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Biomedical subjects

Guido Filler

Publications and source records attributed to Guido Filler.

At least 37 records · Page 2Linked to original sources
PubMed2005

Neonatal renal venous thrombosis: clinical outcomes and prevalence of prothrombotic disorders.

OBJECTIVE: To determine clinical outcomes and the prevalence of prothrombotic conditions in patients who had neonatal renal venous thrombosis (RVT). STUDY DESIGN: A retrospective cohort of neonates with RVT who were admitted to 4 pediatric centers from 1980 to 2001 was identified. Information on clinical presentation, laboratory and radiological investigation, and treatment were abstracted. Survivors were evaluated for renal status and prothrombotic conditions. RESULTS: Forty-three patients with neonatal RVT were identified. RVT was unilateral in 24 patients (56%) and associated with 2thrombi at other sites in 32 patienets (74%). Clinical presentations included renal failure in 24 patients (56%), thrombocytopenia, anemia, or both in 22 patients (51%), and renal mass in 21 patients (49%). Neonatal interventions included anti-coagulants in 28 patients (65%), antihypertensive medications in 9 patients (21%), peritoneal dialysis in 2 patients (5%), and nephrectomy in 2 patients (5%). The median age at follow-up was 3.7 years (range, 0.5-20.2 years). Thirteen patients (34%) had hypertension, and 11 patients (29%) had renal failure. End-stage renal disease developed in 3 patients, and they underwent live-related renal transplants. Twelve of the 28 patients (43%) examined had prothrombotic abnormalities. CONCLUSION: Neonatal RVT is associated with significant renal morbidity and a high prevalence of prothrombotic abnormalities.

Adolescent↗
PubMed2005

Intra-individual variation of cystatin C and creatinine in pediatric solid organ transplant recipients.

There is controversy about the feasibility of cystatin C (CysC) as a marker of glomerular filtration rate (GFR) post-transplant (Tx). We studied intra-patient variability of CysC in comparison with serum creatinine (SCr) in 20 children (11 males, mean age 11.5 +/- 6.4 yr) with solid organ transplants (14 kidney, four liver, and two combined liver + kidney transplants). The mean age at Tx was 7.0 +/- 5.6 yr. A total of 178 simultaneous SCr and CysC measurements (median 8 per patient) were analyzed. In addition, GFR was calculated using the Schwartz and a novel CysC-based formula. Intra-individual coefficient of variations (CV) was calculated as ratio of standard deviation over mean. The mean CV was significantly lower for SCr (7.71 +/- 4.16%) when compared with CysC (10.27 +/- 4.87, p = 0.04), but was no longer significantly different when excluding patients with a bladder augment. The CV of the GFR estimated by Schwartz formula (7.44 +/- 3.77) was significantly lower than GFR calculated from CysC (12.52 +/- 7.37), p = 0.001. The mean ratio between the Schwartz GFR and the GFR calculated from CysC was 102.6 +/- 12.8%, not significantly different from 100% (p = 0.3796). The only potential confounding factors to explain increased CV after Tx were gender and bladder augmentation, whereas calcineurin inhibitors or steroids did not influence CV. With the limitation of a small number of subjects, our data suggest that the CysC and the CysC-calculated GFR is equivalent but not better than SCr and Schwartz formula. We therefore conclude that measurement of CysC can be used for longitudinal intra-individual follow-up of renal function post-Tx.

Child↗
PubMed2005

Four-year data after pediatric renal transplantation: a randomized trial of tacrolimus vs. cyclosporin microemulsion.

