151 results on '"Filler, Guido"'
Search Results
2. Limitations of U25 CKiD and CKD-EPI eGFR formulae in patients 2–20 years of age with measured GFR > 60 mL/min/1.73 m2—a cross-sectional study.
- Author
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Filler, Guido, Ahmad, Fateh, Bhayana, Vipin, Díaz González de Ferris, Maria E., and Sharma, Ajay P.
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GLOMERULAR filtration rate , *CHRONIC kidney failure , *STATISTICS , *CONFIDENCE intervals , *DESCRIPTIVE statistics , *SENSITIVITY & specificity (Statistics) , *DATA analysis , *CREATININE , *CYSTATIN C - Abstract
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]
- Published
- 2024
- Full Text
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3. A novel multiplex biomarker panel for profiling human acute and chronic kidney disease.
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Van Nynatten, Logan R., Miller, Michael R., Patel, Maitray A., Daley, Mark, Filler, Guido, Badrnya, Sigrun, Miholits, Markus, Webb, Brian, McIntyre, Christopher W., and Fraser, Douglas D.
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CHRONIC kidney failure ,RENAL replacement therapy ,KIDNEY diseases ,BIOMARKERS ,ACUTE kidney failure ,URINE - Abstract
Acute and chronic kidney disease continues to confer significant morbidity and mortality in the clinical setting. Despite high prevalence of these conditions, few validated biomarkers exist to predict kidney dysfunction. In this study, we utilized a novel kidney multiplex panel to measure 21 proteins in plasma and urine to characterize the spectrum of biomarker profiles in kidney disease. Blood and urine samples were obtained from age-/sex-matched healthy control subjects (HC), critically-ill COVID-19 patients with acute kidney injury (AKI), and patients with chronic or end-stage kidney disease (CKD/ESKD). Biomarkers were measured with a kidney multiplex panel, and results analyzed with conventional statistics and machine learning. Correlations were examined between biomarkers and patient clinical and laboratory variables. Median AKI subject age was 65.5 (IQR 58.5–73.0) and median CKD/ESKD age was 65.0 (IQR 50.0–71.5). Of the CKD/ESKD patients, 76.1% were on hemodialysis, 14.3% of patients had kidney transplant, and 9.5% had CKD without kidney replacement therapy. In plasma, 19 proteins were significantly different in titer between the HC versus AKI versus CKD/ESKD groups, while NAG and RBP4 were unchanged. TIMP-1 (PPV 1.0, NPV 1.0), best distinguished AKI from HC, and TFF3 (PPV 0.99, NPV 0.89) best distinguished CKD/ESKD from HC. In urine, 18 proteins were significantly different between groups except Calbindin, Osteopontin and TIMP-1. Osteoactivin (PPV 0.95, NPV 0.95) best distinguished AKI from HC, and β2-microglobulin (PPV 0.96, NPV 0.78) best distinguished CKD/ESKD from HC. A variety of correlations were noted between patient variables and either plasma or urine biomarkers. Using a novel kidney multiplex biomarker panel, together with conventional statistics and machine learning, we identified unique biomarker profiles in the plasma and urine of patients with AKI and CKD/ESKD. We demonstrated correlations between biomarker profiles and patient clinical variables. Our exploratory study provides biomarker data for future hypothesis driven research on kidney disease. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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4. Sex differences of burosumab in children with X-linked hypophosphataemic rickets.
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Filler, Guido, Tremblay, Olivia, Chen, Emily, Huang, Susan Shi Han, and Stein, Robert
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PHARMACOGENOMICS , *X-linked genetic disorders , *GENETIC mutation , *RICKETS , *MONOCLONAL antibodies , *RETROSPECTIVE studies , *TREATMENT effectiveness , *SEX distribution , *HYPOPHOSPHATEMIA , *DESCRIPTIVE statistics , *DATA analysis software , *LONGITUDINAL method , *EVALUATION - Abstract
Background: The severity of X-linked hypophosphataemic rickets (XLH) may be affected by genotype and sex. However, burosumab, a fully humanized monoclonal antibody against fibroblast growth factor 23, has the same pediatric dose recommendation for both sexes (0.8 mg/kg every 2 weeks). Patients and methods: In a retrospective cohort study, we describe the burosumab response differences by sex in children with XLH. Results: We treated 10 children (5 females, mean age at initiation 4.2 ± 3.5 years) with XLH with burosumab. Initial mean serum phosphate was 0.69 ± 0.18 mmol/L in males and 0.86 ± 0.22 mmol/L in females (p = 0.108). The mean ratio of tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) was 0.55 ± 0.11 mmol/L in males and 0.76 ± 0.23 mmol/L in females (p = 0.06). The mean starting dose of burosumab was 0.83 ± 0.19 mg/kg subcutaneously every 14 days (males: 0.79 ± 0.19 mg/kg; females: 0.87 ± 0.21 mg/kg, n.s.). Two weeks after starting burosumab, serum phosphate differed significantly between males (0.90 ± 0.21 mmol/L) and females (1.27 ± 0.25 mmol/L) (p = 0.018). All males required a dose increase to try to normalize serum phosphate. On day 140 after starting, the average dose in males increased further to 1.24 ± 0.41 mg/kg to achieve a phosphate of 0.87 ± 0.11 mmol/L while females had a normal phosphate and alkaline phosphatase on the starting dose. After a mean of 458 ± 79 days, the mean burosumab dose/kg in males was 1.68 ± 0.61 mg/kg, mean serum phosphate was 1.08 ± 0.23 mmol/L, mean TmP/GFR was 1.01 ± 0.20, mean alkaline phosphatase had normalized to 303.6 ± 40.7U/L, and mean 1.25(OH)2 vitamin D level was 186.4 ± 16.6 nmol/L. Conclusions: Our findings may suggest a sex difference in response to burosumab in XLH patients. Our data suggest that males may require higher doses. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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5. The urgent need for conducting clinical trials in pediatric nephrology globally.
