180 results on '"Filler, Guido"'
Search Results
2. A step forward for estimating GFR in young adults.
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Filler, Guido and Medeiros, Mara
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YOUNG adults , *BODY surface area , *CYSTATIN C , *CHILD patients , *BLOOD proteins - Abstract
A study published in the Clinical Kidney Journal examined different formulae for estimating glomerular filtration rate (GFR) in young adults. The study found that the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula performed worse than the Lund-Malmö Revised (LMR) and European Kidney Function Consortium (EKFC) equations. The EKFC formula was recommended as a more accurate option for estimating GFR in young adults. However, further research is needed to develop precise and reliable methods for estimating GFR, including the use of additional biomarkers and the consideration of factors such as body weight and age. [Extracted from the article]
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- 2024
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3. Should We Switch to the U25 Creatinine and CysC eGFR to Monitor Pediatric Kidney Transplant Recipients?
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Filler, Guido and Emile, Dougenie
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KIDNEY transplantation , *EPIDERMAL growth factor receptors , *CREATININE , *GLOMERULAR filtration rate , *YOUNG adults - Abstract
The article discusses the use of different formulas to estimate glomerular filtration rate (GFR) in pediatric kidney transplant recipients. The authors compare various formulas based on cystatin C and creatinine with measured GFR in a pediatric cohort. They find that the U25 CKiD formula provides the most accurate estimation of GFR in this population. However, the availability of cystatin C is limited globally. The authors suggest that further research and collaboration are needed to improve the estimation of GFR in pediatric patients. [Extracted from the article]
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- 2024
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4. 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.
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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]
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- 2024
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5. Should urinary CXCL10/creatinine be measured for kidney transplantation?
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Filler, Guido and Sharma, Ajay P.
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KIDNEY transplantation , *BK virus , *INSULIN-like growth factor-binding proteins , *DISEASE risk factors - Abstract
A study published in the journal Pediatric Transplantation explores the use of urinary CXCL10/creatinine ratio as a biomarker for kidney transplantation. The study analyzed urine samples from 72 pediatric kidney transplant recipients and found that urinary CXCL10/creatinine ratio was significantly higher in samples with allograft rejection compared to those without rejection. However, the authors note that further research is needed before this biomarker can be implemented in clinical practice. The study highlights the importance of identifying and validating new biomarkers for kidney allograft function. [Extracted from the article]
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- 2024
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6. 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]
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- 2023
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7. 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.
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- 2023
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8. 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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9. 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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10. 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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11. Histopathological Changes of Long-Term Peritoneal Dialysis Using Physiological Solutions: A Case Report and Review of the Literature.
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Filler, Guido, Haig, Aaron, Merritt, Neil, Alvarez-Elias, Ana Catalina, Teoh, Chia Wei, Filler, Timm Joachim, and Díaz-González de Ferris, Maria Esther
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FOCAL segmental glomerulosclerosis , *PERITONEAL dialysis , *LITERATURE reviews , *HISTOPATHOLOGY , *KLEBSIELLA oxytoca , *CATHETERIZATION - Abstract
Background: Long-term peritoneal dialysis (PD), especially with nonphysiological solutions, is afflicted with the severe complication of encapsulating peritoneal sclerosis (EPS). Physiologic PD solutions have been introduced to reduce pH trauma. Data on peritoneal biopsies in pediatrics with long-term PD using physiological solutions are scant. Case Report: We report an adolescent who had been on 10-h continuous hourly cycles using mostly 2.27% Physioneal™ for 5 years. There were two episodes of peritonitis in October 2017 (Klebsiella oxytoca) and May 2018 (Klebsiella pneumoniae), which were treated promptly. This adolescent, who lost two kidney transplants from recurrent focal and segmental glomerulosclerosis, underwent a peritoneal membrane biopsy at the time of a third PD catheter placement, 16 months after the second renal transplant. Laparoscopically, the peritoneum appeared grossly normal, but fibrosis and abundant hemosiderin deposition were noted on histology. The thickness of the peritoneum was 200–900 (mean 680) µm; normal for age of 14 years is 297 [IQR 229, 384] μm. The peritoneum biopsy did not show specific EPS findings, as the mesothelial cells were intact, and there was a lack of fibrin exudation, neo-membrane, fibroblast proliferation, infiltration, or calcification. Conclusions: While the biopsy was reassuring with respect to the absence of EPS, significant histopathological changes suggest that avoiding pH trauma may not ameliorate the effects of glucose exposure in long-term PD. [ABSTRACT FROM AUTHOR]
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- 2022
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12. The ongoing need to improve long‐term patient survival of pediatric solid organ recipients.
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Filler, Guido, Sharma, Ajay Parkesh, and Díaz González de Ferris, Maria E.
