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Background: When applying Pierce U25 formula for estimating glomerular filtration rate (eGFR), we observed a higher proportion of eGFR < 90 mL/min/1.73 m 2 (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 99 m technetium-diethylene-triamine penta-acetic acid ( 99 Tc 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 m 2 . 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., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Focal segmental glomerular sclerosis (FSGS) is 1 of the primary causes of nephrotic syndrome in both pediatric and adult patients, which can lead to end-stage kidney disease. Recurrence of FSGS after kidney transplantation significantly increases allograft loss, leading to morbidity and mortality. Currently, there are no consensus guidelines for identifying those patients who are at risk for recurrence or for the management of recurrent FSGS. Our work group performed a literature search on PubMed/Medline, Embase, and Cochrane, and recommendations were proposed and graded for strength of evidence. Of the 614 initially identified studies, 221 were found suitable to formulate consensus guidelines for recurrent FSGS. These guidelines focus on the definition, epidemiology, risk factors, pathogenesis, and management of recurrent FSGS. We conclude that additional studies are required to strengthen the recommendations proposed in this review., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Declaration of interests The authors declare that they have no conflict of interest.

Background: The COVID-19 pandemic has led to increased utilization of telemedicine services., Methods: A retrospective analysis of all referral-based ambulatory telemedicine services in Ontario from November 2019 to June 2021 was collected from the Ontario Health Insurance Plan (OHIP) billing database. Only fee-for-service billings were included in the present analysis. Coincident COVID-19 cases were obtained from Public Health Ontario. Comparisons were made based on age bracket, sex, telemedicine and in-person care., Results: Billings for telemedicine services in Ontario increased from $1.7 million CAD in November 2019 to $64 million CAD in April 2020 and the proportions reached a mean peak of 72% in April 2020 and declined to 46% in June 2021. A positive correlation was found between the use of telemedicine and COVID-19 cases (p = 0.05). The age group with the highest proportion of telemedicine use was the 10-20-year-olds, followed by the 20-50-year-olds (61 ± 9.0%, 55 ± 7.3%, p = 0.01). Both age groups remained above 50% telemedicine services at the end of the study period. There seemed to be higher utilization by females (females 54.2 ± 8.0%, males 47.9 ± 7.7%, ANCOVA p = 0.05) for all specialties, however, after adjusting for male to female ratio m:f of 0.952:1.0 according to the 2016 census, this was no longer significant., Conclusions: The use of telemedicine services remained at a high level across groups, particularly the 10-50-year-olds. There were clear age preferences for using telemedicine. Studying these differences may provide insights into how the delivery of non-hospital-based medicine has changed during the COVID-19 pandemic., (© 2023. The Author(s).)

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., Competing Interests: Conflict of interest None., (Copyright © 2023 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Acute and chronic kidney disease continues to confer significant morbidity and mortality in the clinical setting. Despite high prevalence of these conditions, few validated biomarkers exist to predict kidney dysfunction. In this study, we utilized a novel kidney multiplex panel to measure 21 proteins in plasma and urine to characterize the spectrum of biomarker profiles in kidney disease. Blood and urine samples were obtained from age-/sex-matched healthy control subjects (HC), critically-ill COVID-19 patients with acute kidney injury (AKI), and patients with chronic or end-stage kidney disease (CKD/ESKD). Biomarkers were measured with a kidney multiplex panel, and results analyzed with conventional statistics and machine learning. Correlations were examined between biomarkers and patient clinical and laboratory variables. Median AKI subject age was 65.5 (IQR 58.5-73.0) and median CKD/ESKD age was 65.0 (IQR 50.0-71.5). Of the CKD/ESKD patients, 76.1% were on hemodialysis, 14.3% of patients had kidney transplant, and 9.5% had CKD without kidney replacement therapy. In plasma, 19 proteins were significantly different in titer between the HC versus AKI versus CKD/ESKD groups, while NAG and RBP4 were unchanged. TIMP-1 (PPV 1.0, NPV 1.0), best distinguished AKI from HC, and TFF3 (PPV 0.99, NPV 0.89) best distinguished CKD/ESKD from HC. In urine, 18 proteins were significantly different between groups except Calbindin, Osteopontin and TIMP-1. Osteoactivin (PPV 0.95, NPV 0.95) best distinguished AKI from HC, and β2-microglobulin (PPV 0.96, NPV 0.78) best distinguished CKD/ESKD from HC. A variety of correlations were noted between patient variables and either plasma or urine biomarkers. Using a novel kidney multiplex biomarker panel, together with conventional statistics and machine learning, we identified unique biomarker profiles in the plasma and urine of patients with AKI and CKD/ESKD. We demonstrated correlations between biomarker profiles and patient clinical variables. Our exploratory study provides biomarker data for future hypothesis driven research on kidney disease., (© 2023. The Author(s).)

