50 results on '"Filler, Guido"'
Search Results
2. Young Adults With Hereditary Tubular Diseases: Practical Aspects for Adult-Focused Colleagues.
- Author
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Alhasan K, D'Alessandri-Silva C, Mongia A, Topaloglu R, Tasic V, and Filler G
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- Adolescent, Adult, Child, Humans, Young Adult, Acidosis, Renal Tubular diagnosis, Acidosis, Renal Tubular genetics, Acidosis, Renal Tubular therapy, Cystinosis diagnosis, Cystinosis genetics, Cystinosis therapy, Diabetes Insipidus, Nephrogenic, Kidney Diseases diagnosis
- Abstract
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., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)
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- 2022
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3. Nephrological and urological complications of homozygous c.974G>A (p.Arg325Gln) OSGEP mutations.
- Author
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Wang PZT, Prasad C, Rodriguez Cuellar CI, and Filler G
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- Child, Female, Hernia, Hiatal complications, Humans, Kidney Tubules pathology, Microcephaly complications, Nephrosis complications, Point Mutation, Urinary Tract Infections microbiology, Hernia, Hiatal genetics, Kidney Diseases genetics, Metalloendopeptidases genetics, Microcephaly genetics, Nephrosis genetics, Urinary Bladder Diseases genetics, Urinary Tract Infections genetics
- Abstract
Background: Galloway-Mowat syndrome (GAMOS) (OMIM #251300) is a severe autosomal recessive disease characterized by the combination of early-onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies caused by WDR73 as well as OSGEP, TP53RK, TPRKB, or LAGE3 mutations., Objective: We report on the hitherto undescribed urological and nephrological complications of the homozygous c.974G>A (p.Arg325Gln) OSGEP mutations in a 7-year-old Caucasian girl., Case Diagnosis: The patient came to the attention of pediatric nephrology at the age of 3 years and 11 months, when she presented with status epilepticus due to profound hypomagnesemia (0.31 mmol/L, normal 0.65-1.05). A 24-h urine demonstrated a magnesium loss of 0.6 mmol/kg/day with associated proteinuria suggesting renal tubulopathy. Subsequently, she developed recurrent urinary tract infections (UTIs) and was diagnosed with neurogenic bladder dysfunction. The patient continued to have UTIs associated with seizures and sequential cultures growing multi-drug-resistant organisms despite of antibiotic prophylaxis. In addition, the proteinuria (median microalbumin/creatinine ratio 647 mg/mmol) increased, and she developed partial Fanconi syndrome. At age 7, she developed a large bladder calculus (3.3 × 3.2 cm) and three left non-obstructing renal calculi associated with elevated urinary cystine, hypercalciuria, and ongoing hypomagnesemia and required surgical intervention. Glomerular filtration rate (GFR) remained normal and she never developed frank nephrotic syndrome (average albumin 31 g/L)., Conclusions: It is unclear if patients with OSGEP mutations with tubular symptoms rather than nephrotic syndrome should be considered a different entity. Nephrological and urological complications of OSGEP mutations can be challenging and require a multidisciplinary approach.
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- 2018
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4. Estimation of GFR using β-trace protein in children.
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Witzel SH, Huang SH, Braam B, and Filler G
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- Adolescent, Biomarkers blood, Body Height, Body Weight, Child, Child, Preschool, Creatinine blood, Female, Humans, Kidney Diseases blood, Linear Models, Male, Mathematical Concepts, Sex Factors, Technetium Tc 99m Pentetate, Glomerular Filtration Rate, Intramolecular Oxidoreductases blood, Kidney Diseases physiopathology, Lipocalins blood
- Abstract
Background and Objectives: Sex may affect the performance of small molecular weight proteins as markers of GFR because of differences in fat mass between the two sexes. The hypothesis was that the diagnostic performance of β-trace protein, a novel marker of GFR, would be significantly better in boys than in girls., Design, Setting, Participants, & Measurements: GFR, height, weight, serum creatinine, and β-trace protein were measured in 755 children and adolescents (331 girls) undergoing (99)technetium diethylenetriamine penta-acetic acid renal scans from July of 1999 to July of 2006. Boys and girls were separated into formula generation cohorts (284 boys and 220 girls) and formula validation cohorts (140 boys and 111 girls). GFR-estimating formulas on the basis of β-trace protein, creatinine, and height were derived using stepwise linear regression analysis of log-transformed data. The slope of the regression lines of the sex-specific eGFRs were compared. Bland-Altman analysis was used for testing agreement between (99)technetium diethylenetriamine penta-acetic acid GFR and calculated GFR both with this equation in boys and girls as well as previously established Benlamri, White, and Schwartz formulas., Results: In the stepwise regression analysis, β-trace protein (R(2)=0.73 for boys and R(2)=0.65 for girls) was more important than creatinine (which increased R(2) to 0.81 for boys and R(2) to 0.75 for girls) and height (which increased R(2) to 0.88 for boys and R(2) to 0.80 for girls) in the data generation groups. GFR can be calculated using the following formulas:[Formula: see text]and[Formula: see text]Bland-Altman analysis showed better performance in boys than in girls. The new formulas performed significantly better than the previous Benlamri, White, and Schwartz formulas with respect to bias, precision, and accuracy., Conclusions: Improved and sex-specific formulas for the estimation of GFR in children on the basis of β-trace protein, serum creatinine, and height are now available., (Copyright © 2015 by the American Society of Nephrology.)
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- 2015
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5. Native kidney BK virus nephropathy associated with acute lymphocytic leukemia.
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Filler G, Licht C, and Haig A
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- Child, Humans, Kidney pathology, Male, BK Virus, Kidney Diseases etiology, Polyomavirus Infections etiology, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Tumor Virus Infections etiology
- Abstract
Background: Polyoma BK virus nephropathy is a common complication after renal transplantation and is rarely seen in non-renal transplant recipients. There are only a couple of case reports of BK virus nephropathy in native kidneys in non-transplant patients, including a recent report of a 73-year-old patient with chronic lymphatic leukemia. A variety of treatment options, including leflunomide and cidofovir, were reported in these patients., Case Diagnosis/treatment: Here we report the case of a 10-year-old boy with acute lymphatic leukemia who presented with non-oliguric hypertensive acute kidney injury at the 12th maintenance cycle of his chemotherapy. The workup supported the clear diagnosis of BK virus nephropathy with tubulointerstitial changes, and the patient responded favorably to intravenous immunoglobulin therapy., Conclusions: Pediatric nephrologists need to consider BK virus nephropathy as a differential diagnosis of acute kidney injury in immunocompromised non-transplant patients.
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- 2013
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6. The need for ongoing monitoring of adherence to access targets.
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Filler G, Chavannes M, and Yasin A
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- Female, Humans, Male, Appointments and Schedules, Health Services Accessibility statistics & numerical data, Kidney Diseases diagnosis, Referral and Consultation statistics & numerical data, Waiting Lists
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- 2013
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7. Cystatin C for the assessment of GFR in neonates with congenital renal anomalies.
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Filler G, Grimmer J, Huang SH, and Bariciak E
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- Female, Humans, Male, Biomarkers blood, Cystatin C blood, Kidney Diseases diagnosis
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- 2012
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8. High prevalence of hypertension and renal glomerular and tubular dysfunction after orthotopic liver transplantation.
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Filler G and Huang SH
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- Adult, Child, Glomerular Filtration Rate, Humans, Hypertension complications, Hypertension epidemiology, Immunosuppressive Agents therapeutic use, Kidney Diseases complications, Kidney Diseases epidemiology, Kidney Failure, Chronic complications, Kidney Failure, Chronic therapy, Kidney Tubules physiopathology, Liver Failure complications, Longitudinal Studies, Postoperative Complications, Hypertension diagnosis, Kidney Diseases diagnosis, Kidney Glomerulus physiopathology, Liver Failure therapy, Liver Transplantation adverse effects
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- 2012
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9. Monitoring and improving renal outcomes after heart transplantation.
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Filler G and Huang SH
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- Female, Humans, Male, Heart Transplantation methods, Kidney physiopathology, Kidney Diseases etiology, Pediatrics methods
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- 2011
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10. Diagnostic accuracy of cystatin C-based eGFR equations at different GFR levels in children.