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FOCAL segmental glomerulosclerosis , *HEART failure , *CHILD patients , *OVERALL survival , *HEALTH facilities , *DISEASE risk factors - Abstract
Use of sodium-glucose co-transporter 2 inhibitors in solid organ transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus: a systematic review. The ongoing need to improve long-term patient survival of pediatric solid organ recipients Abbreviations CNS congenital nephrotic syndrome MRI magnetic resonance imaging PTLD post-transplant lymphoproliferative disease SGLT2i sodium-glucose cotransporter 2 inhibitors SOT Solid organ transplantation INTRODUCTION Solid organ transplantation (SOT) is the therapy of choice for end-stage organ disease in children and adolescents. Salonen et al.[6] reported survival of all pediatric SOT recipients (kidney, liver and heart) in Finland. [Extracted from the article]
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- 2023
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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]
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- 2021
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14. Impaired kidney function >90 days determines long‐term kidney outcomes.
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Filler, Guido and Sharma, Ajay P.
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KIDNEY diseases , *KIDNEY physiology , *KIDNEYS , *DIABETIC nephropathies , *CHRONIC kidney failure - Abstract
Acute kidney disease predicts chronic kidney disease in pediatric non-kidney solid organ transplant patients. Impaired kidney function >90 days determines long-term kidney outcomes Keywords: acute kidney disease; acute kidney injury; children; transplantation EN acute kidney disease acute kidney injury children transplantation 1 3 3 08/16/22 20220901 NES 220901 Abbreviations AKD acute kidney disease AKI acute kidney injury CKD chronic kidney disease ESKD end-stage chronic kidney disease GFR glomerular filtration rate IDMS isotope-dilution mass spectrometry RAAS renin-angiotensin-aldosterone system INTRODUCTION Some organs of the human body have evolved to a degree that organoids, the functioning units of more complex organs, can only develop until a certain time in the development. Footnotes 1 Editorial for "Acute Kidney Disease Predicts Chronic Kidney Disease in Pediatric Non-Kidney Solid Organ Transplant Patients" by Mital Patel et al. [Extracted from the article]
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- 2022
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15. Marginal parent donors—Process and ethics.
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Filler, Guido, Ferris, Maria E. Diaz‐Gonzalez, and Elliott, Launa
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CHRONIC kidney failure , *PEDIATRIC nephrology , *MEDICAL personnel , *KIDNEY transplantation , *PATIENTS' rights , *MEDICAL ethics laws - Abstract
Background: Pre‐emptive kidney transplantation for end‐stage kidney disease in children has many advantages and may lead to the consideration of marginal parent donors. Methods: Using the example of the transplant of a kidney with medullary sponge disease from a parent to the child, we review the ethical framework for working up such donors. Results: The four principles of health ethics include autonomy (the right of the patient to retain control over his/her own body); beneficence (healthcare providers must do all they can do to benefit the patient in each situation); non‐maleficence ("first do no harm"—providers must consider whether other people or society could be harmed by a decision made, even if it is made for the benefit of an individual patient) and justice (there should be an element of fairness in all medical decisions). Highly motivated donors may derive significant psychological benefit from their donation and may thus be willing to incur more risk. The transplantation team and, ideally, an independent donor advocate team must make a judgment about the acceptability of the risk‐benefit ratio for particular potential donors, who must also make their own assessment. The transplantation team and donor advocate team must be comfortable with the risk‐benefit ratio before proceeding. Conclusions: An independent donor advocacy team that focuses on the donor needs is needed with sufficient multidisciplinary ethical, social, and psychological expertise. The decision to accept or reject the donor should be within the authority of the independent donor advocacy team and not the providers or the donor. [ABSTRACT FROM AUTHOR]
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- 2021
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16. How should we assess renal function in neonates and infants?
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Filler, Guido, Bhayana, Vipin, Schott, Clara, and Díaz‐González de Ferris, Maria E.
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KIDNEY physiology , *NEWBORN infants , *AGE , *INFANTS , *EPIDERMAL growth factor receptors - Abstract
Aim: Review of current knowledge on assessing renal function in term and preterm neonates. Methods: Literature review and analysis of own data. Results: Prematurity, genetic, environmental and maternal factors may alter peak nephron endowment and life‐long renal function. Nephrogenesis continues until 34‐36 weeks of gestation, but it is altered with premature delivery. Variability of nephron endowment has a substantial impact on the clearance of renally excreted drugs. Postnatally, glomerular function rate (GFR) increases daily, doubles by two weeks, and slowly reaches full maturity at 18 months of age. Ideally, renal function biomarkers should be expressed as age‐independent z‐scores, and evidence suggests indexing these values to post‐conceptual age rather than chronological age. Newborn and maternal serum creatinine correlate tightly for more than 72 hours after delivery, rendering this biomarker unsuitable for the assessment of neonatal renal function. Cystatin C does not cross the placenta and may be the preferred biomarker in the neonate. Here, we provide preliminary data on the natural evolution of the cystatin C eGFR in infancy. Conclusion: Cystatin C may be superior for GFR estimation in neonates, but the best approach to drug dosing of renally excreted drugs remains to be established. [ABSTRACT FROM AUTHOR]
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- 2021
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17. Lower prevalence of aortic dilatation among preemptive pediatric renal transplant recipients – A cross‐sectional cohort study.
