intima media thickness (cIMT), and aortic stiffness. Cardiovascular function is also affected by underlying etiologies of hypertension including chronic kidney disease, polycystic kidney disease, coarctation of the aorta, adrenal disorders, renal artery stenosis, obstructive sleep apnea, as well as various drugs and medications (decongestants, stimulants, Non-steroidal Anti-inflammatory Drugs (NSAIDs), and steroids). Methods: An exhaustive literature search was conducted for clinical data regarding pediatric hypertension. Sixty-seven articles were incorporated with data on 189,477 subjects total. The data was then extracted and categorized as relating to hypertension incidence, LVMI, LVH, cIMT, and/or aortic stiffness. Results: The prevalence of pediatric ( < 18 years) hypertension extracted from 47 studies from 1994 to 2018 averaged 4%. The LVMI assessed over 7 studies (n = 661) averaged 39.3 g/ m 2.7 in the hypertensive cohort and 30.1 g/ m 2.7 in the control cohort. The cIMT assessed over 7 studies (n = 580) averaged 0.55 mm in the hypertensive cohort and 0.49 mm in the control cohort. Ambulatory arterial stiffness parameters assessed over 5 studies (n = 573) in the normotensive cohort averaged 99.73 mmHg, 69.81 mmHg, 76.85 mmHg, and 46.90 mmHg, for SBP, DBP, MAP, and PP respectively. Ambulatory arterial stiffness parameters assessed over 5 studies (n = 573) in the hypertensive cohort averaged 129.56 mmHg, 73.69 mmHg, 95.08 mmHg, and 56.80 mmHg, for SBP, DBP, MAP, and PP respectively. Conclusions: The significance of pediatric hypertension is emphasized by evidence of early cardiovascular disease as demonstrated by non-invasive measures including cIMT and arterial stiffness parameters, and target organ damage and including LVH and LVMI factors. Thus, early diagnosis and treatment of high blood pressure is paramount for improving long term cardiovascular health and preventing long term morbidity and mortality.

Association of pulse pressure, pulse pressure index, and ambulatory arterial stiffness index with kidney function in a cross-sectional pediatric chronic kidney disease cohort from the CKiD study.

The morbidity and mortality of adult and pediatric chronic kidney disease (CKD) and end-stage renal disease (ESRD) populations are mainly driven by cardiovascular disease (CVD). Improving CVD outcomes focuses on risk assessment of factors including diastolic blood pressure (DBP), systolic blood pressure (SBP), left ventricular mass index (LVMI), pulse pressure (PP), and pulse pressure index (PPi), which is calculated as PP/SBP. These markers are also proven predictors of CKD progression; however, their role in children has not been established. This study aims to evaluate the relationship between PP, PPi, ambulatory arterial stiffness index (AASI), and proteinuria with kidney function in pediatric CKD patients; it is a retrospective analysis of 620 patients (1-16 years) from the NIDDK Chronic Kidney Disease in Children (CKiD) registry. The authors analyzed data for three separate cohorts: an overall CKD as well as immunological versus non-immunological cause for CKD groups. An inverse relationship was found between SBP, DBP, and PP with iGFR and LVMI in the overall CKD group. Our immunological CKD subgroup showed significantly higher serum creatinine, SBP, DBP, and PP values with significantly lower serum albumin levels compared to the non-immunological group. There were no significant differences with iohexol-based glomerular filtration rate (iGFR), LVMI, PPi, or high-sensitivity C-reactive protein (hs-CRP) between the two groups. A subgroup analysis demonstrated that SBP, DBP, and PP all correlated significantly with LVMI in the immunological CKD patients but not the non-immunological subgroup. Additionally, AASI data in the overall CKD population were significantly correlated with PP, PPi, and DBP. This study is one of the first to correlate noninvasive measurements of vascular compliance including PP, PPi, and AASI with iGFR and LVMI in a pediatric CKD cohort. Improving our understanding of surrogate markers for early CVD is integral to improving the care of pediatric CKD population as these patients have yet to develop the hard end points of ESRD, heart failure, myocardial infarction, or stroke.

Bone mineral density in adolescent urinary stone formers: is sex important?

