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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).sub.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., Author(s): Guido Filler [sup.1] [sup.2] [sup.3] [sup.4] , Olivia Tremblay [sup.5] , Emily Chen [sup.5] , Susan Shi Han Huang [sup.1] [sup.2] [sup.6] , Robert Stein [sup.1] Author Affiliations: (1) [...]

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. Graphical abstract, Author(s): Ajay P. Sharma [sup.1] [sup.2] , Amrit Kirpalani [sup.1] [sup.2] , Ajaya Sharma [sup.1] , Luis Altamirano-Diaz [sup.1] [sup.3] , Guido Filler [sup.1] [sup.2] , Kambiz Norozi [sup.1] [sup.3] [...]

Author(s): Aaron Wightman [sup.1] , Guido Filler [sup.2] [sup.3] [sup.4] [sup.5] , Maria Esther Díaz-González de Ferris [sup.6] Author Affiliations: (1) grid.34477.33, 0000000122986657, Department of Pediatrics, Divisions of Nephrology, Bioethics [...]

Author(s): Guido Filler [sup.1] [sup.2] [sup.3] [sup.4] , Laura Torres-Canchala [sup.5] , Ajay P. Sharma [sup.1] , Maria E. Díaz González de Ferris [sup.6] , Jaime M. Restrepo [sup.7] [sup.8] [...]

Background Sodium-23 magnetic resonance imaging (.sup.23Na MRI) allows non-invasive assessment of tissue sodium concentration ([Na.sup.+]). Age and chronic kidney disease (CKD) are associated with increased tissue [Na.sup.+] in adults, but limited information is available pertaining to children and adolescents. We hypothesized that pediatric CKD is associated with altered tissue [Na.sup.+] 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 .sup.23Na MRI for tissue [Na.sup.+] quantification (whole leg, skin, soleus muscle). CKD was stratified by etiology and patients' tissue [Na.sup.+] 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.sup.+] 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.sup.+] 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.sup.+] Z-scores. Reduced whole-leg [Na.sup.+] Z-scores were found in two patients with tubular disorders (Fanconi syndrome, proximal-distal renal tubular acidosis). All tissue [Na.sup.+] 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.sup.+] compared with healthy controls. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information., Author(s): Fabio R. Salerno [sup.1] [sup.2] , Alireza Akbari [sup.2] [sup.3] , Sandrine Lemoine [sup.2] [sup.4] , Timothy J. Scholl [sup.1] [sup.3] [sup.5] , Christopher W. McIntyre [sup.1] [sup.2] [sup.6] [...]

Author(s): Guido Filler [sup.1] [sup.2] [sup.3] [sup.4] [sup.5] , Ajay P. Sharma [sup.1] Author Affiliations: (1) grid.39381.30, 0000 0004 1936 8884, Department of Pediatrics, Schulich School of Medicine & Dentistry, [...]

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 m.sup.2 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 m.sup.2 and was 68 mL/min/1.73 m.sup.2 at last follow-up. However, a sodium-23 (.sup.23Na) MRI of her thigh revealed ongoing moderate sodium decrease in her skin and substantial Na.sup.+ 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., Author(s): Guido Filler [sup.1] [sup.2] [sup.3] [sup.4] [sup.5] , Rishika Geda [sup.6] [sup.4] , Fabio Salerno [sup.5] [sup.7] , Yun Cong Zhang [sup.2] , Maria E Díaz-González de Ferris [sup.8] [...]

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. [ABSTRACT FROM AUTHOR]