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Surak, Aimann, Filler, Guido, Sharma, Ajay Parkash, Torres Canchala, Laura Alejandra, and Grattan, Michael
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KIDNEY transplantation , *AMBULATORY blood pressure monitoring , *AORTIC rupture , *CHRONIC kidney failure , *CROSS-sectional method - Abstract
Background: Aortic dilatation is a cardiovascular complication in pediatric renal transplant recipients and may have an increased risk of aortic dissection, aortic rupture, and death. Studies failed to show an association between blood pressure and aortic dilatation; however, 24‐hours ambulatory blood pressure monitoring (ABPM) was not performed. There was also no comparison between preemptive transplantation and dialysis. Methods: After ethics approval, a retrospective cross‐sectional study was performed on all prevalent pediatric renal transplant recipients from a single tertiary care center. The presence of aortic dilatation was determined using standard echocardiographic measurements, and those with other risk factors for aortic dilatation were excluded. Associations between 24‐hours ABPM, renal function, dialysis history, and aortic dimensions were determined. Results: We enrolled 37 participants with the following characteristics: 46% female, mean age 14.5 ± 3.7 years, 16% preemptive transplantation, and median end‐stage renal disease (ESRD) combined vintage (time from ESRD onset to echocardiogram) 597 days (range 289‐1290 days). We found 16/37 patients (43%) with aortic dilatation at any level, mostly mild. There was no association between 24‐hours ABPM measurements and aortic dilatation. None of the preemptively transplanted children had aortic dilatation. Conclusion: This study confirms a high prevalence of aortic dilatation among pediatric renal transplant recipients, which appears to be independent of hypertension on 24‐hour ABPM. Patients with preemptive renal transplantation did not have aortic dilatation, suggesting that the effects of dialysis may contribute to the high prevalence of this complication. Pediatric cardiologists need to carefully assess aortic dimensions in these at‐risk patients. [ABSTRACT FROM AUTHOR]
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- 2020
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18. Correction to: Does specialist physician supply affect pediatric asthma health outcomes?
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Filler, Guido, Kovesi, Tom, Bourdon, Erik, Jones, Sarah Ann, Givelichian, Laurentiu, Rockman-Greenberg, Cheryl, Gilliland, Jason, Williams, Marion, Orrbine, Elaine, and Piedboeuf, Bruno
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In the original publication of this article [1], the institutional author's name needs to be revised from The Paediatric Chairs of Canada Mark Bernstein to The Paediatric Chairs of Canada. [ABSTRACT FROM AUTHOR]
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- 2019
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19. 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]
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- 2018
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20. 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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21. Chronic kidney disease stage affects small, dense low-density lipoprotein but not glycated low-density lipoprotein in younger chronic kidney disease patients: a cross-sectional study.
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Filler, Guido, Taheri, Sepideh, McIntyre, Christopher, Smith, Connor, Subramanian, Lakshmimathy, Fusch, Gerhard, and Fusch, Christoph
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Background Small, dense low-density lipoprotein (sd-LDL) and glycated LDL (g-LDL) have been associated with cardiovascular disease (CVD) in chronic kidney disease (CKD) in patients >60 years of age. Since young adult and paediatric patients have shorter exposure to Framingham-type risk factors, our study aims to determine whether younger CKD patients exhibit the same sd-LDL and g-LDL pattern. Methods After ethics board approval, this cross-sectional study was conducted at two universities with 44 patients (mean ± standard deviation age 12.6 ± 4.9, range 2–24 years) with CKD stage of 1–5. Laboratory parameters studied were Cystatin C (CysC), CysC estimated glomerular filtration rate (eGFR) (calculated from the Filler formula), sd-LDL, g-LDL and albumin. Lipid samples were measured for sd-LDL and g-LDL using ELISA. Non-linear correlation analysis was performed to determine the relationship between g-LDL, sd-LDL and eGFR. Clinical Trials Registration is at clinicaltrials.gov, NCT02126293, https://clinicaltrials.gov/ct2/show/NCT02126293. Results Triglycerides, but not total cholesterol and calculated LDL, were associated with CKD stages (ANOVA P = 0.0091). As in adults, sd-LDL was significantly associated with CKD stages (ANOVA P = 0.0133), CysC eGFR (r = −0.6495, P < 0.00001), and body mass index (r = −0.3895, P = 0.0189), but not with age. By contrast, there was no significant correlation between g-LDL and CKD stages or CysC eGFR (P = 0.9678). Conclusions Our study demonstrates that only triglycerides and sd-LDL were associated with CKD stages in this young cohort without confounding Framingham-type CVD risk factors. While larger studies are needed, this study suggests that lowering sd-LDL levels may be a potential target to ameliorate the long-term CVD risks in paediatric CKD patients. [ABSTRACT FROM AUTHOR]
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- 2018
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22. The importance of cardiovascular disease in pediatric transplantation and its link to the kidneys.