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Sharma AP, Yasin A, Garg AX, and Filler G
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- Adolescent, Biomarkers blood, Child, Child, Preschool, Cross-Sectional Studies, Female, Humans, Kidney Diseases blood, Kidney Diseases physiopathology, Male, Ontario, Predictive Value of Tests, Prognosis, Prospective Studies, Radiopharmaceuticals, Reproducibility of Results, Severity of Illness Index, Technetium Tc 99m Pentetate, Cystatin C analysis, Glomerular Filtration Rate, Kidney physiopathology, Kidney Diseases diagnosis, Models, Biological
- Abstract
Background and Objectives: The diagnostic accuracy of cystatin C estimated GFR (eGFR) by various cystatin C equations have varied in different studies. We hypothesized that the GFR level of enrolled patients affects the diagnostic accuracy of a cystatin C equation., Design, Setting, Participants, & Measurements: We analyzed 240 consecutively enrolled children at a single Canadian center in a prospective and cross-sectional study. Cystatin C was analyzed with nephelometry, and cystatin C eGFR was estimated by the equations validated in children. GFR was measured by technetium-99m-diethylene-triamine penta-acetic acid (⁹⁹m)Tc DTPA)., Results: We compared various cystatin C equations across GFR strata < 60, < 90, ≥ 135, and ≥ 150 ml/min per 1.73 m² for an accurate prediction and appropriate classification of the measured GFR. The CKiD, Zappitelli-CysEq, and Zappitelli-CysCrEq equations had a higher accuracy, estimated by eGFR values within 10% and 30% of the respective (99m)Tc DTPA, in the GFR categories < 60 and < 90 ml/min per 1.73 m², whereas the Bökenkamp, Bouvet, and Filler equations had a greater accuracy in the GFR categories ≥ 135 and ≥ 150 ml/min per 1.73 m². The Bouvet, CKiD, Filler, Zappitelli-CysEq, and Zappitelli-CysCrEq equations had a greater sensitivity to classify GFR < 60 and < 90 ml/min per 1.73 m², whereas the Bökenkamp equation had a higher sensitivity for GFR ≥ 135 and ≥ 150 ml/min per 1.73 m²., Conclusions: The diagnostic accuracy of various cystatin C equations varies with GFR. This issue needs consideration while applying these equations in clinical practice and for further research on eGFR equations.
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- 2011
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11. A simple estimate for extracellular volume: too simple?
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Filler G and Huang SH
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- Body Surface Area, Chronic Disease, Humans, Extracellular Space physiology, Glomerular Filtration Rate, Kidney Diseases physiopathology
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- 2011
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12. Are we ready to use aliskiren in children?
- Author
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Kelland EE, McAuley LM, and Filler G
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- Adolescent, Age Factors, Amides administration & dosage, Amides adverse effects, Angiotensin II Type 1 Receptor Blockers therapeutic use, Child, Preschool, Chronic Disease, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Fumarates administration & dosage, Fumarates adverse effects, Humans, Kidney Diseases complications, Kidney Diseases metabolism, Losartan therapeutic use, Male, Off-Label Use, Patient Selection, Proteinuria etiology, Proteinuria metabolism, Renin antagonists & inhibitors, Renin-Angiotensin System drug effects, Risk Assessment, Risk Factors, Treatment Outcome, Amides therapeutic use, Fumarates therapeutic use, Kidney Diseases drug therapy, Proteinuria drug therapy
- Abstract
The objective of this case series was to review the safety and efficacy of aliskiren in combination with losartan in pediatric chronic kidney disease (CKD) patients. This was a retrospective study in which the medical files of all patients who had received aliskiren were reviewed. Four patients were identified between 5 and 18 years of age who had received aliskiren and losartan for the reduction of refractory proteinuria. While proteinuria was reduced in all four of these patients by 45, 96, 53, and 64%, respectively, three patients experienced side effects requiring changes in the aliskiren dose. A significant side effect occurred in the patient with CKD stage 3 who suffered accelerated loss of kidney function leading to dialysis after only a short course of therapy. The data from this preliminary trial strongly suggest that clinicians should exercise caution when prescribing aliskiren in combination with losartan until appropriate pediatric trials establish dosing, efficacy, and safety.
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- 2011
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13. Hyperfiltration affects accuracy of creatinine eGFR measurement.
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Huang SH, Sharma AP, Yasin A, Lindsay RM, Clark WF, and Filler G
- Subjects
- Adolescent, Biomarkers blood, Child, Chromium Radioisotopes, Cystatin C blood, Edetic Acid, Female, Hippurates, Humans, Intramolecular Oxidoreductases blood, Iodine Radioisotopes, Kidney metabolism, Kidney Diseases blood, Kidney Diseases physiopathology, Lipocalins blood, Male, Ontario, Predictive Value of Tests, Renal Plasma Flow, Effective, Reproducibility of Results, Creatinine blood, Glomerular Filtration Rate, Kidney physiopathology, Kidney Diseases diagnosis, Kidney Function Tests, Models, Biological
- Abstract
Background and Objectives: Surrogate markers such as creatinine, cystatin C (CysC), and beta trace protein (BTP) have been used to estimate GFR (eGFR). The accuracy of eGFR may be altered with hyperfiltration and differences in filtration fraction (FF). It is hypothesized that the accuracy of creatinine for eGFR may be affected by hyperfiltration and different effective renal plasma flow (ERPF)., Design, Setting, Participants, & Measurements: A total of 127 pediatric patients with various renal diseases underwent simultaneous measurements of GFR using 51Cr-EDTA renal scan and ERPF (131I-hippurate clearance) to calculate the FF (FF=GFR/ERPF). The eGFRs were calculated using the commonly used Schwartz (creatinine), Filler (CysC), and Benlamri (BTP) formulas. Agreement of the eGFRs with the measured isotope GFRs was assessed by Bland-Altman plots. Correlation analysis was performed using nonparametric tests to compare FF with eGFR-GFR., Results: The 127 children at a median age (with 25th percentile, 75th percentile) of 11.9 (8.5, 14.9) years had a mean 51Cr EDTA-GFR of 100.6±32.1 ml/min per 1.73 m2 and a median 131I-hippurate clearance (ERPF) of 588 (398,739) ml/min per 1.73 m2. Mean FF was 17.7±4.5% with no correlation between the FF and the error (eGFR-GFR) for CysC and BTP eGFR, whereas there was a significant negative correlation between the error for Schwartz eGFR and FF., Conclusions: There is a significant negative correlation between the error for the Schwartz eGFR and the FF. CysC and BTP are not affected by differences in FF.
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- 2011
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14. Association between clinical risk factors and progression of chronic kidney disease in children.
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Staples AO, Greenbaum LA, Smith JM, Gipson DS, Filler G, Warady BA, Martz K, and Wong CS
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- Adolescent, Child, Child, Preschool, Chronic Disease, Cohort Studies, Disease Progression, Female, Glomerular Filtration Rate, Humans, Male, Multivariate Analysis, Retrospective Studies, Risk Factors, Kidney Diseases complications, Kidney Failure, Chronic etiology
- Abstract
Background and Objectives: Children with chronic kidney disease (CKD) have an increased risk of progression to ESRD. There is a need to identify treatments to slow the progression of CKD, yet there are limited data regarding clinical risk factors that may be suitable targets to slow progression., Design, Setting, Participants, & Measurements: We performed a retrospective cohort study using the North American Pediatric Renal Trials and Cooperative Studies CKD database. There were 4166 pediatric subjects with CKD stages II to IV. Disease progression was defined as a GFR on follow-up of <15 ml/min per 1.73 m(2) or termination in the registry because of dialysis or transplantation. We used Kaplan-Meier and Cox proportional hazards methods to describe progression rates and determine factors associated with CKD progression., Results: In the univariate analysis, CKD progression was associated with age, gender, race, primary disease, CKD stage, registration year, hematocrit, albumin, corrected calcium, corrected phosphorus, and use of certain medications. Factors that remained significant in the multivariate analysis were age, primary disease, CKD stage, registration year, hypertension, corrected phosphorus, corrected calcium, albumin, hematocrit, and medication proxies for anemia and short stature., Conclusions: There are multiple risk factors associated with disease progression in the pediatric CKD population. Factors that may be amenable to intervention include anemia, hypoalbuminemia, hyperphosphatemia, hypocalcemia, hypertension, and short stature. Because of the retrospective nature of our study, confirmation of our results from ongoing prospective studies is warranted before recommending prospective interventional trials.