This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with cyclosporin microemulsion (CyA) in pediatric renal recipients. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (<18 yr) were randomly assigned (1:1) to receive either Tac (n = 103) or CyA (n = 93) administered concomitantly with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection (intent-to-treat). Baseline characteristics were comparable between treatment groups. Excluding deceased patients (n = 9) and patients lost to follow-up (n = 31, mostly transferred to adult care), 95% of 2-yr data (159 of 167 possible patients), 87% of 3-yr data (142 of 163) and 73% of 4-yr data (114 of 156) were retrieved. At 1 yr Tac therapy resulted in a significantly lower incidence of acute rejection (36.9%) compared with CyA (59.1%, p = 0.003). The incidence of corticosteroid-resistant rejection was also significantly lower with Tac (7.8% vs. 25.8%, p = 0.001). At 4 yr, patient survival was similar (94% vs. 92%, p = 0.86) but graft survival significantly favored Tac (86% vs. 69%; p = 0.025, log-rank test), respectively. At 1 yr, the mean glomerular filtration rate (GFR) (Schwartz formula, ml/min/1.73 m(2)) was 64.9 +/- 20.7 (n = 84) vs. 57.8 +/- 21.9 (n = 77, p = 0.0355), at 2 yr 64.9 +/- 19.8 (n = 71) vs. 51.7 +/- 20.3 (n = 66, p = 0.0002), at 3 yr 66.7 +/- 26.4 (n = 81) vs. 53.0 +/- 23.3 (n = 55, p = 0.0022), and at 4 yr 71.5 +/- 22.9 (n = 51) vs. 53.0 +/- 21.6 (n = 44, p = 0.0001) for Tac vs. CyA, respectively. Cholesterol remained significantly higher with CyA throughout follow-up. Three patients in each arm developed post-transplant lymphoproliferative disease. Incidence of insulin-dependent diabetes mellitus was not different. Tac was significantly more effective than CyA in preventing acute rejection in pediatric renal recipients. Renal function and graft survival were also superior with Tac. Glomerular filtration rate appears to be an useful surrogate marker for long-term outcome.

Adolescent↗
PubMed2005

Caregiver attitudes towards gastrostomy removal after renal transplantation.

Gastrostomy tube (G-tube) removal has been suggested at 3 months following successful renal transplantation (Tx). We noticed a delay in the removal of G-tubes in our pediatric patients following Tx and therefore conducted a cross-sectional single center survey on all renal transplant recipients to assess the causes of delayed G-tube removal. In total, 17 of 23 patients completed the survey, including all patients with G-tubes (n = 10) and seven patients without G-tubes. Median age at Tx of gastrostomy patients was significantly lower than that of patients without a G-tube (median 3.0 yr, range 1.2-4.7 yr vs. median 14 yr, range 6-17 yr, p < 0.0001) and significantly younger than in previous studies on gastrostomies. At the time of the survey, only three of 10 patients had their G-tube removed at 22, 41 and 61 months after Tx at the ages of 3, 5.5 and 9 yr, respectively. The median age at recent follow up of the remaining seven patients was 4.7 yr (range 2.6-8.75 yr). The most important reason for continued use was fluid intake and medication. Results of our survey showed appropriate concern regarding the risk of prolonged use of the gastrostomy. Caregivers felt that benefits of the gastrostomy in the post-transplant period outweighed the risks. Caregivers felt pressured towards removal by the physicians. Our findings support the decision to remove gastrostomies based on individual patient needs and total fluid intake rather than a fixed time following successful Tx.

Adolescent↗
PubMed2005

Tissue viral DNA is associated with chronic allograft nephropathy.

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.

Adolescent↗
PubMed2005

Cystatin-C and beta trace protein as markers of renal function in pregnancy.

OBJECTIVE: To assess the validity of Cystatin-C (Cys-C) and beta trace protein (BTP) as clinical markers of glomerular filtration rate (GFR) in pregnant women. DESIGN: Prospective cross sectional study. SETTING: Obstetric unit of a tertiary care hospital. POPULATION: One hundred and thirty-seven normal pregnant women and 13 women postpartum. METHODS: Twenty-four hour creatinine clearance (CrCl), serum creatinine, Cys-C and BTP concentrations were measured on normal pregnant women in the first trimester (n= 5), second trimester (n= 68) and third trimester (n= 64) and in 13 women postpartum. Data are given as median (2.5th centile, 97.5th centile). MAIN OUTCOME MEASURES: Serum concentrations of Cys-C and BTP compared with creatinine clearance and serum creatinine. RESULTS: The median serum creatinine throughout gestation was 53 micromol/L (39, 71), and median CrCl was 143 mL/minute (91 to 216). Postpartum, creatinine rose to 74 micromol/L (58, 86) and CrCl decreased to 104 mL/minute (71, 159). For Cys-C, the median concentration was 0.70 mg/L (0.46, 1.32), and 0.54 mg/L (0.36, 0.96) for BTP. Comparing the second and third trimesters, there was no significant difference between CrCl (median 145 vs 141 mL/minute) and BTP concentrations (median 0.51 vs 0.55 mg/L), while median Cys-C was significantly higher in the third trimester (0.61 vs 0.88 mg/L; P < 0.001). Unlike creatinine and BTP, Cys-C levels decreased to 0.72 mg/L (0.57, 0.95) postpartum. The only significant relationship of either of these markers to the standard used for GFR was between Cys-C and CrCl in the third trimester, and the correlation was weak (r= 0.27 for 1/Cys-C vs CrCl). CONCLUSION: These data demonstrate that despite claims to the contrary, Cys-C is a poor marker of GFR during pregnancy. Similarly, BTP shows little promise.

