78 results on '"Filler, Guido"'
Search Results
2. A population-based retrospective cohort study of surgical trends and outcomes of pediatric urolithiasis in Ontario, Canada (2002–2019).
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Gabrigna Berto, Fernanda, Wang, Peter, McClure, J Andrew, Bjazevic, Jennifer, Golomb, Dor, Filler, Guido, Diaz-Gonzalez de Ferris, Maria, Welk, Blayne, Razvi, Hassan, and Dave, Sumit
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The worldwide incidence of pediatric urinary stone disease (PUSD) is increasing. However, there is no commensurate data on whether this translates to an increasing need for surgical intervention for PUSD, given the role of conservative management. We aimed to evaluate the trends and outcomes of clinically significant PUSD, using administrative databases to identify patients surgically treated for PUSD. This retrospective population-based cohort study assessed the incidence and trends of surgically treated PUSD and outcomes in Ontario, Canada in patients <18 years of age who underwent their first PUSD procedure between 2002 and 2019 utilizing administrative databases held at the Institute of Clinical Evaluative Sciences (ICES). We assessed the incidence of surgically treated PUSD, demographics, initial surgical treatment and imaging modality, and risk factors for repeat intervention within 5 years. Statistical analyses summarized demographics, surgical trends, and logistic regression was used to identify risk factors for repeat surgical intervention. We identified 1149 patients (mean age 11.3 years), with 59.6% older than 12 years. There was a decrease in the number of PUSD procedures performed per year that was close to statistical significance (p = 0.059) and a trend towards increased utilization of ureteroscopy (URS) compared with Shockwave Lithotripsy (SWL). In addition, there was a significant increase in the proportion of females surgically treated with PUSD (p = 0.001). In the 706 patients followed for 5 years, 17.7% underwent a repeat procedure within 6 months, while 20.4% underwent a repeat procedure from 6-months to 5 years. Renal stone location (OR 2.79, 95% confidence interval (CI) 1.62–4.80, p = 0.0002) and index SWL (OR 1.66, 95% CI 1.20–2.31, p = 0.0025) were risk factors for repeat surgical intervention within the first 6-months. There was an increasing utilization of ultrasound (US) compared to computerized tomography (CT) (p = 0.0008). Despite the literature reporting increasing PUSD incidence, we observed a non-significant decrease in the number of surgical PUSD procedures performed. Exclusion of those treated conservatively may explain our results. The increase in the proportion of females treated reflects the narrowing gender gap in stone disease. A trend towards increased URS utilization was observed and re-intervention rates were similar to previous studies. The overall rate of surgically treated PUSD did not show an increasing trend in Ontario, Canada from 2002 to 2019. URS was the most common surgical treatment modality, with a corresponding decline in SWL rates. PUSD was associated with a high surgical re-intervention rate within 6 months. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Artificial Intelligence in Pediatric Nephrology—A Call for Action
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Filler, Guido, Gipson, Debbie S., Iyamuremye, Didier, and Díaz González de Ferris, Maria Esther
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Artificial intelligence is playing an increasingly important role in many fields of clinical care to assist health care providers in patient management. In adult-focused nephrology, artificial intelligence is beginning to be used to improve clinical care, hemodialysis prescriptions, and follow-up of transplant recipients. This article provides an overview of medical artificial intelligence applications relevant to pediatric nephrology. We describe the core concepts of artificial intelligence and machine learning and cover the basics of neural networks and deep learning. We also discuss some examples for clinical applications of artificial intelligence in pediatric nephrology, including neonatal kidney function, early recognition of acute kidney injury, renally cleared drug dosing, intrapatient variability, urinary tract infection workup in infancy, and longitudinal disease progression. Furthermore, we consider the future of artificial intelligence in clinical pediatric nephrology and its potential impact on medical practice and address the ethical issues artificial intelligence raises in terms of clinical decision-making, health care provider-patient relationship, patient privacy, and data collection. This article also represents a call for action involving those of us striving to provide optimal services for children, adolescents, and young adults with chronic conditions.
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- 2023
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4. Young Adults With Hereditary Tubular Diseases: Practical Aspects for Adult-Focused Colleagues.
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Alhasan, Khalid, D'Alessandri-Silva, Cynthia, Mongia, Anil, Topaloglu, Rezan, Tasic, Velibor, and Filler, Guido
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- 2022
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5. Functional Sodium MRI Helps to Measure Corticomedullary Sodium Content in Normal and Diseased Human Kidneys
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Akbari, Alireza, Lemoine, Sandrine, Salerno, Fabio, Marcus, Taylor L., Duffy, Tristan, Scholl, Timothy J., Filler, Guido, House, Andrew A., and McIntyre, Christopher W.
- Abstract
Sodium MRI can help measure dynamic changes in the corticomedullary sodium gradient, reflect urine-concentrating ability in healthy volunteers, and provide consistent images for analysis in participants with chronic kidney disease.
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- 2022
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6. Young Adults With Hereditary Tubular Diseases: Practical Aspects for Adult-Focused Colleagues
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Alhasan, Khalid, D'Alessandri-Silva, Cynthia, Mongia, Anil, Topaloglu, Rezan, Tasic, Velibor, and Filler, Guido
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Recent advances in the management of kidney tubular diseases have resulted in a significant cohort of adolescents and young adults transitioning from pediatric- to adult-focused care. Most of the patients under adult-focused care have glomerular diseases, whereas rarer tubular diseases form a considerable proportion of pediatric patients. The purpose of this review is to highlight the clinical signs and symptoms of tubular disorders, as well as their diagnostic workup, including laboratory findings and imaging, during young adulthood. We will then discuss more common disorders such as cystinosis, cystinuria, distal kidney tubular acidosis, congenital nephrogenic diabetes insipidus, Dent disease, rickets, hypercalciuria, and syndromes such as Bartter, Fanconi, Gitelman, Liddle, and Lowe. This review is a practical guide on the diagnostic and therapeutic approach of tubular conditions affecting young adults who are transitioning to adult-focused care.
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- 2022
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7. Renal volume of five-year-old preterm children are not different than full-term controls
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Restrepo, Jaime M., Torres-Canchala, Laura, Cadavid, Juan Carlos Arias, Ferguson, Michael, Villegas, Adriana, Ramirez, Oscar, Rengifo, Martin, and Filler, Guido
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In previous studies, smaller renal volumes were reported in prematurely born infants, however, these renal volumes were not corrected for body surface area, the main determinant of renal size. Given the rapid growth of the renal cortex after premature birth, the authors hypothesized that corrected volumes would not differ from healthy controls.