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Wightman, Aaron, Filler, Guido, and Díaz-González de Ferris, Maria Esther
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CAREGIVER attitudes , *CLINICAL trials , *SOCIAL determinants of health , *HUMAN research subjects , *PATIENT participation , *ETHICAL decision making , *GOVERNMENT regulation , *SERIAL publications , *PEDIATRICS , *WORLD health , *SOCIAL justice , *NEPHROLOGY , *ENDOWMENT of research , *BENEVOLENCE , *PATIENTS' rights , *AUTONOMY (Psychology) , *PHARMACEUTICAL industry , *CHILDREN - Abstract
The authors discuss barriers for clinical trials including the ethical approach to acquiring high level evidence for optimal decision making, lack of funding, paucity of partners, low interest from pharmaceutical industry, regulatory issues, under-recognition of children's rights and autonomy and attitudes of patients/caregivers and providers. Topics include differences between pediatric subspecialties, examples of some pediatric nephrology studies, and ethical considerations and harms.
- Published
- 2023
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6. Impact of the 2022 American Heart Association pediatric ambulatory blood pressure monitoring statement on the diagnosis of hypertension.
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Sharma, Ajay P., Kirpalani, Amrit, Sharma, Ajaya, Altamirano-Diaz, Luis, Filler, Guido, and Norozi, Kambiz
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HYPERTENSION ,STATISTICS ,CONFIDENCE intervals ,LEFT ventricular hypertrophy ,PEDIATRICS ,CLINICS ,COMPARATIVE studies ,ARTERIAL diseases ,AMBULATORY blood pressure monitoring ,RESEARCH funding ,DESCRIPTIVE statistics ,PROFESSIONAL associations ,LOGISTIC regression analysis ,ODDS ratio ,SENSITIVITY & specificity (Statistics) ,DISEASE complications ,CHILDREN ,ADOLESCENCE - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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7. Ideal rather than actual weight for glomerular filtration rate measurement: an issue to be clarified.
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Filler, Guido, Díaz González de Ferris, Maria E., and Medeiros, Mara
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BODY surface area , *KIDNEY function tests , *CREATININE , *BODY weight , *GLOMERULAR filtration rate , *BIOMARKERS , *OBESITY - Published
- 2024
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8. What to do with kidney length and volumes in large individuals?
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Filler, Guido, Torres-Canchala, Laura, Sharma, Ajay P., Díaz González de Ferris, Maria E., and Restrepo, Jaime M.
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KIDNEYS , *CHILDHOOD obesity , *CHILDREN , *ADOLESCENCE - Abstract
An editorial is presented on assessing kidney length in children and adolescents being overweight or obese. Topics include overweight and obese children which being a very interesting finding demonstrating the importance of external validation; and resulting in underestimation of kidney length and kidney volumes in overweight and obese patients overestimating it in thin patients.
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- 2023
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9. Plasma manganese and selenium levels in paediatric chronic kidney disease patients measured by high resolution sector field inductively coupled plasma mass spectrometry.
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Verma, Subhrata, Belostotsky, Vladimir, Yang, Liju, and Filler, Guido
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INDUCTIVELY coupled plasma mass spectrometry ,CHRONIC kidney failure ,CHRONICALLY ill ,CHILD patients ,MANGANESE ,SELENIUM - Abstract
Background: Manganese (Mn) and Selenium (Se) deficiencies are noted in adult patients with chronic kidney disease (CKD). However, levels of these trace elements have not been well studied in the paediatric CKD population. We determined the Mn and Se levels in a single-institution cohort of paediatric patients with CKD. Methods: Ancillary cross-sectional study to a prospective longitudinal randomized control trial on zinc supplementation, which included 42 children and adolescents aged 0 to 19 years with CKD stages I to IV not on dialysis, who had 1–6 trace element measurements. Cystatin C estimated glomerular filtration rate (eGFR) was calculated using the Filler formula. Plasma Mn and Se levels were measured, and anthropomorphic data/blood parameters were collected from electronic health records. The trial was registered on clinicaltrials.gov, NCT02126293. Results: There were 96 Mn and Se levels in 42 patients (age 12.5 ± 4.6 years). The median Mn concentration was 12.61 nmol/L [10.08, 16.42] with a trend towards lower values with lower eGFR (p = 0.0367 one-sided). Mn z-scores were significantly lower than the general paediatric reference population. The mean Se level was 1.661 ± 0.3399 µmol/L with a significant positive correlation with eGFR (p = 0.0159, r = 0.366). However, only 4 patients with low eGFR had abnormally low Se levels. Conclusions: This single-institution study of children with CKD demonstrates a significant decrease in Se levels with decreasing eGFR, but no significant difference between mean Se z-scores of our cohort and the reference population. There was no significant relationship between Mn levels and eGFR however the mean Mn z-score was significantly lower than the theoretical mean. Trial registration: clinicaltrials.gov, NCT02126293, https://clinicaltrials.gov/ct2/show/NCT02126293. Date: April 30, 2014. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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10. Effects of pediatric chronic kidney disease and its etiology on tissue sodium concentration: a pilot study.