Background: Telemedicine use increased during the COVID-19 pandemic. We compared both adolescent/caregiver attitudes towards telemedicine pre- and intra-pandemic., Materials and Methods: In a tertiary care setting with a large remote catchment area, we conducted qualitative analysis of structured interviews with dyads of 11 to 18-year-old patients and their caregivers using NVivo during the pandemic and compared the findings to our previous research [1]., Results: We enrolled 14 dyads (35 ± 27 in-person visits and 4 ± 3 telemedicine visits per participant) and compared these with 11 dyads before the pandemic. Adolescents' mean age was 15.2 ± 2.1 years (range 11.2 - 18.2). The median distance to our medical center was 184.8 km (range 3.9 - 1,214 km, 6 dyads > 100 km). While the preferred ratio of telemedicine to in-person visits was 2 : 1 in caregivers (like pre-pandemic), many emphasized telemedicine as the safer option. Interestingly, adolescents preferred more in-person visits during the pandemic (1 : 1 ratio) compared to pre-pandemic (2 : 1 ratio). Qualitative analysis identified two main themes: consultation-specific factors and contextual factors. Consultation-specific factors were more valued during in-person visits, especially by adolescents. Consultation-specific factors remained the same pre- and post-pandemic, however, adolescents more often emphasized comfort, communication, and personal connection for in-person visits during the pandemic. Contextual factors were valued for telemedicine by adolescents and caregivers, and telemedicine was identified as the norm during the pandemic. Interestingly, the two main contextual themes pre-pandemic: frustration with technological aspects of telemedicine and adolescents not taking telemedicine seriously, disappeared during the pandemic. No disadvantages for telemedicine in the contextual factors were identified during the pandemic., Conclusion: The COVID-19 pandemic changed the user-expressed attitudes (especially among adolescents) on the transfer to telemedicine for chronic care.

Background: Urinary stone disease (USD) historically has affected older men, but studies suggest recent increases in women, leading to a near identical sex incidence ratio. USD incidence has doubled every 10 years, with disproportionate increases amongst children, adolescent, and young adult (AYA) women. USD stone composition in women is frequently apatite (calcium phosphate), which forms in a higher urine pH, low urinary citrate, and an abundance of urinary uric acid, while men produce more calcium oxalate stones. The reasons for this epidemiological trend are unknown., Methods: This perspective presents the extent of USD with data from a Canadian Province and a North American institution, explanations for these findings and offers potential solutions to decrease this trend. We describe the economic impact of USD., Findings: There was a significant increase of 46% in overall surgical interventions for USD in Ontario. The incidence rose from 47.0/100,000 in 2002 to 68.7/100,000 population in 2016. In a single United States institution, the overall USD annual unique patient count rose from 10,612 to 17,706 from 2015 to 2019, and the proportion of women with USD was much higher than expected. In the 10-17-year-old patients, 50.1% were girls; with 57.5% in the 18-34 age group and 53.6% in the 35-44 age group. The roles of obesity, diet, hormones, environmental factors, infections, and antibiotics, as well as the economic impact, are discussed., Interpretation: We confirm the significant increase in USD among women. We offer potential explanations for this sex disparity, including microbiological and pathophysiological aspects. We also outline innovative solutions - that may require steps beyond typical preventive and treatment recommendations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Filler, Dave, Ritter, Ross, Viprakasit, Hatch, Bjazevic, Burton, Gilleskie, Gilliland, Lin, Jain, McClure, Razvi, Bhayana, Wang, Coulson, Sultan, Denstedt, Fearrington and Diaz-Gonzalez de Ferris.)

