Comparison of cyclosporine absorption profiles over a 12-month period in stable pediatric renal transplant recipients.

Evidence suggests that the pharmacokinetic (PK) profile of microemulsion- cyclosporine A (m-CsA) during the 4-hour absorption phase represents an accurate tool to estimate drug exposure. In addition, several reports suggest a close correlation between selected single CsA concentrations at 1, 2, or 3 hours post-dose (C(1), C(2), and C(3)) and the abbreviated area under the curve (AUC)(0-4) among pediatric renal transplant patients. However, it is still unclear whether these PK correlations remain stable and reliable over 12 months posttransplant. In this study, we obtained 4-hour pharmacokinetic profiles (AUC(0-4)) from stable pediatric renal transplant recipients (phase 1) with repeat measurements 12 months later (phase 2). In addition, we evaluated the optimal single sampling point that correlated with the AUC(0-4) during both phases of the study. Over 1 year there was no significant change in the AUC(0-4) of m-CsA in pediatric renal transplant recipients. The mean dose-normalized AUC(0-4) values changed by less than 2.5%, namely, 557 versus 545 ng x h/mL per unit dose, respectively. The C(1) value was the sampling point that showed the best correlation with AUC(0-4); C(0) displayed the weakest correlation. No changes in cyclosporine dosing or glomerular filtration rate estimates were observed throughout the study period. This study demonstrates the stability of drug measurements during m-CsA therapy.

Metabolic effects of HAY's diet.

The aim of the study was, to evaluate the metabolic effect of HAY's diet on protein turnover, fat oxidation, respiratory quotient, body fat and weight loss. Twelve healthy adults received an individually regular diet and thereafter a corresponding isocaloric and isonitrogenous 10-day HAY-diet. Protein turnover and 13C-fat oxidation were investigated after administration of [15N]glycine and an [U-13C]algae lipid mixture. The 15N and 13C enrichment in urine and breath were measured by isotope ratio mass spectrometry. The respiratory quotient was measured by indirect calorimetry. Body fat, total body water and lean body mass were estimated by bio-electric impedance analysis. HAY's diet led to a significantly higher 13C-fat oxidation (15.4 vs. 22.0% P < 0.01), corresponding to a lower respiratory quotient (0.88 vs. 0.81; P < 0.01), whereas the protein turnover remained constant in both diets (3.06 vs. 3.05 g/kg/day). HAY's diet did not reduce total body water, lean body mass, body fat and body weight (72.2 vs. 71.4 kg).

Course of glomerular filtration rate after renal transplantation and the influence of hypertension.

INTRODUCTION: A gradual decline in the glomerular filtration rate (GFR) is a general problem in patients after renal transplantation that may be due to several factors. METHODS: The glomerular filtration rate (GFR) was estimated using the corrected Schwartz formula in 16 pediatric renal transplant recipients over a period of 5 years post-transplant. Several potential risk factors for graft outcome were analyzed. The mean age of the patients (8 female, 8 male) at the time of transplantation was 11.1 years (range: 2.7-17.3). All patients received a cadaveric renal graft for the first time. Immunosuppression consisted of cyclosporine in combination with steroids in all children treated; 3 patients received azathioprine in addition. Blood pressure (BP) was monitored regularly and its extent was expressed by an antihypertensive treatment (AHT) score. RESULTS: At the end of the first post-transplant year the mean GFR was 88 +/- 24 ml/min/1.73 m2. During the following 4 years the GFR declined to 68 +/- 29 ml/min/1.73 m2 representing an overall GFR loss of 20 ml/min/1.73 m2 (23%). With regard to the GFR loss, 2 groups could be distinguished. The first group of 7 patients showed a significant GFR decrease from 89 +/- 26 to 49 +/- 27 ml/min/1.73 m2 (p = 0.0025), whereas the second group of 9 patients had a relatively constant GFR during the 5 years (87 +/- 26 and 83 +/- 24 ml/min/1.73 m2). In each group, two acute rejections were observed in the first post-transplant year. Blood pressure, expressed by an AHT score, increased in Group 1 moresso than in Group 2 during the 5 years. CONCLUSION: During the course of a 5-year period post-transplant the GFR declined significantly in 7 of 16 patients. One of the factors responsible for GFR loss is probably the increase in blood pressure.