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Salerno, Fabio R., Akbari, Alireza, Lemoine, Sandrine, Scholl, Timothy J., McIntyre, Christopher W., and Filler, Guido
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SODIUM metabolism ,CHRONIC kidney failure ,PILOT projects ,CASE-control method ,COMPARATIVE studies ,PEARSON correlation (Statistics) ,PROTEINURIA ,FANCONI syndrome ,INBORN errors of metabolism ,RENAL tubular transport disorders ,CHILDREN - Abstract
Background: Sodium-23 magnetic resonance imaging (
23 Na MRI) allows non-invasive assessment of tissue sodium concentration ([Na+ ]). Age and chronic kidney disease (CKD) are associated with increased tissue [Na+ ] in adults, but limited information is available pertaining to children and adolescents. We hypothesized that pediatric CKD is associated with altered tissue [Na+ ] compared to healthy controls. Methods: This was a case–control exploratory study on healthy children and adults and pediatric CKD patients. Study participants underwent an investigational visit, blood/urine biochemistry, and leg23 Na MRI for tissue [Na+ ] quantification (whole leg, skin, soleus muscle). CKD was stratified by etiology and patients' tissue [Na+ ] was compared against healthy controls by computing individual Z-scores. An absolute Z-score > 1.96 was deemed to deviate significantly from the mean of healthy controls. Pearson correlation was used to compute the associations between tissue [Na+ ] and kidney function. Results: A total of 36 pediatric participants (17 healthy, 19 CKD) and 19 healthy adults completed the study. Healthy adults had significantly higher tissue [Na+ ] compared with pediatric groups; conversely, no significant differences were found between healthy children/adolescents and CKD patients. Four patients with glomerular disease and one kidney transplant recipient due to atypical hemolytic-uremic syndrome had elevated whole-leg [Na+ ] Z-scores. Reduced whole-leg [Na+ ] Z-scores were found in two patients with tubular disorders (Fanconi syndrome, proximal–distal renal tubular acidosis). All tissue [Na+ ] measures were significantly associated with proteinuria and hypoalbuminemia. Conclusions: Depending on etiology, pediatric CKD was associated with either increased (glomerular disease) or reduced (tubular disorders) tissue [Na+ ] compared with healthy controls. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]- Published
- 2023
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11. Biologic sex and the estimation of GFR in pediatric and young adult patients with acute kidney injury.
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Filler, Guido and Sharma, Ajay P.
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GLOMERULAR filtration rate , *HOSPITAL care of teenagers , *SEX distribution , *ACUTE kidney failure , *HOSPITAL care of children , *CREATININE , *CHILDREN , *ADULTS , *ADOLESCENCE - Abstract
The article comments on a paper by Chloe Braun and colleagues on the estimation of glomerular filtration rate in pediatric and adult patients with acute kidney injury (AKI). Topics mentioned include the proposed formula for estimating baseline creatinine by age and sex, the link between serum creatinine and muscle mass, and the use of electronic health records with rule-based algorithms for immediate detection of AKI.
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- 2022
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12. Animal, Human, and 23Na MRI Imaging Evidence for the Negative Impact of High Dietary Salt in Children.
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Filler, Guido, Salerno, Fabio, McIntyre, Christopher William, and de Ferris, Maria E. Díaz-González
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- 2021
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13. Management of severe polyuria in idiopathic Fanconi syndrome.
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Filler, Guido, Geda, Rishika, Salerno, Fabio, Zhang, Yun Cong, de Ferris, Maria E Díaz-González, and McIntyre, Christopher William
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GLOMERULAR filtration rate , *SODIUM , *INDOMETHACIN , *MAGNETIC resonance imaging , *ACADEMIC achievement , *TREATMENT effectiveness , *QUALITY of life , *POLYURIA , *FANCONI syndrome - Abstract
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 m2 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 m2 and was 68 mL/min/1.73 m2 at last follow-up. However, a sodium-23 (23Na) MRI of her thigh revealed ongoing moderate sodium decrease in her skin and substantial Na+ 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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14. Low agreement between kidney volume and kidney length z-scores.
- Author
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Torres-Canchala, Laura, Rengifo, Martin, Filler, Guido, Arias, Juan C., Ramirez, Oscar, and Restrepo, Jaime M.
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BLOOD pressure ,KIDNEYS ,ULTRASONIC imaging ,CROSS-sectional method ,ANTHROPOMETRY ,PAIRED comparisons (Mathematics) ,T-test (Statistics) ,DESCRIPTIVE statistics ,STATISTICAL correlation ,LONGITUDINAL method ,CHILDREN - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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15. Still trouble with serum creatinine measurements.
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Kowalczyk, Alexandra, Diaz-Gonzalez de Ferris, Maria Esther, and Filler, Guido
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GLOMERULAR filtration rate ,CHRONIC kidney failure ,REFERENCE values ,AGE distribution ,RACE ,BIOLOGICAL assay ,SENSITIVITY & specificity (Statistics) ,CREATININE ,EVALUATION ,CHILDREN ,ADULTS ,ADOLESCENCE - Abstract
The article comments on the study "Large Inter-Assay Difference of Serum Creatinine in the Pediatric Population: A Threat to Accurate Staging of Chronic Kidney Disease," by K. Lao and colleagues. Topics noted include the use of creatinine in estimating glomerular filtration rate, the factors that affect the levels of serum creatinine, the difference between the Abbott enzymatic method and the Abbott Jaffe method, and the need to standardize the calibration procedure in creatinine measurement.
- Published
- 2022
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16. Educational review: role of the pediatric nephrologists in the work-up and management of kidney stones.
