Vertebral Body Reshaping after Fractures: An Important Index of Recovery in Glucocorticoid-Treated Children.

PURPOSE: In this 6-year study we identified factors associated with spontaneous vertebral body reshaping in glucocorticoid (GC)-treated children with leukemia, rheumatic disorders, and nephrotic syndrome. METHODS: Subjects were 79 children (mean age 7.4 years) who had vertebral fracture (VF) evaluation on lateral spine radiographs at least 1 year after VF detection. VF were graded using the modified Genant semiquantitative method and fracture burden for individuals was quantified using the spinal deformity index (SDI; sum of grades from T4 to L4). RESULTS: Sixty-five children (82.3%) underwent complete vertebral body reshaping (median time from VF detection to complete reshaping 1.3 years by Cox proportional hazard modeling). Of 237 VF, the majority (83.1%) ultimately reshaped, with 87.2% reshaping in the thoracic region vs 70.7% in the lumbar region (P = .004). Cox models showed that (1) every g/m2 increase in GC exposure in the first year after VF detection was associated with a 19% decline in the probability of reshaping; (2) each unit increase in the SDI at the time of VF detection was associated with a 19% decline in the probability of reshaping [hazard ratio (HR) = 0.81; 95% confidence interval (CI) = 0.71, 0.92; P = .001]; (3) each additional VF present at the time of VF detection reduced reshaping by 25% (HR = 0.75; 95% CI = 0.62, 0.90; P = .002); and (4) each higher grade of VF severity decreased reshaping by 65% (HR = 0.35; 95% CI = 0.21, 0.57; P < .001). CONCLUSION: After experiencing a VF, children with higher GC exposure, higher SDI, more severe fractures, or lumbar VF were at increased risk for persistent vertebral deformity.

Limitations of U25 CKiD and CKD-EPI eGFR formulae in patients 2-20 years of age with measured GFR > 60 mL/min/1.73 m2-a cross-sectional study.

BACKGROUND: When applying Pierce U25 formula for estimating glomerular filtration rate (eGFR), we observed a higher proportion of eGFR < 90 mL/min/1.73 m2 (chronic kidney disease (CKD) stage 2). We compared agreement and accuracy of the Pierce U25 (ages 2-25), Pottel (ages 2-100), and CKD-EPI (ages 18-100) formulae to GFR measurements. METHODS: Post hoc analysis of the three eGFRs compared to 367 99m technetium-diethylene-triamine penta-acetic acid (99Tc DTPA) GFR measurements (240 patients) using 3 sampling points and Brockner/Mørtensen correction (body surface area calculation based on ideal weight) on simultaneous serum creatinine and cystatin C measurements. RESULTS: Overall, the U25 formula performed well with a Spearman r of 0.8102 (95% confidence interval 0.7706 to 0.8435, p < 0.0001) while diagnostic accuracy was low in patients with normal mGFR. The U25 formula reclassified 29.5% of patients with normal mGFR as CKD stage 2; whereas the average of the modified Schwartz formula based on serum creatinine and the Filler formula based on cystatin C, only over-diagnosed CKD stage 2 in 8.5%, 24.5% within 10% and 62.7% within 30%. We therefore combined both. The average Schwartz/Filler eGFR had 36.5% of results within 10%, 84.7% within 30%, and normal mGFR accuracy was 26.8%, 63.9% for 10% and 30%, respectively, outperforming the CKD-EPI and Pottel formulae. CONCLUSIONS: The Pierce U25 formula results correlated well with mGFR < 75 mL/min/1.73 m2. Over the entire GFR range, accuracy was better for patients with a higher mGFR, when averaging the combined Schwartz/Filler formulae. More work is needed to prospectively confirm our findings in other centers.

A population-based retrospective cohort study of surgical trends and outcomes of pediatric urolithiasis in Ontario, Canada (2002-2019).