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- 2022
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8. Variation in paediatric 24-h ambulatory blood pressure monitoring interpretation by Canadian and UK physicians
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Stefanova, Isabella Z., Sinha, Manish D., Stewart, Douglas J., Bamhraz, Abdulaziz, Fournier, Anne, Harris, Kevin C., Filler, Guido, Noone, Damien, Teoh, Chia Wei, Dionne, Janis, and Chanchlani, Rahul
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Twenty-four-hour ambulatory blood pressure monitoring (ABPM) is widely accepted as a more accurate method for measurement of blood pressure (BP) compared to a single office-based measurement of BP. However, it is unclear how physicians interpret ABPM and make management decisions. This study’s goal is to investigate variation in ABPM interpretation among paediatric nephrologists (Canada and UK) and paediatric cardiologists (Canada only) via an online survey. The survey content included baseline demographics, questions on the use and indications for ABPM, interpretation of results, and subsequent management decisions in various clinical scenarios. The survey was sent to 196 Canadian physicians, with 69 (35.2%) total responses. Thirty-five UK clinicians also completed the survey. Most respondents were >44 years old, were in practice for at least 11 years, and were university-based. There were substantial differences among clinicians in ABPM interpretation for isolated systolic, diastolic, and night-time hypertension. For example, only 53.1% of physicians would initiate or modify treatment in those with diastolic HTN in CKD. Further, even for the same abnormal ABPM parameter, the decision to start or alter treatment was influenced by the underlying medical condition. There is significant variation in clinical practice among physicians for interpretation and management of hypertension when using ABPM. Differences in guidelines among various jurisdictions, as well as knowledge gaps in the research on which guidelines are based, create ambiguity regarding ABPM interpretation and management decisions. A more protocolized approach and further insight into the reasoning behind the variation in physicians’ interpretation may help to standardise practice.
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- 2022
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9. Including Race in Pediatric Estimated GFR Equations: Is This a Genuine Need?
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Alvarez-Elías, Ana Catalina and Filler, Guido
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- 2022
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10. GFR and eGFR in Term-Born Neonates
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Filler, Guido, Sharma, Ajay P., and Exantus, Judith
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- 2022
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11. Consensus guidelines for management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy
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Raina, Rupesh, Bedoyan, Jirair K., Lichter-Konecki, Uta, Jouvet, Philippe, Picca, Stefano, Mew, Nicholas Ah, Machado, Marcel C., Chakraborty, Ronith, Vemuganti, Meghana, Grewal, Manpreet K., Bunchman, Timothy, Sethi, Sidharth Kumar, Krishnappa, Vinod, McCulloch, Mignon, Alhasan, Khalid, Bagga, Arvind, Basu, Rajit K., Schaefer, Franz, Filler, Guido, and Warady, Bradley A.
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Hyperammonaemia in children can lead to grave consequences in the form of cerebral oedema, severe neurological impairment and even death. In infants and children, common causes of hyperammonaemia include urea cycle disorders or organic acidaemias. Few studies have assessed the role of extracorporeal therapies in the management of hyperammonaemia in neonates and children. Moreover, consensus guidelines are lacking for the use of non-kidney replacement therapy (NKRT) and kidney replacement therapies (KRTs, including peritoneal dialysis, continuous KRT, haemodialysis and hybrid therapy) to manage hyperammonaemia in neonates and children. Prompt treatment with KRT and/or NKRT, the choice of which depends on the ammonia concentrations and presenting symptoms of the patient, is crucial. This expert Consensus Statement presents recommendations for the management of hyperammonaemia requiring KRT in paediatric populations. Additional studies are required to strengthen these recommendations.
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- 2020
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12. Post-transplant recurrence of focal segmental glomerular sclerosis: consensus statements
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Raina, Rupesh, Jothi, Swathi, Haffner, Dieter, Somers, Michael, Filler, Guido, Vasistha, Prabhav, Chakraborty, Ronith, Shapiro, Ron, Randhawa, Parmjeet S., Parekh, Rulan, Licht, Christopher, Bunchman, Timothy, Sethi, Sidharth, Mangat, Guneive, Zaritsky, Joshua, Schaefer, Franz, Warady, Bradley, Bartosh, Sharon, McCulloch, Mignon, Alhasan, Khalid, Swiatecka-Urban, Agnieszka, Smoyer, William E., Chandraker, Anil, Yap, Hui Kim, Jha, Vivekananda, Bagga, Arvind, and Radhakrishnan, Jai
- Abstract
Focal segmental glomerular sclerosis (FSGS) is 1 of the primary causes of nephrotic syndrome in both pediatric and adult patients, which can lead to end-stage kidney disease. Recurrence of FSGS after kidney transplantation significantly increases allograft loss, leading to morbidity and mortality. Currently, there are no consensus guidelines for identifying those patients who are at risk for recurrence or for the management of recurrent FSGS. Our work group performed a literature search on PubMed/Medline, Embase, and Cochrane, and recommendations were proposed and graded for strength of evidence. Of the 614 initially identified studies, 221 were found suitable to formulate consensus guidelines for recurrent FSGS. These guidelines focus on the definition, epidemiology, risk factors, pathogenesis, and management of recurrent FSGS. We conclude that additional studies are required to strengthen the recommendations proposed in this review.
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- 2024
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13. Discrepant changes of urinary cystatin C and other urinary biomarkers in preterm neonates
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Filler, Guido and Ferris, Maria E. Díaz-González de
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- 2021
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14. Automated Office Blood Pressure Measurement for the Diagnosis of Hypertension.
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Filler, Guido and Díaz-González de Ferris, Maria E.
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- 2020
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15. A Retrospective Study on Mycophenolic Acid Drug Interactions: Effect of Prednisone, Sirolimus, and Tacrolimus With MPA
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Alvarez-Elías, Ana C., Yoo, Elisa C., Todorova, Ekaterina K., Singh, Ram N., and Filler, Guido
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Mycophenolic acid (MPA), the active compound of mycophenolate mofetil (MMF), is widely used as an antirejection drug after renal transplantation. There is growing evidence supporting the notion that there is substantial variability in the intra- and interpatient exposure to MPA. Drug interactions involving MPA with tacrolimus, steroids, and sirolimus have been understudied. The objective of this study was to determine the relationship between MPA, steroids, tacrolimus, and sirolimus. MPA trough concentrations from 37 pediatric renal transplant recipients (mean age 7.6 years at transplant) followed for a median follow-up of 7.8 years were analyzed retrospectively and 2131 dose-normalized MPA trough concentrations were evaluated against all known covariates including all concomitant immunosuppressant drug doses and exposure, age, albumin, hematocrit, and estimated glomerular filtration rate (eGFR). Age, hematocrit, and estimated glomerular filtration rate affected the dose-normalized MPA trough concentrations. The authors used appropriate linear regression univariate models and created 5 different multivariate models to examine individual drug–drug interactions (DDIs). Although the authors' findings support the notion that there is a DDI between MMF and both sirolimus and steroids, the sample size was small, and these findings should be confirmed in future studies. The authors found no DDIs between tacrolimus and MMF, the prodrug of MPA. These findings are important because there is a tendency to under-dose MMF early and to overdose late after transplantation. The DDI between sirolimus and MMF has not been described. Although therapeutic drug monitoring of MMF therapy is often not performed, the data presented here indicate a necessity for therapeutic drug monitoring. This is especially true when converting from tacrolimus to sirolimus, as a way to avoid MPA underexposure and organ rejection.