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Rodriguez Cuellar, Carmen Inés, Wang, Peter Zhan Tao, Freundlich, Michael, and Filler, Guido
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CYSTINURIA ,DIET ,ECOLOGY ,SODIUM content of food ,HYPERCALCIUREA ,KIDNEY stones ,PEDIATRICS ,PHYSICIANS ,URINARY calculi ,OCCUPATIONAL roles ,CHILDREN - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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17. Educational review: measurement of GFR in special populations.
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Filler, Guido and Lee, Misan
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KIDNEY physiology , *BODYBUILDING , *CANCER chemotherapy , *DIET , *GLOMERULAR filtration rate , *ONCOLOGY , *PEDIATRICS , *AT-risk people - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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18. Nephrological and urological complications of homozygous c.974G>A (p.Arg325Gln) OSGEP mutations.
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Wang, Peter Zhan Tao, Prasad, Chitra, Rodriguez Cuellar, Carmen Inés, and Filler, Guido
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GENETIC disorder diagnosis ,PROTEINURIA diagnosis ,URINARY tract infection diagnosis ,NEUROGENIC bladder ,FANCONI syndrome ,BLADDER diseases ,CREATININE ,DRUG resistance in microorganisms ,GENITOURINARY diseases ,GLOMERULAR filtration rate ,KIDNEY diseases ,DISEASES in men ,GENETIC mutation ,NEPHROLOGY ,NEURODEGENERATION ,URINARY calculi ,UROLOGY ,WHITE people ,DISEASE relapse ,STATUS epilepticus ,DIAGNOSIS - Abstract
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 × 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. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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19. Late referrals of pediatric patients with elevated blood pressure.
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Filler, Guido and Torres-Canchala, Laura
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BLOOD pressure , *HYPERTENSION , *MEDICAL referrals , *NEPHROLOGY , *PEDIATRICS , *TIME - Published
- 2020
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20. Generic immunosuppressants.
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Medeiros, Mara, Lumini, Julia, Stern, Noah, Castañeda-Hernández, Gilberto, and Filler, Guido
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CYCLOSPORINE ,TACROLIMUS ,GENERIC drugs ,IMMUNOSUPPRESSIVE agents ,MEDICAL prescriptions ,PATIENT safety ,PHARMACEUTICAL chemistry ,MYCOPHENOLIC acid - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
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21. Handling of Drugs in Children with Abnormal Renal Function.
- Author
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Filler, Guido, Kirpalani, Amrit, and Urquhart, Bradley L.
- Published
- 2016
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22. The compelling case for therapeutic drug monitoring of mycophenolate mofetil therapy.
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Filler, Guido, Alvarez-Elías, Ana, McIntyre, Christopher, and Medeiros, Mara
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DRUG interactions , *DRUG monitoring , *GRAFT rejection , *KIDNEY transplantation , *DRUG administration , *MYCOPHENOLIC acid , *DRUG dosage , *THERAPEUTICS - Abstract
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 × 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. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
23. Developmental changes of MPA exposure in children.
- Author
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Yoo, Elisa, Alvarez-Elías, Ana, Todorova, Ekaterina, and Filler, Guido
- Subjects
AGE distribution ,ANALYSIS of variance ,ANTHROPOMETRY ,BIOTRANSFORMATION (Metabolism) ,CONFIDENCE intervals ,STATISTICAL correlation ,DRUG monitoring ,GLOMERULAR filtration rate ,HEMATOCRIT ,IMMUNOSUPPRESSION ,KIDNEY transplantation ,NEUROPEPTIDES ,PEDIATRICS ,PROBABILITY theory ,MULTIPLE regression analysis ,ALBUMINS ,RETROSPECTIVE studies ,MYCOPHENOLIC acid ,DATA analysis software ,DESCRIPTIVE statistics ,ODDS ratio ,KRUSKAL-Wallis Test ,DRUG administration ,DRUG dosage - Abstract
Background: Developmental changes (ontogeny) of drug disposition of Mycophenolate mofetil (MMF) have been understudied. Methods: The charts of 37 pediatric renal transplant recipients (median age 7.3 years, median follow-up 7.8 (IQR 6.6, 14.3 years) who had regular mycophenolic acid (MPA) trough level monitoring in combination with tacrolimus ( n = 31) or sirolimus ( n = 6) therapy were analyzed retrospectively for their dose-normalized MPA exposure, steroid dose, albumin, hematocrit, and cystatin C estimated glomerular filtration rate (eGFR). Using appropriate univariate and multivariate methods, we determined whether MPA exposure was age dependent when controlling for the confounders. Results: Dose-normalized MPA trough levels could be calculated in 2,128 (median 45/patient) instances. Spearman rank correlation analysis revealed that age correlated with dose-normalized MPA trough level for both body weight and body surface area, as well as serum albumin, hematocrit, steroid dose, and eGFR. In the multivariate analysis, serum albumin and steroid dose were not significant, and hematocrit only being significant when the youngest group of patients <6 years of age was compared. eGFR was the most important confounder, but age dependency remained significant when controlling for all confounders. Conclusions: Small children are at a significantly greater risk for low MPA trough levels than adolescents, highlighting the need for pharmacokinetic monitoring of MPA. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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- View/download PDF
24. Should we stop dosing steroids per body surface area for nephrotics?
- Author
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Filler, Guido and Robinson, Lisa
- Subjects
- *
BODY weight , *DRUG administration , *NEPHROTIC syndrome , *PHARMACEUTICAL arithmetic , *PREDNISONE , *BODY surface area , *PREDNISOLONE - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
25. A step forward towards accurately assessing glomerular filtration rate in newborns.
- Author
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Filler, Guido
- Subjects
- *
BIRTH size , *BODY weight , *GLOMERULAR filtration rate , *KIDNEYS , *NEUROPEPTIDES , *PEDIATRICS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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26. Tandem hemodialysis and plasma exchange.