INTRODUCTION: The worldwide incidence of pediatric urinary stone disease (PUSD) is increasing. However, there is no commensurate data on whether this translates to an increasing need for surgical intervention for PUSD, given the role of conservative management. OBJECTIVE: We aimed to evaluate the trends and outcomes of clinically significant PUSD, using administrative databases to identify patients surgically treated for PUSD. STUDY DESIGN: This retrospective population-based cohort study assessed the incidence and trends of surgically treated PUSD and outcomes in Ontario, Canada in patients <18 years of age who underwent their first PUSD procedure between 2002 and 2019 utilizing administrative databases held at the Institute of Clinical Evaluative Sciences (ICES). We assessed the incidence of surgically treated PUSD, demographics, initial surgical treatment and imaging modality, and risk factors for repeat intervention within 5 years. Statistical analyses summarized demographics, surgical trends, and logistic regression was used to identify risk factors for repeat surgical intervention. RESULTS: We identified 1149 patients (mean age 11.3 years), with 59.6% older than 12 years. There was a decrease in the number of PUSD procedures performed per year that was close to statistical significance (p = 0.059) and a trend towards increased utilization of ureteroscopy (URS) compared with Shockwave Lithotripsy (SWL). In addition, there was a significant increase in the proportion of females surgically treated with PUSD (p = 0.001). In the 706 patients followed for 5 years, 17.7% underwent a repeat procedure within 6 months, while 20.4% underwent a repeat procedure from 6-months to 5 years. Renal stone location (OR 2.79, 95% confidence interval (CI) 1.62-4.80, p = 0.0002) and index SWL (OR 1.66, 95% CI 1.20-2.31, p = 0.0025) were risk factors for repeat surgical intervention within the first 6-months. There was an increasing utilization of ultrasound (US) compared to computerized tomography (CT) (p = 0.0008). DISCUSSION: Despite the literature reporting increasing PUSD incidence, we observed a non-significant decrease in the number of surgical PUSD procedures performed. Exclusion of those treated conservatively may explain our results. The increase in the proportion of females treated reflects the narrowing gender gap in stone disease. A trend towards increased URS utilization was observed and re-intervention rates were similar to previous studies. CONCLUSION: The overall rate of surgically treated PUSD did not show an increasing trend in Ontario, Canada from 2002 to 2019. URS was the most common surgical treatment modality, with a corresponding decline in SWL rates. PUSD was associated with a high surgical re-intervention rate within 6 months.

Investigation of N,N,N-Trimethyl-L-alanyl-L-proline Betaine (TMAP) as a Biomarker of Kidney Function.

Glomerular filtration rate (GFR) is the most widely used tool for the measurement of kidney function, but endogenous biomarkers such as cystatin C and creatinine have limitations. A previous metabolomic study revealed N,N,N-trimethyl-L-alanyl-L-proline betaine (TMAP) to be reflective of kidney function. In this study, we developed a quantitative LCMS assay for the measurement of TMAP and evaluated TMAP as a biomarker of GFR. An assay to measure TMAP was developed using liquid chromatography-mass spectrometry. After validation of the method, we applied it to plasma samples from three distinct kidney disease patient cohorts: nondialysis chronic kidney disease (CKD) patients, patients receiving peritoneal and hemodialysis, and living kidney donors. We investigated whether TMAP was conserved in other mammalian and nonmammalian species, by analyzing plasma samples from Wistar rats with diet-induced CKD and searching for putative matches to the m/z for TMAP and its known fragments in the raw sample data repository "Metabolomics Workbench". The assay can measure plasma TMAP at a lower limit of quantitation (100 ng/mL) with an interday precision and accuracy of 12.8 and 12.1%, respectively. In all three patient cohorts, TMAP concentrations are significantly higher in patients with CKD than in controls with a normal GFR. Further, TMAP concentrations are also elevated in rats with CKD and TMAP is present in the sap produced from Acer saccharum trees. TMAP concentration is inversely related to GFR suggesting that it is a marker of kidney function. TMAP is present in nonmammalian species suggesting that it is part of a biologically conserved process.

Young Adults With Hereditary Tubular Diseases: Practical Aspects for Adult-Focused Colleagues.

Recent advances in the management of kidney tubular diseases have resulted in a significant cohort of adolescents and young adults transitioning from pediatric- to adult-focused care. Most of the patients under adult-focused care have glomerular diseases, whereas rarer tubular diseases form a considerable proportion of pediatric patients. The purpose of this review is to highlight the clinical signs and symptoms of tubular disorders, as well as their diagnostic workup, including laboratory findings and imaging, during young adulthood. We will then discuss more common disorders such as cystinosis, cystinuria, distal kidney tubular acidosis, congenital nephrogenic diabetes insipidus, Dent disease, rickets, hypercalciuria, and syndromes such as Bartter, Fanconi, Gitelman, Liddle, and Lowe. This review is a practical guide on the diagnostic and therapeutic approach of tubular conditions affecting young adults who are transitioning to adult-focused care.

Histopathological Changes of Long-Term Peritoneal Dialysis Using Physiological Solutions: A Case Report and Review of the Literature.