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Johnson, Jonathan N. and Filler, Guido
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CARDIOVASCULAR diseases , *TRANSPLANTATION of organs, tissues, etc. , *HEART diseases , *KIDNEYS , *MORTALITY - Abstract
Abstract: Cardiovascular disease is a frequent cause of morbidity and mortality in pediatric patients following solid organ transplant. CKD is also common in pediatric patients after a solid organ transplant, and the link between CKD and cardiovascular morbidity is strong. In this review, we examine potential etiologies to explain the risk of cardiovascular morbidity and mortality in pediatric solid organ recipients and identify targets for improving outcomes. [ABSTRACT FROM AUTHOR]
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- 2018
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23. Is there a case for early treatment with IVIG for BK transplant nephropathy?
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Kirpalani, Arjun Amrit, Filler, Guido, and Teoh, Chia Wei
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BK virus , *INTRAVENOUS immunoglobulins , *KIDNEY diseases , *TRANSPLANTATION of organs, tissues, etc. - Abstract
Keywords: immunosuppression; IVIG; pediatric kidney transplantation; Polyoma BK virus EN immunosuppression IVIG pediatric kidney transplantation Polyoma BK virus 1 2 2 05/11/22 20220601 NES 220601 Abbreviations BKV BK virus BKVN BK virus nephropathy CNI calcineurin inhibitor IVIG intravenous immunoglobulin MMF mycophenolate mofetil PCR polymerase chain reaction qPCR quantitative polymerase chain reaction INTRODUCTION De novo BKV nephropathy after kidney transplantation is a significant cause of graft dysfunction and loss in pediatrics. At 12 months after starting therapy, only 35% had resolved the BK, while this number rose to 85% after 18 months, yet 30% of patients had persistent viremia.1 These findings suggest that in some patients, persistent BK viremia may persist for a considerable time. [Extracted from the article]
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- 2022
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24. 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]
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- 2017
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25. Practice recommendations for the monitoring of renal function in pediatric non-renal organ transplant recipients.
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Filler, Guido, Melk, Anette, and Marks, Stephen D.
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KIDNEY transplantation , *IMMUNOSUPPRESSION , *CHILD care , *CHILDREN'S health , *BLOOD pressure measurement - Abstract
The management of non-renal pediatric solid organ transplant recipients has become complex over the last decade with innovations in immunosuppression and surgical techniques. Post-transplantation follow-up is essential to ensure that children have functioning allografts for as long as possible. CKD is highly prevalent in these patients, often under recognized, and has a profound impact on patient survival. These practice recommendations focus on the early detection and management of hypertension, proteinuria, and renal dysfunction in non-renal pediatric solid organ transplant recipients. We present seven practice recommendations. Renal function should be monitored regularly in organ transplant recipients, utilizing assessment of serum creatinine and cystatin C. GFR should be calculated using the new Schwartz formula. Transplant physicians should also monitor blood pressure using automated oscillometric devices and confirm repeated abnormal measures with manual blood pressure readings and ambulatory 24-h blood pressure monitoring. Proteinuria and microalbuminuria should also be assessed regularly. Referrals to a pediatric nephrologist should be made for non-renal organ transplant recipients with repeated blood pressures >95th percentile using the Fourth Task Force reference intervals, microalbumin/creatinine ratio >32.5 mg/g (3.7 mg/mmol) creatinine on repeated testing and/or GFR <90 mL/min/1.73 m2. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
26. 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
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27. Minimum mycophenolic acid levels are associated with donor-specific antibody formation.