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- 2010
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15. Racial disparities in hemoglobin concentration in children with CKD.
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Filler G, Huang SH, and Sharma AP
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- Adolescent, Anemia drug therapy, Anemia epidemiology, Anemia ethnology, Child, Child, Preschool, Chronic Disease, Glomerular Filtration Rate physiology, Hematinics therapeutic use, Humans, Kidney Diseases physiopathology, Prevalence, United States epidemiology, Black or African American ethnology, Hemoglobins metabolism, Kidney Diseases blood, Kidney Diseases ethnology, White People ethnology
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- 2010
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16. Adherence to waiting-time targets for pediatric nephrology clinic referrals.
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Radina M, Sharma AP, Yasin A, and Filler G
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- Adolescent, Canada, Child, Child, Preschool, Female, Humans, Infant, Male, Nephrology, Pediatrics, Retrospective Studies, Time Factors, Appointments and Schedules, Health Services Accessibility statistics & numerical data, Kidney Diseases diagnosis, Referral and Consultation statistics & numerical data, Waiting Lists
- Abstract
Waiting times for specialist consultation have not been adequately studied, especially in the pediatric population. The aim of this study was to determine the extent to which pediatric nephrology subspecialty clinic referral waiting times are adhered to with regard to previously determined access targets. Referrals to the pediatric nephrology clinics at Children's Hospital, London, Ontario, Canada, received between October 2007 and November 2008 were retrospectively analyzed. Appointment schedule was allotted by a nephrologist based on the patient's presenting complaint, reported in the referral, in accordance with the previously determined access targets. Adherence to access targets was assessed by the actual clinic visit. There were a total of 250 referrals during the timeframe studied. The median waiting time was 73 (range 0-193) days. Overall, 64% (159/250) of patients met their access target. The median time that patients waited over their access target was 6 (range 0-78) days. Of the patients who did not meet their access targets, 31% (28/91) exceeded their target by 20% or more. Office handling was a component for patients with access target <1 week, whereas availability of clinic space was the main reason for nonadherence to access targets.
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- 2010
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17. Anemia and risk of hospitalization in pediatric chronic kidney disease.
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Staples AO, Wong CS, Smith JM, Gipson DS, Filler G, Warady BA, Martz K, and Greenbaum LA
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- Adolescent, Anemia blood, Anemia drug therapy, Anemia epidemiology, Canada epidemiology, Child, Child, Preschool, Chronic Disease, Erythropoietin therapeutic use, Female, Hematinics therapeutic use, Hematocrit, Humans, Kidney Diseases blood, Kidney Diseases drug therapy, Kidney Diseases epidemiology, Logistic Models, Male, Odds Ratio, Prevalence, Registries, Retrospective Studies, Risk Assessment, Risk Factors, United States epidemiology, Anemia etiology, Hospitalization statistics & numerical data, Kidney Diseases complications
- Abstract
Background and Objectives: Anemia is a well known complication of chronic kidney disease (CKD); however, the prevalence of anemia within CKD stages in the pediatric population has not been established. Additionally, the associated morbidity of anemia in the pediatric CKD population has not been elucidated., Design, Setting, Participants, & Measurements: 2,779 patients ages 2 yr and older in the North American Pediatric Renal Trials and Collaborative Studies database with CKD stage II to V (excluding dialysis or previous transplant patients) were identified. Descriptive statistics and multivariate modeling using logistic regression was performed to determine the prevalence of anemia and to evaluate the correlation between baseline anemia and hospitalization., Results: The prevalence of anemia (hematocrit < 33%) increased from 18.5% in CKD stage II to 68% in CKD stage V (predialysis). Anemic children were 55% more likely to be hospitalized when compared with nonanemic children (odds ratio 1.55; 95% confidence interval 1.23 to 1.94). Similar results were obtained using hematocrit cutoffs of 36 and 39%., Conclusions: In this pediatric predialysis CKD population, anemia increases with increasing CKD stage and is significantly associated with hospitalization risk. Hematocrit levels above 36 and 39% were not associated with increased risk of hospitalization. Further examination into the effect of correcting anemia on hospitalization rates may provide additional useful information.
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- 2009
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18. How to monitor renal function in pediatric solid organ transplant recipients.
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Filler G and Sharma AP
- Subjects
- Albuminuria metabolism, Child, Creatinine metabolism, Cystatin C, Cystatins metabolism, Glomerular Filtration Rate, Humans, Inulin metabolism, Kidney Diseases etiology, Kidney Function Tests, Nephrology methods, Organ Transplantation instrumentation, Predictive Value of Tests, Sensitivity and Specificity, Kidney pathology, Kidney Diseases diagnosis, Organ Transplantation methods
- Abstract
The aim is to review the tools for early detection of renal dysfunction after pediatric solid organ transplantation. Currently, the most widely used marker for detection of renal dysfunction involves measurement of GFR. Inulin clearance forms the "gold standard" method for measuring GFR; however, nuclear medicine methods ((51)Cr EDTA and (99)Tc DTPA isotope clearance studies) have replaced inulin clearance. The measurement of serum creatinine has a low sensitivity for the early detection of renal damage. The Schwartz formula using patient height and serum creatinine requires center-specific constants and has limitations associated with creatinine determination. These limitations may be overcome using a cystatin C-based GFR estimation. In diabetic nephropathy, and more recently in hemolytic uremic syndrome, microalbuminuria has been established as a useful screening tool for renal damage, while its predictive value in the transplantation setting needs to be established. All transplant recipients should be screened for hypertension. Early referral for ambulatory 24-h blood pressure monitoring and involvement of pediatric nephrologists should be considered. All pediatric solid organ transplant recipients receiving CNI should be screened regularly for high blood pressure and early evidence of renal damage using either GFR scans or cystatin C-based GFR estimations.
- Published
- 2008
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19. Complications of chronic kidney disease in children post-renal transplantation - a single center experience.
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Feber J, Wong H, Geier P, Chaudry B, and Filler G
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- Adolescent, Child, Child, Preschool, Chronic Disease, Female, Glomerular Filtration Rate, Humans, Hypercholesterolemia epidemiology, Hypertension epidemiology, Infant, Kidney Diseases surgery, Male, Postoperative Period, Retrospective Studies, Kidney Diseases complications, Kidney Transplantation
- Abstract
Similar to adults, CKD may persist after pediatric RTx. Clinical and laboratory parameters were analyzed retrospectively in 23 RTx recipients (13 males, age 11.9 +/- 5.2 yr), initially treated with prednisone, calcineurin inhibitor (TAC = 18, cyclosporine neoral = 5), and MMF at four months post-RTx (T1) and at 3.4 +/- 2.8 yr post-RTx (T2). Mean (+/-s.d.) cystatin C GFR (mL/min/1.73 m(2)) was 72 +/- 19 at T1 and 70 +/- 22 at T2 (NS). At T2, CKD stage I was present in five patients (22%), stage II in eight patients (35%), and stage III in 10 patients (43%). At T2, calcineurin inhibitors were utilized in 19, MMF in 13, and SIR in 13 patients. The prevalence of hypertension was 69% at T1 and 87% at T2 (p = NS). Anemia was diagnosed in 61% at T1 and 69% at T2 with average therapeutic MMF (2.78 +/- 1.3 mg/mL) and SIR (7.62 +/- 2.3 mg/mL) trough levels. Hypercholesterolemia was detected in 44.0% at T1 and 47% at T2. Bone disease was diagnosed in 26.0% at T1 and 21.7% at T2. Mean height Z-scores were -1.0 +/- 1.2 (T1) and -1.0 +/- 1.59 (T2, NS), with 21% at T1 and 30% at T2 below two SDS. We observed suboptimal growth, hypertension, hypercholesterolemia, bone disease, and anemia in a significant proportion of transplanted children.
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- 2008
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20. Growth impairment shows an age-dependent pattern in boys with chronic kidney disease.
