The reliability of urea kinetic modelling (UKM) in paediatric haemodialysis was tested by comparing results of the classic variable volume model (UKM3), a recently introduced two-sample modification of this (UKM2) and direct quantification by a partial dialysate collection method (PDC). Urea generation rate (G) was also found from a 1-week collection of dialysate and urine (OWC). Nine children aged 2-18 years and weighing 10.6-39.9 kg were examined over 1 week (25 treatments). UKM3 and UKM2 gave almost identical results, but deviated from PDC and OWC. The two indirect methods overestimated G by 24% and 18%. However, the correlations between the results were very high for all variables and all methods (r > or = 0.96). Repeating UKM3 and UKM2 mid-week for 5 consecutive weeks, the following coefficients of variation were found: for the normalised whole body urea clearance (Kt/V) 10% and 11%, respectively; for normalised protein catabolic rate 17% and 14%. It is concluded that all tested methods can be used, but each method requires its own reference interval. Results of UKM seem to vary somewhat more than in adults. This should be considered when assessing children by such methods.

The effects of adrenaline and terbutaline on cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) content, 22Na‐efflux, 42K‐influx and subtetanic contractions have been assessed in soleus muscles isolated from guinea‐pigs which had been maintained on food with or without terbutaline for 5 days. Terbutaline and adrenaline increased cyclic AMP content and suppressed subtetanic contractions, and regression analysis indicates a statistically significant correlation between these two effects (P<0.01). In muscles obtained from terbutaline‐treated animals, the effects of terbutaline and adrenaline on cyclic AMP content, active Na‐K‐transport and subtetanic contractions were all considerably suppressed, but insulin stimulated 22Na‐efflux and affected subtetanic contractions to the same extent as in the muscles obtained from the control group. The results suggest that terbutaline treatment leads to a reduction in the number of β2‐adrenoceptors in skeletal muscle or an impairment of their function. The results provide further support for the idea that the effect of adrenaline or insulin on skeletal muscle contractions is the outcome of stimulation of active Na‐K‐transport.

To test the accuracy of urea kinetic modeling (UKM), the classic fixed-volume model UKM_f, two variable-volume models (UKM_vb and UKM_vd), direct dialysis quantification (DDQ) and a partial dialysate collection method (PDC) were evaluated in 15 stable, high-hematocrit patients. Urea generation rate (G) was also determined from a 1-week collection of total dialysate and urine (OWC). The results, except distribution volumes, were highly correlated. However, Kt/V, the normalized whole-body urea clearance, was about 8% higher with UKM_vb and UKM_vd. Two of three simple equations for Kt/V rendered grossly deviating, but highly correlating, results. The normalized protein catabolic rate was 8% higher with UKM_vd. With OWC as reference, UKM_vb and UKM_vd overestimated G by 19 and 15%, respectively. All results of PDC closely followed those of DDQ. This method may be an alternative for exact quantification. Before using a new UKM method it should be compared to an established reference method.

Comparisons of extra-cellular fluid (ECF) volume estimates made by isotope dilution and electrical impedance techniques have been made in a group of 16 children. For each patient an estimate of ECF volume (Vt) was obtained from measurements of the blood clearance of 99Tcm-diethylene triamine penta-acetate (DPTA) which was compared with two estimates (Vi1 and Vi2) of ECF volume obtained from measurements of the whole-body electrical impedance at 50 frequencies in the range 1 kHz to 1.348 MHz and a third estimate Vh based on patient height, L, alone. The observed frequency response of the impedance measurements was fitted to a three-element equivalent-circuit model of whole-body impedance and gave a value of the ECF resistance R. Vi1 was obtained from Vi1 = a (L2/R) + b. Vi2 was given by c(W1/2L2/R)2/3 where W is the patient weight, and Vh was given by dL2 + e. The constants a, b, c, d, e were determined by comparison with Vt and were equal to 0.335 l omega m-2 (standard error = 0.01 1 omega m-2), 0.42 l (0.25 l), 0.33 l (omega 2kg-1m-4)1/2 0.007 l (omega 2kg-1m-4)1/3, 4.92 l m-2 (2.8 x 10(-5) lm-2), 0.13 l (0.41 l), respectively. Vi1, Vi2, Vh were linearly correlated with Vt (r2 = 0.98, 0.99, 0.95, respectively, p < 0.001), and upper and lower levels of agreement were given by +/- 0.95 l (Vt and Vi1), 1.44 l and -1.12 l (Vt and Vi2), +/- 1.5 l (Vt and Vh), respectively. Thus inclusion of the impedance data accounted for greater volume variation, but differences between the techniques were not significant (paired t-test and Mann-Whitney analysis) suggesting that more accurate and detailed measurements are required.

The pharmacokinetics and the effect of ticlopidine on platelet aggregation were determined in patients with chronic renal failure (n = 6), who were not on dialysis and had glomerular filtration of 16.9 +/- 4.4 mL/min, and were matched with the pharmacokinetics and effects in healthy volunteers (n = 7). Participants were studied after acute oral administration of ticlopidine at the beginning of the study and after 36 days of treatment with 250 mg twice daily. For unchanged ticlopidine there were no significant differences between the concentration profiles for the two study groups. By day 36 the minimum concentrations in plasma were identical (0.35 +/- 0.22 mg/L and 0.36 +/- 0.21 mg/L, respectively). Using 14C-labeled ticlopidine, the concentration profiles of radioactivity on day 1 were similar to those on day 36 for both groups. However, maximum concentrations and area under the concentration-time curve at 72 hours were both higher in patients with renal failure than in healthy volunteers. Treatment with ticlopidine progressively decreased sensitivity to adenosine diphosphate-induced platelet aggregation. At day 36, the concentration of adenosine diphosphate required to achieve 50% platelet aggregation was approximately 2.5 times greater than before treatment. Both patients and healthy volunteers exhibited closely comparable changes. The response to collagen-induced platelet aggregation was not changed in patients by treatment with ticlopidine. In contrast, volunteers required a three- to fourfold increase in collagen concentration to achieve 50% platelet aggregation after 36 days of therapy. Although some differences in both pharmacokinetics and pharmacodynamics of ticlopidine have been demonstrated between patients and and healthy volunteers, results in this study demonstrated that a change of dosage is not required in renal failure.