Background: The severity of X-linked hypophosphataemic rickets (XLH) may be affected by genotype and sex. However, burosumab, a fully humanized monoclonal antibody against fibroblast growth factor 23, has the same pediatric dose recommendation for both sexes (0.8 mg/kg every 2 weeks)., Patients and Methods: In a retrospective cohort study, we describe the burosumab response differences by sex in children with XLH., Results: We treated 10 children (5 females, mean age at initiation 4.2 ± 3.5 years) with XLH with burosumab. Initial mean serum phosphate was 0.69 ± 0.18 mmol/L in males and 0.86 ± 0.22 mmol/L in females (p = 0.108). The mean ratio of tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) was 0.55 ± 0.11 mmol/L in males and 0.76 ± 0.23 mmol/L in females (p = 0.06). The mean starting dose of burosumab was 0.83 ± 0.19 mg/kg subcutaneously every 14 days (males: 0.79 ± 0.19 mg/kg; females: 0.87 ± 0.21 mg/kg, n.s.). Two weeks after starting burosumab, serum phosphate differed significantly between males (0.90 ± 0.21 mmol/L) and females (1.27 ± 0.25 mmol/L) (p = 0.018). All males required a dose increase to try to normalize serum phosphate. On day 140 after starting, the average dose in males increased further to 1.24 ± 0.41 mg/kg to achieve a phosphate of 0.87 ± 0.11 mmol/L while females had a normal phosphate and alkaline phosphatase on the starting dose. After a mean of 458 ± 79 days, the mean burosumab dose/kg in males was 1.68 ± 0.61 mg/kg, mean serum phosphate was 1.08 ± 0.23 mmol/L, mean TmP/GFR was 1.01 ± 0.20, mean alkaline phosphatase had normalized to 303.6 ± 40.7U/L, and mean 1.25(OH) 2 vitamin D level was 186.4 ± 16.6 nmol/L., Conclusions: Our findings may suggest a sex difference in response to burosumab in XLH patients. Our data suggest that males may require higher doses., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: The diagnosis of hypertension and hypertension-induced target organ injury by the 2022 American Heart Association (AHA) ambulatory blood pressure threshold as compared with 2014 AHA and 2016 European Society of Hypertension (ESH) thresholds has not been evaluated., Methods: In a cross-sectional study (n = 291, aged 5-18 years, at a tertiary care outpatient clinic), we compared 2022 AHA with 2014 AHA and ESH thresholds (revised with 2018 adult ESH thresholds where applicable) to diagnose ambulatory hypertension (AH), and detect ambulatory arterial stiffness index (AASI) and left ventricular target organ injury (LVTOI)., Results: The 2022 AHA threshold diagnosed significantly more AH (53%) than the 2014 AHA (42%, p < 0.01) and ESH (36%, p < 0.001) thresholds. The 2022 AHA threshold demonstrated only a moderate agreement with the 2014 AHA (kappa (k) = 0.77) and ESH (k = 0.66) thresholds to diagnose AH. Adjusted logistic regression analysis found that only the 2022 AHA threshold predicted elevated AASI significantly (odds ratio 2.40, 95% CI 1.09, 5.25, p = 0.02; AUC 0.61, p < 0.01). In those with elevated AASI, more participants had AH by the 2022 AHA threshold (72%) than the 2014 AHA (46%, p = 0.02) and ESH (48%, p = 0.03) thresholds. AH defined by the 2022 AHA threshold continued to maintain higher odds, larger AUC, and higher sensitivity to identify LVTOI than the 2014 AHA and ESH thresholds; however, the difference did not reach a statistically significant level., Conclusions: AH defined by the 2022 AHA threshold diagnoses more children with hypertension and identifies more children with hypertension-induced target organ injury than the 2014 AHA and ESH thresholds. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Introduction: Growth retardation is a common problem in pediatric patients with chronic kidney disease. It is unknown if the growth of children on peritoneal dialysis (PD) can be augmented by more dialysis., Methods: We studied the effect of various peritoneal adequacy parameters on delta height standard deviation scores (SDSs) and growth velocity z-scores in 53 children (27 males) on PD, who underwent 2 longitudinal adequacy tests at 9-month intervals. None of the patients were on growth hormone. Intraperitoneal pressure and standard KDOQI guidelines were compared to the outcome measures delta height SDS and height velocity z-scores, using univariate and multivariate tests., Results: At the time of the second PD adequacy test, their mean age was 9.2 ± 5.3 years; mean fill volume was 961 ± 254 mL/m2; and median total infused dialysate volume was 5.26 L/m2/day (range 2.03-15.32 L). The median total weekly Kt/V was 3.79 (range 0.9-9.5), and the median total creatinine clearance was 56.6 (range 7.6-133.48) L/week, higher than previous pediatric studies. The delta height SDS was a median of -0.12 (range -2 to +3.95)/year. The mean height velocity z-score was -1.6 ± 4.0. The only relationships discovered were between the delta height SDS and age, bicarbonate, and intraperitoneal pressure, but not for Kt/V or creatinine clearance., Conclusion: Our findings highlight the importance of normalization of bicarbonate concentrations to improve height z-score., (© 2023 S. Karger AG, Basel.)