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Zivicnjak M, Franke D, Filler G, Haffner D, Froede K, Nissel R, Haase S, Offner G, Ehrich JH, and Querfeld U
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- Adolescent, Adult, Age Factors, Age of Onset, Anthropometry, Body Height, Child, Child, Preschool, Growth Disorders etiology, Growth Disorders therapy, Humans, Kidney Diseases complications, Male, Growth, Kidney Diseases physiopathology
- Abstract
The impact of chronological age on longitudinal body growth from early childhood through adolescence using detailed anthropometric methods has not yet been studied in children with chronic kidney disease (CKD). We have evaluated growth failure by measuring four components of linear growth: body height (HT), sitting height (SHT), arm length (AL) and leg length (LL). Data were prospectively collected for up to 7 years on 190 boys (3-21 years old) with congenital or hereditary CKD (all had developed at least stage 2 CKD by the age of 10 years). Patients showed the most severe growth failure in early childhood, followed by an acceleration in growth in pre-puberty, a slowing-down of growth at puberty, as expected, and thereafter a late speeding-up of growth until early adulthood. This pattern was observed irrespective of the degree of CKD and different treatment modalities, such as conservative treatment, recombinant human growth hormone (rhGH) therapy or transplantation. LL showed the most dynamic growth changes of all the parameters evaluated and emerged as the best indicator of statural growth in children with CKD. A specific age-dependent pattern of physical growth was identified in pediatric male CKD patients. This growth pattern should be considered in the evaluation of individual growth and the assessment of treatment efficacy such as rhGH therapy.
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- 2007
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21. Influence of commonly used drugs on the accuracy of cystatin C-derived glomerular filtration rate.
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Foster J, Reisman W, Lepage N, and Filler G
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- Adolescent, Child, Child, Preschool, Cystatin C, Dose-Response Relationship, Drug, Female, Humans, Infant, Male, Reproducibility of Results, Retrospective Studies, Cystatins blood, Glomerular Filtration Rate, Kidney Diseases drug therapy, Kidney Diseases urine
- Abstract
There is controversy about the effect of certain drugs on cystatin C (CysC) concentrations, which would limit the usability of CysC for estimation of glomerular filtration rate (GFR) in patients with renal disease. Seventy-one children (ages 2.6 months to 18 years) with renal disease and on at least one study medication (tacrolimus, cyclosporine, mycophenolate mofetil, corticosteroids, fosinopril, ramipril and enalapril, losartan, cotrimoxazole) were tested in 85 nuclear medicine GFR clearance studies with simultaneous CysC determinations. We analyzed the relationship between the dose per kilogram and the ratio of the measured GFR to the CysC-derived GFR, with a ratio of 1 resembling agreement. A non-zero slope in linear regression analysis was considered significant for a drug effect on CysC. No significant relationship was found between the doses of the medication and the cystatin C GFR for any of the medications. Only cotrimoxazole showed a GFR ratio that was significantly lower than 1, which may be related to small numbers; otherwise the value was always 1. CysC provides accurate data for calculating GFR independent of the drug doses studied and avoids the use of methods of direct GFR measurement.
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- 2006
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22. Cystatin C intrapatient variability in children with chronic kidney disease is less than serum creatinine.
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Sambasivan AS, Lepage N, and Filler G
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- Biomarkers blood, Child, Chronic Disease, Cystatin C, Female, Glomerular Filtration Rate, Humans, Male, Creatinine blood, Cystatins blood, Kidney Diseases blood
- Published
- 2005
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23. Tissue viral DNA is associated with chronic allograft nephropathy.
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Sebeková K, Feber J, Carpenter B, Shaw L, Karnauchow T, Diaz-Mitoma F, and Filler G
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- Adolescent, Child, Child, Preschool, Chronic Disease, Cytomegalovirus isolation & purification, Female, Glomerular Filtration Rate, Graft Rejection virology, Herpesvirus 4, Human isolation & purification, Herpesvirus 6, Human isolation & purification, Herpesvirus 7, Human isolation & purification, Humans, Infant, Kidney physiopathology, Kidney Diseases etiology, Kidney Diseases physiopathology, Male, Polymerase Chain Reaction, DNA, Viral analysis, Kidney virology, Kidney Diseases virology, Kidney Transplantation adverse effects
- Abstract
Viral infections post-renal transplant (Tx) impact on outcome. Increased rejection rates and decreased renal function secondary to acute CMV, EBV and HHV-6 infections are well described. However, the clinical significance of a mere presence of these viruses on kidney tissue biopsy remains questionable. Thirty-six kidney biopsies obtained from 17 renal transplants (five females) and two combined liver-kidney recipients (one female) were retrospectively evaluated. Age at Tx ranged from 1.7 to 17.2 yr (median = 7.4). Biopsies were performed as protocol biopsies or when renal function deteriorated, between 6 weeks and 11 yr post-Tx (median = 1.2 yr). Immunosuppression included steroids and combination of tacrolimus/cyclosporin, mycophenolate mofetil/azathioprin and induction therapy. Fourteen patients received antiviral prophylaxis (ganciclovir/valganciclovir/acyclovir). Renal tissue was classified according to Banff '97 criteria. Tissue CMV, EBV, HHV-6 and HHV-7 was analyzed by PCR. We used an estimation of GFR from average plasma Cystatin C (CysC) and slopes of 1/CysC to assess renal function. The 16/36 biopsies were positive for one virus; 5/36 biopsies were positive for two viruses. In the infected group, Banff '97 scores for interstitial fibrosis (ci) and tubular degeneration/atrophy (ct) were significantly higher (p < 0.03 vs. the non-infected group for both). The slope of 1/CysC, or the proportion of patients on antiviral prophylaxis, did not differ significantly between both groups. In conclusion, a significant number of kidney biopsies showed PCR positivity for CMV, EBV, HHV-6 and HHV-7. This was associated with a significantly higher Banff score for ci and ct; while renal function was not affected. Further controlled studies are required.
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- 2005
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24. Combination of ceftriaxone and acyclovir - an underestimated nephrotoxic potential?
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Vomiero G, Carpenter B, Robb I, and Filler G
- Subjects
- Adolescent, Child, Child, Preschool, Creatinine blood, Drug Combinations, Female, Humans, Infant, Kidney pathology, Kidney Diseases pathology, Kidney Function Tests, Male, Retrospective Studies, Acyclovir adverse effects, Antiviral Agents adverse effects, Ceftriaxone adverse effects, Cephalosporins adverse effects, Kidney Diseases chemically induced
- Abstract
Management of meningo-encephalitis often involves the need for antibiotic and antiviral treatment. We report a retrospective analysis over a 6-month period of 17 patients (age range 1-14 years) who were treated with combination therapy of ceftriaxone and acyclovir. Mean acyclovir and ceftriaxone doses were 1,222+/-304 and 2,315+/-509 mg/m(2) per day, respectively. Three patients developed acute renal failure with a peak creatinine of up to 865% above baseline, occurring 2-3 days after starting combination therapy. Patients revealed a tubular proteinuria pattern. Renal biopsy of 1 patient showed a tubulotoxic picture but no evidence of crystals. In 12 of 17 patients (70%) there was a significant increase in serum creatinine. This was significantly greater than literature reports of 16% with acyclovir monotherapy. The degree of renal impairment in our patients correlated significantly with the acyclovir dose, while no correlation was found with the ceftriaxone dose. We conclude that the addition of a second nephrotoxic drug aggravated the extent of renal injury in our patients. The mechanism is tubulotoxicity. Caution should be exercised when using this potentially nephrotoxic cocktail, with clear criteria established for the initiation of combination therapy and close monitoring of serum creatinine.
- Published
- 2002
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25. Beta-trace protein, cystatin C, beta(2)-microglobulin, and creatinine compared for detecting impaired glomerular filtration rates in children.
