Recent studies in adults have suggested that parenteral 1,25-dihydroxyvitamin D3 (1,25OH2D3) may have advantages over oral therapy in the management of renal osteodystrophy. The purpose of this study ...was to determine whether there were clear differences between oral and IP 1,25(OH)2D3 treatments in children who did not pose a treatment problem. Seven children (5 males, 2 females, aged 1.8 to 16 years, median 4.8 years) undergoing peritoneal dialysis were initially treated with oral 1,25(OH)2D3 for a one month equilibration period They were randomly assigned to 3 months of either oral or intraperitoneal (IP) therapy with 1,25(OH)2D3 followed by 3-months-treatment using the alternative route. No significant differences in serum creatinine, phosphate, or parathyroid hormone concentrations were found between the different routes of administration in the patients. No significant differences in height standard deviation scores or renal osteodystrophy scores were found over the six-month study. Paired oral and IP pharmacokinetic studies were performed on these 7 patients and 2 other children who had been treated for at least 2 months using either oral or IP 1,25(OH)2D3. Serum was taken prior to one of the usual 1,25(OH)2D3 doses and 0.5, 1.5, 3, 6, and 24 h afterward. The highest measured concentrations of 1,25(OH)2D3 were found at 1.5 h for both oral and IP treatments (mean Cmax SD: oral 116 23 pmol/l, IP 121 24 pmol/l, p > 0.05). The AUC's for oral and IP therapy were similar (1701 276 and 1645 301 pmol/h/l, respectively). In the paired pharmacokinetic studies no significant differences were found between oral and IP treatments for the serum half life (27.4 11.6 h and 19.2 8.1 h, respectively) and total body clearance (15.3 2.1 h and 18.4 3.3 h, respectively) of 1,25(OH)2D3. In children who respond appropriately to oral 1,25(OH)2D3 there is no biological advantage to the use of IP 1,25(OH)2D3.
Measurement of mass transfer area coefficients (MTAC) in children of different sizes to determine if solute transport varies with age and to compare with published adult values.
Mass transfer area ...coefficients calculated from prospectively collected data in 28 selected patients.
All children starting maintenance peritoneal dialysis at the Hospital for Sick Children. Selected patients were also studied if hospitalized for unrelated reasons.
Mean MTAC values for creatinine and glucose were 4.0 and 4.5 mL/min, respectively, both considerably lower than adult values. When scaled per 70 kg body weight, these results were greater, and when scaled per 1.73 m2 surface area, they were lower than reported adult values. The MTAC/kg body weight was inversely correlated to age.
Solute transport in children is directly related to age and does not approach adult values until later childhood. However, more rapid transport per unit body weight is observed in children and may reflect an increased effective peritoneal surface area.
After repair of coarctation of the aorta, some patients with normal blood pressure at rest have an exaggerated hypertensive response to activity. Blood pressure response to exercise was studied in 15 ...children, aged 5 to 15 years, prior to and at periods up to 6 months following coarctectomy. Preoperatively, 11 of 15 children had systolic hypertension at rest and 12 of 15 after exercise. After surgery, only one child had mild systolic hypertension at rest, whereas exercise-induced hypertension persisted in 33% of patients (all older than 10 years). Exercise plasma renin activity was elevated preoperatively but normalized following surgery. No significant difference was seen in resting and exercise plasma catecholamine levels measured before and after surgery. Over the follow-up period of 6 months, echocardiographic evidence of left ventricular hypertrophy regressed in the younger patients but not in the older patients with exercise-induced hypertension. Exercise testing defines a subgroup of patients with exercise-induced hypertension evident soon after surgery. Structural upper segment arterial vessel wall changes in the older patient may explain these observations.