Twenty-four-hour ambulatory blood pressure monitoring (ABPM) is widely accepted as a more accurate method for measurement of blood pressure (BP) compared to a single office-based measurement of BP. However, it is unclear how physicians interpret ABPM and make management decisions. This study's goal is to investigate variation in ABPM interpretation among paediatric nephrologists (Canada and UK) and paediatric cardiologists (Canada only) via an online survey. The survey content included baseline demographics, questions on the use and indications for ABPM, interpretation of results, and subsequent management decisions in various clinical scenarios. The survey was sent to 196 Canadian physicians, with 69 (35.2%) total responses. Thirty-five UK clinicians also completed the survey. Most respondents were >44 years old, were in practice for at least 11 years, and were university-based. There were substantial differences among clinicians in ABPM interpretation for isolated systolic, diastolic, and night-time hypertension. For example, only 53.1% of physicians would initiate or modify treatment in those with diastolic HTN in CKD. Further, even for the same abnormal ABPM parameter, the decision to start or alter treatment was influenced by the underlying medical condition. There is significant variation in clinical practice among physicians for interpretation and management of hypertension when using ABPM. Differences in guidelines among various jurisdictions, as well as knowledge gaps in the research on which guidelines are based, create ambiguity regarding ABPM interpretation and management decisions. A more protocolized approach and further insight into the reasoning behind the variation in physicians' interpretation may help to standardise practice., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

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., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Preterm birth is associated with decreased nephron endowment. Currently, there is no reliable non-invasive biomarker to identify or monitor decreased nephron number in at-risk patients. Urinary Kidney Injury Molecule-1 (KIM-1) is a biomarker of acute and chronic renal injury. We measured urinary KIM-1 among a wide array of other potential biomarkers., Methods: We conducted an ambispective cohort study of 5-years-old children born prematurely and healthy controls identified from city schools. Detailed anthropometrics, renal ultrasound dimensions, and biochemical parameters were measured. Urinary KIM-1 was measured using Luminex® technology. Age independent z-scores were calculated and compared. Spearman correlations were used for estimating the association between measures and KIM-1., Results: We enrolled 129 children, 97 (75.2%) born pre-term and 32 (24.8%) healthy controls born at full-term. Pre-term patients had significantly lower weight and body surface area than controls. Pre-term patients and controls did not differ in current age, sex, race, height, blood pressure, urinary sodium, fractional sodium excretion, serum creatinine and estimated GFR. All spearman correlation between KIM-1 and gestational age, renal and serum measurements were weak without statistical significance., Conclusion: In 5-year-old children born prematurely, KIM-1 was not correlated with gestational age. Further prospective studies need to confirm this finding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Restrepo, Torres-Canchala, Bonventre, Arias, Ferguson, Villegas, Ramirez and Filler.)