- Author
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Filler G, Priem F, Lepage N, Sinha P, Vollmer I, Clark H, Keely E, Matzinger M, Akbari A, Althaus H, and Jung K
- Subjects
- Adolescent, Biomarkers blood, Child, Child, Preschool, Cystatin C, Female, Humans, Infant, Kidney Diseases physiopathology, Lipocalins, Male, Reference Values, Creatinine blood, Cystatins blood, Glomerular Filtration Rate, Intramolecular Oxidoreductases blood, Kidney Diseases diagnosis, beta 2-Microglobulin blood
- Abstract
Background: Because of the limitations of serum creatinine as a marker of glomerular filtration rate (GFR) in children, we assessed the diagnostic accuracy of the novel marker beta-trace protein (BTP) in comparison with cystatin C (Cys-C), beta(2)-microglobulin (beta(2)-MG), and creatinine as conventional indicators of reduced GFR., Methods: We obtained serum samples from 225 children (age range, 0.2-18 years) with various renal pathologies who were referred for nuclear medicine clearance investigations (technetium-diethylenetriamine pentaacetic acid or chromium-EDTA). We measured Cys-C, BTP (nephelometric tests; Dade Behring), beta(2)-MG (Tinaquant; Roche), and creatinine (enzymatic assay; Creatinine-PAP; Roche)., Results: Seventy-five children had reduced GFR (<90 mL x min(-1) x 1.73 m(-2)). One hundred fifty children (independent of gender and age) with values >90 mL x min(-1) x 1.73 m(-2) comprised the control group with gaussian distributions of BTP and Cys-C concentrations. The upper reference limits (97.5 percentile) were 1.01 mg/L for BTP and 1.20 mg/L for Cys-C. The correlations of nuclear medicine clearance with the reciprocals of BTP, Cys-C, and the Schwartz GFR estimate were significantly higher (r = 0.653, 0.765, and 0.706, respectively; P <0.05) than with the reciprocal of creatinine or beta(2)-MG (r = 0.500 and 0.557, respectively). ROC analysis showed a significantly higher diagnostic accuracy of BTP, Cys-C, and the GFR estimate for the detection of impaired GFR than serum creatinine (P <0.05). Compared to creatinine, BTP increased the diagnostic sensitivity by approximately 30%, but it was not more sensitive than Cys-C or the Schwartz GFR estimate., Conclusions: BTP is superior to serum creatinine and an alternative for Cys-C to detect mildly reduced GFR in children, but it is not better than the Schwartz GFR estimate.
- Published
- 2002
26. A novel multiplex biomarker panel for profiling human acute and chronic kidney disease.
- Author
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Van Nynatten, Logan R., Miller, Michael R., Patel, Maitray A., Daley, Mark, Filler, Guido, Badrnya, Sigrun, Miholits, Markus, Webb, Brian, McIntyre, Christopher W., and Fraser, Douglas D.
- Subjects
CHRONIC kidney failure ,RENAL replacement therapy ,KIDNEY diseases ,BIOMARKERS ,ACUTE kidney failure ,URINE - Abstract
Acute and chronic kidney disease continues to confer significant morbidity and mortality in the clinical setting. Despite high prevalence of these conditions, few validated biomarkers exist to predict kidney dysfunction. In this study, we utilized a novel kidney multiplex panel to measure 21 proteins in plasma and urine to characterize the spectrum of biomarker profiles in kidney disease. Blood and urine samples were obtained from age-/sex-matched healthy control subjects (HC), critically-ill COVID-19 patients with acute kidney injury (AKI), and patients with chronic or end-stage kidney disease (CKD/ESKD). Biomarkers were measured with a kidney multiplex panel, and results analyzed with conventional statistics and machine learning. Correlations were examined between biomarkers and patient clinical and laboratory variables. Median AKI subject age was 65.5 (IQR 58.5–73.0) and median CKD/ESKD age was 65.0 (IQR 50.0–71.5). Of the CKD/ESKD patients, 76.1% were on hemodialysis, 14.3% of patients had kidney transplant, and 9.5% had CKD without kidney replacement therapy. In plasma, 19 proteins were significantly different in titer between the HC versus AKI versus CKD/ESKD groups, while NAG and RBP4 were unchanged. TIMP-1 (PPV 1.0, NPV 1.0), best distinguished AKI from HC, and TFF3 (PPV 0.99, NPV 0.89) best distinguished CKD/ESKD from HC. In urine, 18 proteins were significantly different between groups except Calbindin, Osteopontin and TIMP-1. Osteoactivin (PPV 0.95, NPV 0.95) best distinguished AKI from HC, and β2-microglobulin (PPV 0.96, NPV 0.78) best distinguished CKD/ESKD from HC. A variety of correlations were noted between patient variables and either plasma or urine biomarkers. Using a novel kidney multiplex biomarker panel, together with conventional statistics and machine learning, we identified unique biomarker profiles in the plasma and urine of patients with AKI and CKD/ESKD. We demonstrated correlations between biomarker profiles and patient clinical variables. Our exploratory study provides biomarker data for future hypothesis driven research on kidney disease. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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27. Impaired kidney function >90 days determines long‐term kidney outcomes.
- Author
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Filler, Guido and Sharma, Ajay P.
- Subjects
- *
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]
- Published
- 2022
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28. Renal length z‐score for the detection of dysfunction in children with solitary functioning kidney.
- Author
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Restrepo, Jaime M., Torres‐Canchala, Laura, Viáfara, Lina M., Agredo, Maria A., Quintero, Ana M., and Filler, Guido
- Subjects
LEAN body mass ,KIDNEY diseases ,BODY mass index ,RECEIVER operating characteristic curves ,ODDS ratio - Abstract
Aim: To evaluate whether renal length z‐scores predict renal dysfunction in children with a solitary functioning kidney (SFK). Methods: In a single‐centre retrospective cohort of children with SFK, we correlated body mass index z‐scores, extracellular volume and lean body mass to renal length z‐scores. We grouped these z‐scores to other markers of renal dysfunction (proteinuria, hypertension, extracellular volume and abnormal estimated glomerular function rate [eGFR]) and analysed renal length z‐score with multivariate analysis, receiver‐operated characteristics (ROC) plots and Youden's index to determine an appropriate cut‐off. Results: 111 children had a median follow‐up 5.08 years, eGFR 80.8 mL/min/1.73 m2, and age at last follow‐up 7.4 (3.8‐13.4 years). The median renal length z‐scores of those without any renal dysfunction (n = 37, 25.1%) were greater (+3.66, interquartile range 3.02‐4.47) than those with renal dysfunction (median 3.11, interquartile range 1.76‐4.11, P =.0107, Mann‐Whitney test). Using a cut‐off of z‐score of >+1.911, the odds ratio for having no renal dysfunction was 0.07 (95% CI 0.002‐0.459, P =.0010). However, accuracy of the renal length z‐score was poor (ROC curve 0.6488). Conclusion: In this cohort of children with SKF, using the renal length z‐score as a biomarker of renal dysfunction at 7 years of age is not recommended. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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29. Deviations from the expected relationship between serum FGF23 and other markers in children with CKD: a cross-sectional study.
- Author
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Liu, Daisy, Alvarez-Elías, Ana Catalina, Wile, Brooke, Belostotsky, Vladimir, and Filler, Guido
- Subjects
FIBROBLAST growth factors ,KIDNEY diseases ,PHOSPHATES ,ACIDOSIS ,MULTIVARIATE analysis ,CALCIUM ,CHRONIC kidney failure ,GROWTH factors ,PARATHYROID hormone ,VITAMIN D ,CROSS-sectional method ,DIAGNOSIS - Abstract
Background: High levels of fibroblast growth factor-23 (FGF23) are associated with mortality. In chronic kidney disease (CKD), FGF23 levels rise as renal function declines. We analyzed the contribution of laboratory values to the variance of FGF23 levels in relationship to a curve of expected FGF23 levels for a given GFR.Methods: Following approval by the research ethics boards, we measured FGF23, CysC eGFR, creatinine, urea, albumin, calcium, phosphate, vitamin D metabolites, PTH, alkaline phosphatase, CRP, and venous gases in 141 pediatric CKD patients (45, 37, 32, 13 and 14 CKD stages I, II, III, IV, and V, respectively). Data were expressed as median (25th, 75th percentile).Results: FGF23 correlated significantly with CysC, CysC eGFR, PTH, 1.25 (OH)2 vitamin D, phosphate, and pH. The correlation of the latter three remained significant in the multivariate analysis. We calculated a formula for the expected FGF23 value for a given level of eGFR which reads Y = 1295 * e-0.07247*X + 38.35. Deviation by more than 20% from the curve also depended on phosphate, 1.25 (OH)2 vitamin D and pH.Conclusions: Our data emphasize the importance of phosphate and 1.25 (OH)2 vitamin D levels. The impact of acidosis on FGF23 warrants further studies. [ABSTRACT FROM AUTHOR]- Published
- 2017
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30. 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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31. Can the new CKD-EPI BTP-B2M formula be applied in children?