Biomarkers↗
PubMed2005

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 > or =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 ((99)Tc DTPA) glomerular filtration rate (GFR) renal scan. Calculations were performed in Systeme 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 > or =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 > or =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 > or =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 > or =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 < or =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.

Adolescent↗
PubMed2005

Adding sirolimus to tacrolimus-based immunosuppression in pediatric renal transplant recipients reduces tacrolimus exposure.

In adult renal recipients, coadministration of tacrolimus (TAC) and sirolimus (SIR) results in reduced exposure to TAC at SIR doses of 2 mg/day. Eight pediatric renal recipients (median age at transplant 2.0 years, range: 1.2-12.9 years) were converted to TAC- and SIR-based immunosuppression as a rescue therapy. All patients had biopsy-proven chronic allograft nephropathy. TAC levels were measured using a commercially available EMIT assay and SIR levels with a newly developed assay based on the LC-MS MS technology. SIR was started at 0.13+/-0.05 mg/kg/day (3.51+/-1.26 mg/m2/day) in two divided doses. TAC was given at 0.14+/-0.09 mg/kg/day, resulting in a trough level of 6.3+/-2.5 ng/mL. After the addition of SIR, the median dose required to keep TAC blood trough concentrations within the target range increased by 71.2% (range: 21.9-245.4%), dose-normalized TAC exposure (AUC) decreased to 67.1% and the dose-normalized C(max), a surrogate for absorption rate, to 53.8% (both geometric means) while terminal half-life (t1/2), a pharmacokinetic parameter characterizing systemic elimination, remained unchanged (p<0.93). Adding SIR to TAC-based immunosuppression in young pediatric renal transplant recipients results in a significant decrease of TAC exposure. TAC trough levels should be monitored frequently.

Adolescent↗
PubMed2005

Pseudo-tumoral eosinophilic cystitis in a 3 year-old girl.

Eosinophilic cystitis (EC) is an uncommon form of bladder inflammation. It is a rare disorder in children and fewer than 25 cases have been described in the literature. We report a case of eosinophilic cystitis mimicking a bladder tumor in a 3 year-old girl with symptoms of urinary frequency. The diagnosis was confirmed with pathology and she underwent clinical treatment with corticosteroids.

Child, Preschool↗
PubMed2004

To what extent does the understanding of pharmacokinetics of mycophenolate mofetil influence its prescription.

Within a short period, we have witnessed a dramatic increase in the use of mycophenolate mofetil (MMF) in pediatric renal transplantation, with the drug often replacing azathioprine in combination with calcineurin inhibitor therapy. When the drug was introduced, the manufacturer considered therapeutic drug monitoring (TDM) unnecessary. However, TDM studies revealed substantial inter- and intra-individual variability and drug interactions. There is a substantial drug interaction between MMF and cyclosporine, and lower doses are required in combination with tacrolimus (~500-800 mg/m(2) per day) than with cyclosporine (~1,200 mg/m(2) per day). Patients with autoimmune disease require an intermediate dose when receiving no concomitant calcineurin inhibitor (~900 mg/m(2) per day). It has been possible to detect drug interactions and to minimize adverse events only with TDM. This is especially important with increasing use of combination therapies. Pharmacodynamic monitoring (measuring the biological response to a drug) coupled with pharmacokinetics allow optimization of drug dosing, with maximum efficacy and minimal toxicity. More work is required to establish specific target ranges with the various drug combinations--especially for the pediatric population.