Background: Sodium-23 magnetic resonance imaging ( 23 Na MRI) allows non-invasive assessment of tissue sodium concentration ([Na + ]). Age and chronic kidney disease (CKD) are associated with increased tissue [Na + ] in adults, but limited information is available pertaining to children and adolescents. We hypothesized that pediatric CKD is associated with altered tissue [Na + ] compared to healthy controls., Methods: This was a case-control exploratory study on healthy children and adults and pediatric CKD patients. Study participants underwent an investigational visit, blood/urine biochemistry, and leg 23 Na MRI for tissue [Na + ] quantification (whole leg, skin, soleus muscle). CKD was stratified by etiology and patients' tissue [Na + ] was compared against healthy controls by computing individual Z-scores. An absolute Z-score > 1.96 was deemed to deviate significantly from the mean of healthy controls. Pearson correlation was used to compute the associations between tissue [Na + ] and kidney function., Results: A total of 36 pediatric participants (17 healthy, 19 CKD) and 19 healthy adults completed the study. Healthy adults had significantly higher tissue [Na + ] compared with pediatric groups; conversely, no significant differences were found between healthy children/adolescents and CKD patients. Four patients with glomerular disease and one kidney transplant recipient due to atypical hemolytic-uremic syndrome had elevated whole-leg [Na + ] Z-scores. Reduced whole-leg [Na + ] Z-scores were found in two patients with tubular disorders (Fanconi syndrome, proximal-distal renal tubular acidosis). All tissue [Na + ] measures were significantly associated with proteinuria and hypoalbuminemia., Conclusions: Depending on etiology, pediatric CKD was associated with either increased (glomerular disease) or reduced (tubular disorders) tissue [Na + ] compared with healthy controls. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Artificial intelligence is playing an increasingly important role in many fields of clinical care to assist health care providers in patient management. In adult-focused nephrology, artificial intelligence is beginning to be used to improve clinical care, hemodialysis prescriptions, and follow-up of transplant recipients. This article provides an overview of medical artificial intelligence applications relevant to pediatric nephrology. We describe the core concepts of artificial intelligence and machine learning and cover the basics of neural networks and deep learning. We also discuss some examples for clinical applications of artificial intelligence in pediatric nephrology, including neonatal kidney function, early recognition of acute kidney injury, renally cleared drug dosing, intrapatient variability, urinary tract infection workup in infancy, and longitudinal disease progression. Furthermore, we consider the future of artificial intelligence in clinical pediatric nephrology and its potential impact on medical practice and address the ethical issues artificial intelligence raises in terms of clinical decision-making, health care provider-patient relationship, patient privacy, and data collection. This article also represents a call for action involving those of us striving to provide optimal services for children, adolescents, and young adults with chronic conditions., (Copyright © 2022 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The agreement between the commonly used ambulatory blood pressure (ABP) thresholds to diagnose ambulatory hypertension in children (patient's 24-h mean ABP classified by 24-h 95th ABP percentile threshold, American Heart Association [AHA] threshold, or patient's day and night mean ABP classified by day-night 95th ABP percentile thresholds) is not known. We evaluated the agreement among 24-h ABP threshold, AHA threshold, and day-night ABP thresholds to diagnose ambulatory hypertension, white coat hypertension (WCH) and masked hypertension (MH)., Methods: In a cross-sectional study design, we analyzed ABP recordings from 450 participants with suspected hypertension from a tertiary care outpatient hypertension clinic. The American Academy of Pediatrics thresholds were used to diagnose office hypertension., Results: The 24-h ABP threshold and day-night ABP thresholds classified 19% ABP (95% confidence interval [CI], 0.15-0.23) differently into ambulatory normotension/hypertension (kappa [κ], 0.58; 95% CI, 0.51-0.66). Ambulatory hypertension diagnosed by 24-h ABP threshold in 27% participants (95% CI, 0.22-0.32) was significantly lower than that by day-night ABP thresholds in 44% participants (95% CI, 0.37-0.50; P < 0.001). The AHA threshold had a stronger agreement with 24-h ABP threshold than with day-night ABP thresholds for classifying ABP into ambulatory normotension/hypertension (k 0.94, 95% CI 0.91-0.98 vs. k 0.59, 95% CI 0.52-0.66). The diagnosis of ambulatory hypertension by the AHA threshold (26%; 95% CI, 0.21-0.31) was closer to that by 24-h ABP threshold (27%, P = 0.73) than by day-night ABP thresholds (44%, P < 0.001). Similar agreement pattern persisted among these ABP thresholds for diagnosing WCH and MH., Conclusions: The 24-h ABP threshold classifies a lower proportion of ABP as ambulatory hypertension than day-night ABP thresholds. The AHA threshold exhibits a stronger agreement with 24-h ABP than with day-night ABP thresholds for diagnosing ambulatory hypertension, WCH and MH. Our findings are relevant for a consistent interpretation of hypertension by these ABP thresholds in clinical practice., (© 2022. The Author(s).)