- Author
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Filler, Guido, Alvarez-Elías, Ana, Westreich, Katherine, Huang, Shih-Han, and Lindsay, Robert
- Subjects
- *
BIOMARKERS , *CHI-squared test , *CHRONIC kidney failure , *CONFIDENCE intervals , *GLOMERULAR filtration rate , *KIDNEY function tests , *KIDNEY diseases , *REGRESSION analysis , *DATA analysis software - Abstract
Although measuring creatinine to determine kidney function is currently the clinical standard, new markers such as beta-trace protein (BTP) and beta-2-microglobulin (B2M) are being investigated in an effort to measure glomerular filtration rate more accurately. In their recent publication, Inker et al. (Am J Kidney Dis 2015; 67:40-48) explored the use of these two relatively new markers in combination with some commonly available clinical characteristics in a large cohort of adults with chronic kidney disease. Their research led them to develop three formulae using BTP, B2M, and a combination of the two. The combined formula is particularly attractive as it removes all gender bias, which applies to both serum creatinine and cystatin C. Using data from a cohort of 127 pediatric patients from our center, we sought to determine whether these formulae would be equally as effective in children as in adults. Unfortunately, we found that the formulae cannot be applied to the pediatric population. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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32. Trace elements in dialysis.
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Filler, Guido and Felder, Sarah
- Subjects
- *
TREATMENT of chronic kidney failure , *DRUGS , *HEMODIALYSIS , *KIDNEY diseases , *LEAD , *SELENIUM , *THERAPEUTICS , *TRACE elements , *ZINC - Abstract
In end-stage chronic kidney disease (CKD), pediatric nephrologists must consider the homeostasis of the multiple water-soluble ions that are influenced by renal replacement therapy (RRT). While certain ions such as potassium and calcium are closely monitored, little is known about the handling of trace elements in pediatric dialysis. RRT may lead to accumulation of toxic trace elements, either due to insufficient elimination or due to contamination, or to excessive removal of essential trace elements. However, trace elements are not routinely monitored in dialysis patients and no mechanism for these deficits or toxicities has been established. This review summarizes the handling of trace elements, with particular attention to pediatric data. The best data describe lead and indicate that there is a higher prevalence of elevated lead (Pb, atomic number 82) levels in children on RRT when compared to adults. Lead is particularly toxic in neurodevelopment and lead levels should therefore be monitored. Monitoring of zinc (Zn, atomic number 30) and selenium (Se, atomic number 34) may be indicated in the monitoring of all pediatric dialysis patients to reduce morbidity from deficiency. Prospective studies evaluating the impact of abnormal trace elements and the possible therapeutic value of intervention are required. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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33. 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
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34. 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
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35. 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
- *
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]
- Published
- 2012
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36. Chronic renal disease is more prevalent in patients with hemolytic uremic syndrome who had a positive history of diarrhea.
- Author
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Sharma, Ajay P., Filler, Guido, Dwight, Prabo, and Clark, William F.
- Subjects
- *
KIDNEY diseases , *HEMOLYTIC-uremic syndrome , *DIARRHEA , *KIDNEY glomerulus , *ESCHERICHIA coli - Abstract
Many uncontrolled studies and a subsequent meta-analysis suggest that hemolytic uremic syndrome (HUS) with a positive history for diarrhea is associated with a significant increase in chronic renal disease. Two recent controlled studies that followed children with this type of HUS after Escherichia coli O157:H7 outbreaks, and where the controls were selected from a group exposed in the outbreak, gave conflicting results. To clarify this apparent difference, we retrospectively compared a cohort of 30 children with sporadic diarrhea-positive HUS with 30 healthy controls who had no history of bloody diarrhea or HUS and who had similar age and gender. Significantly more children with previous HUS than the controls had albuminuria over a median follow-up of 6.2 years. Of these albuminuric patients, one-third had macroalbuminuria compared with none of the controls. Following HUS, children were three times more prone to hypertension and prehypertension, although the difference was not statistically significant. Glomerular filtration rates, estimated by cystatin C, were significantly lower by 30 ml/min/1.73 m2. Thus, children with sporadic HUS with positive history of diarrhea compared with unexposed controls had a higher prevalence of chronic renal disease; results consistent with the meta-analysis. Prospective studies with appropriate controls are needed to completely resolve this issue. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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37. Bicarbonate therapy improves growth in children with incomplete distal renal tubular acidosis.
- Author
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Sharma, Ajay P., Singh, Ram N., Yang, Connie, Sharma, Raj K., Kapoor, Rakesh, and Filler, Guido
- Subjects
ACIDOSIS ,OSTEOPOROSIS ,DWARFISM ,KIDNEY diseases ,SODIUM bicarbonate ,ACIDIFICATION ,PEDIATRIC nephrology - Abstract
Incomplete distal renal tubular acidosis (idRTA) has recently been associated with osteoporosis and growth retardation, attributed to the mild persistent metabolic acidosis. We hypothesized a therapeutic benefit from bicarbonate therapy on growth parameters in children with idRTA. In a study group of 40 surgically treated patients with posterior urethral valve (PUV) and normal estimated glomerular filtration rate, we evaluated the change in height standard deviation scores (SDSs) while they were on bicarbonate therapy in the presence of idRTA and complete distal renal tubular acidosis (dRTA). Age- and gender-matched healthy subjects constituted the control group ( n = 55). Incomplete dRTA was evaluated by ammonium chloride acidification. The baseline height SDS of −1.94 ± 0.41 and −5.31 ± 1.95 in the groups with idRTA and complete dRTA, respectively, were significantly lower than that of the controls. After a follow-up period of 24.7 ± 8.3 months on sodium bicarbonate therapy, the idRTA patients had a 66% increase in height SDS compared with 26% and 3% increases in the patients with PUV with complete dRTA and without dRTA, respectively. At the end of follow-up, mean height SDS in the group with idRTA no longer remained significantly lower than that of the controls ( P = 0.42). We concluded that bicarbonate therapy improves height SDS in idRTA. This issue needs further validation in larger studies. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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- View/download PDF
38. High prevalence of chronic kidney disease in pediatric solid organ transplantation.
- Author
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Filler, Guido and Sharma, Ajay P.
- Subjects
- *
TRANSPLANTATION of organs, tissues, etc. , *KIDNEY transplantation , *KIDNEY diseases , *ACUTE kidney failure , *CHRONIC kidney failure - Abstract
The article presents questions and answers related to chronic kidney disease in children including surveillance of renal function, glomerular filtration rate (GFR) and alternatives to creatinine-based GFR estimation.
- Published
- 2009
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39. Intravenous immunoglobulin as rescue therapy for BK virus nephropathy.
- Author
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Sharma, Ajay P., Moussa, Madeleine, Casier, Shelley, Rehman, Faisal, Filler, Guido, and Grimmer, Joanne
- Subjects
IMMUNOSUPPRESSION ,IMMUNOREGULATION ,IMMUNODEFICIENCY ,KIDNEY diseases ,HOMOGRAFTS - Abstract
BKVN has emerged as an important cause of pediatric renal allograft nephropathy, with significant graft dysfunction in majority of the cases. Reduced immunosuppression and cidofovir therapy are the most commonly used therapeutic options for the treatment of BKVN in these patients. Recently, a preliminary study in adult renal allograft recipients with BKVN showed a therapeutic response to a combined approach of immunosuppression reduction and IVIg administration. A therapeutic benefit of IVIg without another concomitant treatment intervention has not been evaluated. We report stabilization of renal functions, histological resolution of BKVN and significant reduction in BK viremia in pediatric renal transplant with the use of IVIg, after an inadequate response to immunosuppression reduction and cidofovir therapy. In addition, we review the current literature on the use of cidofovir in pediatric renal transplant patients with BKVN and the potential of IVIg use in this condition. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