Child↗
PubMed2004

Challenges in the management of infantile factor H associated hemolytic uremic syndrome.

We describe a 1-year old with four episodes of recurrent hemolytic uremic syndrome (HUS). Family history suggested an autosomal dominant mode of inheritance. Factor H concentrations in the blood were normal in the affected family members. Mutation screening in the human complement factor H gene ( HF-1) revealed a novel mutation in exon 23 (c.3546_3581dup36). The HF-1 gene encodes complement factor H and the mutation leads to the insertion of 12 additional amino acids after codon 1176 in factor H. The recurrent HUS responded to plasma infusions and renal function improved from a glomerular filtration rate of 21 to 50 ml/min per 1.73 m(2). The infusions of fresh-frozen plasma were necessary at once-weekly intervals at a dose of 40-45 ml/kg in order to maintain remission and resulted in significant hyperproteinemia. This was addressed by intermittent plasma exchange through an arterio-venous fistula. The prognosis and therapeutic dilemmas are discussed.

Complement Factor H↗
PubMed2004

The safety and use of short-acting nifedipine in hospitalized hypertensive children.

Recent reports suggest that calcium channel blockers are harmful in the treatment of acute hypertension in adults. However, short-acting nifedipine is an effective and useful medication in pediatric hypertension and is currently utilized for hypertensive emergencies. This study will address these safety concerns in hypertensive children. Medical records (from five Canadian pediatric hospitals) of all pediatric hypertensive hospitalized children who were treated with short-acting nifedipine from January 1995 to December 1998 were retrospectively reviewed for patient demographics, dosing regimen, use of concomitant medications, co-morbid conditions, and presence/absence of minor and serious adverse events. Final data were extracted from 182 patients. Each patient had an average of 2.6 episodes of hypertension in hospital that required treatment, totaling 477 episodes. Within the 477 episodes, 1,162 doses of short-acting nifedipine were administered. The mean dose was 0.22 mg/kg (range 0.043-0.67 mg/kg, median 0.19 mg/kg) with 55.6% (260/468 episodes) receiving the drug via the sublingual route. Hypertension resolved in 85.5% (408/477) of the episodes. There were only 29 of 574 (5.1%) minor adverse events that were definitely or probably related to short-acting nifedipine administration. Two patients experienced a serious adverse event that involved of a reduction in blood pressure of more than 40%, but neither had any symptomatology from the serious adverse event and recovered spontaneously within 2 h. Short-acting nifedipine in hypertensive, hospitalized children appears to be a safe and efficacious medication with minimal side effects.

Adolescent↗
PubMed2004

Abbreviated mycophenolic acid AUC from C0, C1, C2, and C4 is preferable in children after renal transplantation on mycophenolate mofetil and tacrolimus therapy.

In order to allow a similar algorithm to be used for both adults and children on tacrolimus-based and mycophenolate mofetil [MMF, a pro-drug for mycophenolic acid (MPA)]-based immunosuppression, a limited sampling technique from the trough level (C0) and the levels 30 min (C0.5) and 2 h (C2) after intake was to be developed from MPA area under the time-concentration curves (AUC). We retrospectively analyzed 49 full ten-point pharmacokinetic (PK) profiles from 29 pediatric patients on MMF and tacrolimus. We used stepwise multiple regression analysis to calculate limited sampling approaches. Agreement with the AUC was tested by means of Bland and Altman analysis. The correlation between AUC and pre-dose trough concentration was r(2)=0.5188 ( P<0.0001) and between AUC and post-dose trough concentration r(2)=0.6924 ( P<0.0001). The next best correlations were with 2 h (C2, r(2)=0.6711, P<0.0001), 4 h (C4, r(2)=0.6411, P<0.0001), 1.5 h (C1.5, r(2)=0.6344, P<0.0001), and 6 h (C6, r(2)=0.6219, P<0.0001). Three-point estimates at C0, C0.5, and C2 resulted in an acceptable correlation between predicted AUC and AUC from the full profile when we used the formula AUC = 10.01391+3.94791xC0+3.24253xC0.5+1.0108xC2, Pearson's r=0.8996, 95% confidence interval 0.8277-0.9424. However, even better results could be obtained when we used AUC = 8.217+3.163xC0+0.994xC1+1.334xC2+4.183xC4, Pearson's r=0.9456, 95% confidence interval 0.9051-0.9691. Bland and Altman analysis revealed good agreement between AUC predicted from C0, C0.5, and C2 and AUC from the full profile, but was inferior to the four-point approach. Also, the previously reported formula derived for adults was not usable in these patients. A special formula must be used for children. The AUC of MPA can be predicted by limited sampling including C0, C0.5, and C2, while an approach using C0, C1, C2, and C4 is preferable.