- Author
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Filler, Guido, Clark, William, and Huang, Shih-Han
- Subjects
- *
PLASMA exchange (Therapeutics) , *KIDNEY failure , *CENTRIFUGATION , *COMBINED modality therapy , *FILTERS & filtration , *HEMODIALYSIS , *PEDIATRICS , *QUESTIONNAIRES , *DESCRIPTIVE statistics , *THERAPEUTICS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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27. Spot urine protein to creatinine ratio.
- Author
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Filler, Guido and Huang, Shih-Han
- Subjects
- *
PROTEINURIA diagnosis , *CREATININE , *RESEARCH methodology , *PROTEINS , *URINALYSIS , *RANDOMIZED controlled trials , *CROSS-sectional method , *RETROSPECTIVE studies , *CHILDREN - Abstract
In a recent article in Pediatric Nephrology, EM Yang and colleagues (Pediatr Nephrol 2017: doi:) 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. 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. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
28. Can the new CKD-EPI BTP-B2M formula be applied in children?
- Author
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Filler, Guido, Alvarez-Elías, Ana, Westreich, Katherine, Huang, Shih-Han, and Lindsay, Robert
- Subjects
- *
BIOMARKERS , *CHI-squared test , *CHRONIC kidney failure , *CONFIDENCE intervals , *GLOMERULAR filtration rate , *KIDNEY function tests , *KIDNEY diseases , *REGRESSION analysis , *DATA analysis software - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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- View/download PDF
29. Trace elements in dialysis.
- Author
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Filler, Guido and Felder, Sarah
- Subjects
- *
TREATMENT of chronic kidney failure , *DRUGS , *HEMODIALYSIS , *KIDNEY diseases , *LEAD , *SELENIUM , *THERAPEUTICS , *TRACE elements , *ZINC - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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- View/download PDF
30. Methods of assessing renal function.
- Author
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Filler, Guido, Yasin, Abeer, and Medeiros, Mara
- Subjects
- *
KIDNEY physiology , *CREATININE , *GLOMERULAR filtration rate , *GLUCANS , *MAGNETIC resonance imaging , *NEUROPEPTIDES , *RADIOISOTOPES - Abstract
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 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
31. Nighttime blood pressure, systolic blood pressure variability, and left ventricular mass index in children with hypertension.
- Author
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Sharma, Ajay, Mohammed, Javed, Thomas, Benson, Lansdell, Nathan, Norozi, Kambiz, and Filler, Guido
- Subjects
HEART ventricle diseases ,AMBULATORY blood pressure monitoring ,BLOOD pressure ,BLOOD pressure measurement ,CHI-squared test ,LEFT heart ventricle diseases ,HYPERTENSION ,REGRESSION analysis ,T-test (Statistics) ,U-statistics ,LOGISTIC regression analysis ,CROSS-sectional method ,RETROSPECTIVE studies ,DATA analysis software ,DESCRIPTIVE statistics - Abstract
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 (β) 0.23; p < 0.05] and daytime systolic BP variability (β 0.37; p < 0.05) had significant association with LVMI. Conclusions: In children with primary hypertension, nighttime systolic BP load and daytime systolic BP variability had a stronger association with LVMI than casual BP and other ABPM parameters. Future longitudinal studies are needed to establish the causality among these variables. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
32. Cystatin C adaptation in the first month of life.
- Author
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Filler, Guido and Lepage, Nathalie
- Subjects
- *
KIDNEY physiology , *BIOMARKERS , *GESTATIONAL age , *GLOMERULAR filtration rate , *PEPTIDES - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
33. Non-invasive measurement of cardiac output in obese children and adolescents: comparison of electrical cardiometry and transthoracic Doppler echocardiography.
- Author
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Rauch, Ralf, Welisch, Eva, Lansdell, Nathan, Burrill, Elizabeth, Jones, Judy, Robinson, Tracy, Bock, Dirk, Clarson, Cheril, Filler, Guido, and Norozi, Kambiz
- Abstract
The objective of this study was to evaluate the reliability and accuracy of electrical cardiometry (EC) for the noninvasive determination of cardiac output (CO) in obese children and adolescents. We compared these results with those obtained by transthoracic echocardiography. Sixty-four participants underwent simultaneous measurement of CO. Cardiac output was measured by EC using the ICON device. Simultaneously CO was determined by using transthoracic Doppler echocardiography from parasternal long-axis and apical view. The median age was 12.52 years (range 7.9-17.6 years) and 36 (56 %) were female. A strongly significant correlation was found between the CO and CO measurements ( p < 0.0001, r = 0.91). Significant correlations were also found between CO and age (r = 0.37, p = 0.002), weight (r = 0.57, p < 0.0001), height (0.60, p < 0.0001) and BMI (r = 0.42, p = 0.001). The mean difference between the two methods (CO − CO) was 0.015 l min. According to the Bland and Altman method, the upper and lower limits of agreement, defined as mean difference ±2 SD, were +1.21 and −0.91 l min, respectively. Compared to the transthoracic Doppler echocardiography, Electrical Cardiometry provides accurate and reliable CO measurements in obese children and adolescents. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
34. Why multidisciplinary clinics should be the standard for treating chronic kidney disease.
- Author
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Filler, Guido and Lipshultz, Steven
- Subjects
- *
TREATMENT of chronic kidney failure , *HEALTH care teams , *MEDICAL care costs , *PEDIATRICS - Abstract
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 workders 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 progession 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 establihs guidelines for forming multidisciplinary clinics throughout the world. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