BACKGROUND: Long-term peritoneal dialysis (PD), especially with nonphysiological solutions, is afflicted with the severe complication of encapsulating peritoneal sclerosis (EPS). Physiologic PD solutions have been introduced to reduce pH trauma. Data on peritoneal biopsies in pediatrics with long-term PD using physiological solutions are scant. CASE REPORT: We report an adolescent who had been on 10-h continuous hourly cycles using mostly 2.27% Physioneal™ for 5 years. There were two episodes of peritonitis in October 2017 (Klebsiella oxytoca) and May 2018 (Klebsiella pneumoniae), which were treated promptly. This adolescent, who lost two kidney transplants from recurrent focal and segmental glomerulosclerosis, underwent a peritoneal membrane biopsy at the time of a third PD catheter placement, 16 months after the second renal transplant. Laparoscopically, the peritoneum appeared grossly normal, but fibrosis and abundant hemosiderin deposition were noted on histology. The thickness of the peritoneum was 200-900 (mean 680) µm; normal for age of 14 years is 297 [IQR 229, 384] µm. The peritoneum biopsy did not show specific EPS findings, as the mesothelial cells were intact, and there was a lack of fibrin exudation, neo-membrane, fibroblast proliferation, infiltration, or calcification. CONCLUSIONS: While the biopsy was reassuring with respect to the absence of EPS, significant histopathological changes suggest that avoiding pH trauma may not ameliorate the effects of glucose exposure in long-term PD.

Renal Autologous Cell Therapy to Stabilize Function in Diabetes-Related Chronic Kidney Disease: Corroboration of Mechanistic Action With Cell Marker Analysis.

Introduction: Chronic kidney disease (CKD) is a worldwide disease without cure. Selected renal cells (SRCs) can augment kidney function in animal models. This study correlates the phenotypical characteristics of autologous homologous SRCs (formulated product called Renal Autologous Cell Therapy [REACT]) injected into patients' kidneys with advanced type 2 diabetes-related CKD (D-CKD) to clinical and laboratory findings. Methods: A total of 22 adults with type 2 D-CKD underwent a kidney biopsy followed by 2 subcortical injections of SRCs, 7 ± 3 months apart. There were 2 patients who had only 1 injection. We compared annualized estimated glomerular filtration rate (eGFR) slopes pre- and post-REACT injection using the 2009 CKD-EPI formula for serum creatinine (sCr) and the 2012 CKD-EPI Creatinine-Cystatin C equation and report clinical/laboratory changes. Fluorescent Activated Cell Sorting (FACS) Analysis for renal progenitor lineages in REACT and donor vascular endothelial growth factor A (VEGF-A) analysis were performed. Longitudinal parameter changes were analyzed with longitudinal linear mixed effects model. Results: At baseline, the mean diabetes duration was 18.4 ± 8.80 years, glycated hemoglobin (Hgb) was 7.0 ± 1.05, and eGFR was 40.3 ± 9.35 ml/min per 1.73 m2 using the 2012 CKD-EPI cystatin C and sCr formulas. The annualized eGFR slope (2012 CKD-EPI) was -4.63 ml/min per 1.73 m2 per year pre-injection and improved to -1.69 ml/min per 1.73 m2 per year post-injection (P = 0.015). There were 7 patients who had an eGFR slope of >0 ml/min per 1.73 m2 postinjection. SRCs were found to have cell markers of ureteric bud, mesenchyme cap, and podocyte sources and positive VEGF. There were 2 patients who had remote fatal adverse events determined as unrelated with the biopsies/injections or the REACT product. Conclusion: Our cell marker analysis suggests that SRCs may enable REACT to stabilize and improve kidney function, possibly halting type 2 D-CKD progression.

Renal volume of five-year-old preterm children are not different than full-term controls

Abstract Objective: In previous studies, smaller renal volumes were reported in prematurely born infants, however, these renal volumes were not corrected for body surface area, the main determinant of renal size. Given the rapid growth of the renal cortex after premature birth, the authors hypothesized that corrected volumes would not differ from healthy controls. Methods: Ambispective cohort study with prospective follow-up of prematurely born babies in a large specialized center and retrospectively recruited healthy control group. Children were assessed for renal length and renal volumes at age 5 by three independent ultrasonographers. Detailed anthropometry, blood pressure and renal function were also obtained. Age independent z-scores were calculated for all parameters and compared using descriptive statistics. Results: Eighty-nine premature study participants (median 32 weeks gestational age) and 33 healthy controls (median 38 weeks gestational age) were studied. Study participants did not differ in age, sex, Afro-Colombian descent, height, blood pressure, serum creatinine, or new Schwartz eGFR. Premature study participants had a significantly lower weight (17.65 ± 2.93 kg) than controls (19.05 ± 2.81 kg, p = 0.0072) and lower body surface area. The right renal volumes were significantly smaller (39.4 vs 43.4 mL), but after correction for body surface area, the renal volume and renal length z-scores were identical for both kidneys (mean right kidney -0.707 vs -0.507; mean left kidney -0.498 vs -0.524, respectively). Conclusion: Renal volumes need to be corrected to body surface area. After correction for body surface area, 5-year-old healthy and prematurely born children have comparable renal volumes.