The effects of the nonselective beta blocker, propranolol, on coarctectomy-induced hypertension were evaluated relative to changes in cardiac function, sympathetic tone, and plasma renin activity ...(PRA). A randomized, placebo-controlled, double-blind, age-stratified design was employed. Propranolol (n = 11, mean age 9.4 years) or placebo (n = 12, mean age 10.2 years) was started 2 days before surgery and continued until 6 days after surgery. In patients on placebo, systolic and diastolic blood pressure, heart rate, and cardiac index increased rapidly and peaked within 1 day after surgery. Over the ensuing days these increases gradually abated. Plasma epinephrine and PRA increased markedly within 12 hours after surgery, but returned quickly toward preoperative levels. In contrast, plasma norepinephrine increased more gradually and remained elevated longer. In patients on propranolol, systolic blood pressure, heart rate, cardiac index and PRA showed only negligible increases. However, diastolic blood pressure, increased even faster with propranolol than with placebo but to the same extent. Plasma catecholamines showed similar increases on the two treatments. Only in the placebo group was the code broken in the intensive care unit because of hypertension uncontrolled by sodium nitroprusside; this occurred in 6 of 12 patients. We conclude that nonselective beta blockade ameliorates the hyperdynamic circulation and increase in systolic blood pressure following coarctectomy. The initial increase in diastolic blood pressure following surgery in the propranolol group may have been caused by vascular beta-2-receptor blockade resulting in unopposed alpha-receptor-mediated vasoconstriction.
Factors contributing and predisposing to peritonitis were studied retrospectively in 83 children treated with continuous ambulatory (CAPD) or continuous cycling peritoneal dialysis (CCPD) from 1978 ...to 1988. Recurrent peritonitis was the most frequent complication and the major reason for peritoneal dialysis failure. Fifty patients had 171 episodes of peritonitis during the ten years and 33 remained peritonitis-free. The duration of dialysis was significantly shorter in the peritonitis-free group. The incidence of peritonitis was lower with CCPD than with CAPD. Leucopenia was not a predisposing factor nor was blood leucocytosis helpful in diagnosing peritonitis. Serum IgG was low in 33% of patients with episodes of peritonitis, but there was no correlation or predictive value in this finding. The C3 component of complement was relatively lower than the C4 but both components was relatively lower than the C4 but both components were usually in the normal range. Serum albumin was low in all patients, but lower in those with peritonitis episodes. Age, sex, primary disease, diapers, pyelostomies, dialysis training, and living conditions were not significantly associated risk factors. Sterile dressings gave no benefit over the shower technique. Patient noncompliance, upper respiratory tract infection, skin infections, and dental treatment were potential risk factors. However, peritonitis seemed to be distributed randomly among the patients.
We report two female siblings (ages 4 and 9 years) and one 8-year-old male with the syndrome of apparent mineralocorticoid excess (AME) presenting with low renin hypertension and hypoaldosteronism. ...The deficiency of 11 beta-hydroxysteroid dehydrogenase results in a defect of the peripheral metabolism of cortisol (F) to cortisone (E). As a result, the serum cortisol half-life (T1/2) is prolonged, ACTH is suppressed, and serum F is normal. The specific diagnosis of the disorder was made by the decreased ratio of the urinary metabolites of E (tetrahydrocortisone, THE) and F (tetrahydrocortisol, THF). Continuous i.v. hydrocortisone administration caused an increase in blood pressure and decrease in serum potassium demonstrating the abnormal mineralocorticoid activity of cortisol in these patients. Addition of spironolactone resulted in a decrease in blood pressure, rise in serum potassium and a gradual increase in plasma renin activity. These studies suggest that an abnormality in cortisol action or metabolism results in cortisol behaving as a potent mineralocorticoid and causing the syndrome of AME.
Tracer kinetics and actions of oral and intraperitoneal 1,25-dihydroxy-vitamin D3 administration in rats. Tracer kinetic parameters of 3H-1,25(OH)2D3 were calculated from data obtained following its ...acute oral (p.o.) or intraperitoneal (i.p.) administration. In normal rats studied after the tracer had distributed into the body, the slope and intercept of the log-serum 3H-1,25(OH)2D3 versus time relationship were not significantly influenced by the route of administration. Pretreatment with 1,25(OH)2D3 (0.2 µg/100 g/day) by the same route as the tracer resulted in the following changes: in p.o. rats the serum 3H-1,25(OH)2D3 intercept was much lower but the slope was not changed; in i.p. rats the intercept was not changed but the slope was increased. Both p.o. and i.p. treatment with 1,25(OH)2D3 lowered the weight gain and diet consumption, and increased serum calcium, kidney tissue calcium and urinary excretion of orally administered 45Ca. All the measures of bioactivity were greater in the i.p. dosed rats than in the p.o. dosed rats. We conclude that the p.o 1,25(OH)2D3 was less potent because of diminished bioavailability due to self induction of its presystemic metabolism and inactivation.
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