Search

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 Pediatric nephrologists use kidney length and kidney volume z-scores to longitudinally assess normal nephron endowment. However, most radiologists only report kidney length. Agreement between kidney length and kidney volume z-scores in children has been understudied. This study aims to assess agreement between kidney length and kidney volume z-scores in children. Methods This novel cross-sectional cohort study prospectively followed prematurely born babies from a large specialized prematurity follow-up center. A healthy control group matched the cases by age and sex and was recruited from schools. Children were assessed for kidney length and kidney volumes at age 5 by three independent ultrasonographers. All measurements were performed in triplicate. Detailed anthropometry, blood pressure, and kidney function were also obtained. Age-independent z-scores were calculated for all parameters according to Scholbach and Weitzel and compared using descriptive statistics. Results We studied 89 premature patients (median 32 weeks gestational age) and 33 healthy controls (median 38 weeks gestational age). There were 732 determinations of kidney length, width, and thickness. The mean z-score of the right kidney length was 0.65 ± 0.08 (SEM) compared with 0.88 ± 0.08 of the left kidney length (p = 0.0003, two-sided paired t test). The squared correlation coefficient for kidney volume to kidney length was 0.32 (p < 0.0001). Bland and Altman analysis revealed considerable bias with - 1.36 ± 0.76 standard deviations and 95% limits of agreement from - 2.83 to - 0.16. Conclusion Reporting only kidney length results in significant overestimation of age-independent z-scores. Based on our findings, consideration to measuring all kidney dimensions may be more appropriate., Author(s): Laura Torres-Canchala [sup.1] , Martin Rengifo [sup.2] , Guido Filler [sup.3] [sup.4] , Juan C. Arias [sup.5] , Oscar Ramirez [sup.6] [sup.7] , Jaime M. Restrepo [sup.8] Author Affiliations: [...]

Author(s): Alexandra Kowalczyk [sup.1] , Maria Esther Diaz-Gonzalez de Ferris [sup.2] , Guido Filler [sup.1] [sup.3] [sup.4] [sup.5] Author Affiliations: (1) grid.39381.30, 0000 0004 1936 8884, Departments of Paediatrics and [...]

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 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 [...]

Author(s): Guido Filler [sup.1] [sup.2] , Laura Torres-Canchala [sup.2] [sup.3] Author Affiliations: (1) grid.39381.30, 0000 0004 1936 8884, Departments of Paediatrics, Medicine and Pathology and Laboratory Medicine, Paediatric Nephrology, Schulich [...]

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 [...]

In this edition of Pediatric Nephrology, Vaishnavi Raman et al. have published an open-labeled randomized clinical trial of 100 children with idiopathic nephrotic syndrome who were allocated either a body weight- or body surface area-based prednisolone dosing for a duration of 12 weeks. The authors used Kaplan-Meier analysis for comparison of the time to remission. They also compared the relapse rate and found no difference. This editorial discusses the strengths of the current study as well some limitations. The inclusion of relapsing patients in the study protocol is problematic. The follow-up period of only 6 months forms another limitation. No subgroup analysis by age was performed. This editorial also highlights the lack of correlation between steroid dose and steroid exposure and the need for considering the age dependency (ontogeny) of drug disposition. Finally, the need for adherence to CONSORT criteria for reporting randomized controlled clinical trials is emphasized., Author(s): Guido Filler[sup.1] [sup.2] [sup.3] , Lisa A. Robinson[sup.4] [sup.5] [sup.6] [sup.7] Author Affiliations: (1) Department of Pediatrics, Schulich School of Medicine & Dentistry, Western University, 800 Commissioners Road East, [...]

In this edition of Pediatric Nephrology, Milena Treiber and colleagues have published a study on cystatin C (CysC) concentrations in relation to renal volumetry in 50 small-for-gestational age (SGA) and 50 appropriate-for-gestational age (AGA) neonates, deriving a new formula for estimating neonatal glomerular filtration rate (GFR). The study builds on previous work which established that renal volumetry together with CysC blood levels is a superior method for establishing GFR in term and pre-term newborns [The Journal of Pediatrics (2014) 164:1026-1031.e2]. Treiber et al. use the expected difference between SGA and AGA renal volumes to document the superiority of their new formula, which is based on total renal volume, CysC and body surface area, but does not incorporate gold-standard inulin clearance. Treiber et al.'s study adds new knowledge to the field that will hopefully improve the safety of renally excreted critical dose drugs in the newborn period. This editorial discusses the strengths and limitations of the current study., Author(s): Guido Filler[sup.1] [sup.2] [sup.3] [sup.4] Author Affiliations: (1) Department of Pediatrics, Schulich School of Medicine & Dentistry, Western University, N6A 5 W9, London, ON, Canada (2) Department of Pathology [...]

The combination of hemodialysis and plasma exchange as one tandem procedure was first described in 1999 by Siami et al. (ASAIO J 45:229-233), but larger pediatric case series were not described until 2012. Even in adults, there are only limited case series. If performed in sequence, up to 8 h of treatment time may be required. With the use of the tandem procedure in stable patients, the same procedures can be completed during the same time as a routine hemodialysis, which is more convenient for patients and may reduce healthcare costs. Little is known about the utilization of the combination of hemodialysis and plasma exchange in children. The purpose of this review is to summarize the adult and scarce pediatric experience. The results of a survey carried out by the authors using the Internet listserver 'PedNeph' to obtain an overview of the current practice patterns of pediatric nephrologists are also presented. Keywords Tandem procedure * Plasma exchange * Hemodialysis * Plasmapheresis * Atypical hemolytic uremic syndrome * Antibody-mediated rejection, Introduction Hemodialysis (HD) is indicated for severe acute and chronic kidney failure. It removes uremic toxins by allowing the equilibration of these toxins between plasma water and dialysate across a [...]