Renal volume of five-year-old preterm children are not different than full-term controls.

OBJECTIVE: In previous studies, smaller renal volumes were reported in prematurely born infants, however, these renal volumes were not corrected for body surface area, the main determinant of renal size. Given the rapid growth of the renal cortex after premature birth, the authors hypothesized that corrected volumes would not differ from healthy controls. METHODS: Ambispective cohort study with prospective follow-up of prematurely born babies in a large specialized center and retrospectively recruited healthy control group. Children were assessed for renal length and renal volumes at age 5 by three independent ultrasonographers. Detailed anthropometry, blood pressure and renal function were also obtained. Age independent z-scores were calculated for all parameters and compared using descriptive statistics. RESULTS: Eighty-nine premature study participants (median 32 weeks gestational age) and 33 healthy controls (median 38 weeks gestational age) were studied. Study participants did not differ in age, sex, Afro-Colombian descent, height, blood pressure, serum creatinine, or new Schwartz eGFR. Premature study participants had a significantly lower weight (17.65 ± 2.93 kg) than controls (19.05 ± 2.81 kg, p = 0.0072) and lower body surface area. The right renal volumes were significantly smaller (39.4 vs 43.4 mL), but after correction for body surface area, the renal volume and renal length z-scores were identical for both kidneys (mean right kidney -0.707 vs -0.507; mean left kidney -0.498 vs -0.524, respectively). CONCLUSION: Renal volumes need to be corrected to body surface area. After correction for body surface area, 5-year-old healthy and prematurely born children have comparable renal volumes.

Management of severe polyuria in idiopathic Fanconi syndrome.

BACKGROUND: Polyuria is a common problem in patients with tubular diseases, especially for those with CKD and high-output Fanconi syndrome. There are currently no guidelines on how to treat debilitating polyuria, in children or adults, and vasopressin is usually not effective. CASE-DIAGNOSIS/TREATMENT: A 13-year-old female with idiopathic Fanconi syndrome and an eGFR of 69 mL/min/1.73 m2 was severely affected by polyuria of 5 L per day (voiding at least 11 times during the day and up to 8 times at night), impacting her mood (measured by the RCADS-child) and academic performance at school. In the absence of guidelines and with literature discouraging the use of indomethacin in this condition, we attempted indomethacin treatment at a dose of 2 mg/kg divided in two doses with substantial success. Urine output dropped to 2.5L and this was accompanied by a substantial decrease of her sodium wasting from 24.6 to 7.7 mmol/kg/day. Over the course of 18 months, the patient's eGFR dropped temporarily to 60 mL/min/1.73 m2 and was 68 mL/min/1.73 m2 at last follow-up. However, a sodium-23 (23Na) MRI of her thigh revealed ongoing moderate sodium decrease in her skin and substantial Na+ decrease in her muscle when compared to age-matched peers with normal kidney function. CONCLUSIONS: Indomethacin may be a safe and effective treatment option for polyuria in idiopathic Fanconi syndrome.

Abdominal compartment syndrome secondary to chronic constipation in MECP2 duplication syndrome.

Abdominal compartment syndrome (ACS) is an infrequently encountered life-threatening disorder characterised by elevated abdominal pressure with evidence of new organ dysfunction. It is rarely reported in paediatrics. We describe an extremely unusual presentation of a 13-year-old boy with long-standing constipation who developed ACS complicated by refractory septic shock and multiorgan failure. He was treated with emergent decompressive laparotomy and supportive critical care. This case highlights the need for early diagnosis and timely management of ACS to improve its outcome.

Postoperative outcomes of ureteroscopy for pediatric urolithiasis: A secondary analysis of the National Surgical Quality Improvement Program Pediatric.