Urinary stone disease (USD) is affecting a greater number of children and low bone mineral density (BMD) and increased skeletal fractures have been demonstrated in stone patients; however, the mechanism(s) driving bone disease remain unclear. This pilot study was undertaken to assess an adolescent kidney stone cohort's BMD and evaluate for an inverse correlation between BMD and urine concentration of lithogenic minerals and/or inflammatory levels. Prospective case-control study was carried out at a large pediatric center. 15 participants with USD (12-18 years of age, 8 female) were matched by age, sex, and body mass index to 15 controls. Lumbar and total body BMD z-score did not differ between groups. When stone formers were separated by sex, there was a significant difference between male stone formers vs. controls total body BMD z-score (Fig. 1). BMD z-score did not significantly correlate with urine calcium, oxalate, citrate or magnesium. Higher urine IL-13 did significantly correlate with higher total body BMD z-score (r = 0.677, p = 0.018). Total body BMD z-score did significantly correlate with body mass index (BMI) as expected for the control group (r = 0.6321, p = 0.0133). However, this relationship was not present in the USD group (r = - 0.1629, p = 0.5619). This is a small but hypothesis-generating study which demonstrates novel evidence of male-specific low BMD in adolescent stone formers. Furthermore, we demonstrated a positive association between urine IL-13 and total body BMD z-score USD patients as well as a lack of a positive BMD and BMI correlations in stone formers.

The Role of Endothelin and Endothelin Antagonists in Chronic Kidney Disease.

BACKGROUND: Endothelins (ET) are a family of peptides that act as potent vasoconstrictors and pro-fibrotic growth factors. ET-1 is integral to renal and cardiovascular pathophysiology and exerts effects via autocrine, paracrine and endocrine signaling pathways tied to regulation of aldosterone, catecholamines, and angiotensin. In the kidney, ET-1 is critical to maintaining renal perfusion and controls glomerular arteriole tone and hemodynamics. It is hypothesized that ET-1 influences the progression of chronic kidney disease (CKD), and the objective of this review is to discuss the pathophysiology, and role of ET and endothelin receptor antagonists (ERAs) in CKD. SUMMARY: The use of ERAs in hypertensive nephropathy has the potential to decrease proteinuria, and in diabetic nephropathy has the potential to restore glycocalyx thickness, also decreasing proteinuria. Focal segmental glomerular sclerosis has no specific Food and Drug Administration-approved therapy currently, however, ERAs show promise in decreasing proteinuria and slowing tissue damage. ET-1 is a potential biomarker for autosomal dominant polycystic kidney disease progression and so it is thought that ERAs may be of some therapeutic benefit. KEY MESSAGES: Multiple studies have shown the utility of ERAs in CKD. These agents have shown to reduce blood pressure, proteinuria, and arterial stiffness. However, more clinical trials are needed, and the results of active or recently concluded studies are eagerly awaited.

Acute Kidney Injury Associated With Urinary Stone Disease in Children and Young Adults Presenting to a Pediatric Emergency Department.

Background: Acute kidney injury (AKI) due to urinary stone disease (USD) is rare in adults; AKI rates in children with USD may be higher, and emerging data links stones to chronic kidney disease (CKD) development in adults. Methods: This study is a retrospective analysis of USD patients at a single pediatric hospital system's emergency department (ED). Patients were initially identified by USD ICD codes; USD was then confirmed by imaging or physician documentation; patients had to have baseline creatinine (Cr) and Cr in the ED for comparison to be included. AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO), Acute Kidney Injury Network (AKIN), and Pediatric Risk, Injury, Failure, Loss, End Stage (pRIFLE). Results: Of the 589 total visits, 264/589 (45%) had data to evaluate for AKI, 23% were AKI(+) and 77% were AKI(-). pRIFLE was most common (82%) and 18% were only positive by AKIN/KDIGO. AKI(+) were more likely to be younger (16.7 vs. 17.4 years, p = 0.046) and more likely to present with vomiting {odds ratio [OR] [95% confidence interval (CI)]: 2.4 [1.4-4.3], p = 0.002}; also, the proportion of AKI(+) was significantly higher in <18 vs. ≥18 years [26.9 vs. 15.5%, p = 0.032, OR (95% CI): 2.0 (1.1-3.9)]. Urinary tract infection (UTI) and obstruction rates were similar between groups. AKI(+) patients had a significant OR <1 suggesting less risk of receiving non-steroidal anti-inflammatory drugs (NSAIDs); however, 51% of them did receive NSAIDs during their ED encounter. AKI(+) patients were more likely to require admission to the hospital (53 vs. 32%, p = 0.001). Conclusion: We have demonstrated a novel association between USD-induced renal colic and AKI in a group of young adults and children. AKI(+) patients were younger and were more likely to present with vomiting. AKI(+) patients did not have higher rates of obstruction or UTI, and 51% of AKI(+) received NSAIDs.