In a recent article in Pediatric Nephrology, EM Yang and colleagues (Pediatr Nephrol 2017: doi:10.1007/s00467-016-3587-6) published a retrospective cross-sectional study involving a cohort of 442 children with an mean estimated glomerular filtration rate of >60 mL/min/1.73 m.sup.2. The authors measured 24-h urine protein excretion (24-h UProt) alongside the morning spot urine protein to creatinine ratio (Prot/Cr) in this group of patients. While the Prot/Cr may be the only feasible way to routinely estimate the daily protein excretion of a young child, inter-individual variability in childrens' urinary creatinine excretion (UCr) may heavily influence the result. The authors sought to determine which equation was the most accurate in predicting UCr. Not only did they discover that the adult Cockcroft-Gault equation worked best, they also found that multiplying the Prot/Cr by the estimated UCr significantly improved the accuracy of the 24-h UProt estimate. In this editorial we discuss both the strengths and limitations of the study by EM Yang and colleagues. We also highlight the importance of adhering to internationally agreed upon reporting guidelines such as the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement., Author(s): Guido Filler [sup.1] [sup.2] [sup.3] [sup.4] , Shih-Han Susan Huang [sup.1] [sup.3] Author Affiliations: (1) 0000 0004 1936 8884grid.39381.30Department of Pediatrics, Schulich School of Medicine & Dentistry, Western University, [...]

Although measuring creatinine to determine kidney function is currently the clinical standard, new markers such as beta-trace protein (BTP) and beta-2-microglobulin (B2M) are being investigated in an effort to measure glomerular filtration rate more accurately. In their recent publication, Inker et al. (Am J Kidney Dis 2015; 67:40-48) explored the use of these two relatively new markers in combination with some commonly available clinical characteristics in a large cohort of adults with chronic kidney disease. Their research led them to develop three formulae using BTP, B2M, and a combination of the two. The combined formula is particularly attractive as it removes all gender bias, which applies to both serum creatinine and cystatin C. Using data from a cohort of 127 pediatric patients from our center, we sought to determine whether these formulae would be equally as effective in children as in adults. Unfortunately, we found that the formulae cannot be applied to the pediatric population., Author(s): Guido Filler[sup.1] [sup.2] [sup.3] [sup.4] , Ana Catalina Alvarez-Elias[sup.1] , Katherine D. Westreich[sup.5] , Shih-Han S. Huang[sup.1] [sup.3] [sup.6] , Robert M. Lindsay[sup.3] [sup.6] Author Affiliations: (1) Pediatric Nephrology [...]

In end-stage chronic kidney disease (CKD), pediatric nephrologists must consider the homeostasis of the multiple water-soluble ions that are influenced by renal replacement therapy (RRT). While certain ions such as potassium and calcium are closely monitored, little is known about the handling of trace elements in pediatric dialysis. RRT may lead to accumulation of toxic trace elements, either due to insufficient elimination or due to contamination, or to excessive removal of essential trace elements. However, trace elements are not routinely monitored in dialysis patients and no mechanism for these deficits or toxicities has been established. This review summarizes the handling of trace elements, with particular attention to pediatric data. The best data describe lead and indicate that there is a higher prevalence of elevated lead (Pb, atomic number 82) levels in children on RRT when compared to adults. Lead is particularly toxic in neurodevelopment and lead levels should therefore be monitored. Monitoring of zinc (Zn, atomic number 30) and selenium (Se, atomic number 34) may be indicated in the monitoring of all pediatric dialysis patients to reduce morbidity from deficiency. Prospective studies evaluating the impact of abnormal trace elements and the possible therapeutic value of intervention are required. Keywords Zinc * Lead * Manganese * Selenium * Mercury * Chronic kidney disease * Hemodialysis, Introduction Dialysis removes uremic toxins by allowing the equilibration of plasma water and dialysate across a semi-permeable membrane. Dialysate is created by adding regulated quantitates of essential ions such as [...]

Accurate assessment of renal function is critical for appropriate drug dosing of renally excreted compounds. Glomerular filtration rate (GFR) is considered the best marker of kidney function. Inulin clearance forms the gold standard for measuring GFR, both in adults and in children. The method is invasive, cumbersome, and smaller children require urinary catheterization for accurate timed urine collections. Nuclear medicine methods replaced inulin clearance in the 1970s after [sup.51]Cr EDTA clearance was introduced. Inulin has no plasma protein binding, whereas all commonly used radioisotopes have a small amount of plasma protein binding that leads to lower values. Only iohexol does not have significant plasma protein binding. The underestimation due to plasma protein binding is partially offset by overestimation due to the use of non-compartmental pharmacokinetic modeling of the plasma disappearance of the radioisotope. The problem could be overcome with a urinary nuclear medicine clearance method, but these have not been validated in children. Endogenous markers of GFR include serum creatinine and low molecular weight proteins such as cystatin C and beta-trace protein. Of these, estimation of GFR using cystatin C appears to be the most promising, although its accuracy in pregnancy and in the neonatal period may be limited. Keywords Inulin * Nuclear medicine * Cystatin C * eGFR * Creatinine * Chronic kidney disease, Introduction Adequate measurement of kidney function is important for the management of all children and adolescents. In the neonatal period, there is considerable ontogeny of drug disposition, largely due to [...]