Background To the knowledge of the authors, urinary osmolarity is the only tool currently available to assess kidney corticomedullary gradient (CMG). Comparisons between CMG and urinary osmolarity and the use of modalities such as sodium MRI to evaluate renal disease in humans are lacking. Purpose To investigate the ability of sodium MRI to measure CMG dynamics compared with urinary osmolarity after water load in healthy volunteers and CMG in participants with kidney disease. Materials and Methods A prospective study was conducted from July 2020 to January 2021 in fasting healthy volunteers undergoing water load and participants with chronic kidney disease (CKD) from cardiorenal syndrome included in a clinical trial. In both groups, CMG was estimated by measuring the medulla-to-cortex signal ratio from sodium MRI at 3.0 T. A custom-built two-loop (diameter, 18 cm) butterfly radiofrequency surface coil, tuned for sodium frequency (33.786 MHz), was used to acquire renal sodium images. Two independent observers measured all sodium MRI cortical and medullary values for each region of interest to compute the intraclass correlation coefficient. Pearson correlation was performed between urinary osmolarity and CMG. Results Five participants with CKD (mean age, 77 years ± 12 [standard deviation]; all men) and 10 healthy volunteers (mean age, 42 years ± 15; six men, four women) were evaluated. A reduction was observed between baseline and peak urinary dilution time for both mean medulla-to-cortex ratios (1.55 ± 0.11 to 1.31 ± 0.09, respectively; P < .001) and mean urinary osmolarity (756 mOsm/L ± 157 to 73 mOsm/L ± 14, respectively; P < .001) in healthy volunteers. Medulla-to-cortex and corresponding urinary osmolarity were correlated in both groups ( r 2 = 0.22; P < .001). Kidney sodium tissue content was successfully acquired in all five participants with CKD. The intraclass correlation coefficient measurement was 0.99 ( P < .001). Conclusion Functional sodium MRI accurately depicted corticomedullary gradient (CMG) dynamic changes in healthy volunteers and demonstrated feasibility of CMG measurement in participants with reduced kidney function. Clinical trial registration no. NCT04170855. © RSNA, 2022 Online supplemental material is available for this article . See also the editorial by Laustsen and Bøgh in this issue.

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., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

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., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