INTRODUCTION: Incidence of pediatric urinary stone disease (PUSD) has increased over recent decades. Innovations in ureteroscopic technology has expanded the role of endourologic stone management in children. However, there is currently no consensus on the optimal use of ureteroscopy (URS) within the heterogenous PUSD population. OBJECTIVE: The primary objective was to investigate the rate of 30-day unplanned readmissions in pediatric patients after URS. The secondary objective was to examine the influence of demographic, perioperative, postoperative, and reoperation variables as predictors of an increased risk of unplanned readmission in this sample. STUDY DESIGN: A secondary analysis was performed on retrospectively collected data from the National Surgical Quality Improvement Program Pediatric between 2015 and 2018. Pediatric patients diagnosed with PUSD and treated with URS were identified. Patients undergoing concurrent or additional surgeries during the URS procedure were excluded. Data on demographic, perioperative, postoperative, and unplanned reoperation variables were examined for their possible influence on 30-day unplanned readmissions. Descriptive statistics were used to characterize the study cohort. Continuous and categorical variables were analyzed using independent samples t-test, one-way ANOVA with Tukey post-hoc test, and Chi-square Tests or Fisher's Exact Test, respectfully. Multivariate analysis was performed using stepwise logistic regression. RESULTS: A total of 2510 patients were identified within the study period. The majority of children undergoing URS were between 12 and 18 years of age (66.1%), female (56.9%), and had renal calculi (45.2%). Of these, 162 (6.5%) experienced a 30-day unplanned readmission related to the URS procedure. The most common reasons for an unplanned readmission was urinary tract infection (31.4%), new/unresolved stone (28.3%), and postoperative pain (8.2%). Multivariate modelling showed that females (Relative Risk [RR]: 2.03; 95% Confidence Interval [95%CI]: 1.34-3.07), patients with renal stones (RR: 1.77; 95%CI: 1.10-2.83), and inpatients at the time of surgery (RR: 1.61; 95%CI: 1.03-2.51) were more at risk of an unplanned readmission within 30-days of an URS procedure. CONCLUSION: This study reports on short-term unplanned readmission rates in pediatric patients who underwent an URS procedure. Further it highlights possible predictors of unplanned readmission rates within a sampling of patients from NSQIP affiliated institutions. The findings from this study can be used to guide future studies around the safe use of URS in pediatric patients.

How should we assess renal function in neonates and infants?

AIM: Review of current knowledge on assessing renal function in term and preterm neonates. METHODS: Literature review and analysis of own data. RESULTS: Prematurity, genetic, environmental and maternal factors may alter peak nephron endowment and life-long renal function. Nephrogenesis continues until 34-36 weeks of gestation, but it is altered with premature delivery. Variability of nephron endowment has a substantial impact on the clearance of renally excreted drugs. Postnatally, glomerular function rate (GFR) increases daily, doubles by two weeks, and slowly reaches full maturity at 18 months of age. Ideally, renal function biomarkers should be expressed as age-independent z-scores, and evidence suggests indexing these values to post-conceptual age rather than chronological age. Newborn and maternal serum creatinine correlate tightly for more than 72 hours after delivery, rendering this biomarker unsuitable for the assessment of neonatal renal function. Cystatin C does not cross the placenta and may be the preferred biomarker in the neonate. Here, we provide preliminary data on the natural evolution of the cystatin C eGFR in infancy. CONCLUSION: Cystatin C may be superior for GFR estimation in neonates, but the best approach to drug dosing of renally excreted drugs remains to be established.

Renal length z-score for the detection of dysfunction in children with solitary functioning kidney.

AIM: To evaluate whether renal length z-scores predict renal dysfunction in children with a solitary functioning kidney (SFK). METHODS: In a single-centre retrospective cohort of children with SFK, we correlated body mass index z-scores, extracellular volume and lean body mass to renal length z-scores. We grouped these z-scores to other markers of renal dysfunction (proteinuria, hypertension, extracellular volume and abnormal estimated glomerular function rate [eGFR]) and analysed renal length z-score with multivariate analysis, receiver-operated characteristics (ROC) plots and Youden's index to determine an appropriate cut-off. RESULTS: 111 children had a median follow-up 5.08 years, eGFR 80.8 mL/min/1.73 m2 , and age at last follow-up 7.4 (3.8-13.4 years). The median renal length z-scores of those without any renal dysfunction (n = 37, 25.1%) were greater (+3.66, interquartile range 3.02-4.47) than those with renal dysfunction (median 3.11, interquartile range 1.76-4.11, P = .0107, Mann-Whitney test). Using a cut-off of z-score of >+1.911, the odds ratio for having no renal dysfunction was 0.07 (95% CI 0.002-0.459, P = .0010). However, accuracy of the renal length z-score was poor (ROC curve 0.6488). CONCLUSION: In this cohort of children with SKF, using the renal length z-score as a biomarker of renal dysfunction at 7 years of age is not recommended.