35. High prevalence of elevated lead levels in pediatric dialysis patients.
- Author
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Filler, Guido, Roach, Elizabeth, Yasin, Abeer, Sharma, Ajay, Blake, Peter, and Yang, Liju
- Subjects
- *
METABOLIC disorder treatment , *PHOSPHORUS in the body , *ACADEMIC medical centers , *C-reactive protein , *CALCIUM carbonate , *CONFIDENCE intervals , *DIALYSIS (Chemistry) , *GLOMERULAR filtration rate , *HEMODIALYSIS , *LEAD , *MASS spectrometry , *PARATHYROID hormone , *QUALITY assurance , *REGRESSION analysis , *STATISTICS , *DATA analysis , *MULTIPLE regression analysis , *DISEASE prevalence , *CROSS-sectional method , *DATA analysis software , *DESCRIPTIVE statistics , *THERAPEUTICS ,CHRONIC kidney failure complications - Abstract
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 <0.00018 mg/l, which is below the accepted limit for water for dialysis of 0.005 mg/l. 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. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
36. Prevention of chronic kidney disease in spina bifida.
- Author
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Filler, Guido, Gharib, Mireille, Casier, Shelley, Lödige, Petra, Ehrich, Jochen, and Dave, Sumit
- Abstract
Objective: The prevalence of progressive chronic kidney disease (CKD) in children and adults with spina bifida is considerable, rising, and entirely preventable. Removing the cause: prevention of spina bifida: The best prevention of CKD in spina bifida is prevention of spina bifida itself through strategies that include folate supplementation, ideally before pregnancy. The cause of CKD: Dysfunctional bladder outlet causes febrile Urinary Tract Infections (UTI), even with clean intermittent catheterization (CIC), and subsequent renal scarring. The development of secondary vesicoureteric reflux (VUR) increases the risk of renal scarring and CKD. Finding the ideal marker for measurement of renal function in spina bifida: Creatinine-based methods are insensitive because of low muscle mass and underdeveloped musculature in the legs. Only Cystatin C-based eGFR can reliably assess global renal function in these patients. However, unilateral renal damage requires nuclear medicine scans, such as Tc DMSA. (Video)Urodynamics studies (UDS): Early treatment is recommended based on UDS with anticholinergics, CIC, and antibiotic prophylaxis when indicated. Overnight catheter drainage, Botox, and eventually augmentation cystoplasty are required for poorly compliant bladders. A continent child or one rendered continent following surgery is at a higher risk of renal damage. Conclusion: A multidisciplinary approach is required to reduce the burden of CKD in patients with spina bifida. The right tools have to be utilized to monitor these patients, particularly if recurrent UTIs occur. Cystatin C eGFR is preferred for monitoring renal damage in these patients, and Tc DMSA scans have to be used to detect unilateral renal scarring. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
37. Ontario children have outgrown the Broselow tape.
- Author
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Milne, William Ken, Yasin, Abeer, Knight, Janine, Noel, Daniel, Lubell, Richard, and Filler, Guido
- Subjects
ACADEMIC medical centers ,BODY weight ,LONGITUDINAL method ,OBESITY ,PEDIATRICS ,RESUSCITATION ,STATISTICS ,DATA analysis ,PEDIATRIC emergency services ,ELECTRONIC health records ,DESCRIPTIVE statistics ,EQUIPMENT & supplies - Abstract
Copyright of CJEM: Canadian Journal of Emergency Medicine is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2012
- Full Text
- View/download PDF
38. The effect of seniority and education on departmental dictation utilization.
- Author
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Bax, Kevin, Norozi, Kambiz, Sharma, Ajay, and Filler, Guido
- Published
- 2011
- Full Text
- View/download PDF
39. Should we consider MMF therapy after rituximab for nephrotic syndrome?
- Author
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Filler, Guido, Huang, Shih-Han, and Sharma, Ajay
- Subjects
- *
STEROID drugs , *IMMUNOSUPPRESSIVE agents , *RITUXIMAB , *GRAFT rejection prevention , *DRUG resistance , *NEPHROTIC syndrome , *HEALTH outcome assessment , *TREATMENT effectiveness , *CHILDREN , *THERAPEUTICS - Abstract
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 CD20-positive 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. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
40. Are we ready to use aliskiren in children?
- Author
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Kelland, Erin, McAuley, Leanne, and Filler, Guido
- Subjects
LOSARTAN ,COMBINATION drug therapy ,CHRONIC kidney failure ,GLOMERULAR filtration rate ,ANTIHYPERTENSIVE agents ,METABOLIC disorders ,POTASSIUM in the body ,PROTEINURIA ,OFF-label use (Drugs) ,RENIN-angiotensin system ,DRUG dosage ,CHILDREN ,PHYSIOLOGY ,THERAPEUTICS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
41. Age-related stature and linear body segments in children with X-linked hypophosphatemic rickets.
- Author
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Živičnjak, Miroslav, Schnabel, Dirk, Billing, Heiko, Staude, Hagen, Filler, Guido, Querfeld, Uwe, Schumacher, Marius, Pyper, Anke, Schröder, Carmen, Brämswig, Jürgen, and Haffner, Dieter
- Subjects
STEROID drugs ,AGE distribution ,ANALYSIS of variance ,ANTHROPOMETRY ,ARM ,COMPUTER software ,CONFIDENCE intervals ,LEG ,LONGITUDINAL method ,MEDICAL cooperation ,METABOLIC disorders ,PHOSPHATES ,PHOSPHORUS in the body ,RESEARCH ,RESEARCH funding ,RICKETS ,STATISTICS ,STATURE ,T-test (Statistics) ,U-statistics ,DATA analysis ,REPEATED measures design ,GENETICS ,THERAPEUTICS - Abstract
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= 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 = 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. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