Overview of Monogenic or Mendelian Forms of Hypertension.

Monogenic or Mendelian forms of hypertension are described as a group of conditions characterized by insults to the normal regulation of blood pressure by the kidney and adrenal gland. These alterations stem from single mutations that lead to maladaptive overabsorption of electrolytes with fluid shift into the vasculature, and consequent hypertension. Knowledge of these various conditions is essential in diagnosing pediatric or early-onset adult hypertension as they directly affect treatment strategies. Precise diagnosis with specific treatment regimens aimed at the underlying physiologic derangement can restore normotension and prevent the severe sequelae of chronic hypertension.

Adolescents with urinary stones have elevated urine levels of inflammatory mediators.

Urinary stones are increasing in children, primarily during adolescence. Although urinary stones are often viewed in the context of intermittent stone events, increasing evidence indicates that stones are a metabolic process associated with chronic kidney disease and cardiovascular disease. These aforementioned stone-associated conditions may have pediatric origins. To compare urine inflammatory markers in otherwise healthy stone forming children versus matched controls. Urine samples were collected from 12 adolescents with urinary stones along with 15 controls. The levels of 30 urine cytokines were measured using a Mesoscale 30-Plex Human Cytokine panel and normalized to urine creatinine levels. Macrophage inflammatory protein 1ß and interleukin 13 levels were significantly elevated in the urine of the stone forming adolescents compared to controls. Interleukin 17A was elevated in the urine of controls. This study indicates that urine levels of cytokines involved in chronic inflammation and fibrosis are elevated in urinary stone formers as early as adolescence. Because stone formers are at risk for chronic kidney disease, macrophage inflammatory protein 1ß and interleukin 13 represent investigative targets.

Comparison of Risk Factors for Pediatric Kidney Stone Formation: The Effects of Sex.

Background: Urinary stones are affecting more children, and pediatric stone formers have unique pathophysiology compared to adults. While adult stone formers are most frequently male, children have an age dependent sex prevalence. Under 10 years, a majority of stone formers are boys; adolescent stone formers are mostly female. Previous adult studies have shown that stone composition is influenced by the sex and age of the stone former. Thus, we hypothesize that female and male stone forming children will also have sex and age specific stone phenotypes. Methods: Retrospective chart review of a large pediatric center's stone forming children 6/1/2009 to 6/1/2016. Patients were identified by ICD 9 codes: N20, N20.1, and N20.9. Charts were reviewed for radiographic evidence of stones or documented visualized stone passage. Results: One hundred and thirty six subjects: 54 males and 82 females. Females were older, median age 14 years [interquartile range (IQR): 11, 15] vs. males' median age 12 years (IQR: 11, 14) (p < 0.01). Females had lower height z-scores, median 0.2 (IQR: -0.8, 0.8) vs. males' median 0.8 (IQR: -0.2, 1.8) (p < 0.01). Presenting symptoms were similar except flank pain affecting 39% of females vs. 22% of males (p = 0.04). Leukocyte esterase was positive in more females than males (33 vs. 4%) (p < 0.001). Males had a higher BUN/Cr ratio, mean ± standard deviation of 19.8 ± 6.3 vs. 16.6 ± 6.5 in females (p = 0.01). Glomerular hyperfiltration was present in 9% of patients while 35% of patients had estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m2. Treatment strategies and clinical course were similar except females were told to increase dietary citrate more frequently than males (21 vs. 4%) (p < 0.01). Conclusion: We have provided a novel analysis and demonstrated that low height z-score and pyuria are more common in female stone formers. We have also shown that 9% of pediatric stone formers have labs consistent with hyperfiltration. Whether high protein intake and/or chronic dehydration are associated with hyperfiltration and long-term renal function in children with kidney stones will be an area for future research.

