In this retrospective study 351 children (<16.0 years) with end-stage renal disease (ESRD) accepted for renal replacement therapy (RRT) in the four Dutch pediatric centers were analyzed for the period 1987-2001. The data were compared with a previous study performed in 1979-1986. Eighty patients were of non-Dutch origin. An annual ESRD incidence of 5.8 patients per million of the child population (p.m.c.p.) was calculated, without significant changes with time. The final prevalence in Dutch children under 15 years of ESRD was 38.7 p.m.c.p. The most frequent primary renal disease leading to ESRD was urethral valves, with a significant increase vs. the previous observation period (14% vs. 6%). The distribution of primary renal diseases was similar in patients of non-Dutch origin and in Dutch patients. Peritoneal dialysis was the most frequent dialysis procedure initially applied (62% vs. 26% in the earlier observation period). Thirteen percent of all first transplantations (n=278) were pre-emptive and 19% from living donors. Five-year graft survival after a living-donor and a cadaver graft was 80% and 73%, respectively. Overall patient survival after 10 years on RRT was 94%.

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Abstract:The study was conducted to formulate a physiologically motivated time-delay (PM TD) mathematical model for human beings, which incorporates disintegration of a drug formulation, dissolution, discontinuous gastric emptying and enterohepatic circulation (EHC) of a drug. Piroxicam, administered to 24 European, healthy individuals in 20 mg capsules Feldene® Pfizer, was used as a model drug. Plasma was analysed for piroxicam by a validated high-performance liquid chromatography method. The PM TD mathematical model was developed using measured plasma piroxicam concentrationtime profiles of the individuals and tools of a computationally efficient mathematical analysis and modeling, based on the theory of linear dynamic systems. The constructed model was capable of (i) quantifying different fractions of the piroxicam dose sequentially disposable for absorption and (ii) estimating time delays between time when the piroxicam dose reaches stomach and time when individual of fractions of the piroxicam dose is disposable for absorption. The model verification was performed through a formal proof, based on comparisons of observed and model-predicted plasma piroxicam concentration-time profiles. The model verification showed an adequate model performance and agreement between the compared profiles. Accordingly, it confirmed that the developed model was an appropriate representative of the piroxicam fate in the individuals enrolled. The presented model provides valuable information on factors that control dynamic mechanisms of EHC, that is, information unobtainable with the models proposed for the EHC analysis previously.Numerous drugs and other foreign substances undergo extensive elimination via bile in an unchanged or conjugated form and are available for re-absorption in the gastrointestinal tract. This is a multistep and erratic process under the control of many factors, which is referred to as enterohepatic circulation (EHC). EHC prolongs not only time required for the substance to be irreversibly eliminated from the body but also substance effects. In most cases, EHC yields to multiple peaks in plasma drug concentration-time profiles. The occurrence of multiple peaks in plasma drug concentrationtime profiles is also called 'a saw-tooth effect' [1,2]. During the past decades, extensive efforts have been made to enhance the understanding of the complicated process of EHC, using various theoretical approaches and mathematical models, as reviewed recently [3]. As a result, today there are a number of models describing behaviour of drugs possessing EHC, but models capable of estimating time delays in dynamic processes involved in EHC are missing. Therefore, this work was aimed at extending the scope of the previously published model by introducing the time-delay parameter in the EHC process.Piroxicam, a member of the oxicam group of non-steroidal anti-inflammatory drugs [4], is known under various trade names, for example, Apo-Piroxicam, Feldene, Novo-Pirocam, Nu-Pirox, Proxalyoc or PMS-piroxicam. It is recognized fo...

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In this prospective study, selected biochemical markers of glomerular and tubular function, proteinuria, and ultrasound findings in 62 pediatric patients who underwent surgery for obstructive uropathy were examined. Patients were younger than 12 months, normocreatininemic at the time of surgery, and examined at a mean age of 6.3+/-0.9 years. Out of the markers tested, serum concentration of cystatin C was significantly higher in patients when compared with the control group (p<0.001), and serum creatinine concentration was within reference interval in all patients. With respect to tubular function, 26% of patients had decreased concentration ability. Proteinuria was detected in 4.8% of patients. On ultrasound, 66.7% of kidneys after surgery had residual dilatation of the renal pelvis. The patients thrive well, and their somatic parameters do not differ from their peers. Half of the patients had one or more urinary tract infections from the date of surgery to the date of examination. Study results support the need for long-term nephrologic follow-up in patients after surgery for obstructive uropathy. The hypothesis that renal function in patients undergoing surgery aged younger than 3 or 6 months is better when compared with those aged 6 to 12 months has not been confirmed.