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- 2017
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16. Chromium: Rise and Shine in Peritoneal Dialysis Patients?
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Filler, Guido and McIntyre, Christopher
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Some trace elements are altered with chronic kidney disease. Selenium, zinc, and manganese tend to be wasted, and there is growing evidence that selenium deficiency is associated with mortality on dialysis. Other trace elements accumulate, such as chromium, cobalt, lead, molybdenum, and vanadium. The highest chromium levels are found in dialysis patients. The dialysis modality may further affect these levels, especially in hemodialysis patients, where even small contaminations in the dialysis feed water may lead to a concentration gradient that increases the concentration of certain trace elements. Chromium levels in peritoneal dialysis (PD) patients have been understudied. A single cross-sectional study found substantially higher chromium levels in PD patients. In that study, the chromium concentration in the spent dialysate decreased substantially, suggesting that PD fluid could be a source of chromium. Chromium-lactate complexes may have been formed, which are easily absorbed. In our center, we observed a decrease in chromium level when using physiological PD fluids. This review discusses the potential mechanisms and raises the question of whether this accumulation of chromium is unlikely to be associated with a beneficial outcome.
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- 2019
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17. Rapid Resolution of Tacrolimus Intoxication-Induced AKI With a Corticosteroid and Phenytoin.
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Bax, Kevin, Tijssen, Janice, Rieder, Michael J, and Filler, Guido
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- 2014
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18. Rapid Resolution of Tacrolimus Intoxication--Induced AKI With a Corticosteroid and Phenytoin.
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Bax, Kevin, Tijssen, Janice, Rieder, Michael J., and Filler, Guido
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- 2014
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19. Are Tacrolimus Pharmacokinetics Affected by Nephrotic Stage?
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Medeiros, Mara, Valverde, Saúl, Del Moral, Irma, Velásquez-Jones, Luis, Hernández, Ana María, Castañeda-Hernández, Gilberto, Reyes, Herlinda, and Filler, Guido
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- 2016
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20. Assessment of glomerular filtration rate in the neonate: is creatinine the best tool?
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Filler, Guido, Guerrero-Kanan, Ricardo, and Alvarez-Elías, Ana Catalina
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- 2016
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21. The Search for More Reliable Estimated GFR Biomarkers
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Filler, Guido, Huang, Shih-Han S., and Lindsay, Robert M.
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- 2016
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22. Measuring Physicians' Productivity: A Three-Year Study to Evaluate a New Remuneration System.
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Filler, Guido, Burkoski, Vanessa, and Tithecott, Gary
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- 2014
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23. More Realistic Estimation of Time to ESRD in Children
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Filler, Guido and McIntyre, Christopher W.
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- 2018
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24. Innovating to educate paediatric consultant generalists for the new Canadian health care.
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Tithecott, Gary, Levin, Simon, and Filler, Guido
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Responsibility for training general paediatricians in Canada lies primarily with the 17 paediatric academic health sciences centres with more programmatic emphasis on subspecialty training and less on preparing residents for general paediatrics. However, the greatest unmet demand in the paediatric workforce will be for consulting paediatric generalists. Here, we define the need for paediatric generalists and list deficiencies in current models to promote more consulting community general paediatricians. The limited presence of general paediatricians as role models reduces the potential for learners to better understand the role of generalists in our specialty. Nationally, we need to advocate for change in teaching models to guide the career choices of our graduates to meet societal needs through better mentorship and educational models that heavily include community-based paediatric consulting generalists. This will be essential to meet our responsibility of supporting primary care colleagues closer to home for our funders, patients and families.
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- 2018
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25. The Tc-DTPA Urinary Clearance Method May Be Preferable to the Plasma Disappearance Method for Assessing Glomerular Filtration Rate in Diabetic Nephropathy
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Huang, Shih-Han S., Eliasziw, Misha, Spence, J. David, Filler, Guido, Vezina, William C., Churchill, David N., Cattran, Daniel C., Richardson, Bonnie, and House, Andrew A.
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AbstractBackground:Isotopic glomerular filtration rate (iGFR) measurement is comparable to the inulin method. In this study, we compared urinary and plasma iGFR methodologies in patients with diabetic nephropathy. Methods:A total of 147 patients from 3 sites in the Diabetic Intervention with Vitamins to Improve Nephropathy (DIVINe) trial provided 213 sets of urine and blood collections, at baseline, 18 and 36 months. Results:The mean (with standard deviation) plasma iGFR of 60.7 (24.9) ml/min/1.73 m2compared to urinary iGFR of 52.0 (28.0) ml/min/1.73 m2was statistically significant (p value <0.001). Although plasma and urinary iGFRs were highly related (R2= 0.86), plasma iGFR increasingly overestimated urinary iGFRs at lower GFRs. In contrast to the cross-sectional analyses, the two measures of iGFR were weakly related (R2= 0.32) in regard to patients' change over 18 months of follow-up. Conclusion:Plasma iGFR may not be a suitable method for accurately measuring GFR in patients with advancing degrees of chronic kidney disease from diabetic nephropathy.© 2015 S. Karger AG, Basel
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- 2015
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26. Propranolol therapy for infantile hemangioma is less toxic but longer in duration than corticosteroid therapy
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Sawa, Kathryn, Yazdani, Arjang, Rieder, Michael J, and Filler, Guido
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Background Infantile hemangioma is the most common benign, self-limiting tumour of childhood. Treatment is reserved for hemangiomas that obstruct vital structures or cause significant disfigurement. Traditionally, corticosteroids have been the medical treatment of choice. Since 2008, however, propranolol has been rapidly adopted as an effective pharmacological treatment for infantile hemangioma. Published data regarding the long-term side effects of propranolol are currently lacking.Objective To describe the long-term effects of propranolol and corticosteroids on anthropometric measurements (height, body mass index [BMI]) and blood pressure in children.Methods A prospective database analysis of all infantile hemangioma patient visits to the pediatric vascular abnormality clinic at the authors' institution between October 2007 and February 2012 was performed. Anthropometric measures (height and BMI) and blood pressure were analyzed.Results A total of 290 visits (119 patients) to the pediatric vascular abnormality clinic were reviewed. Of these, 18 patients received medical treatment and their anthropometry was analyzed. BMI percentile increased significantly in patients treated with corticosteroids (P=0.0039). Corticosteroid treatment also resulted in a significant decrease in height percentile (P=0.0078). Anthropometric measures did not cross percentiles in children treated with propranolol. A significant decrease in systolic blood pressure was noted in the propranolol group (P=0.03), but no hypotensive values were recorded. Median treatment duration was significantly longer when patients received propranolol (372 versus 133 days; P=0.0033).Conclusion Propranolol for the treatment of infantile vascular abnormalities does not share the unfavourable effects on patient anthropometry that corticosteroids exhibit; however, a longer duration of therapy is required.