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 m 2 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 m 2 per year pre-injection and improved to -1.69 ml/min per 1.73 m 2 per year post-injection ( P  = 0.015). There were 7 patients who had an eGFR slope of >0 ml/min per 1.73 m 2 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., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Management of acute liver failure (ALF) and acute on chronic liver failure (ACLF) in the pediatric population can be challenging. Kidney manifestations of liver failure, such as hepatorenal syndrome (HRS) and acute kidney injury (AKI), are increasingly prevalent and may portend a poor prognosis. The overall incidence of AKI in children with ALF has not been well-established, partially due to the difficulty of precisely estimating kidney function in these patients. The true incidence of AKI in pediatric patients may still be underestimated due to decreased creatinine production in patients with advanced liver dysfunction and those with critical conditions including shock and cardiovascular compromise with poor kidney perfusion. Current treatment for kidney dysfunction secondary to liver failure include conservative management, intravenous fluids, and kidney replacement therapy (KRT). Despite the paucity of evidence-based recommendations concerning the application of KRT in children with kidney dysfunction in the setting of ALF, expert clinical opinions have been evaluated regarding the optimal modalities and timing of KRT, dialysis/replacement solutions, blood and dialysate flow rates and dialysis dose, and anticoagulation methods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Raina, Sethi, Filler, Menon, Mittal, Khooblall, Khooblall, Chakraborty, Adnani, Vijayvargiya, Teo, Bhatt, Koh, Mourani, de Sousa Tavares, Alhasan, Forbes, Dhaliwal, Raghunathan, Broering, Sultana, Montini, Brophy, McCulloch, Bunchman, Yap, Topalglu and Díaz-González de Ferris.)

Background: Sodium-23 magnetic resonance imaging ( 23 Na MRI) allows the measurement of skin sodium concentration ([Na + ]). In patients requiring dialysis, no data are available relating to the clinical outcomes associated with skin sodium accumulation or the determinants of increasing deposition., Methods: This was an exploratory, observational study of adult hemodialysis (HD) and peritoneal dialysis (PD) patients. Participants underwent skin [Na + ] quantification with leg 23 Na MRI at the study's beginning. Outcomes of interest were all-cause mortality and composite all-cause mortality plus major adverse cardiovascular events. Cumulative total and event-free survival were assessed using the Kaplan-Meier survival function after stratification into skin [Na + ] quartiles. Cox proportional hazards regression was used to model the association between skin [Na + ] and outcomes of interest. Multiple linear regression was used to model the predictors of skin [Na + ]., Results: A total of 52 participants (42 HD and 10 PD) underwent the study procedures. The median follow-up was 529 days (interquartile range: 353-602). Increasing skin [Na + ] quartiles were associated with significantly shorter overall and event-free survival (log-rank χ 2 (1) = 3.926, log-rank χ 2 (1) = 5.685; P for trend <0.05 in both instances). Skin [Na + ] was associated with all-cause mortality {hazard ratio (HR) 4.013, [95% confidence interval (95% CI) 1.988-8.101]; P < 0.001} and composite events [HR 2.332 (95% CI 1.378-3.945); P < 0.01], independently of age, sex, serum [Na + ] and albumin. In multiple regression models, dialysate [Na + ], serum albumin and congestive heart failure were significantly associated with skin [Na + ] in HD patients ( R 2 adj  = 0.62)., Conclusions: Higher skin [Na + ] was associated with worse clinical outcomes in dialysis patients and may represent a direct therapeutic target., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

The agreement between the traditionally-used ambulatory blood pressure (ABP)-load thresholds in children and recently-recommended pediatric American Heart Association (AHA)/European Society of Hypertension (ESH) ABP thresholds for diagnosing ambulatory hypertension (AH), white coat hypertension (WCH), and masked hypertension (MH) has not been evaluated. In this cross-sectional study on 450 outpatient participants, the authors evaluated the agreement between previously used ABP-load 25%, 30%, 40%, 50% thresholds and the AHA/ESH thresholds for diagnosing AH, WCH, and MH. The American Academy of Pediatrics thresholds were used to diagnose office hypertension. The AHA threshold diagnosed ambulatory normotension/hypertension closest to ABP load 50% in 88% (95% CI 0.79, 0.96) participants (k 0.67, 95% CI 0.59, 0.75) and the ESH threshold diagnosed ambulatory normotension/hypertension closest to ABP load 40% in 86% (95% CI 0.77, 0.94) participants (k 0.66, 95% CI 0.59, 0.74). In contrast, the AHA/ESH thresholds had a relatively weaker agreement with ABP load 25%/30%. Therefore, the diagnosis of AH was closest between the AHA threshold and ABP load 50% (difference 3%, 95% CI -2.6%, 8.6%, p = .29) and between the ESH threshold and ABP load 40% (difference 4%, 95% CI -2.1%, 10.1%, p = .19) than between the AHA/ESH and ABP load 25%/30% thresholds. A similar agreement pattern persisted between the AHA/ESH and various ABP load thresholds for diagnosing WCH and MH. The AHA and ESH thresholds diagnosed AH, WCH, and MH closest to ABP load 40%/50% than ABP load 25%/30%. Future outcome-based studies are needed to guide the optimal use of these ABP thresholds in clinical practice., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

