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Biomedical subjects

Guido Filler

Publications and source records attributed to Guido Filler.

At least 19 recordsLinked to original sources
PubMed2007

How to define anemia in children with chronic kidney disease?

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 m(2) in patients with stage I CKD (n=196), 76 +/- 8 mL/min/1.73 m(2) for stage II (n=104), 45 +/- 9 mL/min/1.73 m(2) for stage III (n=36), and 22 +/- 5 mL/min/1.73 m(2) 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.

Adolescent↗
PubMed2006

Growth impairment shows an age-dependent pattern in boys with chronic kidney disease.

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.

Adolescent↗
PubMed2006

Pharmacokinetics of pyridostigmine in a child with postural tachycardia syndrome.

Pyridostigmine has been proposed for the treatment of postural orthostatic tachycardia syndrome in adults at a dose of 60 mg twice daily, but no dosing recommendation exists for children. With the approval of our local ethics board, we tested the pharmacokinetics of pyridostigmine in 6 children with myasthenia and a pediatric index patient with severe postural orthostatic tachycardia syndrome whose condition failed all conventional therapy and who had developed significant postural hypertension. Pyridostigmine was quantified by using a validated, semiautomated, and specific high-performance liquid chromatography/tandem mass spectrometry assay in combination with online column-switching extraction and turbo electrospray ionization. The patient with postural orthostatic tachycardia syndrome showed a dose-dependent favorable response to oral pyridostigmine. Pharmacokinetic evaluation revealed a short half-life of 2.29 hours, similar to the 2.0 +/- 0.63 hours in the patients with myasthenia. The patient with postural orthostatic tachycardia syndrome has subsequently been treated at a dose of 45 mg in the morning, 30 mg at lunchtime, and 15 mg at bedtime; after 9 months, there has been persistent positive effect and without additional blood pressure medication. No major adverse effects occurred. Pyridostigmine has been a safe and effective treatment modality for this child with postural orthostatic tachycardia syndrome. The short half-life suggests that dosing 3 times per day is preferable.

Adolescent↗
PubMed2006

Unexpectedly high exposure to enteric-coated mycophenolate sodium upon once-daily dosing.

Enteric-coated mycophenolate sodium (EC-MPS) has a mean half-life of 11.7 hours, which encouraged hope of using this drug once daily in a nonadherent adolescent SLE patient. This is a case report on a 17-year-old adolescent with a history of noncompliance who was switched from twice-daily mycophenolate mofetil (MMF) to once-daily EC-MPS. The EC-MPS dose was equimolar to the daily MMF dose (1 g MMF BID and 1.44 g of EC-MPS OD). The active compound of both drugs, mycophenolic acid, was measured using a commercially available EMIT assay. Both drugs were well-tolerated and maintained remission of the SLE. The average of three 12-hour areas under the time-concentration curves (AUC) on 1 g of MMF BID was 59.0 mgxh/L. In contrast, the 24-hour AUC after 1.44 g EC-MPS OD was 283.2 mgxh/L, more than double the expected 118.0 mgxh/L of two MMF dosing intervals. A repeat 24-hour AUC after 1.08 g of EC-MPS was 218.2 mgxh/L. EC-MPS once daily may be a well-tolerated therapeutic option for nonadherent adolescent lupus patients, but may be associated with a significantly higher exposure than the equivalent MMF BID dose.

Adolescent↗
PubMed2006

Pseudomonas aeruginosa infection: an uncommon cause of post-renal obstruction following induction therapy for acute lymphoblastic leukemia.

A 14-month-old infant presented with gastroenteritis with febrile pancytopenia and was diagnosed with acute lymphocytic leukemia (ALL). Ten days post induction therapy, the patient developed hypertension that was ascribed to steroid therapy and treated with metoprolol and amlodipine. As leukocyte numbers began to recover the asymptomatic patient became anuric. Ultrasound showed echoic floating structures in the bladder. Following cystoscopy and retrograde pyelography examination, purulent debris was irrigated from the bladder and grew Pseudomonas aeruginosa. Ciprofloxacin therapy was initiated and renal function was restored within 2 days. The case highlights the potential for renal obstruction after neutropenia recovery in children undergoing induction therapy for ALL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Management of severe hypertension in a child with tuberous sclerosis-related major vascular abnormalities.