Background Nighttime blood pressure (BP) and systolic BP variability on ambulatory blood pressure monitoring (ABPM) have been strongly associated with target-organ damage in hypertensive adults. The clinical relevance of these variables in children with hypertension remains under-studied. Methods The study group included children aged 5-18 years old referred to the outpatient nephrology clinic for an elevated casual BP who underwent an ABPM and echocardiography (ECHO) study and did not have secondary hypertension. The interpretation of ABPM parameters and left ventricular mass index (LVMI) was based on normative references. Results Seventy-two children fulfilled the inclusion criteria. The association of various potential predictors including age, BMI z-score, casual BP z-score and ABPM parameters (BP z-score, BP load, nocturnal dipping and BP variability-within-subject standard deviation (SD) of BP) with LVMI was analyzed. On adjusted regression analysis, nighttime systolic BP load [standardized regression coefficient ([beta]) 0.23; p Keywords Ambulatory blood pressure monitoring Systolic blood pressure variability * Left ventricular hypertrophy * Nighttime blood pressure load * Left ventricular mass index, Background Recent population-based studies have demonstrated an increased prevalence of high blood pressure (BP) in children [1]. High BP increases the risk of target-organ damage, and especially increases in left [...]

Je-Hyan Lee et al. have published a study on cystatin C concentrations in the first 30 days of life in 127 pre-term and 119 term neonates in this edition of Pediatric Nephrology, thereby closing a knowledge gap of detailed cystatin C concentrations beyond 72 h of life by day of life and by post-conceptional age. While the study objective has merit and a large number of measurements were included, there are some methodological limitations that bring the validity of the data into question as pure reference intervals for children up to 1 month of age, mostly because of the inclusion of patients that potentially could have an impaired glomerular filtration rate (GFR), for instance due to exposure to nephrotoxic drugs. We discuss the strengths and weaknesses of the study and outline an approach to definitely close this knowledge gap. We call for a worldwide collaboration to use Box-Cox transformations similar to the methodology used with growth charts to calculate age-independent z-scores and percentiles of neonatal and infant markers of GFR. This could also lead to better definitions of acute kidney injury in infants if GFR markers cross the percentiles based on post-conceptional or chronological age. Keywords Cystatin C * Post-conceptional age * Reference intervals * Renal function * Postnatal adaptation of renal function, Introduction Accurate measurements of renal function are important for the dosing of drugs excreted by the kidneys. This is particularly challenging in neonates. While all nephrons are terminally differentiated at [...]

In adults, strong evidence indicates that slowing progression of chronic kidney disease (CKD) requires an integrated, multidisciplinary approach. In children, however, this approach has not been studied. This editorial commentary to the study by Ajarmeh et al in this volume of Pediatric Nephrology highlights how a dedicated, multidisciplinary team of physicians, nurses, pharmacists, dieticians, social workers and clinic data managers slowed the progression of CKD in children to a remarkable degree. We discuss the strengths and limitations of the study and its cost implications, as well as the issue of determining the optional complement of physicians and allied health care professionals in such clinics. Our calculations indicate that the additional costs of such clinics would be recovered in one year, even if the progression of CKD were to be delayed by 1 year in only 2% of affected children. Here, we call on the international pediatric nephrology community to establish guidelines for forming multidisciplinary clinics throughout the world. Keywords Chronic kidney disease * Children * Dialysis * Health care costs * Anemia * Growth and nutrition * Blood pressure * Disease progression * Hospitalization, Chronic kidney disease (CKD) is a disease with multiple complications that worsen with progression [1]. Managing adults with CKD requires a careful, integrated approach to all comorbidities and complications. In [...]

Background After parents raised concerns about potential lead (Pb) contamination of calcium carbonate for treatment of hyperphosphatemia in chronic kidney disease (CKD), we measured blood Pb using high-resolution sector field inductively coupled mass spectrometry in a quality-assurance investigation of ten pediatric dialysis patients (nine on hemodialysis) and six patients before dialysis. Methods We assessed the kidney function as cystatin C estimated glomerular filtration rate (eGFR), blood Pb levels, calcium carbonate dose, and standard laboratory parameters, as well as Pb levels in the dialysis feed water. Results Mean blood Pb concentration in the 16 pediatric CKD patients was 21.1 ± 15.8 µg/l with a maximum of 58 (µg/l, which was significantly higher than that of 467 apparently healthy controls (median 6.35 (µg/l, interquartile range 4.47, 8.71) and comparable to that of ten adult peritoneal dialysis (PD) patients. Lead levels correlated with red blood cell distribution width, eGFR, and calcium carbonate dose. Pb in dialysate feed water was always Conclusions We found a high prevalence of elevated Pb levels in pediatric CKD patients that correlated with the calcium carbonate dose and GFR. Lead levels should be monitored in these patients. Keywords Lead * Anemia * CystatinC * eGFR * Calcium carbonate * Dialysis feed water * Iron deficiency, Background Increased lead (Pb) absorption from environmental exposure has long been recognized as a threat to child health [1]. Other risk factors for increased Pb absorption include zinc deficiency [2] [...]

The management of steroid-dependent nephrotic syndrome, especially in patients who have failed to respond to cytotoxic drugs, such as cyclophosphamide, remains challenging. Rituximab represents a new (off-label) therapeutic option. In a significant portion of patients, it has a short serum half-life following the recovery of CD20positive cells. The addition of mycophenolate mofetil (MMF) as a maintenance therapy is also an attractive option, but one which requires testing in a prospective randomized clinical trial with therapeutic drug monitoring and mechanistic ancillary studies. Keywords Rituximab * Steroid-dependent nephrotic syndrome * Evidence-based treatment * MMF, Introduction The treatment of childhood nephrotic syndrome (NS) is more evidence-based than most other pediatric nephrology conditions. Publication of the International Study of Kidney Disease in Children (ISKDC) study, which [...]