- Author
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Filler, Guido, Todorova, Ekaterina Kirilova, Bax, Kevin, Alvarez‐Elías, Ana Catalina, Huang, Shih‐Han Susan, and Kobrzynski, Marta Caroline
- Subjects
- *
TISSUE-specific antibodies , *MYCOPHENOLIC acid , *IMMUNOGLOBULINS , *KIDNEY transplantation , *TRANSPLANTATION of organs, tissues, etc. in children - Abstract
Although de novo DSA are associated with inferior graft survival, there are no effective strategies to prevent their formation. Underexposure to MPA (prodrug: MMF) also contributes to rejection rates early after transplantation, but the effect of this phenomenon on the formation of DSA long-term post-transplantation is unknown. Data are expressed as mean (standard deviation). All available data from 32 renal transplant recipients (age at transplantation 7.5 [4.5] yr) on tacrolimus and MPA immunosuppression with an average follow-up of 9.4 (s.d. 4.6) yr were analyzed. DSA were measured using the Luminex assay (>500 MFI was considered DSA-positive). Tacrolimus and MPA levels were measured with the Abbot Tacro II and EMIT assay, respectively. Among 1964 MPA and 3462 tacrolimus trough levels, the average MPA trough level was 3.2 (1.5) mg/L and the average tacrolimus level was 6.7 (2.8) ng/mL. At last follow-up, only 5/32 patients had undetectable DSA, with 5/32 having no class I antibodies and 6/32 having no class II antibodies. DSA formation was associated with a lower minimum MPA trough level (0.27 [0.23] vs. 0.47 [0.18] mg) and cystatin C eGFR (48 [21] vs. 70 [23] mL/min/1.73 m2) for class I DSA formers. The average eGFR of patients without class I DSA was 70 (23) mL/min/1.73 m2, whereas the average eGFR of patients with class I DSA was 48 (21) mL/min/1.73 m2 (p = 0.0071). MPA trough levels <1.3 mg/L long-term post-transplantation are associated with the formation of DSA. The association between the formation of DSA and minimum MPA exposure may support a strategy for preventing the formation of DSA. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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- View/download PDF
28. The urgent need for more research on how to treat recurrent focal and segmental glomerulosclerosis.
- Author
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Filler, Guido and Restrepo, Jaime M.
- Subjects
- *
FOCAL segmental glomerulosclerosis , *KIDNEY transplantation - Abstract
An introduction is presented in which the editor discusses an article in the issue reporting a 25-year study period for treatment of recurrent focal and segmental glomerulosclerosis from the Australian and New Zealand Dialysis and Transplant Registry.
- Published
- 2018
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29. Is there a case for eculizumab for pediatric renal transplantation?
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Filler, Guido, Huang, Shih‐Han Susan, and Licht, Christoph
- Subjects
- *
REPERFUSION injury , *HOMOGRAFTS , *GRAFT rejection , *ECULIZUMAB , *KIDNEY glomerulus , *WOUNDS & injuries - Abstract
The article talks about reperfusion injury (RI) that has multiple effects on a transplanted allograft, including delayed or impaired graft function, compromised long-term survival, and increased incidence of rejection. Eculizumab, a monoclonal antibody blocking terminal complement activation, has been postulated to be an effective agent in the prevention of RI. Eculizumab-treated patients had a significantly better early graft function, less arteriolar hyalinosis and chronic glomerulopathy.
- Published
- 2018
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30. We have to do more for former paediatric renal transplant recipients!
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Filler, Guido and Diaz‐Gonzalez de Ferris, Maria
- Subjects
- *
KIDNEY transplantation , *CHRONIC kidney failure , *QUALITY of life , *LYMPHOBLASTIC leukemia , *PEDIATRIC nephrology - Abstract
The article offers information on studies related to renal transplantation which is a therapy used for end stage kidney disease (ESKD) in children and adolescents. It mentions need for enhancing social rehabilitation and health-related quality of life (HRQOL) of paediatric renal transplant recipients. It states that public awareness campaign is required to help raise funds for research aimed at rehabilitation of children and adolescents with ESKD and acute lymphoblastic leukemia (ALL).
- Published
- 2018
- Full Text
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31. A step forward towards accurately assessing glomerular filtration rate in newborns.
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Filler, Guido
- Subjects
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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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32. Euvolemia in Hemodialysis Patients: A Potentially Dangerous Goal?
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Huang, Shih‐Han S., Filler, Guido, Lindsay, Robert, and McIntyre, Chris W.
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KIDNEY disease treatments , *HEMODIALYSIS patients , *BLOOD filtration , *CARDIOVASCULAR diseases , *HEMODIALYSIS , *THERAPEUTICS - Abstract
Dialysis patients have high mortality rate and the leading cause of death is cardiovascular disease. Uremic cardiomyopathy differs from that due to conventional atherosclerosis, where cardiovascular changes result in ineffective circulation and lead to tissue ischemia. Modern dialysis has significant limitations with fluid management probably the most challenging. Current evidence suggests that both volume overload and aggressive fluid removal can induce circulatory stress and multi-organ injury. Furthermore, we do not have accurate volume assessment tools. As a result, targeting euvolemia might result in more harm than benefit with conventional hemodialysis therapy. Therefore, it might be time to consider a degree of permissive over-hydration until we have better tools to both determine ideal weight and improve current renal replacement therapy so that the process of achieving it is not so fraught with the current dangers. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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33. Tandem hemodialysis and plasma exchange.