OBJECTIVE: We report the case of a 4-year-old girl with tuberous sclerosis who presented with severe renovascular hypertension secondary to compression of the renal arteries by a large infradiaphragmatic abdominal aortic aneurysm. DESIGN: Case report of a previously unreported case. RESULTS: Normotension could not be achieved despite conservative treatment with three antihypertensive drugs at high doses. An aortic graft was performed successfully but failed to correct the hypertension. Postoperatively, the child experienced acute renal failure after attempting treatment with additional enalapril. Further investigations revealed ischaemia of the left kidney and stenosis of the right renal artery. Subsequently, a combination of maximum dose minoxidil, a calcium antagonist, clonidine and peripheral alpha and beta-blockers, and diuretics was used, but her blood pressure control remained poor. A bypass between the hepatic artery and the right renal artery restenosed at the proximal anastomosis. Her renovascular hypertension was finally improved with an autotransplantation of her right kidney into the right iliac fossa. Fibromuscular dysplasia and abundant collagen deposition were the predominant features seen on histology. She is currently normotensive on moderate doses of a beta-blocker, amlodipine and a diuretic. CONCLUSION: Hypertension in this case was impossible to control medically, and the surgical approach was compromised by numerous complications. This case illustrates the challenges in the management of renovascular hypertension in a child with disease-associated vascular malformations.

Aortic Aneurysm, Abdominal↗
PubMed2006

Preventing sensitization with mycophenolate mofetil in a pediatric kidney recipient.

Sensitization, as measured by panel reactive antibodies (PRAs), occurs as a result of previous organ transplantation, blood transfusions, or pregnancy. The high-PRA levels increase the risk of complications during transplantation and may result in long time duration for future transplants. Mycophenolate mofetil (MMF) has been shown to decrease lymphocyte proliferation and antibody formation. We report the use of prophylactic MMF in preventing the formation of PRAs in a pediatric renal transplant recipient with multiple donor exposures. A four-yr-old girl received an unsuccessful living-related renal transplant in February 2003 and was subject to multiple blood transfusions in the perioperative period. MMF, 500 mg/m2/day in two divided doses, achieved suppression of PRAs to less than 20% and allowed successful renal transplantation within nine months. No side effects occurred. This approach may reduce the risk of sensitization in future potential organ donor recipients in similar situations.

Cell Proliferation↗
PubMed2006

Cyclosporin twice or three times daily dosing in pediatric transplant patients - it is not the same!

Not infrequently, physicians elect to divide CyA-ME from b.i.d. to t.i.d. dosing in an effort to minimize toxicity. Equivalent exposure is assumed. Few studies have compared 24-h PK profiles on both dosing regimes in the same patient. We retrospectively studied a heterogeneous population of seven pediatric patients (one heart transplant, five renal transplants and one FSGS patient) on both dosing regimes who had complete 24-h PK profiles on CyA-ME. Four patients were converted from b.i.d. to t.i.d. and three patients from t.i.d. to b.i.d. dosing. There was no difference in the dose/kg (5.66 +/- 2.52 mg/kg on b.i.d. dosing and 5.75 +/- 1.81 mg/kg on t.i.d. dosing, p = 0.8578, two-sided t-test). When comparing the dose-normalized AUCs over 24 h, every single patient demonstrated lower CyA-ME exposure on t.i.d. than on b.i.d. dosing with an average relative bioavailability that was 37.9% lower on t.i.d. than on b.i.d. dosing. The median dose-normalized AUC(0-->24h) dropped from 1620 ng x h x kg/mL x mg (range: 1253-4319) on b.i.d. to 1016 ng x h x kg/mL x mg (range: 712-1485, p = 0.02, Wilcoxon's matched pairs test) on t.i.d. dosing. Our results indicate t.i.d. dosing of CyA-ME results in significantly lower exposure when the same total dose is administered in two divided doses. This reduced exposure may potentially increase the risk for rejection.

Adolescent↗
PubMed2005

Influence of commonly used drugs on the accuracy of cystatin C-derived glomerular filtration rate.

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.

Adolescent↗
PubMed2005

Estimating glomerular filtration rate in kidney transplantation: a comparison between serum creatinine and cystatin C-based methods.