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- 2014
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27. Rapid Resolution of Tacrolimus Intoxication–Induced AKI With a Corticosteroid and Phenytoin
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Bax, Kevin, Tijssen, Janice, Rieder, Michael J., and Filler, Guido
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Objective:To report a novel approach to the management of tacrolimus intoxication that leads to rapid normalization of serum tacrolimus concentrations. Case Summary:A 9-year-old female renal transplant recipient developed a severe tacrolimus intoxication as a result of prolonged diarrhea, which resulted in acute kidney injury, severe dehydration, and neurological symptoms. We used a combination of intravenous steroids and intravenous phenytoin to normalize the tacrolimus level from 32 to 5 ng/mL in less than 24 hours, with complete resolution of symptoms and signs. Discussion:Tacrolimus intoxication is a rare event but may result in life-threatening complications. Treatment recommendations beyond holding the drug and enzyme induction with phenytoin or phenobarbital are elusive. This approach leads to a relatively slow normalization of the tacrolimus level over 72 hours. The authors hypothesized that additional induction of the p-glycoprotein through steroids was synergistic. Conclusions:The combination of phenytoin and a corticosteroid may be an effective approach that leads to rapid normalization of severely elevated tacrolimus levels.
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- 2014
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28. Performance of the creatinine-based and the cystatin C-based glomerular filtration rate (GFR) estimating equations in a heterogenous sample of patients referred for nuclear GFR testing.
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Huang, Shih-Han S., Macnab, Jennifer J., Sontrop, Jessica M., Filler, Guido, Gallo, Kerri, Lindsay, Robert M., and Clark, William F.
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Cystatin C may be a more accurate marker of the glomerular filtration rate (GFR) than creatinine. We evaluated the performance of the creatinine-based abbreviated modification of diet in renal disease (MDRD), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, and 6 cystatin C-based equations in estimating GFR (eGFR) in a heterogeneous sample of patients. Measured GFR (mGFR) was obtained from the plasma clearance of
99m technetium Diethylenetriaminepentaacetic acid in 42 adult patients referred for nuclear GFR testing (January to March 2008). We evaluated the bias, precision, and accuracy of the abbreviated MDRD, CKD-EPI, Filler, Grubb, Hoek, Larsson, Le Bricon, and Rule eGFR equations. Participants had a mean mGFR of 70.9 mL/min/1.73m2 (range: 22–125 mL/min/1.73m2 ), a median age of 57 years (interquartile range: 45, 66), were 62% male, and were 38% liver transplant recipients. Correlation coefficients between eGFRs and mGFR ranged from 0.65 to 0.87 (each P < 0.001). The cystatin C-based Hoek equation had the best overall performance with a low bias (–1.4 mL/min/1.73m2 ), good precision (13.3 mL/min/1.73m2 ), and greatest accuracy, with 93% of values within 30% of mGFR. Although the CKD-EPI equation had the lowest bias (–0.6 mL/min/1.73m2 ), it had poor precision (20.7 mL/min/1.73m2 ) and low accuracy, with only 69% of values within 30% of mGFR. The Hoek equation remained accurate and had the least bias when patients were grouped according to the history of liver transplantation and the mGFR above or below 60 mL/min/1.73m2 . In this heterogeneous sample, the cystatin C-based Hoek equation performed the best overall, regardless of mGFR level or history of liver transplantation. [ABSTRACT FROM AUTHOR]- Published
- 2011
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29. Pediatric aspects of therapeutic drug monitoring of mycophenolic acid in renal transplantation.
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Tönshoff, Burkhard, David-Neto, Elias, Ettenger, Robert, Filler, Guido, van Gelder, Teun, Goebel, Jens, Kuypers, Dirk R.J., Tsai, Eileen, Vinks, Alexander A., Weber, Lutz T., and Zimmerhackl, Lothar Bernd
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PEDIATRICS ,MYCOPHENOLIC acid ,DRUG monitoring ,KIDNEY transplantation ,HEART transplantation ,ONTOGENY ,PHARMACOKINETICS - Abstract
Abstract: Mycophenolate mofetil (MMF) is widely used for maintenance immunosuppressive therapy in pediatric renal and heart transplant recipients. Children undergo developmental changes (ontogeny) of drug disposition, which may affect drug metabolism of the active compound mycophenolic acid (MPA). Therefore, a detailed characterization of MPA pharmacokinetics and pharmacodynamics in this patient population is required. In general, the overall efficacy and tolerability of MMF in pediatric patients appear to be comparable with those in adults, except for a higher prevalence of gastrointestinal adverse effects in children younger than 6 years. The currently recommended dose in pediatric patients with concomitant cyclosporine is 1200 mg/m
2 per day in 2 divided doses; the recommended MMF dose with concomitant tacrolimus or without a concurrent calcineurin inhibitor is 900 mg/m2 per day in 2 divided doses. Recent data suggest that fixed MMF dosing results in MPA underexposure (MPA–area under the concentration-time curve (AUC0–12 ), <30 mg × h/L) early posttransplant in approximately 60% of patients. To achieve adequate MPA exposure in most patients, an initial MMF dose of 1800 mg/m2 per day with concomitant cyclosporine and 1200 mg/m2 per day with concomitant tacrolimus for the first 2 to 4 weeks posttransplant has been suggested. As in adults, there is an approximately 10-fold variability in dose-normalized MPA–AUC0–12 values between pediatric patients after renal transplantation, strengthening the argument for concentration-controlled dosing of the drug. Although the clinical utility of therapeutic drug monitoring of MPA for graft outcome and patient survival is still controversial, potential indications are the avoidance of underimmunosuppression, particularly in patients with high immunologic risk in the initial period posttransplant, in patients who are treated with protocols that explore the possibilities of calcineurin inhibitor minimization, withdrawal or even complete avoidance, and steroid withdrawal or avoidance regimens that might also benefit from intensified therapeutic drug monitoring of MPA. An additional indication especially in adolescent patients is the monitoring of drug adherence. Therapeutic drug monitoring of MPA in pediatric solid organ transplantation using limited sampling strategies is preferable over drug dosing based on trough level monitoring only. Several validated pediatric limited sampling strategies are available. Clearly, more research is required to determine whether pediatric patients will benefit from therapeutic drug monitoring of MPA for long-term maintenance immunosuppression with MMF. [Copyright &y& Elsevier]- Published
- 2011
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30. Relationships Among Serum Iron, Inflammation, and Body Mass Index in Children.
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Sharma, Ajay P., McKenna, Ann Marie, Lepage, Nathalie, Nieuwenhuys, Ed, and Filler, Guido
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- 2009
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31. Neonatal Renal Venous Thrombosis: Clinical Outcomes and Prevalence of Prothrombotic Disorders.
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Marks, Stephen D., Massicotte, M. Patricia, Steele, Brian T., Matsell, Douglas G., Filler, Guido, Shah, Prakesh S., Perlman, Max, Rosenblum, Norman D., and Shah, Vibhuti S.