42. Development of a beta-trace protein based formula for estimation of glomerular filtration rate.
- Author
-
Benlamri, Amina, Nadarajah, Renisha, Yasin, Abeer, Lepage, Nathalie, Sharma, Ajay, and Filler, Guido
- Subjects
PEDIATRIC nephrology ,GLOMERULAR filtration rate ,KIDNEY function tests ,LIPOPROTEINS ,CREATININE - Abstract
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
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 + (0.9515xLOG(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. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
43. Rituximab in refractory nephrotic syndrome.
- Author
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Prytuła, Agnieszka, Iijima, Kazumoto, Kamei, Koichi, Geary, Denis, Gottlich, Errol, Majeed, Abdul, Taylor, Mark, Marks, Stephen, Tuchman, Shamir, Camilla, Roberta, Ognjanovic, Milos, Filler, Guido, Smith, Graham, and Tullus, Kjell
- Subjects
RITUXIMAB ,DRUG efficacy ,NEPHROTIC syndrome in children ,ANTINEOPLASTIC agents ,PEDIATRIC nephrology ,KIDNEY transplantation ,KIDNEY disease treatments ,QUESTIONNAIRES - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
44. Adherence to waiting-time targets for pediatric nephrology clinic referrals.
- Author
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Radina, Maria, Sharma, Ajay, Yasin, Abeer, and Filler, Guido
- Abstract
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 <1 week, whereas availability of clinic space was the main reason for nonadherence to access targets. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
45. Bicarbonate therapy improves growth in children with incomplete distal renal tubular acidosis.
- Author
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Sharma, Ajay P., Singh, Ram N., Yang, Connie, Sharma, Raj K., Kapoor, Rakesh, and Filler, Guido
- Subjects
ACIDOSIS ,OSTEOPOROSIS ,DWARFISM ,KIDNEY diseases ,SODIUM bicarbonate ,ACIDIFICATION ,PEDIATRIC nephrology - Abstract
Incomplete distal renal tubular acidosis (idRTA) has recently been associated with osteoporosis and growth retardation, attributed to the mild persistent metabolic acidosis. We hypothesized a therapeutic benefit from bicarbonate therapy on growth parameters in children with idRTA. In a study group of 40 surgically treated patients with posterior urethral valve (PUV) and normal estimated glomerular filtration rate, we evaluated the change in height standard deviation scores (SDSs) while they were on bicarbonate therapy in the presence of idRTA and complete distal renal tubular acidosis (dRTA). Age- and gender-matched healthy subjects constituted the control group ( n = 55). Incomplete dRTA was evaluated by ammonium chloride acidification. The baseline height SDS of −1.94 ± 0.41 and −5.31 ± 1.95 in the groups with idRTA and complete dRTA, respectively, were significantly lower than that of the controls. After a follow-up period of 24.7 ± 8.3 months on sodium bicarbonate therapy, the idRTA patients had a 66% increase in height SDS compared with 26% and 3% increases in the patients with PUV with complete dRTA and without dRTA, respectively. At the end of follow-up, mean height SDS in the group with idRTA no longer remained significantly lower than that of the controls ( P = 0.42). We concluded that bicarbonate therapy improves height SDS in idRTA. This issue needs further validation in larger studies. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
46. Pediatric reference intervals for soluble transferrin receptor and transferrin receptor-ferritin index.
- Author
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Ooi, Cara, Lepage, Nathalie, Nieuwenhuys, Ed, Sharma, Ajay, and Filler, Guido
- Abstract
Recent studies showing an improved diagnosis of iron deficiency (ID) with soluble transferrin receptor (sTfR) and sTfR-ferritin index did not take into account the age-dependency of sTfR and ferritin. Moreover, there is a paucity of data on pediatric reference intervals for sTfR and sTfR-ferritin index. A study cohort of 436 apparently healthy children was analyzed to establish reference intervals for ferritin, transferrin, sTfR and sTfR-ferritin index. To account for age-dependency, standard deviation scores (Z-scores) for these markers were calculated. The association between these parameters and C-reactive protein (CRP) was analyzed. The Z-scores of ferritin, transferrin and sTfR had a significant association with CRP, whereas the Z-score of sTfR-ferritin did not correlate with CRP. The reference intervals of these parameters were reported. Among the different markers of ID, the Z-scores of sTfR, transferrin and ferritin, but not sTfR-ferritin index, associate with the inflammatory status. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
47. Novel HGPRT 293 A>G point mutation presenting as neonatal acute renal failure.
- Author
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Wong, Hubert, Feber, Janusz, Chakraborty, Pranesh, Drukker, Alfred, and Filler, Guido
- Subjects
GENETIC mutation ,ACUTE kidney failure ,NEONATAL diseases ,KIDNEY glomerulus ,NEUROBEHAVIORAL disorders - Abstract
We report on a rare case of hypoxanthine guanine phosphoribosyl transferase (HGPRT) deficiency that presented in the newborn period with acute renal failure (ARF). The clinical diagnosis was made on the basis of non-oliguric ARF and evidence of crystal nephropathy on renal biopsy. HGPRT deficiency was eventually confirmed by enzymatic and genetic testing, showing a novel point mutation, 293 A>G. Immediate treatment consisted of peritoneal dialysis with, initially, lactate- then bicarbonate-buffered 1.36% glucose solution together with oral administration of allopurinol. Follow-up after more than 4 years continued to show hyper-echogenic kidneys with almost normal renal glomerular function. There continues to be no neurobehavioural abnormalities. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
