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Background The incidence of nephrolithiasis in children and adolescents is increasing and appears to double every 10 years. The most important role of the pediatric nephrologist is to diagnose and modify various metabolic and non-metabolic risk factors, as well as prevent long-term complications especially in the case of recurrent nephrolithiasis. Objective The purpose of this review is to summarize the existing literature on the etiology and management of pediatric nephrolithiasis. Results The incidence of kidney stones is increasing; dietary and environmental factors are probably the main causes for this increased incidence. In most pediatric patients, the etiology for the kidney stones can be identified. Metabolic factors, such as hypercalciuria and hypocitraturia, urinary tract infection, and urinary stasis, constitute leading causes. Herein, we review the etiologies, diagnostic work-up, and treatment options for the most prevalent causes of kidney stones. The detrimental effects of excessive dietary sodium, reduced fluid intake, and the benefits of plant-based over animal-based protein consumption on urinary crystal formation are discussed. We also review the long-term complications. Conclusions Pediatric nephrologists have an important role in the diagnostic work-up and prevention of recurring nephrolithiasis., Author(s): Carmen Inés Rodriguez Cuellar [sup.1] [sup.2] [sup.3] [sup.4] , Peter Zhan Tao Wang [sup.5] , Michael Freundlich [sup.6] , Guido Filler [sup.1] [sup.4] [sup.7] [sup.8] [sup.9] [sup.10] Author Affiliations: [...]

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]

BackgroundFibroblast growth factor-23 (FGF-23), a novel marker of bone disease in chronic kidney disease (CKD) has been shown to correlate with vascular calcifications. We aimed to describe the effect of the calcium phosphate product (Ca*P) on FGF-23 concentrations in children and young adults without confounding cardiovascular disease.MethodsPediatric and young adult patients with CKD stages I-V were recruited in this cross sectional study to measure FGF-23, cystatin C, vitamin D-metabolites and other serum markers of bone metabolism. FGF-23 levels were determined with an enzyme-linked immunosorbent assay. The association between FGF-23 and (Ca*P) was assessed using non-parametric methods. Patients were divided into two age groups, less than 13 years of age and greater than 13 years of age.ResultsThis cross-sectional study measured serum FGF-23, in 81 patients (42 females, 51.9%) at London Health Sciences Centre, aged 2 to 25 years, with various stages of CKD (Cystatin C estimated glomerular filtration rate, eGFR=10.7-213.0 ml/min). For the whole entire group of patients, FGF-23 levels were found to correlate significantly with age (Spearman r= 0.26, p=0.0198), Cystatin C eGFR (Spearman r=-0.40 p=0.0002), CKD stage (Spearman r=0.457, p

Background Galloway-Mowat syndrome (GAMOS) (OMIM #251300) is a severe autosomal recessive disease characterized by the combination of early-onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies caused by WDR73 as well as OSGEP, TP53RK, TPRKB, or LAGE3 mutations. Objective We report on the hitherto undescribed urological and nephrological complications of the homozygous c.974G>A (p.Arg325Gln) OSGEP mutations in a 7-year-old Caucasian girl. Case diagnosis The patient came to the attention of pediatric nephrology at the age of 3 years and 11 months, when she presented with status epilepticus due to profound hypomagnesemia (0.31 mmol/L, normal 0.65-1.05). A 24-h urine demonstrated a magnesium loss of 0.6 mmol/kg/day with associated proteinuria suggesting renal tubulopathy. Subsequently, she developed recurrent urinary tract infections (UTIs) and was diagnosed with neurogenic bladder dysfunction. The patient continued to have UTIs associated with seizures and sequential cultures growing multi-drug-resistant organisms despite of antibiotic prophylaxis. In addition, the proteinuria (median microalbumin/creatinine ratio 647 mg/mmol) increased, and she developed partial Fanconi syndrome. At age 7, she developed a large bladder calculus (3.3 x 3.2 cm) and three left non-obstructing renal calculi associated with elevated urinary cystine, hypercalciuria, and ongoing hypomagnesemia and required surgical intervention. Glomerular filtration rate (GFR) remained normal and she never developed frank nephrotic syndrome (average albumin 31 g/L). Conclusions It is unclear if patients with OSGEP mutations with tubular symptoms rather than nephrotic syndrome should be considered a different entity. Nephrological and urological complications of OSGEP mutations can be challenging and require a multidisciplinary approach., Author(s): Peter Zhan Tao Wang [sup.1] , Chitra Prasad [sup.2] [sup.3] , Carmen Inés Rodriguez Cuellar [sup.2] , Guido Filler [sup.2] [sup.3] [sup.4] [sup.5] [sup.6] Author Affiliations: (Aff1) 0000 0004 [...]