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Objective: To determine clinical outcomes and the prevalence of prothrombotic conditions in patients who had neonatal renal venous thrombosis (RVT). Study design: A retrospective cohort of neonates with RVT who were admitted to 4 pediatric centers from 1980 to 2001 was identified. Information on clinical presentation, laboratory and radiological investigation, and treatment were abstracted. Survivors were evaluated for renal status and prothrombotic conditions. Results: Forty-three patients with neonatal RVT were identified. RVT was unilateral in 24 patients (56%) and associated with 2thrombi at other sites in 32 patienets (74%). Clinical presentations included renal failure in 24 patients (56%), thrombocytopenia, anemia, or both in 22 patients (51%), and renal mass in 21 patients (49%). Neonatal interventions included anti-coagulants in 28 patients (65%), antihypertensive medications in 9 patients (21%), peritoneal dialysis in 2 patients (5%), and nephrectomy in 2 patients (5%). The median age at follow-up was 3.7 years (range, 0.5-20.2 years). Thirteen patients (34%) had hypertension, and 11 patients (29%) had renal failure. End-stage renal disease developed in 3 patients, and they underwent live-related renal transplants. Twelve of the 28 patients (43%) examined had prothrombotic abnormalities. Conclusion: Neonatal RVT is associated with significant renal morbidity and a high prevalence of prothrombotic abnormalities. [Copyright &y& Elsevier]
- Published
- 2005
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32. Barriers to the Implementation of Lipoprotein Apheresis in Canada
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Filler, Guido, Lee, Misan, and Hegele, Robert A.
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This article details the effectiveness of using lipoprotein apheresis (LA) rather than plasmapheresis in patients with homozygous familial hypercholesterolemia (HoFH), using results from the first HoFH pediatric patient treated with LA in Ontario. We further detail the barriers involved in adhering to international guidelines by implementing this as a first-line treatment for this condition in Ontario, and the potential savings that would be gained with treating the remaining HoFH patients in this province with LA. A primary barrier has been the division of responsibility that exists in Canada, where the delivery of medical services and the delivery of blood products are separated, artificially discounting the price of plasmapheresis and making it seem like the less expensive option. We would like to implement LA as a first-line therapy, to not only improve patient quality of life and outcomes, but to also to potentially save our federal and provincial governments' taxpayer money.
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- 2017
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33. Similar MPA Exposure on Modified Release and Regular Tacrolimus
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Filler, Guido, Vinks, Alexander A., Huang, Shih-Han S., Jevnikar, Anthony, and Muirhead, Norman
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Concomitant immunosuppression may affect the mycophenolate mofetil exposure. Astellas developed a once-daily modified release formulation of tacrolimus (TacMR) with the potential to reduce the likelihood of nonadherence. It is unknown whether mycophenolic acid (MPA) area under the concentration–time curve (AUC) differs between the 2 tacrolimus (Tac) formulations. In a 2-by-2 crossover design, 20 stable renal transplant recipients on twice-daily Tac either continued their usual Tac therapy (n = 10, group 1) or switched to TacMR for a 12-week period (n = 10, group 2), after which the patients crossed over to the other formulation for another 12-week period. Pharmacokinetic profiles using limited sampling strategies were obtained before randomization (visit 1), and at 12 (visit 2) and 24 weeks (visit 3) at steady state. MPA AUC was calculated using the Pawinski formula. When analyzing visits on Tac, TacMR, and back on Tac combined, the MPA AUC for all 20 patients at baseline was 42.24 (16.98), 37.18 (13.75), and 40.09 (16.69) mg·h·L−1, respectively, which was not statistically significant using repeated measures (P= 0.1327, R2= 0.1109). We conclude that MPA pharmacokinetic profiles are not altered when converting patients from Tac to TacMR.
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- 2014
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34. Do we need to worry about mycophenolate overdose?
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Filler, Guido and Ferrand, Amaryllis
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Introduction:To discuss the significance of the recent observational case series from the Swiss Toxicological Information Centre (STIC). Mycophenolic acid (MPA) and its prodrug mycophenolate mofetil are immunosuppressive agents that are frequently prescribed in renal transplant recipients, and their safety profiles must be established.Areas covered:This case series and systemic literature analysis consists of 15 cases of MPA overdose from the STIC and a systemic analysis of the literature over the past 18 years. This study focuses on acute overdosing, the effects of which are presumably mild. In contrast, the effects of long-term overdosing may be much more severe. Substantial underreporting is likely. The pharmacokinetic monitoring of MPA is rarely performed, which is both striking and does not coincide with findings in academic literature. The scant data on pharmacokinetic monitoring presented demonstrated that MPA has a short terminal half-life, which suggests that decontamination and activated charcoal treatment in acute overdose may not be necessary.Expert opinion:The case series and systematic literature analysis of acute mycophenolate overdose represent an important contribution toward increasing the safety of MPA therapy.
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- 2014
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35. Postoperative outcomes of ureteroscopy for pediatric urolithiasis: A secondary analysis of the National Surgical Quality Improvement Program Pediatric.
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Davidson, Jacob, Ding, Youshan, Chan, Ernest, Dave, Sumit, Bjazevic, Jennifer, Filler, Guido, and Wang, Peter Zhan Tao
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Incidence of pediatric urinary stone disease (PUSD) has increased over recent decades. Innovations in ureteroscopic technology has expanded the role of endourologic stone management in children. However, there is currently no consensus on the optimal use of ureteroscopy (URS) within the heterogenous PUSD population. The primary objective was to investigate the rate of 30-day unplanned readmissions in pediatric patients after URS. The secondary objective was to examine the influence of demographic, perioperative, postoperative, and reoperation variables as predictors of an increased risk of unplanned readmission in this sample. A secondary analysis was performed on retrospectively collected data from the National Surgical Quality Improvement Program Pediatric between 2015 and 2018. Pediatric patients diagnosed with PUSD and treated with URS were identified. Patients undergoing concurrent or additional surgeries during the URS procedure were excluded. Data on demographic, perioperative, postoperative, and unplanned reoperation variables were examined for their possible influence on 30-day unplanned readmissions. Descriptive statistics were used to characterize the study cohort. Continuous and categorical variables were analyzed using independent samples t-test, one-way ANOVA with Tukey post-hoc test, and Chi-square Tests or Fisher's Exact Test, respectfully. Multivariate analysis was performed using stepwise logistic regression. A total of 2510 patients were identified within the study period. The majority of children undergoing URS were between 12 and 18 years of age (66.1%), female (56.9%), and had renal calculi (45.2%). Of these, 162 (6.5%) experienced a 30-day unplanned readmission related to the URS procedure. The most common reasons for an unplanned readmission was urinary tract infection (31.4%), new/unresolved stone (28.3%), and postoperative pain (8.2%). Multivariate modelling showed that females (Relative Risk [RR]: 2.03; 95% Confidence Interval [95%CI]: 1.34–3.07), patients with renal stones (RR: 1.77; 95%CI: 1.10–2.83), and inpatients at the time of surgery (RR: 1.61; 95%CI: 1.03–2.51) were more at risk of an unplanned readmission within 30-days of an URS procedure. Summary Table Multivariate analysis of patient variables associated with 30-day unplanned readmission following ureteroscopy Summary Table Relative Risk (95% CI) Sex Male Ref. Female 2.03 (1.34–3.07) Stone location Renal 1.77 (1.10–2.83) Both ureteric and renal stone 1.29 (0.74–2.25) Ureteric Ref. Previous Cardiac Surgery Yes 6.60 (2.55–17.08) No Ref. Patient status at time of surgery Inpatient 1.61 (1.03–2.51) Outpatient Ref.