Accurate measurement of GFR is critical for the evaluation of new therapies and the care of renal transplant recipients. Although not accurate in renal transplantation, GFR is often estimated using creatinine-based equations. Cystatin C is a marker of GFR that seems to be more accurate than creatinine. Equations to predict GFR based on the serum cystatin C concentration have been developed, but their accuracy in transplantation is unknown. GFR was estimated using four equations (Filler, Le Bricon, Larsson, and Hoek) that are based on serum cystatin C and seven equations that are based on serum creatinine in 117 adult renal transplant recipients. GFR was measured using radiolabeled diethylenetriaminepentaacetic acid (99mTc-DTPA), and the bias, precision, and accuracy of each equation were determined. The mean (99m)Tc-DTPA GFR was 58 +/- 23 ml/min per 1.73 m(2). The cystatin C-based equations of Filler and Le Bricon had the lowest bias (-1.7 and -3.8 ml/min per 1.73 m2), greatest precision (11.4 and 11.8 ml/min per 1.73 m2), and highest accuracy (87 and 89% within 30% of measured GFR, respectively). The cystatin C equations remained accurate even when the measured GFR was >60 ml/min per 1.73 m2. The creatinine-based equations were not as accurate, with only 53 to 80% of estimates within 30% of measured GFR. Cystatin C-based equations are more accurate at predicting GFR in renal transplant recipients than traditional creatinine-based equations. Further prospective studies with repetitive measurement of cystatin C are needed to determine whether cystatin C-based estimates of GFR will be sufficiently accurate to monitor long-term allograft function.

Adult↗
PubMed2005

Plasma exchange using a continuous venovenous hemofiltration machine in children.

BACKGROUND: There is considerable interest in using continuous venovenous hemofiltration machines for plasma exchange therapy in children. METHODS: Retrospective study of 7 patients and 61 plasma exchange treatments using the Baxter/Edwards Lifesciences BM25 machine with commercially available plasma filters (mostly Asahi Plasmaflo). RESULTS: The average total exchange volume was 1.5 times the plasma volume, achieved at a blood flow rate of 100 ml/m(2) (3.5 ml/kg/min) and a turnover rate of 25 ml/kg/h over a 3-hour duration. Fifty-six percent of the time, a mean heparin bolus of 29 units/kg resulted in subtherapeutic activated clotting times. Mean heparin infusion rates of 35 units of heparin/kg/h achieved effective anticoagulation. A calcium infusion rate of 0.11 +/- 0.05 mmol/kg/h avoided hypocalcemia. One patient experienced the serious complication of membrane reaction. CONCLUSIONS: This setup provides a safe approach to plasma exchange in children. A similar method could be implemented in other centers.

Adolescent↗
PubMed2005

Changing trends in the referral patterns of pediatric nephrology patients.

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 a Z-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.

Adolescent↗
PubMed2005

Icodextrin re-absorption varies with age in children on automated peritoneal dialysis.

Information on the use of Icodextrin in children remains scarce; however, it is believed that the characteristics are similar across all ages. We report the use of Icodextrin in a cohort of pediatric automated peritoneal dialysis (APD) patients younger than those previously reported (n=8, median age of 2.8, range 0.02-17.1 years). Net Icodextrin daytime dwell ultrafiltration was calculated in each patient for every day on therapy as ml/h/m2. Half of the patients showed re-absorption even when reducing Icodextrin dwells from a median of 10 to 6 h. All four patients who re-absorbed the Icodextrin (ranging from -23.7+/-7.5 to -2.5+/-6.0 ml/h/m2) were treated with cyclic nocturnal APD, and three of these four patients were high transporters on the peritoneal equilibration test (PET). Icodextrin fluid removal correlated significantly with age (Spearman rank r=0.8571, P=0.0107). The data suggest that Icodextrin behaves differently in young children.

Absorption↗
PubMed2005

Cystatin C as a marker of GFR--history, indications, and future research.

OBJECTIVE: To summarize recent knowledge on the small molecular weight protein cystatin C (cys-C) and its use as a marker of the glomerular filtration rate (GFR). METHODS: A multinational expert meeting was held in April 2002 in Marburg, Germany. Contributors summarized their main findings. CONCLUSIONS: Cys-C is at least equal if not superior to serum creatinine as a marker of GFR. The independence from height, gender, age, and muscle mass is advantageous. Select patient groups such as children, the elderly, and patients with reduced muscle mass benefit in particular.

Adolescent↗