Importance Changes in kidney function are typically followed by the sequential estimation of glomerular filtration rate (eGFR). Formulae for eGFR work well on a population basis, but there are well-known conditions where they do not work. Objective The purpose of this review is to summarize the existing literature on special populations in the pediatric age range and provide recommendations on how to estimate GFR in these populations. Findings The reliability of creatinine depends on muscle mass, while cystatin C (not widely available) is limited by inflammation and changes in protein catabolism. Various dietary factors can alter eGFR. Renal function in neonates changes drastically every day, and there are currently no satisfactory reference intervals for routine pediatric use. Gender effects and conditions such as wasting disease and obesity require alternative ways to obtain eGFR. In oncology patients, chemotherapy may negatively affect renal function, and nuclear GFR measurements may be necessary. For body builders, high muscle mass may lead to underestimation of eGFR using creatinine. Conclusions and relevance Clinicians should be aware of special populations that may yield misleading eGFRs with conventional creatinine-based formulae, and that the alternative methods may be more appropriate for some populations., Author(s): Guido Filler [sup.1] [sup.2] [sup.3] [sup.4] , Misan Lee [sup.1] Author Affiliations: (Aff1) 0000 0004 1936 8884, grid.39381.30, Department of Pediatrics, Schulich School of Medicine & Dentistry, University of [...]

Immunosuppressive drugs for solid organ transplantation are critical dose drugs with a narrow therapeutic index. Many of the most commonly used innovator drugs are off patent and have been replicated by generic counterparts, often at substantial cost-savings to the patient. However, serious adverse events caused by the transition from innovator to generic medications, specifically in pediatric solid organ transplant recipients, have questioned these autosubstitutions. The purpose of this review is to summarize the criteria set forth by the regulatory bodies, and to examine how major immunosuppressive drugs conform to these recommendations. Regulatory bodies have established inconsistent criteria to demonstrate bioequivalence between innovator and generic medications, causing approved generic variations to have varying levels of equivalence with the innovator drugs. In order to minimize the risk for under-immunosuppression, the following recommendations have been concluded. Brand prescribing of cyclosporine and tacrolimus are recommended due to evidence of adverse events after conversion to generic formulations and differences in dissolution parameters. Mycophenolate mofetil (MMF) shows better bioequivalence between innovator and generic formulations, however caution should be advised when switching between formulations. The institution of 'innovator only' policies may be appropriate at this time in order to minimize the risk of under-immunosuppressing patients until the evidence of more stringent bioequivalence has been established., Author(s): Mara Medeiros [sup.1] [sup.2] , Julia Lumini [sup.3] , Noah Stern [sup.4] , Gilberto Castañeda-Hernández [sup.5] , Guido Filler [sup.4] [sup.6] [sup.7] [sup.8] Author Affiliations: (Aff1) 0000 0004 0633 [...]

We have reviewed current evidence on the therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) in relationship to drug efficacy and safety. The relationship between actual MPA exposure and mycophenolate mofetil (MMF) dose has been shown to be weak in children and adolescents. The TDM of MPA exposure should ideally be performed using full pharmacokinetic profiles or limited sampling strategies. Recent evidence has provided some rationale for using the post-dose trough level as a single measure. In terms of short-term efficacy, there is strong evidence that a MPA area under the time-concentration curve of >30 mg x h/L reduces acute rejection episodes early after renal transplantation, and there is evolving evidence that aiming for the same exposure over the long term may be a viable strategy to reduce the formation of donor-specific antibodies. Strong evidence also supports the existence of important drug interactions and age/developmental dependent differences in drug metabolism that may necessitate the need for TDM of MMF therapy. Based on these findings and given the substantial inter- and intra-patient variability of MPA exposure, it would appear that MMF therapy should be subject to TDM to avoid over- and under-dosing. This may be a viable strategy to reduce treatment-emergent adverse events and to increase the effective pediatric transplant survival rates., Author(s): Guido Filler[sup.1] [sup.2] [sup.3] [sup.7] , Ana Catalina Alvarez-Elias[sup.1] [sup.4] [sup.5] , Christopher McIntyre[sup.3] , Mara Medeiros[sup.5] [sup.6] Author Affiliations: (1) Department of Pediatrics, Schulich School of Medicine & [...]

Byline: Ajay. Sharma, Jeremy. Burton, Guido. Filler, Sumit. Dave The incidence of nephrolithiasis is increasing worldwide. Understanding how gut microbiome influences oxalate homeostasis has the potential to offer new strategies [...]