48. Calcineurin Inhibitors in Pediatric Renal Transplant Recipients.
- Author
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Filler, Guido
- Subjects
- *
RESEARCH , *IMMUNOSUPPRESSIVE agents , *CYCLOSPORINE , *CHEMICAL inhibitors , *DRUG side effects , *KIDNEY tubules , *PEDIATRICS , *SURGERY - Abstract
The calcineurin inhibitors, cyclosporine (ciclosporin) [microemulsion] and tacrolimus, are the principal immunosuppressants prescribed for adult and pediatric renal transplantation. For pediatric patients, both drugs should be dosed per body surface area, and pharmacokinetic monitoring is mandatory. While monitoring of the trough levels may suffice for tacrolimus, cyclosporine therapy that utilizes the microemulsion formulation requires additional monitoring (e.g. determination of 2-hour post-dose levels). In a well designed randomized study in children, as in studies in adults, there was no difference in short-term patient and graft survival with cyclosporine microemulsion and tacrolimus. However, tacrolimus was significantly more effective than cyclosporine microemulsion in preventing acute rejection after renal transplantation when used in conjunction with azathioprine and corticosteroids. With regard to long-term outcome, the difference in acute rejection episodes resulted in a better glomerular filtration rate at 1 year after transplantation and eventually in better graft survival 4 years after renal transplantation. Whether this difference persists when calcineurin inhibitors are used in combination with mycophenolate mofetil has not been determined. The prevalence of hypomagnesemia was higher in the tacrolimus group whereas hypertrichosis and gingival hyperplasia occurred more frequently in the cyclosporine group. In contrast with adults, the incidence of post-transplantation diabetes mellitus was not significantly different between tacrolimus- and cyclosporine-treated patients. There was also no difference with regard to post-transplantation lymphoproliferative disorder. Medication costs were similar, but in view of the lower rejection episodes and better long-term graft survival as well as the more favorable cosmetic side effect profile, tacrolimus may be preferable. The recommendation drawn from the available data is that both cyclosporine and tacrolimus can be used safely and effectively in children. We recommend that cyclosporine should be chosen when patients experience tacrolimus-related adverse events. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
49. How to define anemia in children with chronic kidney disease?
- Author
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Filler, Guido, Mylrea, Kyle, Feber, Janusz, and Wong, Hubert
- Subjects
- *
KIDNEY diseases , *BLOOD proteins , *BLOOD testing , *JUVENILE diseases , *PEDIATRIC nephrology , *INTERNAL medicine , *NEPHROLOGY - Abstract
In a cross-sectional study, we compared the prevalence of anemia based on age- and gender-specific reference intervals for hemoglobin (Hgb) and hematocrit (Hct) with the Kidney Disease Outcomes Quality Initiative (KDOQI) anemia definition (Hgb < 110 g/L) in 351 children with chronic kidney disease (CKD) stages I–V. Cystatin C-based GFRs were 122 ± 36 mL/min/1.73 m2 in patients with stage I CKD ( n = 196), 76 ± 8 mL/min/1.73 m2 for stage II ( n = 104), 45 ± 9 mL/min/1.73 m2 for stage III ( n = 36), and 22 ± 5 mL/min/1.73 m2 in patients with stage IV+V CKD ( n = 15). Fifty-nine patients received iron therapy and 32 patients were treated with Darbepoetin. For Hgb, a total of 90 patients fit the age and gender derived criteria, compared to only 54 patients identified by the KDOQI guidelines ( p = 0.0010). Similarly, for Hct, a total of 78 patients fit the age and gender derived criteria, which was a significantly higher proportion than the 56 identified by the KDOQI guidelines ( r = 0.22, p = 0.0435). There was a significant correlation between the GFR and both the Hgb Z-score ( p = 0.0068) and the Hct Z-score ( p = 0.0128). There was poor agreement between conventional and KDOQI definitions of anemia in children with CKD. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
50. Growth impairment shows an age-dependent pattern in boys with chronic kidney disease.
- Author
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Živičnjak, Miroslav, Franke, Doris, Filler, Guido, Haffner, Dieter, Froede, Kerstin, Nissel, Richard, Haase, Sanny, Offner, Gisela, Ehrich, Jochen H. H., and Querfeld, Uwe
- Subjects
SEX factors in disease ,GROWTH disorders ,CHRONIC kidney failure ,KIDNEY diseases ,CHRONIC diseases - Abstract
The impact of chronological age on longitudinal body growth from early childhood through adolescence using detailed anthropometric methods has not yet been studied in children with chronic kidney disease (CKD). We have evaluated growth failure by measuring four components of linear growth: body height (HT), sitting height (SHT), arm length (AL) and leg length (LL). Data were prospectively collected for up to 7 years on 190 boys (3–21 years old) with congenital or hereditary CKD (all had developed at least stage 2 CKD by the age of 10 years). Patients showed the most severe growth failure in early childhood, followed by an acceleration in growth in pre-puberty, a slowing-down of growth at puberty, as expected, and thereafter a late speeding-up of growth until early adulthood. This pattern was observed irrespective of the degree of CKD and different treatment modalities, such as conservative treatment, recombinant human growth hormone (rhGH) therapy or transplantation. LL showed the most dynamic growth changes of all the parameters evaluated and emerged as the best indicator of statural growth in children with CKD. A specific age-dependent pattern of physical growth was identified in pediatric male CKD patients. This growth pattern should be considered in the evaluation of individual growth and the assessment of treatment efficacy such as rhGH therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
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