Urinary stone disease in pediatric and adult metabolic bone clinic patients.

Kidney stones are increasing in the pediatric and adult populations; similarly osteoporosis is increasingly recognized in children. While kidney stone formers are known to suffer from low bone density, metabolic bone patients have not been considered a high risk population for kidney stones. Retrospective chart review of Nationwide Children's Hospital Metabolic Bone Clinic patients from October 2009-2013. Patients were identified by ICD 9 codes for osteoporosis, osteopenia, low bone density and kidney stones. Only patients with radiologic evidence of both diseases were included.Twenty-six of 889 patients met criteria; this is equivalent to an incidence of 30 per 100,000 patients. Osteoporosis was the most frequent bone diagnosis. Males were the majority (68%). Most common secondary diagnoses: seizure (52%) and cerebral palsy (44%). TREATMENT: calcium (48%), vitamin D (40%), bisphosphonates (48%). The majority (75%) were non-ambulatory. Most frequent lithogenic medications: Topiramate (42%) and corticosteroids (27%). This is one of the first studies to consider metabolic bone patients as high risk for urinary stone disease. We found a higher rate of kidney stones in pediatric metabolic bone patients compared to data available for the general pediatric kidney stone population. The most common risk factor for bone and stone disease was nonambulatory status. Males were more frequently affected than females; this is the reverse of general adolescent kidney stone population. The predominance of cerebral palsy and seizure patients can be attributed to their frequency of non-ambulatory status and lithogenic medications such as Topiramate.

Renal Calcium Oxalate Deposits Induce a Pro-Atherosclerotic and Pro-Osteoporotic Response in Mice.

Urinary stone disease (USD) is increasing in adult and pediatric populations. Adult and pediatric studies have demonstrated decreased bone mineral density and increased fracture rates. USD has also been independently linked to increased rates of myocardial infarction and cerebral vascular accidents. Although USD is a multisystem disorder involving the kidneys, bone, and vasculature, the molecular mechanisms linking these three organs remain unknown. Calcium oxalate nephropathy was induced in C57BL/6J mice with intra-peritoneal (ip) injection of sodium glyoxolate. Half of each kidney underwent Pizzalato staining and half was snap frozen for RNA extraction. RT2 Profiler Mouse Atherosclerosis, Osteoporosis, and Calcium Signaling PCR Arrays (Qiagen) were performed. Only results that passed quality checks in PCR array reproducibility and genomic DNA contamination were included. Genes had to show at least fourfold differential expression and P < 0.01 to be considered significant. Atherosclerosis array showed upregulation of 19 genes by fourfold, 10 of which were ≥10-fold. All 19 had P ≤ 0.002. The Osteoporosis array showed fourfold upregulation of 10 genes, five showed >10-fold increase. All 10 have P ≤ 0.003. The calcium signaling array showed significant fourfold upregulation of 10 genes, four of which were ≥10-fold. All 10 have P ≤ 0.03. We have demonstrated that calcium oxalate nephropathy can induce upregulation of atherosclerotic, metabolic bone, and calcium homeostasis genes in a murine model. This may be and initial step in identifying the molecular mechanisms linking stone, bone, and cardiovascular disease. J. Cell. Biochem. 118: 2744-2751, 2017. © 2017 Wiley Periodicals, Inc.

Pediatric Origins of Nephrolithiasis-Associated Atherosclerosis.

OBJECTIVES: To determine if nephrolithiasis-associated atherosclerosis has pediatric origins and to consider possible association between kidney stones and atherosclerosis-related proteins. STUDY DESIGN: We matched children aged 12-17 years with kidney stones and without kidney stones. Carotid artery intima-media thickness (cIMT) was measured by ultrasound. Participants' urine was investigated by enzyme-linked immunosorbent assay for the atherosclerosis-related proteins fibronectin 1, macrophage scavenger receptor 1, osteopontin, and vascular cell adhesion molecule 1 levels, and normalized to urine creatinine levels. RESULTS: Subjects with nephrolithiasis had higher cIMT in the right common carotid artery and overall mean measurement. Urine osteopontin and fibronectin 1 were significant predictors of cIMT. CONCLUSIONS: We have provided initial preliminary evidence that nephrolithiasis-associated atherosclerosis has pediatric origins and performed studies that begin to identify potential reasons for the association of nephrolithiasis and vascular disease.