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., Competing Interests: Conflicts of interests All authors declare no conflict of interest., (Copyright © 2021 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Pre-emptive kidney transplantation for end-stage kidney disease in children has many advantages and may lead to the consideration of marginal parent donors., Methods: Using the example of the transplant of a kidney with medullary sponge disease from a parent to the child, we review the ethical framework for working up such donors., Results: The four principles of health ethics include autonomy (the right of the patient to retain control over his/her own body); beneficence (healthcare providers must do all they can do to benefit the patient in each situation); non-maleficence ("first do no harm"-providers must consider whether other people or society could be harmed by a decision made, even if it is made for the benefit of an individual patient) and justice (there should be an element of fairness in all medical decisions). Highly motivated donors may derive significant psychological benefit from their donation and may thus be willing to incur more risk. The transplantation team and, ideally, an independent donor advocate team must make a judgment about the acceptability of the risk-benefit ratio for particular potential donors, who must also make their own assessment. The transplantation team and donor advocate team must be comfortable with the risk-benefit ratio before proceeding., Conclusions: An independent donor advocacy team that focuses on the donor needs is needed with sufficient multidisciplinary ethical, social, and psychological expertise. The decision to accept or reject the donor should be within the authority of the independent donor advocacy team and not the providers or the donor., (© 2021 Wiley Periodicals LLC.)

Introduction: The slow increase in use of telemedicine began to expand rapidly, along with reimbursement changes, during the coronavirus disease-2019 (COVID-19) pandemic. Standardized protocols for these services are lacking but are needed for effective and equitable health care. In this study, we queried pediatric nephrologists and their patients about their telemedicine experiences during the pandemic., Methods: Surveys that were in compliance with the Health Insurance Portability and Accountability Act were deployed online to patients and physicians., Results: We collected survey responses from 400 patients and 197 pediatric nephrologists. Patients reported positive experiences with telemedicine visits as it was logistically easier than in-person visits. Patients also felt that the quality of their visits were equivalent to what they would receive in person. Physicians used a wide variety of online systems to conduct synchronous telemedicine with Zoom (23%), EPIC (9%), Doxy.me (7%), services not specified (37%), or a mix of local or smaller services (24%). Most physicians' concerns were related to technological issues and the ability to procure physical exams and/or laboratory results., Conclusions: There is a paucity of published trials on telemedicine services in pediatric nephrology. Virtual care was feasible and acceptable for patients, caregivers, and providers during the COVID-19 pandemic., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Derangements of trace elements often occur in patients with renal failure and play a crucial role in chronic kidney disease. The natural history of trace element deposition with worsening chronic kidney disease has been poorly described. Some essential trace elements may get wasted (e.g., selenium, zinc, and manganese) while other trace elements accumulate (e.g., cobalt, lead, molybdenum, and vanadium). Data are most readily available relating to hemodialysis patients. Continuous renal replacement therapies (for the treatment of acute kidney injury) and chronic kidney disease patients without need for renal replacement therapy remain largely unstudied. We have synthesized all available data on mode of absorption and elimination, volume of distribution, plasma protein binding, and proteinuria to summarize the existing literature, identify future areas of research and to allow some prediction of the fate of individual trace elements in clinical scenarios where no direct observational data are available. More prospective studies evaluating the impact of abnormal trace elements and the possible therapeutic value of intervention are required to improve how robust the current international guideline recommendations (KDOQI) are with respect to trace element monitoring.