40. How to define anemia in children with chronic kidney disease?
- Author
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Filler, Guido, Mylrea, Kyle, Feber, Janusz, and Wong, Hubert
- Subjects
- *
KIDNEY diseases , *BLOOD proteins , *BLOOD testing , *JUVENILE diseases , *PEDIATRIC nephrology , *INTERNAL medicine , *NEPHROLOGY - Abstract
In a cross-sectional study, we compared the prevalence of anemia based on age- and gender-specific reference intervals for hemoglobin (Hgb) and hematocrit (Hct) with the Kidney Disease Outcomes Quality Initiative (KDOQI) anemia definition (Hgb < 110 g/L) in 351 children with chronic kidney disease (CKD) stages I–V. Cystatin C-based GFRs were 122 ± 36 mL/min/1.73 m2 in patients with stage I CKD ( n = 196), 76 ± 8 mL/min/1.73 m2 for stage II ( n = 104), 45 ± 9 mL/min/1.73 m2 for stage III ( n = 36), and 22 ± 5 mL/min/1.73 m2 in patients with stage IV+V CKD ( n = 15). Fifty-nine patients received iron therapy and 32 patients were treated with Darbepoetin. For Hgb, a total of 90 patients fit the age and gender derived criteria, compared to only 54 patients identified by the KDOQI guidelines ( p = 0.0010). Similarly, for Hct, a total of 78 patients fit the age and gender derived criteria, which was a significantly higher proportion than the 56 identified by the KDOQI guidelines ( r = 0.22, p = 0.0435). There was a significant correlation between the GFR and both the Hgb Z-score ( p = 0.0068) and the Hct Z-score ( p = 0.0128). There was poor agreement between conventional and KDOQI definitions of anemia in children with CKD. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
41. Sirolimus is not always responsible for new-onset proteinuria after conversion for chronic allograft nephropathy.
- Author
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Abdurrahman, Zainab, Sarwal, Minnie, Millan, Maria, Robertson, Susan, and Filler, Guido
- Subjects
RAPAMYCIN ,IMMUNOSUPPRESSIVE agents ,MACROLIDE antibiotics ,PROTEINURIA ,KIDNEY diseases ,HOMOGRAFTS ,TRANSPLANTATION of organs, tissues, etc. - Abstract
An eight-yr-old combined liver and kidney transplant recipient for hyperoxaluria type I developed significant proteinuria and hypertension after conversion of a Tacrolimus, MMF, and corticosteroids-based immunosuppression to Sirolimus, low-dose Tacrolimus, and corticosteroids six and a half yr after the transplant for chronic allograft nephropathy. There was only one class I HLA match and the recipient had multiple blood exposures prior to transplantation. The patient was treated with combined hemodialysis and peritoneal dialysis while awaiting transplantation to reduce the oxalate load. A renal biopsy revealed a de novo transplant glomerulopathy that was associated with specific HLA antibodies unrelated to the donor (HLA DR 17 and 18). After reintroduction of MMF, these antibodies became undetectable and the proteinuria completely resolved. We hypothesize that HLA antibodies may cause transplant glomerulopathy even if they are not donor-specific. Their production appears more susceptible to MMF therapy. A thorough work-up of new-onset proteinuria after conversion to Sirolimus should be performed, including an immunological work-up and a renal biopsy. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
42. The Cockcroft-Gault formula should not be used in children.
- Author
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Filler, Guido, Foster, Jennifer, Acker, Amy, Lepage, Nathalie, Akbari, Ayub, and Ehrich, Jochen H.H.
- Subjects
- *
CHILDREN'S health , *MEDICAL research , *COHORT analysis , *KIDNEY diseases , *TECHNETIUM compounds , *GLOMERULAR filtration rate , *KIDNEY radiography , *KIDNEY disease diagnosis , *KIDNEYS , *PREDICTIVE tests , *RESEARCH methodology , *TECHNETIUM , *MATHEMATICS , *COMPARATIVE studies , *SEX distribution , *DESCRIPTIVE statistics , *DIAGNOSIS , *URINARY organ diseases , *SENSITIVITY & specificity (Statistics) , *LONGITUDINAL method , *CYSTATIN C , *MEASUREMENT errors , *CREATININE , *CHILDREN - Abstract
The Cockcroft-Gault formula should not be used in children.Background.Although designed for adults, the Cockcroft-Gault formula was recently proposed for use in children≥13 years of age.Methods.We compared the feasibility of the Cockcroft-Gault formula against the standard pediatric Schwartz formula and a novel cystatin C–based formula. Our patient cohort included 262 children aged 1 to 18 years with various renal pathologies, who underwent a 99-technetium diethylenetriaminepentaacetate (99Tc DTPA) glomerular filtration rate (GFR) renal scan. Calculations were performed in Système International (SI) units using published constants and recalculated constants from our patient population. Agreement was assessed using Bland and Altman analysis.Results.Published and recalculated constants for the Cockcroft-Gault formula were 1.23 and 0.96, respectively, for boys, and 1.05 and 0.90, respectively, for girls. The published and recalculated constants for the Schwartz formula were 48 and 49.9, respectively, for boys≥13 years old, and 38 and 46.2, respectively, for all girls and for boys<13 years old. Using published constants, there was agreement between GFR and Cockcroft-Gault formula in boys≥13 years old (average bias 5.0± 23.5%) while there was an average error of−19.0%± 36.4% for all ages. Similarly, the average bias with Schwartz for boys≥13 years old was−6.8± 24.0% and for all patients was−12.8± 24.2%. Using recalculated constants, the average bias with Cockcroft-Gault in boys≥13 years old was−19.8± 23.5% and for all patients was−38.5± 35.2%. Similarly, the average bias with Schwartz for boys≤13 years old was−1.1± 24.3% and for all patients was 3.0± 24.0%. The novel cystatin C–based GFR calculations showed an average error of−4.9± 20.3% in the adolescent boys and 2.4± 20.4% for all ages.Conclusion.Cockcroft-Gault formula showed the worst agreement with GFR, regardless of using published or recalculated constants. The cystatin C–based approach resulted in the least error, and should be used for estimation of GFR. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
43. Changing trends in the referral patterns of pediatric nephrology patients.
- Author
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Filler, Guido, Payne, Robert, Orrbine, Elaine, Clifford, Tammy, Drukker, Alfred, and McLaine, Peter
- Subjects
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CHRONIC kidney failure , *PEDIATRICS , *NEPHROLOGY , *OBESITY , *DIABETES , *KIDNEY diseases - Abstract
This study investigates the changing referral patterns of young patients to a tertiary pediatric nephrology center with a well-defined catchment area over two consecutive 8.5-year periods. We paid special attention to the known increase of obesity and diabetes mellitus in childhood. Demographic data (site of residence, height, weight, gender and renal diagnosis) were collected on 6,154 children aged 0-19 years, referred as in- and outpatients to the Children’s Hospital of Eastern Ontario for nephrological work-up. Body mass index (BMI)Z-scores were calculated on the basis of data from the National (USA) Center for Health Statistics (2000). In 6,124 (99.5%) patients a final renal diagnosis could be made, allowing calculation of the incidence of a variety of renal diseases in pediatric patients, data that are not readily available. BMI increased significantly over the years, with aZ-score that rose from a median of +0.20 to +0.32 in the two 8.5-year study periods (p<0.0001). The increase in obesity coincided with a significant increase in the incidence of chronic renal insufficiency (CRI). The combined incidence of CRI and end stage renal disease rose from 0.994 to 2.334 per 100,000 children per year (p=0.0014). This study provides new information on the (changing) pattern of pediatric renal disease over almost two decades. Pediatric renal patients became progressively overweight and showed an increase in the incidence of CRI. This is the first time that this phenomenon, well known in adults, has been observed in the pediatric age group. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
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44. Should the Schwartz formula for estimation of GFR be replaced by cystatin C formula?