The objective of this case series was to review the safety and efficacy of aliskiren in combination with losartan in pediatric chronic kidney disease (CKD) patients. This was a retrospective study in which the medical files of all patients who had received aliskiren were reviewed. Four patients were identified between 5 and 18 years of age who had received aliskiren and losartan for the reduction of refractory proteinuria. While proteinuria was reduced in all four of these patients by 45, 96, 53, and 64%, respectively, three patients experienced side effects requiring changes in the aliskiren dose. A significant side effect occurred in the patient with CKD stage 3 who suffered accelerated loss of kidney function leading to dialysis after only a short course of therapy. The data from this preliminary trial strongly suggest that clinicians should exercise caution when prescribing aliskiren in combination with losartan until appropriate pediatric trials establish dosing, efficacy, and safety. Keywords Aliskiren * Renin-angiotensin system * Chronic kidney disease * Losartan * Combination therapy *Safety, Introduction Proteinuria has been identified as one of the most important risk factors for the progression of chronic kidney disease and cardiovascular events [1]. Treatment of the underlying etiology is [...]

Children with X-linked hypophosphatemic rickets (XLH) are prone to severe stunting. A multicenter mixed-longitudinal study was conducted to assess age-related stature, sitting height, arm and leg length in XLH patients on continuous treatment with phosphate and calcitriol. Mean standard deviation scores (SDS) for all body dimensions were markedly reduced and differed significantly among each other at the initial and subsequent evaluations (baseline: stature -2.48 SDS; sitting height -0.99 SDS; arm length -1.81 SDS; leg length -2.90 SDS; each p < 0.001). A strong association between stature and leg length ([r.sup.2] = 0.87, p < 0.001) was noted. Leg length SDS decreased progressively during childhood (2-9 years) and adolescence (12-15 years; each p < 0.001). Sitting height SDS increased significantly during late childhood, indicating uncoupled growth of the legs and trunk and resulting in an ever increasing sitting height index (i.e. ratio of sitting height to stature; age 2 years 2.0 SDS; age 10 years 3.3 SDS; p < 0.001) that was associated with the degree of stunting ([r.sup.2] = 0.314, p < 0.001). Mean serum phosphate levels were positively associated with stature and leg length, but negatively with sitting height index. Based on these results, we can conclude that growth of the legs and trunk is uncoupled in XLH and related to serum phosphate levels. Keywords Anthropometry * Disproportion * Linear growth * Puberty * X-linked hypophosphatemic rickets, Introduction X-linked hypophosphatemic rickets (XLH, MIM #307800) is an inherited disorder of phosphate homeostasis characterized by short stature, rickets, osteomalacia, hypophosphatemia, aberrant phosphate reabsorption, and suppressed 1 a-hydroxylation of 25(OH) [...]

Beta-trace protein (BTP) is a novel marker of glomerular filtration rate (GFR). To date, no pediatric formula for calculating GFR based on BTP has been developed. We measured GFR, serum creatinine and BTP in 387 children who underwent 474 [sup.99m]Tc-diethylene triamine pentaacetic acid renal scans. A BTP-based formula for estimating GFR was derived using stepwise linear regression analysis. A separate control group of 116 measurements in 99 children was used to validate the novel formula. A formula was also developed for each gender. The novel formula is: GFR = 10^(1.902 + (0.9515 x LOG(1/BTP))).The Spearman rank correlation coefficient between the BTP-derived GFR estimate and the measured GFR was 0.80 [95% confidence interval (CI) 0.76-0.83], which is substantially better than that derived with the Schwartz formula (r = 0.70, 95% CI 0.65-0.74). The Bland-Altman analysis revealed a mean bias of 1.21% [standard deviation (SD) 28%] in the formula development dataset, which was virtually identical to the 1.03% mean bias (29.5% SD) in the validation group and no different from the Schwartz formula bias. The percentage of values within 10% (33.0 vs. 28.3%) and 30% deviation (76.8 vs. 72.6%) were better for BTP-based formula than for the Schwartz formula. Separate formulas according to gender did not perform better than that for the pediatric population. This BTP-based formula was found to estimate GFR with reasonable precision and provided improved accuracy over the Schwartz GFR formula. Keywords Agreement * Beta-trace protein * Bland-Altman analysis * eGFR * Glomerular filtration rate * Schwartz formula, Introduction Inulin clearance forms the gold standard for measuring glomerular filtration rate (GFR). However, due to the lack of availability of inulin, this practice has been replaced by nuclear medicine [...]

The aim of this study was to establish the efficacy and safety of rituximab in refractory nephrotic syndrome (NS). Members of the International Paediatric Nephrology Association were asked to retrospectively fill in a questionnaire with details on the use of rituximab in their centres. We divided the data into three groups: group 1, patients with steroid-dependent and frequently relapsing NS; group 2, with steroid-resistant NS; group 3, with post-transplant recurrence of NS. Seventy questionnaires from 25 centres described the outcome of 28, 27 and 15 patients in groups 1, 2 and 3, respectively. Of these, 82% of patients in group 1, 44% of patients in group 2 and 60% of patients in group 3 had a good initial response. Side effects were observed in 27% of the patients, and these were mostly acute reactions. We present a large multicentre series of children with refractory NS. Children in group 1 showed the best response. The good initial response in group 3 can be biased by the accompanying treatments that were administered at the same time as rituximab. Controlled prospective trials are required to establish the value of rituximab in idiopathic NS. Keywords Pediatric * Nephrotic syndrome * Remission * Renal transplantation, Introduction Most children with idiopathic nephrotic syndrome (NS) will respond well to steroid therapy. They enter remission and will later experience a limited number of relapses before finally outgrowing the [...]