Adolescent↗
PubMed2004

Patients with autosomal dominant polycystic kidney disease hyperfiltrate early in their disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) ranks among the most common genetic disorders. The development of end-stage renal failure usually is after the fourth decade of life. Angiotensin-converting enzyme (ACE) inhibitors often are used as agents to slow the progression of renal failure, although their effectiveness and starting point in ADPKD remain unclear. METHODS: We measured technetium 99m diethylenetriamine pentaacetic acid glomerular filtration rate (GFR) and serum cystatin C (Cys-C) levels in 18 children with ADPKD and 41 control patients. Data are given as mean +/- SD. Mean age was 9.8 +/- 5.9 years, mean height was 137.5 +/- 34.3 cm, and mean weight was 39.2 +/- 22.8 kg in the ADPKD group, not significantly different from controls, with an average age of 10.4 +/- 4.9 years, height of 138.0 +/- 26.1 cm, and weight of 38.0 +/- 16.8 kg. RESULTS: Mean serum creatinine levels did not differ between the ADPKD (0.6 +/- 0.2 mg/dL [51.1 +/- 20.4 micromol/L]) and control groups (0.7 +/- 0.2 mg/dL [59.8 +/- 15.3 micromol/L]; P = 0.19). Mean GFR was 142 +/- 33.2 mL/min/1.73 m2 in the ADPKD group, significantly greater than that in controls (110 +/- 12 mL/min/1.73 m2; P < 0.0001). Mean Cys-C level for the ADPKD group was 0.71 +/- 0.11 mg/L, significantly lower than that of controls (0.81 +/- 0.12 mg/L; P = 0.0011). No patient with ADPKD had hypertension, and only 1 patient had minimal microalbuminuria. Although renal length on ultrasound was significantly increased, there was no correlation between renal length and GFR or number of cysts. CONCLUSION: Therefore, the high GFR measurements represent early hyperfiltration in children and adolescents with ADPKD, which may give a rationale to start ACE inhibitor therapy.

Adolescent↗
PubMed2004

MDR1 haplotypes derived from exons 21 and 26 do not affect the steady-state pharmacokinetics of tacrolimus in renal transplant patients.

AIM: This retrospective study investigated the influence of MDR1 haplotypes derived from the polymorphisms 2677G > T (exon 21) and 3435C > T (exon 26) on the pharmacokinetics of the immunosuppressant drug tacrolimus in 73 renal transplant patients. METHODS: Based on both variants of SNPs 2677 and 3435, four different haplotypes and eight different genotypes were identified in the study sample. Tacrolimus trough concentrations (C(0)) were compared between different SNP variants and genotypes, as well as between carriers and noncarriers of each haplotype. Additionally, CYP3A5 genotype (6956G > A) was determined. RESULTS: No significant differences were observed between groups. Differences in mean tacrolimus C(0) values between carriers and noncarriers of each haplotype ranged from -0.04 microg/litre (95% confidence interval: -0.53 to 0.60) to -23 microg/litre (-1.07 to 1.53). No association was found between CYP3A5*1/*3 genotype and tacrolimus Co concentractions. CONCLUSION: MDR1 haplotypes derived from the SNPs 2677G > T (exon 21) and 3435C > T (exon 26) do not influence the pharmacokinetics of tacrolimus in renal transplant patients.

Adolescent↗