1 The following variables were also included in the multivariate model, but were not statistically significant: age group, weight quartile, ureteral stent, American Society of Anesthesiologists (ASA) class, case type, previous cardiac surgery, and premature birth. This study reports on short-term unplanned readmission rates in pediatric patients who underwent an URS procedure. Further it highlights possible predictors of unplanned readmission rates within a sampling of patients from NSQIP affiliated institutions. The findings from this study can be used to guide future studies around the safe use of URS in pediatric patients. [ABSTRACT FROM AUTHOR]- Published
- 2021
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36. Are the career choices of paediatric residents meeting the needs of academic centres in Canada?
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Piedboeuf, Bruno, Jones, Sarah, Orrbine, Elaine, and Filler, Guido
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Responsibility for training paediatric medical subspecialists in Canada lies primarily with the 16 academic paediatric departments. There has been no mechanism to assess whether the number of residents in training will meet the needs of currently vacant positions and/or the predicted vacancies to be created by anticipated faculty retirement in the next five years across the different paediatric medical subspecialties.
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- 2012
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37. Ontario children have outgrown the Broselow tape
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Milne, William Ken, Yasin, Abeer, Knight, Janine, Noel, Daniel, Lubell, Richard, and Filler, Guido
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ABSTRACTObjective:The Broselow Pediatric Emergency Tape (Armstrong Medical Industries, Inc., Lincolnshire, IL) (BT) is a well-established length-based tool for estimation of body weight for children during resuscitation. In view of pandemic childhood obesity, the BT may no longer accurately estimate weight. We therefore studied the BT in children from Ontario in a large recent patient cohort.Methods:Actual height and weight were obtained from an urban and a rural setting. Children were prospectively recruited between April 2007 and July 2008 from the emergency department and outpatient clinics at the London Health Science Centre. Rural children from junior kindergarten to grade 4 were also recruited in the spring of 2008 from the Avon Maitland District School Board. Data for preschool children were obtained from three daycare centres and the electronic medical record from the Maitland Valley Medical Centre. The predicted weight from the BT was compared to the actual weight using Spearman rank correlation; agreement and percent error (PE) were also calculated.Results:A total of 6,361 children (46.2% female) were included in the study. The median age was 3.9 years (interquartile range [IQR] 1.56-7.67 years), weight was 17.2 kg (IQR 11.6-25.4 kg), and height was 103.5 cm (IQR 82-124.4 cm). Although the BT weight estimate correlated with the actual weight (r = 0.95577, p < 0.0001), the BT underestimated the actual weight by 1.62 kg (7.1% ± 16.9% SD, 95% CI -26.0-40.2). The BT had an = 10% PE 43.7% of the time.Conclusions:Although the BT remains an effective method for estimating pediatric weight, it was not accurate and tended to underestimate the weight of Ontario children. Until more accurate measurement tools for emergency departments are developed, physicians should be aware of this discrepancy.
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- 2012
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38. Correction to: Variation in paediatric 24-h ambulatory blood pressure monitoring interpretation by Canadian and UK physicians
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Stefanova, Isabella Z., Sinha, Manish D., Stewart, Douglas J., Bamhraz, Abdulaziz, Fournier, Anne, Harris, Kevin C., Filler, Guido, Noone, Damien, Teoh, Chia Wei, Dionne, Janis, and Chanchlani, Rahul
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- 2022
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39. Growth hormone therapy in HHRH
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Filler, Guido, Schott, Clara, Salerno, Fabio, Ens, Andrea, McIntyre, Christopher William, de Ferris, Maria Esther Díaz González, and Stein, Robert
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Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) (SLC34A3gene, OMIM 241530) is an autosomal recessive disorder that results in a loss of function of the sodium-phosphate NPT2c channel at the proximal tubule. Phosphate supplementation rarely improves serum phosphate, hypercalciuria, nephrocalcinosis, 1,25(OH)2vitamin D (1,25(OH)2D) levels or short stature.
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- 2022
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40. Pharmacokinetics of Mycophenolate Mofetil and Sirolimus in Children
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Filler, Guido, Bendrick-Peart, Jamie, and Christians, Uwe
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This review summarizes the pharmacokinetics in children and youths of 2 commonly used immunosuppressive drugs, mycophenolate mofetil (MMF) and sirolimus (Sir), as presented at the IATDMCT 2007 conference. The review focuses on the developmental changes of drug disposition during childhood and adolescence. Regarding mycophenolate mofetil, the authors were unable to demonstrate age dependency of MMF in combination with cyclosporine. By contrast, there was an inverse relationship between age and the dose-normalized mycophenolate (MPA) area-under-the-time-concentration curve (AUC) in children who received concomitant tacrolimus (Tac). Dose-normalized MPA AUCs were higher than commonly observed in adult patients. It can be hypothesized that the age dependency is related to developmental changes in the expression of the UDP-glucuronosyltransferases. Sirolimus half-life and mean residence time (MRT) are shorter than in adults. Similar to that in adults, there is a profound drug-drug interaction between cyclosporine and Sir. In our own experience, Sir was started at 0.13 ± 0.05 mg/kg/day. The average Sir AUC was 64.9 ± 29.7 ng*h/mL. The median (range) AUC for each metabolite was as follows: 12-hydroxy-Sir, 7.6 (0.2-18.8); 46-hydroxy-Sir, 3.1 (0.0-12.4); 24-hydroxy-Sir, 4.3 (0.0-12.6); piperidine-hydroxy-Sir, 3.5 (0.0-8.3); 39-desmethyl-Sir, 3.6 (0.0-11.3); 16-desmethyl-Sir, 5.0 (0.1-9.9); and di-hydroxy-Sir, 4.3 (0.0-32.5) ng*h/mL. Of the total metabolite AUC, 77.5% was due to hydroxylated metabolites, while 39-O-desmethyl Sir (the main metabolite in adults) comprised only 8.4% of the metabolites. This is clinically relevant, as 39-O-desmethyl Sir shows 86% to 127% cross-reactivity with the Sir immunoassay. Metabolites reached a median AUC of 60% of that of Sir, but the range was 2.6% to 136%. The age dependency of Sir metabolite formation was confirmed in a human liver microsome model. On the basis of the age dependency of piperidine-hydroxy Sir, the authors postulate that the ontogeny of the drug disposition can be largely explained by developmental changes of the CYP2C8 expression. In conclusion, both Sir and MMF drug disposition vary in children and adolescents from adult patients, most likely because of developmental changes of biliary transporters and metabolic enzymes.