Waiting times for specialist consultation have not been adequately studied, especially in the pediatric population. The aim of this study was to determine the extent to which pediatric nephrology subspecialty clinic referral waiting times are adhered to with regard to previously determined access targets. Referrals to the pediatric nephrology clinics at Children's Hospital, London, Ontario, Canada, received between October 2007 and November 2008 were retrospectively analyzed. Appointment schedule was allotted by a nephrologist based on the patient's presenting complaint, reported in the referral, in accordance with the previously determined access targets. Adherence to access targets was assessed by the actual clinic visit. There were a total of 250 referrals during the timeframe studied. The median waiting time was 73 (range 0-193) days. Overall, 64% (159/250) of patients met their access target. The median time that patients waited over their access target was 6 (range 0-78) days. Of the patients who did not meet their access targets, 31% (28/91) exceeded their target by 20% or more. Office handling was a component for patients with access target, Author(s): Maria Radina [sup.1] , Ajay P. Sharma [sup.1] , Abeer Yasin [sup.1] , Guido Filler [sup.1] Author Affiliations: (1) grid.39381.30, 0000000419368884, Department of Pediatrics, Division of Nephrology, Children's Hospital, [...]

Waiting times for specialist consultation have not been adequately studied, especially in the pediatric population. The aim of this study was to determine the extent to which pediatric nephrology subspecialty clinic referral waiting times are adhered to with regard to previously determined access targets. Referrals to the pediatric nephrology clinics at Children's Hospital, London, Ontario, Canada, received between October 2007 and November 2008 were retrospectively analyzed. Appointment schedule was allotted by a nephrologist based on the patient's presenting complaint, reported in the referral, in accordance with the previously determined access targets. Adherence to access targets was assessed by the actual clinic visit. There were a total of 250 referrals during the timeframe studied. The median waiting time was 73 (range 0-193) days. Overall, 64% (159/250) of patients met their access target. The median time that patients waited over their access target was 6 (range 0-78) days. Of the patients who did not meet their access targets, 31% (28/91) exceeded their target by 20% or more. Office handling was a component for patients with access target Keywords Wait time one * Access targets * General pediatric Nephrology * Hospital resources * Processing * Consults, Introduction Waiting times are a growing concern in the Canadian health care system, and extensive research has been conducted to study both the waiting time 1 (primary care provider visit [...]

This article reviews the currently available tools for measuring glomerular filtration rate (GFR) and early detection of chronic kidney disease in pediatric transplant recipients. GFR measurement remains the mainstay to detect renal dysfunction. Inulin clearance formed the earlier gold standard method to measure GFR. In current clinical practice, it has been replaced by nuclear medicine techniques (.sup.51 Cr EDTA and .sup.99 Tc DTPA isotope clearance studies). GFR estimation based on surrogate markers allows more frequent GFR monitoring in a clinical setting. Serum creatinine has a low sensitivity to detect early renal dysfunction and its muscle mass dependency hampers its clinical utility. The Schwartz formula accounts for age-dependent muscle changes in children, but requires center-specific constants. Cystatin C offers the advantage of a constant production and a higher sensitivity in diagnosing renal dysfunction. Microalbuminuria has been an established screening tool in diabetic renal disease. It offers the advantage of detecting underlying renal damage even before a decrease in GFR. Its diagnostic value in other conditions needs evaluation. Hypertension is known to accelerate the progression of chronic kidney disease. A 24-h ambulatory blood pressure is a useful tool to diagnose hypertension, to quantify blood pressure load and to characterize nocturnal blood pressure dipping. GFR scans, serum creatinine and cystatin C form the cornerstone of currently used tools to evaluate kidney dysfunction., Author(s): Ajay Parkash Sharma [sup.1] , Guido Filler [sup.[[dagger]]] [sup.2] Keywords: Keywords [sup.51] Cr EDTA; [sup.99] Tc DTPA; blood pressure z-score; creatinine; cystatin C; iohexol; microalbuminuria; Schwartz formula Chronic kidney [...]

Abstract There is controversy about the effect of certain drugs on cystatin C (CysC) concentrations, which would limit the usability of CysC for estimation of glomerular filtration rate (GFR) in [...]

Abstract This study investigates the changing referral patterns of young patients to a tertiary pediatric nephrology center with a well-defined catchment area over two consecutive 8.5-year periods. We paid special [...]

Byline: Guido Filler (1), Nathalie Lepage (2) Keywords: Pediatric renal transplantation; Mycophenolate mofetil; Therapeutic drug monitoring; Pharmacokinetics; Combination therapy Abstract: Within a short period, we have witnessed a dramatic increase in the use of mycophenolate mofetil (MMF) in pediatric renal transplantation, with the drug often replacing azathioprine in combination with calcineurin inhibitor therapy. When the drug was introduced, the manufacturer considered therapeutic drug monitoring (TDM) unnecessary. However, TDM studies revealed substantial inter- and intra-individual variability and drug interactions. There is a substantial drug interaction between MMF and cyclosporine, and lower doses are required in combination with tacrolimus (~500--800 mg/m.sup.2 per day) than with cyclosporine (~1,200 mg/m.sup.2 per day). Patients with autoimmune disease require an intermediate dose when receiving no concomitant calcineurin inhibitor (~900 mg/m.sup.2 per day). It has been possible to detect drug interactions and to minimize adverse events only with TDM. This is especially important with increasing use of combination therapies. Pharmacodynamic monitoring (measuring the biological response to a drug) coupled with pharmacokinetics allow optimization of drug dosing, with maximum efficacy and minimal toxicity. More work is required to establish specific target ranges with the various drug combinations--especially for the pediatric population. Author Affiliation: (1) Division of Pediatric Nephrology, Children&apos;s Hospital of Eastern Ontario, Ottawa University, 401 Smyth Road, Ottawa, Ontario, K1H 8L1, Canada (2) Department of Laboratory Medicine and Pathology, Children&apos;s Hospital of Eastern Ontario, Ottawa University, 401 Smyth Road, Ottawa, Ontario, K1H 8L1, Canada Article History: Registration Date: 16/06/2004 Received Date: 13/02/2004 Accepted Date: 04/06/2004 Online Date: 15/07/2004

