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Vitamin D deficiency is frequent in pediatric nephrology. The 2017 European guidelines recommend keeping 25OH vitamin D (25-D) levels within the 75-120 nmol/L range, ideally with daily supplementation. Intermittent supplementation with D3 has also been proposed. We aimed to assess the influence of our local protocol of intermittent vitamin D supplementation on the evolution of 25-D levels between baseline and 2 months. VITATOL is a prospective single-center study performed in our tertiary unit in children and teenagers followed for chronic kidney disease (CKD), kidney transplantation, or stable chronic nephrotic syndrome with 25-D levels below 75 nmol/L. Intermittent oral cholecalciferol (100,000 IU) was administered depending on baseline vitamin D levels and body weight. The primary outcome was the change in 25-D levels between baseline and 2 months. Secondary outcomes were the evolution of the main mineral biomarkers. Thirty-seven patients were included. Two months after beginning supplementation, corresponding to a median(min-max) of 46 (14-79) days after the last dose of vitamin D, 25-D levels increased from 50 to 76 nmol/L (p < 0.001), 18 patients having 25-D levels within the target range and 2 above. All patients displayed 25-D levels above 50 nmol/L. There were no significant changes in phosphate, PTH, alkaline phosphatase, and FGF23 levels before and after supplementation. Calcium levels increased from 2.39 to 2.44 mmol/L (p = 0.017), but no differences in calciuria and urinary calcium/creatinine ratio were observed.Conclusion: This vitamin D supplementation protocol using intermittent moderate doses of cholecalciferol seems efficient in 54% of cases, with neither significant overdose nor hypercalciuria. What is Known: • Vitamin D deficiency is frequent in pediatric nephrology. • The 2017 European guidelines recommend keeping 25OH vitamin D levels within the 75-120 nmol/L range ideally with daily supplementation, but intermittent supplementation with D3 has also been proposed. What is New: • We assessed the influence of a local protocol of intermittent vitamin D supplementation on the evolution of 25-D levels between baseline and 2 months in children and teenagers followed in pediatric nephrology. • The intermittent cholecalciferol supplementation protocol seems efficient in 54% of cases, with neither significant overdose nor hypercalciuria.

Objective: To evaluate safety and efficacy of recombinant human growth hormone treatment in children on long-term glucocorticoid therapy., Methods: A 5-year prospective open-label study included children on glucocorticoid therapy with either standard deviation score (SDS)<-2 for height for chronological age (CA) if naïve to growth hormone treatment, or annual growth rate≥0 SDS for CA if currently receiving growth hormone., Results: Ninety-eight patients began treatment, 63 discontinued; 59 were analyzed for safety and 58 for efficacy. There was male predominance (78.0%). Median age was 13.0 years. Median height screening was 136.0cm (range, 95.1-159.7cm). Mean SDS for height for CA in the efficacy analysis set was -2.91±1.19 (range, -7.49 to -0.96). Mean growth hormone dose was 0.4, 0.4, 0.4 and 0.3mg/kg/week at month 0, M12, M24, and M36, respectively. Primary analysis of change in SDS for height for CA from baseline to M36 showed a significant increase of 0.80±1.03. Twenty patients in the safety analysis set had≥1 treatment-emergent adverse event (TEAE) related to study treatment. Two patients experienced serious treatment-related TEAEs: 1 case of poor compliance, and 1 of mild hyperglycemia, both already observed under growth hormone treatment., Conclusion: This study suggests that growth hormone treatment could be effective in increasing height in children on long-term glucocorticoid treatment with a safety profile comparable to that in approved rhGH treatment indications., Clinical Trial Registration: NCT00163189., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: The management of tubulopathies after renal transplantation (RTx) may require high doses of sodium and bicarbonate, reducing the quality of life and therapeutic compliance of the patient. Some studies on adult patients have highlighted the benefits of fludrocortisone (fludro) in the treatment of severe tubulopathies., Methods: This study was a retrospective review of the medical charts of 15 children, aged 12.4 (range 3.6-17.4) years who received fludro after RTx., Results: With the administration of fludro, both sodium bicarbonate and chloride supplementation decreased, from 10 (range 0-14) to 0 (0-5) g/day, and from 9 (0-20) to 0 (0-3) g/day, respectively (both p < 0.001). Serum potassium also significantly decreased (4.6 ± 0.4 vs. 3.3 ± 0.6 mmol/L; p < 0.001), but there was no significant effect on renal function. Both systolic and diastolic blood pressure increased significantly. Fludro therapy was stopped in six patients due to side-effects (arterial hypertension, hypokalemia during acute diarrhea, gastric pain, n = 3), parental decision (n = 1), inefficacy and/or non-compliance (n = 1) and scheduled withdrawal (n = 1). Four of these patient had subsequent increasing requirements for bicarbonate and/or sodium supplementation, which ultimately required the re-introduction of fludro in two of these patients., Conclusions: Based on our findings, fludro would appear to be an effective therapy in most cases of severe tubulopathy after RTx. Further prospective studies are required to validate this indication and to determine the optimal dose and timing of treatment to avoid side-effects as well as the clinical and biological follow-up.