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- 2008
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41. New trends in immunosuppression for pediatric renal transplant recipients
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Atkison, Paul and Filler, Guido
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Rapidly growing information, published in a large variety of journals, poses a challenge to pediatric transplant physicians. This review aims at summarizing the most important manuscripts published over the last 1–2 years.
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- 2007
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42. Safety considerations with mycophenolate sodium
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Filler, Guido and Buffo, Ilan
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Following 10 years of clinical use of mycophenolate mofetil (MMF), a prodrug of mycophenolic acid, the FDA has approved enteric-coated mycophenolate sodium (EC-MPS). EC-MPS was developed to reduce the upper-gastrointestinal (GI) effects of MMF. Unlike oral MMF, where absorption starts in the stomach, EC-MPS releases MPA in the small intestine. Along with the pharmacology and pharmacokinetics, three randomized, controlled clinical trials in solid-organ transplantation, comparing MMF and EC-MPS, are reviewed. Disappointingly, EC-MPS was similar to MMF in efficacy and safety and did not significantly improve the GI side effects. Moreover, bioequivalence dosing has only been established with concomitant ciclosporin. The pharmacokinetic characteristics must be studied in greater detail. EC-MPS is a safe and effective immunosuppressive agent approved for use in the prevention of acute rejection after renal transplantation. However, the anticipated improvement of GI side effects has not been forthcoming.
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- 2007
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43. How to Measure Renal Function in Children - What is the Role of Cystatin C?
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Filler, Guido
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Assessment of renal function is important. The gold-standard marker is glomerular filtration rate (GFR) measured by inulin clearance normalized to a standard body surface area of 1.73 m2. Inulin, no longer available in North America, has been replaced by nuclear medicine tests such as 51Cr EDTA, 99mTc DTPA and iothalamate clearances. The use of serum creatinine as a surrogate endogenous marker is hampered by height, gender and muscle mass variability,substantial tubular secretion in advanced renal failure and non-standardized measurements. The limitations of creatinine can be reduced when applying height/creatinine ratios with gender and age-dependent constants that have to be established for each center. The small molecular weight protein cystatin CysC shows a significantly better diagnostic performance for the detection of impaired GFR than serum creatinine. It also does not undergo tubular secretion in chronic renal failure, nor does it show significant non-renal elimination. Its concentration falls in the first year of life with the rise of GFR and remains constant thereafter until 60 years of age in both sexes. GFR can be estimated reliably with a recently published formula without the need for any additional anthropological data. CysC allows for reliable estimation of GFR in children.
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- 2006
44. Adding Sirolimus to Tacrolimus-Based Immunosuppression in Pediatric Renal Transplant Recipients Reduces Tacrolimus Exposure
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Filler, Guido, Womiloju, Taiwo, Feber, Janusz, Lepage, Nathalie, and Christians, Uwe
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In adult renal recipients, coadministration of tacrolimus (TAC) and sirolimus (SIR) results in reduced exposure to TAC at SIR doses of 2 mg/day. Eight pediatric renal recipients (median age at transplant 2.0 years, range: 1.2–12.9 years) were converted to TAC- and SIR-based immunosuppression as a rescue therapy. All patients had biopsy-proven chronic allograft nephropathy. TAC levels were measured using a commercially available EMIT assay and SIR levels with a newly developed assay based on the LC-MS MS technology. SIR was started at 0.13 ± 0.05 mg/kg/day (3.51 ± 1.26 mg/m2/day) in two divided doses. TAC was given at 0.14 ± 0.09 mg/kg/day, resulting in a trough level of 6.3 ± 2.5 ng/mL. After the addition of SIR, the median dose required to keep TAC blood trough concentrations within the target range increased by 71.2% (range: 21.9–245.4%), dose-normalized TAC exposure (AUC) decreased to 67.1% and the dose-normalized Cmax, a surrogate for absorption rate, to 53.8% (both geometric means) while terminal half-life (t1/2), a pharmacokinetic parameter characterizing systemic elimination, remained unchanged (p < 0.93). Adding SIR to TAC-based immunosuppression in young pediatric renal transplant recipients results in a significant decrease of TAC exposure. TAC trough levels should be monitored frequently.
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- 2005
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45. Adding Sirolimus to Tacrolimus‐Based Immunosuppression in Pediatric Renal Transplant Recipients Reduces Tacrolimus Exposure
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Filler, Guido, Womiloju, Taiwo, Feber, Janusz, Lepage, Nathalie, and Christians, Uwe
- Abstract
In adult renal recipients, coadministration of tacrolimus (TAC) and sirolimus (SIR) results in reduced exposure to TAC at SIR doses of 2 mg/day. Eight pediatric renal recipients (median age at transplant 2.0 years, range: 1.2–12.9 years) were converted to TAC‐ and SIR‐based immunosuppression as a rescue therapy. All patients had biopsy‐proven chronic allograft nephropathy. TAC levels were measured using a commercially available EMIT assay and SIR levels with a newly developed assay based on the LC‐MS MS technology. SIR was started at 0.13 ± 0.05 mg/kg/day (3.51 ± 1.26 mg/m2/day) in two divided doses. TAC was given at 0.14 ± 0.09 mg/kg/day, resulting in a trough level of 6.3 ± 2.5 ng/mL. After the addition of SIR, the median dose required to keep TAC blood trough concentrations within the target range increased by 71.2% (range: 21.9–245.4%), dose‐normalized TAC exposure (AUC) decreased to 67.1% and the dose‐normalized Cmax, a surrogate for absorption rate, to 53.8% (both geometric means) while terminal half‐life (t1/2), a pharmacokinetic parameter characterizing systemic elimination, remained unchanged (p < 0.93). Adding SIR to TAC‐based immunosuppression in young pediatric renal transplant recipients results in a significant decrease of TAC exposure. TAC trough levels should be monitored frequently.