Byline: Guido Filler (1), Seetha Radhakrishnan (1), Lisa Strain (4), Andrew Hill (2), Greg Knoll (3), Timothy H. Goodship (4) Keywords: Atypical hemolytic uremic syndrome; Plasma exchange; Factor H; HF-1 gene Abstract: We describe a 1-year old with four episodes of recurrent hemolytic uremic syndrome (HUS). Family history suggested an autosomal dominant mode of inheritance. Factor H concentrations in the blood were normal in the affected family members. Mutation screening in the human complement factor H gene (HF-1) revealed a novel mutation in exon 23 (c.3546_3581dup36). The HF-1 gene encodes complement factor H and the mutation leads to the insertion of 12 additional amino acids after codon 1176 in factor H. The recurrent HUS responded to plasma infusions and renal function improved from a glomerular filtration rate of 21 to 50 ml/min per 1.73 m.sup.2. The infusions of fresh-frozen plasma were necessary at once-weekly intervals at a dose of 40--45 ml/kg in order to maintain remission and resulted in significant hyperproteinemia. This was addressed by intermittent plasma exchange through an arterio-venous fistula. The prognosis and therapeutic dilemmas are discussed. Author Affiliation: (1) Department of Pediatrics, Children&apos;s Hospital of Eastern Ontario, The Ottawa Hospital, University of Ottawa, 401 Smyth Road, K1H 8L1, Ottawa, Ontario, Canada (2) Department of Surgery, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada (3) Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada (4) Institute of Human Genetics, University of Newcastle upon Tyne, Newcastle, NE1 4LP, UK Article History: Registration Date: 03/05/2004 Received Date: 10/02/2004 Accepted Date: 21/04/2004 Online Date: 16/06/2004

Byline: Verna Yiu (1), Elaine Orrbine (2), Rhonda J. Rosychuk (1), Peter MacLaine (2), Paul Goodyer (3), Colette Girardin (3), Manjula Gowrishankar (1), Malcolm Ogborn (4), Julian Midgley (5), Guido Filler (2), Frances Harley (1) Keywords: Hypertension; Nifedipine; Safety Abstract: Recent reports suggest that calcium channel blockers are harmful in the treatment of acute hypertension in adults. However, short-acting nifedipine is an effective and useful medication in pediatric hypertension and is currently utilized for hypertensive emergencies. This study will address these safety concerns in hypertensive children. Medical records (from five Canadian pediatric hospitals) of all pediatric hypertensive hospitalized children who were treated with short-acting nifedipine from January 1995 to December 1998 were retrospectively reviewed for patient demographics, dosing regimen, use of concomitant medications, co-morbid conditions, and presence/absence of minor and serious adverse events. Final data were extracted from 182 patients. Each patient had an average of 2.6 episodes of hypertension in hospital that required treatment, totaling 477 episodes. Within the 477 episodes, 1,162 doses of short-acting nifedipine were administered. The mean dose was 0.22 mg/kg (range 0.043--0.67 mg/kg, median 0.19 mg/kg) with 55.6% (260/468 episodes) receiving the drug via the sublingual route. Hypertension resolved in 85.5% (408/477) of the episodes. There were only 29 of 574 (5.1%) minor adverse events that were definitely or probably related to short-acting nifedipine administration. Two patients experienced a serious adverse event that involved of a reduction in blood pressure of more than 40%, but neither had any symptomatology from the serious adverse event and recovered spontaneously within 2 h. Short-acting nifedipine in hypertensive, hospitalized children appears to be a safe and efficacious medication with minimal side effects. Author Affiliation: (1) Department of Pediatrics, University of Alberta, Edmonton, Alberta, T6G 2R7, Canada (2) Department of Pediatrics, University of Ottawa, Ottawa, Canada (3) Department of Pediatrics, McGill University, Canada (4) Department of Pediatrics, University of Manitoba, Canada (5) Department of Pediatrics, University of Calgary, Canada Article History: Registration Date: 06/02/2004 Received Date: 04/06/2003 Accepted Date: 21/01/2004 Online Date: 31/03/2004

Membrane cofactor protein (MCP; CD46) is a widely expressed transmembrane complement regulator. Like factor H it inhibits complement activation by regulating C3b deposition on targets. Factor H mutations occur in 10-20% of patients with hemolytic uremic syndrome (HUS). We hypothesized that MCP mutations could predispose to HUS, and we sequenced MCP coding exons in affected individuals from 30 families. MCP mutations were detected in affected individuals of three families: a deletion of two amino acids (D237/S238) in family 1 (heterozygous) and a substitution, $206P, in families 2 (heterozygous) and 3 (homozygous). We evaluated protein expression and function in peripheral blood mononuclear ceils from these individuals. An individual with the D237/$238 deletion had reduced MCP levels and [approximately or equal to] 50% C3b binding compared with normal controls. Individuals with the $206P change expressed normal quantities of protein, but demonstrated [approximately or equal to] 50% reduction in C3b binding in heterozygotes and complete lack of C3b binding in homozygotes. MCP expression and function was evaluated in transfectants reproducing these mutations. The deletion mutant was retained intracellularly. S206P protein was expressed on the cell surface but had a reduced ability to prevent complement activation, consistent with its reduced C3b binding and cofactor activity. This study presents further evidence that complement dysregulation predisposes to development of thrombotic microangiopathy and that screening patients for such defects could provide informed treatment strategies.