Beneficial effects of intravenous pamidronate treatment in children with osteogenesis imperfecta under 24 months of age.

Osteogenesis imperfecta (OI) is an inherited disorder characterized by bone fragility and low bone mass. Low bone density and fracture is a cause of morbidity. Limited data exists on bisphosphonate treatment in patients under 24 months of age. The objective of the study was to examine the safety and efficacy of pamidronate in children under 24 months with OI. To do so, we carried out a retrospective chart review and analysis of OI patients started on intravenous pamidronate under 24 months of age. Pamidronate was administered in three-day cycles. Growth, the number of fractures, and lumbar bone mineral densities were recorded both prior to and after treatment initiation. A total of 18 patients were reviewed. Five were classified as OI type I, seven were type III, and six were type IV. The mean age at treatment initiation was 12 months (range 11 days to 23 months). The mean lumbar z score at baseline was -3.63, which improved to -1.53 at one year (P < 0.01) and 0.79 (P < 0.01) at the end of the study. The fracture rate improved from 68 fractures in 209 months (0.32 fractures/patient-month) before treatment to 41 fractures in 1,248 months (0.03 fractures/patient-month) post-treatment (P < 0.05). Height standard deviation score (SDS) was conserved from baseline to end of study (-2.12 ± 2.45 vs. -2.45 ± 2.73) (P = 0.05) with an average follow-up of 73 months. The only adverse effect recorded in six infants was fever during the initial pamidronate infusion. Treatment with intravenous pamidronate is safe, significantly improves lumbar bone mineral density (L-BMD), and reduces fracture rates in young infants with OI while preserving linear growth.

Trends in pediatric urolithiasis: patient characteristics, associated diagnoses, and financial burden.

BACKGROUND: The goal of this study was to examine national trends in hospitalization, emergency department (ED) utilization, secondary diagnoses, and charges associated with pediatric urolithiasis. METHODS: Data were evaluated from the Kids' Inpatient Database of the Healthcare Costs and Utilization Project (HCUP) database from 1997 to 2012 and the HCUP National ED Sample from 2006 to 2011. RESULTS: Pediatric nephrolithiasis discharges increased by 18%, while ureterolithiasis discharges decreased by 17%. Hospital charges increased by 20% when accounting for inflation, despite an overall decrease in discharges by 2.5%. Female patients and those aged 15-17 years were more commonly affected. Pediatric ED visits increased by 9%. The most common secondary diagnoses during 2003-2009 were urinary tract infections (UTI) (13%), asthma (9%), epilepsy (4%), and paralysis (4%). CONCLUSIONS: Decreased hospitalizations and increased ED visits indicate a shift to outpatient care. Inpatient health care charges associated with pediatric urolithiasis continue to rise. Comorbidities include UTI, asthma, epilepsy, attention deficit hyperactivity disorder (ADHD), and mood disorders. Because of the significant health care burden and the increased risk to children of developing long-term sequelae there is a strong need for increased research into the mechanism of this systemic inflammatory disease and improved therapeutic targets.

Pediatric nephrolithiasis and the link to bone metabolism.

PURPOSE OF REVIEW: To review the recent publications describing the link between pediatric nephrolithiasis and bone metabolism. RECENT FINDINGS: Nephrolithiasis incidence is increasing in children and is associated with low bone mineral density (BMD). Affected children are conceptually at risk for fractures and osteoporosis. In addition to abnormal calcium metabolism, inflammation, genetic makeup and dietary habits are being recognized as important factors in the pathophysiology of nephrolithiasis and low bone density. Findings from retrospective reviews suggest that low BMD in children may be improved with citrate or thiazide treatment. SUMMARY: The healthcare burden from low BMD with subsequent osteoporosis and fracture risk is immense with potential far-reaching effects in patient quality of life and healthcare expense. Bone mass is acquired in the pediatric age range, thus it is important to identify and treat at-risk children. Retrospective reviews in pediatric patients indicate that citrate or thiazide diuretic treatment may improve BMD. We now understand that a relationship exists between nephrolithiasis and low BMD. To improve healthcare for our current patients as well as protect their future health it is important to identify low BMD and initiate strategies to improve BMD in 'at-risk' children.