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- 2005
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46. Plasma Exchange Using a Continuous Venovenous Hemofiltration Machine in Children
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Ciechanska, Ewa EC, Segal, Lauren LS, Wong, Hubert HW, Chretien, Christine CC, Feber, Janusz JF, and Filler, Guido GF
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AbstractBackground: There is considerable interest in using continuous venovenous hemofiltration machines for plasma exchange therapy in children. Methods: Retrospective study of 7 patients and 61 plasma exchange treatments using the Baxter/Edwards Lifesciences BM25 machine with commercially available plasma filters (mostly Asahi Plasmaflo). Results: The average total exchange volume was 1.5 times the plasma volume, achieved at a blood flow rate of 100 ml/m2 (3.5 ml/kg/min) and a turnover rate of 25 ml/kg/h over a 3-hour duration. Fifty-six percent of the time, a mean heparin bolus of 29 units/kg resulted in subtherapeutic activated clotting times. Mean heparin infusion rates of 35 units of heparin/kg/h achieved effective anticoagulation. A calcium infusion rate of 0.11 ± 0.05 mmol/kg/h avoided hypocalcemia. One patient experienced the serious complication of membrane reaction. Conclusions: This setup provides a safe approach to plasma exchange in children. A similar method could be implemented in other centers.Copyright © 2005 S. Karger AG, Basel
- Published
- 2005
47. Patients with autosomal dominant polycystic kidney disease hyperfiltrate early in their disease
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Wong, Hubert, Vivian, Laura, Weiler, Gabrielle, and Filler, Guido
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Background:Autosomal dominant polycystic kidney disease (ADPKD) ranks among the most common genetic disorders. The development of end-stage renal failure usually is after the fourth decade of life. Angiotensin-converting enzyme (ACE) inhibitors often are used as agents to slow the progression of renal failure, although their effectiveness and starting point in ADPKD remain unclear. Methods:We measured technetium 99m diethylenetriamine pentaacetic acid glomerular filtration rate (GFR) and serum cystatin C (Cys-C) levels in 18 children with ADPKD and 41 control patients. Data are given as mean ± SD. Mean age was 9.8 ± 5.9 years, mean height was 137.5 ± 34.3 cm, and mean weight was 39.2 ± 22.8 kg in the ADPKD group, not significantly different from controls, with an average age of 10.4 ± 4.9 years, height of 138.0 ± 26.1 cm, and weight of 38.0 ± 16.8 kg. Results:Mean serum creatinine levels did not differ between the ADPKD (0.6 ± 0.2 mg/dL [51.1 ± 20.4 μmol/L]) and control groups (0.7 ± 0.2 mg/dL [59.8 ± 15.3 μmol/L]; P= 0.19). Mean GFR was 142 ± 33.2 mL/min/1.73 m2in the ADPKD group, significantly greater than that in controls (110 ± 12 mL/min/1.73 m2; P< 0.0001). Mean Cys-C level for the ADPKD group was 0.71 ± 0.11 mg/L, significantly lower than that of controls (0.81 ± 0.12 mg/L; P= 0.0011). No patient with ADPKD had hypertension, and only 1 patient had minimal microalbuminuria. Although renal length on ultrasound was significantly increased, there was no correlation between renal length and GFR or number of cysts. Conclusion:Therefore, the high GFR measurements represent early hyperfiltration in children and adolescents with ADPKD, which may give a rationale to start ACE inhibitor therapy.
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- 2004
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48. Is there really an increase in non-minimal change nephrotic syndrome in children?
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Filler, Guido, Young, Elizabeth, Geier, Pavel, Carpenter, Blair, Drukker, Alfred, and Feber, Janusz
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Background:Reports on the worldwide increase in focal segmental glomerulosclerosis (FSGS) in childhood may have been hampered by referral bias. A true increase in FSGS possibly could alter the current practice of withholding renal biopsy in childhood nephrotic syndrome (NS) unless the patient fails to respond to a 28-day course of corticosteroid therapy. Methods:With these questions in mind, we analyzed a 17-year database covering a 275,000-child population with mandatory referral. The incidence of NS per 100,000 childhood population per year was calculated, charts of 159 patients with NS seen between 1985 and 2002 were reviewed, and a receiver operating characteristic (ROC) plot analysis was performed to analyze the diagnostic performance of remission time. Results:Results show that 115 of 159 patients had minimal change NS, diagnosed either on the basis of corticosteroid response (n = 89), verified by renal biopsy (n = 14), or with minimal change plus mesangial immunoglobulin M on histological examination (n = 12). The remaining 44 patients underwent a renal biopsy showing FSGS (n = 29; 18.2%), diffuse mesangial hypercellularity (n = 8; 5%), membranoproliferative glomerulonephritis (n = 1; 0.6%), membranous nephropathy (n = 3; 1.9%), or other diagnoses (n = 3). The incidence of FSGS increased significantly (P= 0.0253) from 0.37 to 0.94/100,000-child population/y in the two 8½-year intervals of our study. ROC plot analysis confirmed diagnostic sensitivity and specificity greater than 80% for remission time between 21 and 28 days of therapy. Conclusion:We confirm the increasing incidence of FSGS in children with idiopathic NS in a well-defined catchment area and, at the same time, find no reason to change the initial therapy and current indications to perform renal biopsy in childhood NS.
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- 2003
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49. One hundred percent patient and kidney allograft survival with simultaneous liver and kidney transplantation in infants with primary hyperoxaluria a single-center experience1
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Millan, Maria T., Berquist, William E., So, Sam K., Sarwal, Minnie M., Wayman, Karen I., Cox, Kenneth L., Filler, Guido, Salvatierra, Oscar, and Esquivel, Carlos O.
- Abstract
Combined liver-kidney transplantation is the definitive treatment for end-stage renal disease caused by primary hyperoxaluria type I (PH1). The infantile form is characterized by renal failure early in life, advanced systemic oxalosis, and a formidable mortality rate. Although others have reported on overall results of transplantation for PH1 covering a wide age spectrum, none has specifically addressed the high-risk infantile form of the disease.
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- 2003
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50. Treatment of nephrotic syndrome in children and controlled trials
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Filler, Guido
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Aim. To determine the sequential therapy of childhood nephrotic syndrome (NS) with presumed minimal change nephropathy using the evidence from clinical trials.Methods. Meta-analysis of 22 randomized controlled trials was performed, using frequency of relapse and side effects of therapeutic regimes.Results. A meta-analysis of seven trials comparing duration of therapy for initial onset showed that duration of at least 3 months significantly reduced the risk of relapse at 12-24 months (relative risk 0.73; 95% confidence interval 0.60-0.89) without an increase in adverse events. Five trials were performed for steroid treatment of relapse. Deflazacort reduced relapses during therapy, but is not generally available. No difference was observed when comparing single and divided dosing of prednisone. Frequency of relapses could not be influenced by duration of relapse therapy. Alternate day therapy was more effective than intermittent use of prednisone. Two studies out of five on cyclophosphamide or chlorambucil showed consistently that alkylating agents should be used before cyclosporine as alternative therapy to steroids.Conclusions. Children with initial onset of NS should be treated with prednisone at a dose of 60 mg/m2/day for 6 weeks, followed by a dose of 40 mg/m2/48 h for at least another 6 weeks. If steroid toxicity for treatment of relapsing NS requires alternative treatment, cyclophosphamide (2 mg/kg/day for at least 8 weeks) remains the drug of choice with a curative potential. If children still relapse after alkylating agents, levamisole may serve as an alternative only for frequent relapsing NS, whereas steroid-dependent NS should be treated with cyclosporine.
- Published
- 2003
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