Byline: Andreas Lun (1), Miroslav Ivandic (2), Friedrich Priem (1), Guido Filler (3), Martin Kirschstein (4), Jochen H. H. Ehrich (3), Walter G. Guder (2) Keywords: Key wordsaProteinuria; Knowledge-based system; Expert system; Evaluation; Decision support Abstract: A computerized Urine Protein Expert System (UPES) measuring creatinine, total protein, albumin, IgG, [alpha].sub.1-microglobulin, [alpha].sub.2-macroglobulin, and N-acetyl-[beta]-D-glucosaminidase, together with urine dipstick testing for granulocyte esterase and hemoglobin pseudoperoxidase, and measurement of serum creatinine had been found to be useful in adults for differentiating between renal disorders. The objective of this study was to investigate UPES for identifying the different types of proteinuria and their underlying prerenal, glomerular, tubular, and postrenal causes in 146 children characterized by routine and invasive nephrological investigations. UPES proved to be a useful tool in pediatric renal patients after refinements were implemented in the program. Comparing UPES with the pediatric nephrologist&apos;s interpretation of all available clinical and laboratory data, UPES diagnosed glomerulopathies in 46 (75%) of 61 patients. In a further 23% it suggested glomerular involvement by indicating either a disturbed glomerular permeability or increased excretion of albumin. Tubular proteinuria was correctly described by UPES in 23 (100%) patients with different tubulopathies. UPES revealed normal kidney function in all healthy children and all children with remission of renal disorders. Therefore, UPES can be regarded as a useful tool in the automated differentiation of renal diseases in children. Author Affiliation: (1) Institute of Laboratory Medicine and Pathobiochemistry, Charite Hospital, Humboldt University, Berlin, Germany, DE (2) Institute of Clinical Chemistry, Municipal Hospital Munich Bogenhausen, Munich, Germany, DE (3) Department of Pediatric Nephrology, Charite Hospital, Humboldt University, Berlin, Germany, DE (4) University Children&apos;s Hospital, Lubeck, Germany, DE (5) Department of Pediatric Nephrology, Hanover Medical School, Carl Neuberg Strasse 1, D-30625 Hanover, Germany e-mail: ehrich.jochen@mh-hannover.de Tel.: +49-511-532-3212, Fax: +49-511-532-3911, DE Article note: Received: 23 July 1998 / Revised: 7 December 1998 / Accepted: 13 December 1998

Author(s): Tanya Holt [sup.1] , Guido Filler [sup.2] [sup.3] Author Affiliations: (1) Division of Critical Care, Department of Paediatrics, University of Saskatchewan, 0000 0001 2154 235X, grid.25152.31, , Saskatoon, SK, [...]

Byline: Guido Filler (1), Dagmar Lampe (2), Moritz A. von Bredow (1), Marianne Lappenberg-Pelzer (2), Sonja Rocher (2), Jurgen Strehlau (1), Jochen H. H. Ehrich (1) Keywords: Key words: Oral ganciclovir; Pharmacokinetics and dose recommendations; Cytomegalovirus prophylactic therapy; Renal transplantation; Renal insufficiency Abstract: Ganciclovir alone or in combination with hyperimmunoglobulin is replacing other treatment modalities for the prophylactic treatment of cytomegalovirus (CMV) infections. No dose recommendations are available for oral ganciclovir therapy in children with impaired renal function after renal transplantation of a kidney from a CMV IgG-positive donor. We undertook a pharmacokinetic study in 14 pediatric renal transplant recipients who were CMV IgG negative and had received a graft from a CMV IgG-positive donor. We estimated the daily dosage of oral ganciclovir in relation to the glomerular filtration rate (GFR). Oral ganciclovir was administered at a starting dose of 3 x 1 g for children with a weight above 50 kg, 3 x 750 mg for children between 50 and 37.5 kg, and 3 x 500 mg for children between 37.5 and 24 kg. The starting dose was reduced by 50% for GFR values a$?50 ml/min per 1.73 m.sup.2 and by 75% for GFR values a$?25 ml/min per 1.73 m.sup.2. The daily dose was divided into three daily doses unless GFR was &lt 40 ml/min per 1.73 m.sup.2, when only two daily doses were given. Doses were adjusted according to the measured plasma trough concentrations (c) using the simple formula: c .sub.ganciclovir(measured)/c .sub.ganciclovir(desired) = dosage rate(used)/dosage rate(adjusted). Mean stable plasma trough concentration was 0.91+-0.68 ug/ml. The dosage rate, adjusted to a trough concentration of 1.0 ug/ml, correlated with the GFR. The dose per day could be calculated according to a simple equation for a GFR &lt 100 ml/min per 1.73 m.sup.2: dosage per day (mg/kg per day) = GFR. No CMV disease developed in any of the patients during oral ganciclovir, but 1 patient developed an acute rejection episode and a positive pp65 antigen 5 weeks after discontinuation of ganciclovir. The drug was well tolerated and without side effects. Author Affiliation: (1) Department of Pediatric Nephrology, Charite Hospital, Humboldt University, Berlin, Germany, DE (2) Institute of Clinical Toxicology and Pharmacology, BBGes, Berlin, Germany, DE Article note: Received March 3, 1997 received in revised form July 25, 1997 accepted July 30, 1997