Data on long-term outcomes after pediatric renal transplantation (Tx) are still limited. We report on a 20-year single-center experience. Medical charts of all consecutive pediatric Tx performed between 1987 and 2007 were reviewed. Data of patients who had been transferred to adult units were extracted from the French databases of renal replacement therapies. Outcomes were assessed using Kaplan-Meier and Cox models. Two hundred forty Tx were performed in 219 children (24.1% pre-emptive and 17.5% living related donor Tx). Median age at Tx was 11.1 years and median follow-up was 10.4 years. Patient survival was 94%, 92%, and 91% at 5, 10, and 15 years post-Tx, respectively. Overall, transplant survival was 92%, 82%, 72%, and 59% at 1, 5, 10, and 15 years post-Tx, respectively. The expected death-censored graft half-life was 20 years. Sixteen patients developed malignancies during follow-up. Median height at 18 years of age was 166 cm in boys and 152 cm in girls with 68% of patients being in the normal range. The proportion of socially disadvantaged young people was higher than in general population. Excellent long-term outcomes can be achieved in pediatric renal Tx, but specific problems such as malignancies, growth, and social outcome remain challenging., (© 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.)

Graft survival is worse in recipient aged less than 5 years due to the greater risk of vascular thrombosis. Thrombosis may be prevented by the choice of the donor, method of surgery, perioperative hemodynamic optimisation and preventive anti-coagulation. Normal growth is a major objective of the management of transplanted children. The mean final height increased during the 20 last years to be between -1.63 and -0.92 SDS depending on age and period of the transplantation., (Copyright © 2011. Published by Elsevier SAS.)

Bone damage in children with chronic kidney disease (CKD) is a challenge for pediatric nephrologists. Areal measurements of bone mineral density (BMD) by dual x-ray absorptiometry (DXA) have been routinely performed to assess bone mass but recent international guidelines have concluded that DXA was of less value in CKD. The aim of this study is to evaluate bone quality in CKD children using new bone imaging techniques in a pilot cross-sectional single-center study. We performed bone imaging (high-resolution peripheral quantitative computed tomography, HR-pQCT, XtremeCT, Scanco Medical AG, Switzerland), to assess compartmental volumetric BMD and trabecular microarchitecture in 22 CKD children and 19 controls. In seven younger patients (i.e., under 10 years of age), we performed bone texture analysis (BMA, D3A Medical Systems, France) in comparison to 15 healthy prepubertal controls. Among older children, CKD patients had significantly lower height and body weight without significant impairment of BMD and microarchitecture than healthy controls. In univariate analysis, there were significant correlations between cortical BMD and glomerular filtration rate (r= -0.46), age (r=0.60) and body mass index (r=0.67). In younger children, bone texture parameters were not different between patients and controls. Our results did not show significant differences between healthy controls and CKD children for compartmental bone densities and microarchitecture, but the small sample size and the heterogeneity of the CKD group require caution in the interpretation. Novel bone imaging techniques seem feasible in children, and further longitudinal studies are required to thoroughly explore long-term cardiovascular and bone consequences of phosphate-calcium metabolism deregulation during CKD.

The deposition of calcium oxalate crystals in the kidney and bone is a hallmark of primary hyperoxaluria type 1 (PH1). We report here an evaluation of the bone status of 12 PH1 children based on bone biomarkers [parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23)] and radiological assessments (skeletal age, three-dimensional high-resolution peripheral quantitative computed tomography, HR-pQCT) carried out within the framework of a cross-sectional single-center study. The controls consisted of healthy and children with chronic kidney disease already enrolled in local bone and mineral metabolism studies. The mean age (+ or - standard deviation) age of the patients was 99 (+ or - 63) months. Six children suffered from fracture. Bone maturation was accelerated in five patients, four of whom were <5 years. The combination of new imaging techniques and biomarkers highlighted new and unexplained features of PH1: advanced skeletal age in young PH1 patients, increased FGF23 levels and decreased total volumetric bone mineral density with bone microarchitecture alteration.

Primary hyperoxaluria type 1, the most common form of primary hyperoxaluria, is an autosomal recessive disorder caused by a deficiency of the liver-specific enzyme alanine: glyoxylate aminotransferase (AGT). This results in increased synthesis and subsequent urinary excretion of the metabolic end product oxalate and the deposition of insoluble calcium oxalate in the kidney and urinary tract. As glomerular filtration rate (GFR) decreases due to progressive renal involvement, oxalate accumulates and results in systemic oxalosis. Diagnosis is still often delayed. It may be established on the basis of clinical and sonographic findings, urinary oxalate +/- glycolate assessment, DNA analysis and, sometimes, direct AGT activity measurement in liver biopsy tissue. The initiation of conservative measures, based on hydration, citrate and/or phosphate, and pyridoxine, in responsive cases at an early stage to minimize oxalate crystal formation will help to maintain renal function in compliant subjects. Patients with established urolithiasis may benefit from extracorporeal shock-wave lithotripsy and/or JJ stent insertion. Correction of the enzyme defect by liver transplantation should be planned, before systemic oxalosis develops, to optimize outcomes and may be either sequential (biochemical benefit) or simultaneous (immunological benefit) liver-kidney transplantation, depending on facilities and access to cadaveric or living donors. Aggressive dialysis therapies are required to avoid progressive oxalate deposition in established end-stage renal disease (ESRD), and minimization of the time on dialysis will improve both the patient's quality of life and survival.

In order to identify additional genotypes in primary hyperoxaluria type 1, we sequenced the AGXT genes of 9 patients. We report 5 new mutations. Three are splice-site mutations situated at the end of intron 4 and 8 (647-1G>A, 969-1G>C, 969-3C>G), one is a missense mutation in exon 5 (D183N), and one is a short duplication in exon 2 (349ins7). Their consequence is always a lack of enzymatic activity of the Alanine-Glyoxylate Aminotransferase (AGT); for 4 of them, we were able to deduce that they were associated to the absence of AGT protein. These mutations are rare, as they have been found on one allele in our study (except 969-3C>G present in 2 unrelated families), and have not been previously reported.