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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
- Full Text
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34. Spot urine protein to creatinine ratio.
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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
35. Improving long-term outcomes after pediatric renal transplantation by addressing dyslipidemia.
- Author
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Filler, Guido and Medeiros, Mara
- Subjects
- *
KIDNEY transplantation , *DYSLIPIDEMIA , *BLOOD lipoprotein metabolism disorders , *KIDNEY diseases , *PEDIATRICS - Abstract
The article presents the author's views on the improvement of the long-term outcomes after pediatric kidney transplantation which addresses dyslipidemia. Topics mention including the association of cardiovascular morbidity with chronic kidney diseases (CKD), disordered lipids and elevated levels of cholesterol and triglyceride.
- Published
- 2017
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36. 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
- Full Text
- View/download PDF
37. Beta-trace protein as a marker of GFR — History, indications, and future research.
- Author
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Filler, Guido, Kusserow, Carola, Lopes, Laudelino, and Kobrzyński, Marta
- Subjects
- *
BIOMARKERS , *GLOMERULAR filtration rate , *CREATININE , *KIDNEY transplantation , *CARDIOVASCULAR diseases risk factors , *CYSTATINS - Abstract
Objectives Recent findings suggest that beta-trace protein (BTP), a small molecular weight protein, is at least equal if not superior to serum creatinine as a marker of glomerular filtration rate (GFR), particularly since it is independent from height, gender, age, and muscle mass. The authors sought to summarize knowledge on BTP and its use as a marker of GFR using the most recent literature available. Design and methods The authors compiled key articles and all relevant recent literature on this topic. Physical and chemical features of the molecule are described, as well as factors that may affect its expression. The use of BTP in estimating GFR as a whole and in specific patient groups, including pregnant women, neonates and infants, children and adolescents, and patients who have undergone renal transplantation is discussed. The use of BTP as a marker for cardiovascular risk factors is also briefly addressed. Results Although its performance in the general population is marginally inferior to cystatin C, studies have suggested that it may be superior in accurately estimating GFR in select patient groups such as pregnant women and neonates. Conclusions This novel marker shows promise, but further research is required to clarify findings from available data. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
38. 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
- Full Text
- View/download PDF
39. Using individual DSA titers to assess for accommodation after late humoral rejection.
- Author
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Filler, Guido, Grimmer, Joanne, Ball, Edward, Sharma, Ajay P., and Huang, Shih‐Han Susan
- Subjects
- *
GRAFT rejection , *IMMUNOGLOBULINS , *KIDNEY transplantation , *IMMUNOSUPPRESSION , *BIOPSY - Abstract
Management of late humoral rejection remains challenging, and DSA may persist. A case report illustrates how individual DSA titers using solid-phase-based assays may help to assess for accommodation. A male cystinosis patient received a cadaveric renal transplant at the age of 12 yr with a daclizumab, tacrolimus, MMF, and steroids-based immunosuppression. After three acute rejection episodes over the first eight months, interstitial fibrosis/tubular atrophy ( IF/ TA) was diagnosed on biopsy, while the immunosuppression was left unchanged with a high target exposure for both tacrolimus and MPA. One yr later, AMR type III (C4d and DSA positive) was treated with daily plasmapheresis, IVIG 100 mg/kg and pulse steroids 5 mg/kg. DSA ( DR 53, DQ4, and DQ 2) were not responding until the plasma volume was increased to 2.5 plasma volumes. A second rise of creatinine confirmed worse humoral rejection; daily plasma exchange was resumed, and two doses of rituximab (375 mg/m2) were given. Subsequently, all DSA dropped, but only DR53 DSA remained unchanged, whereas the DQ antibodies rebounded to very strong titers. With a follow-up of over 120 days after recovery of the CD19 count, off all additional treatment and on identical immunosuppression with tacrolimus and MMF and prednisone, the patient's creatinine remained stable between 45 and 50 u m while DQ DSA remain strong to very strong. We conclude that the patient is in a state of accommodation. DSA titers should be monitored when managing late humoral rejection. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