- Author
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Filler, Guido and Lepage, Nathalie
- Subjects
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GLOMERULAR filtration rate , *KIDNEY diseases , *CHILDREN , *REGRESSION analysis - Abstract
It is common practice to estimate glomerular filtration rate (GFR) from the Schwartz formula (a height creatinine/ratio), although it has its limitations. Cystatin C was found to be a superior marker of GFR. No formula has been validated to estimate GFR from cystatin C in children. Children (aged 1.0–18 years, n=536) with various renal pathologies undergoing nuclear medicine GFR clearance studies ([sup 99m]Tc-DTPA single-injection technique) were tested. Cystatin C was measured with a nephelometric assay. The Schwartz GFR was calculated using enzymatically determined serum creatinine in micromoles per liter using the constant 48 for adolescent males and 38 otherwise. Using multiple stepwise regression analysis on log/log-transformed data, we derived the following relationship between the cystatin C concentration and GFR: . Using the Bland and Altman analysis to test agreement between the Schwartz formula and gold standard GFR showed considerable bias, with a mean difference of +10.8% and a trend towards overestimation of the GFR by the Schwartz formula with lower GFRs. In contrast, the Bland and Altman analysis applied on the GFR estimate derived from cystatin C showed the mean difference to be negligible at +0.3% and no trend towards overestimation of the GFR with lower GFRs. In the regression analysis of the estimate and the GFR, the Schwartz estimate showed significant deviation from linearity, whereas the cystatin C estimate did not. In conclusion, the data suggest that this novel cystatin C-based GFR estimate shows significantly less bias and serves as a better estimate for GFR in children. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
45. Treatment of FSGS with plasma exchange and immunadsorption.
- Author
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Franke, Doris, Zimmering, Miriam, Wolfish, Norman, Ehrich, Jochen H. H., and Filler, Guido
- Subjects
KIDNEY diseases ,PROTEINURIA ,PLASMA exchange (Therapeutics) ,CYCLOSPORINE - Abstract
In primary focal and segmental glomerulosclerosis (FSGS) renal prognosis is poor if no remission of proteinuria can be achieved with treatment. Currently, most children with FSGS are treated with cyclosporine and steroids after establishing steroid resistance, and approximately 60% of patients benefit from this therapy. For the remaining 40%, no generally approved therapeutic recommendations exist for children. We treated nine children with cyclosporine-resistant primary FSGS with plasma exchange (PE), two with relapsing FSGS after renal transplantation and seven with FSGS in their native kidneys. Three patients did not respond to PE, but five came into complete remission and one patient achieved partial remission. Three patients relapsed between 6 weeks and 2 years following cessation of PE, and were subsequently treated with plasma immunadsorption (PIA), which also reliably reduced proteinuria. The patients without response to PE tended to have a longer duration of the disease. We conclude that PE and PIA are a useful option for treatment of steroid- and cyclosporine-resistant FSGS, particularly if applied early in the course of the disease. Although more demanding on supportive resources, PIA seems preferable to PE, since there is no necessity for additional albumin or fresh-frozen plasma, as with PE. [ABSTRACT FROM AUTHOR]
- Published
- 2000
- Full Text
- View/download PDF
46. Combined liver-kidney transplantation for hyperoxaluria type II?
- Author
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Filler, Guido and Hoppe, Bernd
- Subjects
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KIDNEY diseases , *TRANSPLANTATION of organs, tissues, etc. , *RESEARCH , *CONSANGUINITY - Abstract
The article presents the author's views on the issue of primary hyperoxaluria (PH), a form of endstage renal disease (ESRD) in which kidney of the patient is transplanted. Various factors related to PH are discussed including its three types, management during dialysis and combined liver-kidney transplantation. According to a research, the disease is found in people from consanguineous marriages of North Africa and Middle East.
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- 2014
- Full Text
- View/download PDF
47. Impaired GFR is the most important determinant for FGF-23 increase in chronic kidney disease
- Author
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Filler, Guido, Liu, Daisy, Huang, Shih-Han Susan, Casier, Shelley, Chau, Luan A., and Madrenas, Joaquín
- Subjects
- *
FIBROBLAST growth factors , *KIDNEY diseases , *MOLECULAR weights , *CROSS-sectional method , *CYSTATINS , *BIOMARKERS , *REGRESSION analysis - Abstract
Abstract: Objectives: It is unclear whether fibroblast growth factor-23 (FGF-23) increases in response to phosphate accumulation or to decrease clearance in chronic kidney disease (CKD) as is the case with other low molecular weight proteins such as cystatin C (CysC). Design and methods: This cross-sectional study measured serum FGF-23, CysC, and other serum markers of bone metabolism in 69 patients, aged 18months–24years, with various stages of CKD (eGFR=11–214mL/min). Results: FGF-23 levels were significantly correlated with CysC and parathyroid hormone levels (PTH) on univariate non-linear regression analysis. In multivariate linear regression analysis, log (CysC) (β =0.660, p <0.0001), log (PTH) (β =0.038, p =0.37), and phosphate (β =0.222, p =0.028) explained 69.1% of the variance of FGF-23. Conclusions: CysC had the largest unique contribution to FGF-23 variance in this model, supporting the hypothesis that renal clearance may be the most responsible factor for elevated FGF-23 levels in early stages of CKD. [Copyright &y& Elsevier]
- Published
- 2011
- Full Text
- View/download PDF
48. Residual renal function assessment with cystatin C.
- Author
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Filler, Guido, Huang, Shih-Han, and Lindsay, Robert
- Subjects
- *
TREATMENT of chronic kidney failure , *BLOOD proteins , *KIDNEY diseases , *MEDICAL protocols , *HEALTH outcome assessment , *PERITONEAL dialysis , *THERAPEUTICS , *TREATMENT effectiveness , *CHILDREN - Abstract
Su Jin Kim and coworkers from Korea published an important study on the relationship of residual renal function (RRF) and cystatin in pediatric peritoneal dialysis (PD) patients in this issue of Pediatric Nephrology, both in anuric patients and patients with RRF. Based on a lack of correlation between cystatin C and standard small solute-based dialysis adequacy parameters such as Kt/V but a significant correlation with RRF, the authors concluded that cystatin C may be a good tool to monitor RRF. The editorial reviews the available literature in adults, the different handing between urea and cystatin C, and the determinants of cystatin C clearance in dialysis patients. In adults, cystatin C levels are determined predominantly by RRF, but not exclusively. In anephric hemodialysis and PD patients, there is a correlation with standard weekly Kt/V. Cystatin C levels will also depend on ultrafiltration. Despite these factors that affect cystatin C levels beyond RRF, cystatin C is a useful parameter for monitoring PD patients that may be more closely related to long-term outcomes than small solute adequacy parameters. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
49. Is it time for a multi-specialty approach to cardio-renal dysfunction in children with cyanotic congenital heart disease?
- Author
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Holt, Tanya and Filler, Guido
- Subjects
- *
ACUTE kidney failure , *ALBUMINURIA , *HYPOXEMIA , *CONGENITAL heart disease , *KIDNEYS , *KIDNEY diseases , *SERIAL publications , *CHILDREN - Abstract
The article presents the author's views regarding an approach to cardio-renal dysfunction in children diagnosed with congenital heart disease. Identification on the pathophysiological interplay between kidney and heart as cardiorenal syndrome (CRS), is highlighted. Also cited is the significant early CRS recognition to guide therapy and improve results of affected patients.
- Published
- 2018
- Full Text
- View/download PDF
50. Kidney disease and organ transplantation in methylmalonic acidaemia.
- Author
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Noone, Damien, Riedl, Magdalena, Avitzur, Yaron, Atkison, Paul, Sharma, Ajay P, Filler, Guido, Prasad, Chitra, and Siriwardena, Komudi
- Subjects
TRANSPLANTATION of organs, tissues, etc. ,KIDNEY diseases ,KIDNEY failure ,LOW-protein diet ,LIVER transplantation ,UBIQUINONES ,VITAMIN E - Abstract
Objectives: MMA is associated with chronic tubulointerstitial nephritis and a progressive decline in GFR. Optimal management of these children is uncertain. Our objectives were to document the pre‐, peri‐, and post‐transplant course of all children with MMA who underwent liver or combined liver‐kidney transplant in our centers. Design and methods: Retrospective chart review of all cases of MMA who underwent organ transplantation over the last 10 years. Results: Five children with MMA underwent liver transplant (4/5) and combined liver‐kidney transplant (1/5). Three were Mut0 and two had a cobalamin B disorder. Four of five were transplanted between ages 3 and 5 years. Renal dysfunction prior to transplant was seen in 2/5 patients. Post‐transplant (one liver transplant and one combined transplant) renal function improved slightly when using creatinine‐based GFR formula. We noticed in 2 patients a big discrepancy between creatinine‐ and cystatin C‐based GFR calculations. One patient with no renal disease developed renal failure post–liver transplantation. Serum MMA levels have decreased in all to <300 μmol/L. Four patients remain on low protein diet, carnitine, coenzyme Q, and vitamin E post‐transplant. Conclusions: MMA is a complex metabolic disorder. Renal disease can continue to progress post–liver transplant and close follow‐up is warranted. More research is needed to clarify best screening GFR method in patients with MMA. Whether liver transplant alone, continued protein restriction, or the addition of antioxidants post‐transplant can halt the progression of renal disease remains unclear. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
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