Background Polyoma BK virus nephropathy is a common complication after renal transplantation and is rarely seen in non-renal transplant recipients. There are only a couple of case reports of BK virus nephropathy in native kidneys in non-transplant patients, including a recent report of a 73-year-old patient with chronic lymphatic leukemia. A variety of treatment options, including leflunomide and cidofovir, were reported in these patients. Case diagnosis/treatment Here we report the case of a 10-year-old boy with acute lymphatic leukemia who presented with non-oliguric hypertensive acute kidney injury at the 12th maintenance cycle of his chemotherapy. The workup supported the clear diagnosis of BK virus nephropathy with tubulointerstitial changes, and the patient responded favorably to intravenous immunoglobulin therapy. Conclusions Pediatric nephrologists need to consider BK virus nephropathy as a differential diagnosis of acute kidney injury in immunocompromised non-transplant patients. Keywords Polyomavirus BK virus * Nephropathy * Renal transplantation * Acute lymphocytic leukemia, Introduction Polyomavirus BK virus nephropathy is a well-recognized complication after renal transplantation, especially with the recent introduction of more potent immunosuppression [1]. Seroepidemiological studies suggest that the virus is normally [...]

Steroid-resistant rejection after pediatric renal transplantation forms a rare but severe complication with a guarded prognosis particularly if this occurs late after transplantation. There is a paucity of data on how to manage these challenging rejection episodes, particularly in the pediatric literature. Mohan Shenoy et al. published a case series of 15 patients who were treated with anti-thymocyte globulin for steroid-resistant acute allograft rejection over a 15-year period in a single center in this issue of Pediatric Nephrology. While the results for the early rejection group were encouraging, the results in the eight patients with late rejection episodes after transplantation were unfavorable and afflicted with a high incidence of side-effects. Important diagnostic tools such as C4d staining of the renal transplant biopsy and the measurement of donor-specific antibodies were underutilized. The editorial reviews the importance of the differentiation between humoral and cellular rejection and the challenges of treating late antibody-mediated acute rejection in these patients. A multi-center approach is required to establish a registry of these events and ideally prospective randomized interventions should be designed to provide some evidence base for the management of this challenging complication after pediatric renal transplantation. Keywords Acute rejection * Donor-specific antibodies C4d staining * Anti-thymocyte globulin * Steroid-resistant rejection * Children, Despite the improvement in immunosuppressive protocols for pediatric renal transplantation, a small percentage of acute rejection episodes is unavoidable [1]. Strong immunosuppression that results in complete absence of rejection episodes [...]

Su Jin Kim and coworkers from Korea published an important study on the relationship of residual renal function (RRF) and cystatin in pediatric peritoneal dialysis (PD) patients in this issue of Pediatric Nephrology, both in anuric patients and patients with RRF. Based on a lack of correlation between cystatin C and standard small solute-based dialysis adequacy parameters such as [Kt/V.sub.urea] but a significant correlation with RRF, the authors concluded that cystatin C may be a good tool to monitor RRF. The editorial reviews the available literature in adults, the different handing between urea and cystatin C, and the determinants of cystatin C clearance in dialysis patients. In adults, cystatin C levels are determined predominantly by RRF, but not exclusively. In anephric hemodialysis and PD patients, there is a correlation with standard weekly Kt/[V.sub.urea]. Cystatin C levels will also depend on ultrafiltration. Despite these factors that affect cystatin C levels beyond RRF, cystatin C is a useful parameter for monitoring PD patients that may be more closely related to long-term outcomes than small solute adequacy parameters. Keywords Cystatin C * Residual renal function * Peritoneal dialysis * Hemodialysis * End-stage renal disease * Ultrafiltration, Introduction Practicing pediatric nephrologists have felt for some time that prescribing more dialysis should improve outcomes. In adults, the result of the National Cooperative Dialysis Study showed a survival benefit [...]

Abstract Enteric-coated mycophenolate sodium (ECMPS) has a mean half-life of 11.7 hours, which encouraged hope of using this drug once daily in a nonadherent adolescent SLE patient. This is a [...]

Abstract Information on the use of Icodextrin in children remains scarce; however, it is believed that the characteristics are similar across all ages. We report the use of Icodextrin in [...]

Byline: Guido Filler (1), Doris Franke (1), Peter Amendt (2), Jochen H. H. Ehrich (1) Keywords: Key words: Recombinant human growth hormone; Chronic renal failure; Diabetes; Intravenous glucose tolerance test; Idiopathic Fanconi syndrome Abstract: A 12-year-old girl with short stature due to idiopathic Fanconi syndrome and chronic renal failure was treated with recombinant human growth hormone (rhGH). There was no family history of diabetes mellitus and the glucose tolerance before treatment was normal. Intravenous glucose tolerance tests were performed before, during and after treatment. Two months after starting rhGH the early phase of insulin secretion (1-+3-min values) was diminished, and the patient developed manifest diabetes mellitus with hyperglycemia and an elevated hemoglobin A.sub.1c. Following discontinuation of rhGH, glucose tolerance slowly returned to normal. Author Affiliation: (1) Department of Pediatric Nephrology, Charite Children&apos;s Hospital, Humboldt University, Berlin, Germany, DE (2) Division of Pediatric Endocrinology, Charite Children&apos;s Hospital, Humboldt University, Berlin, Germany, DE Article note: Received May 29, 1997 received in revised form November 5, 1997 accepted November 12, 1997