40. 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
41. 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
42. Evaluating Canadian children: WHO, NHANES or what?
- Author
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Yasin, Abeer and Filler, Guido
- Subjects
- *
CHILDREN , *DIETITIANS , *HEALTH & Nutrition Examination Survey , *COHORT analysis - Abstract
Aim The 2006 World Health Organization ( WHO) growth charts have been widely adopted by Canadian dieticians for growth monitoring of Canadian children rather than the National Health and Nutrition Examination Survey ( NHANES III) reference data. It has been unclear as to which is the most appropriate. Methods We calculated height and weight z-scores of 3086 consecutive patients (1530 female, 49.6%) aged 0-5 years, attending outpatient clinics at a single tertiary care centre using reference data of the latest NHANES survey and the 2006 WHO growth charts. To address age dependency, data were stratified into age groups. Gender dependency was also investigated. Results Using NHANES III reference intervals, medians of both height z-score (+0.24) and weight z-score (+0.32) were significantly non-zero. The WHO growth charts yielded medians of height z-score (−0.15) and weight z-score (+0.36) respectively, also significantly non-zero. When comparing both reference populations for the entire cohort, Canadian children had significantly different height z-scores whereas weight z-scores did not differ. Age classification revealed a significant age dependency with NHANES III charts yielding higher weight z-scores for up to 8 months and lower z-scores from 8 to 26 months. No significant differences were observed for older than 26 months. Throughout, height z-scores were significantly higher with NHANES III charts across all age groups, with a degree of overestimation higher in younger boys than older ones. Conclusion Our results reveal substantial differences between both reference populations and thus interpretation needs to be done with caution, especially when labelling results as abnormal. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
43. High prevalence of renal dysfunction also after small bowel transplantation.
- Author
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Filler, Guido and Huang, Shih‐Han Susan
- Subjects
- *
KIDNEY diseases , *PEDIATRICS , *CHILDREN'S health ,EDITORIALS - Abstract
The author reflects on the study of Olivia Boyer and colleagues regarding renal abnormalities' prevalence in non-renal transplant recipients among pediatrics. The author states that based on the biopsy findings of the study, chronic kidney disease's etiology is multifactorial. The author says that calcineurin-sparing is not always possible in patients although some of them benefited from it.
- Published
- 2013
- Full Text
- View/download PDF
44. Ω3 fatty acids may reduce hyperlipidemia in pediatric renal transplant recipients.
- Author
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Filler, Guido, Weiglein, Geneva, Gharib, Mireille Tina, and Casier, Shelley
- Subjects
- *
FATTY acids , *HYPERLIPIDEMIA treatment , *DOCOSAHEXAENOIC acid , *EICOSAPENTAENOIC acid , *PEDIATRICS , *LIFE expectancy , *THERAPEUTICS - Abstract
Filler G, Weiglein G, Gharib MT, Casier S. Ω3 fatty acids may reduce hyperlipidemia in pediatric renal transplant recipients. Abstract: Life expectancy after pediatric renal transplantation remains lower than that of the normal population largely due to cardiovascular morbidity and mortality. Hyperlipidemia is a potentially modifiable risk factor for cardiovascular morbidity. Retrospective chart review of all available pediatric renal transplant patients (26) in a single center with assessment of anthropometry, renal function, steroid, calcineurin or mTOR inhibitor exposure and Ω3 FA supplementation. Eighteen transplant recipients without Ω3 FA supplementation served as control. Nutrition and supplement surveys were conducted with standardized questionnaires. Fasting cholesterol values were compared using the latest value prior to start of Ω3 FA and at last follow-up. Eight patients (five receiving mTOR inhibitor) started Ω3 FA supplementation at a mean dose of 29.2 ± 12 mg of EPA/kg and 16.1 ± 7.4 mg DHA/kg body weight. Median duration of treatment was 2.5 yr (range 0.8-5.9 yr) and their total fasting cholesterol at last follow-up dropped significantly from 5.08 ± 0.97 (control group 3.77 ± 0.81, p = 0.0084) to 4.17 ± 0.54 m m (p = 0.0158). High-density lipoprotein cholesterol increased not significantly from 1.74 ± 0.49 to 2.02 ± 0.93 m m. No patient had increased bleeding. Supplementation of omega-3 FAs may reduce hyperlipidaemia after pediatric renal transplantation. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
45. The usefulness of cystatin C and related formulae in pediatrics.
- Author
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Filler, Guido, Huang, Shih-Han S., and Yasin, Abeer
- Subjects
- *
CYSTATINS , *CYSTEINE proteinase inhibitors , *PEDIATRICS , *CHILDREN'S health , *KIDNEY diseases - Abstract
Serum creatinine does not share the properties of an ideal marker of glomerular filtration rate (GFR) like inulin, but continues to be the most widely used endogenous marker of GFR. In the search of a better biomarker of GFR, the small molecular weight protein cystatin C has been introduced with features more similar to that of inulin, such as constant production and no non-renal elimination. However, it has not enjoyed widespread use despite its significantly improved diagnostic performance in the detection of impaired GFR and its independence of body composition. A variety of formulae based on either cystatin C or creatinine or both have been developed to estimate GFR. We summarize the currently used methods of GFR measurement, their limitations and analytical errors. The review also summarizes the history, features and the feasibility of cystatin C measurements as well as the most widely used formulae for the estimation of GFR in children. The diagnostic performance of the cystatin C derived eGFR formulae at various levels of GFR is also discussed. An eGFR formula derived from pooled studies analyzing both creatinine and cystatin C, and using a biology-based mathematical approach may be advantageous. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
46. 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
47. 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
48. Are fibroblast growth factor 23 concentrations in renal transplant patients different from non-transplanted chronic kidney disease patients?
- Author
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Filler, Guido, Liu, Daisy, Sharma, Ajay Parkash, and Grimmer, Joanne
- Subjects
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FIBROBLAST growth factors , *KIDNEY diseases , *KIDNEY transplantation , *METABOLISM , *VITAMIN D - Abstract
Filler G, Liu D, Sharma AP, Grimmer J. Are fibroblast growth factor 23 concentrations in renal transplant patients different from non-transplanted chronic kidney disease patients? Pediatr Transplantation 2012: 16: 73-77. © 2011 John Wiley & Sons A/S. Abstract: To compare the pattern of serum FGF23 levels in pediatric renal transplant recipients and GFR-matched controls. We performed a cross-sectional matched pair study in 19 stable pediatric renal transplant recipients and 19 GFR-matched controls with native CKD. After assessment for normal distribution, demographic and bone metabolism parameters were compared with Student's t-test, Wilcoxon's matched pairs (for non-normal distribution) test, and correlation analysis. The groups were comparable for anthropometric parameters, cystatin C eGFR (71.10 ± 37.28 vs. 76.11 ± 26.80 mL/min/1.73 m2), cystatin C, urea, creatinine, intact PTH, pH, CRP, alkaline phosphatase, phosphate, calcium, ionized calcium, FGF-23 (63.44 [IQR 38.42, 76.29], 49.92 [IQR 42.48, 76.97]), albumin, and urinary calcium/creatinine ratio. The renal transplant patients had significantly lower 25-(OH) vitamin D levels (66.63 ± 17.54 vs. 91.42 ± 29.16 ng/mL), and higher 1,25-(OH)2 vitamin D levels (95.78 ± 34.54 vs. 67.11 ± 35.90 p m). FGF-23 levels correlated negatively with cystatin C eGFR ( r = −0.3571, p = 0.02770) and positively with PTH ( r = 0.5063, p = 0.0026), but not with serum phosphate ( r = 0.2651, p = 0.1077). We conclude that the increase in FGF23 levels with GFR decline in pediatric renal transplant patients remains similar to that in the patients with CKD. The relationship between FGF23 and serum vitamin D needs further evaluation. [ABSTRACT FROM AUTHOR]
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- 2012
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49. Should we consider MMF therapy after rituximab for nephrotic syndrome?
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Filler, Guido, Huang, Shih-Han, and Sharma, Ajay
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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]
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- 2011
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50. Challenges in pediatric transplantation: The impact of chronic kidney disease and cardiovascular risk factors on long-term outcomes and recommended management strategies.
- Author
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Filler, Guido
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TRANSPLANTATION of organs, tissues, etc. in children , *KIDNEY transplantation , *KIDNEY disease risk factors , *CARDIOVASCULAR diseases risk factors , *EVALUATION of medical care , *DISEASE management - Abstract
Filler G. Challenges in pediatric transplantation: The impact of chronic kidney disease and cardiovascular risk factors on long-term outcomes and recommended management strategies. Pediatr Transplantation 2011: 15:25-31. © 2010 John Wiley & Sons A/S. Barriers to successful outcomes following pediatric transplantation have shifted from ischemic reperfusion injury and rejection to more long-term complications. Of particular concern is the high prevalence of CKD owing to preexisting damage and nephrotoxicity, as well as other CV complications such as hypertension and cardiomyopathy. All of these contribute to graft loss and shortened life expectancy, thereby limiting the success story of solid-organ transplantation. Managing CKD and related CV morbidity should be integral to the care of pediatric transplant patients, and timely detection of any irregularities would increase the chances of restoring lost kidney function. GFR is still the widely accepted indicator of renal function, and nuclear medicine techniques are the gold standard measurement methods. These methods are limited by costs, radiation exposure and substrate injection, and current practice still uses the Schwartz estimate, despite its well-documented limitations. Newer endogenous markers of GFR, such as cystatin C clearance, give a more accurate measure of true GFR but have not been embraced in the management of pediatric transplant recipients. Furthermore, indirect markers (e.g., microalbuminuria and hypertension) could also aid early detection of renal damage. The effects of mainstay immunosuppressants on kidney and heart function are varied, with available data indicating favorable outcomes with tacrolimus compared with ciclosporin. There is a need for appropriately designed and powered randomized controlled trials to validate innovative concepts for tailored immunosuppression in the pediatric population. To date, very few studies have generated long-term data in pediatric renal transplant patients - results of 1-4-yr study favored tacrolimus over ciclosporin, but other immunosuppressive agents also need to be evaluated. [ABSTRACT FROM AUTHOR]
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- 2011
- Full Text
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