RESUMEN
Because controlled trials in adults have shown accelerated deterioration of renal function in a small number of patients receiving calcitriol for renal osteodystrophy, we initiated a prospective, randomized, double-blind study of the use of calcitriol versus dihydrotachysterol in children with chronic renal insufficiency. We studied children aged 1 1/2 through 10 years, with a calculated glomerular filtration rate between 20 and 75 ml/min per 1.73 m2, and with elevated serum parathyroid hormone concentrations. Ninety-four patients completed a mean of 8.0 months of control observations and were randomly assigned to a treatment period; 82 completed the treatment period of at least 6 months while receiving a calcitriol dosage (mean +/- SD) of 17.1 +/- 5.9 ng/kg per day or a dihydrotachysterol dosage of 13.8 +/- 3.3 micrograms/kg per day. With treatment the height z scores for both calcitriol- and dihydrotachysterol-treated groups showed no differences between the two groups. In relation to cumulative dose, there was a significant decrease in glomerular filtration rate for both calcitriol and dihydrotachysterol; for calcitriol the rate of decline was significantly steeper (p = 0.0026). The treatment groups did not differ significantly with respect to the incidence of hypercalcemia (serum calcium concentration > 2.7 mmol/L (> 11 mg/dl)). We conclude that careful follow-up of renal function is mandatory during the use of either calcitriol or dihydrotachysterol because both agents were associated with significant declines in renal function. There was no significant difference between calcitriol and dihydrotachysterol in promoting linear growth or causing hypercalcemia in children with chronic renal insufficiency. Dihydrotachysterol, the less costly agent, can be used with equal efficacy.
Asunto(s)
Calcitriol/uso terapéutico , Dihidrotaquisterol/uso terapéutico , Trastornos del Crecimiento/tratamiento farmacológico , Fallo Renal Crónico/complicaciones , Calcitriol/farmacología , Niño , Preescolar , Dihidrotaquisterol/farmacología , Método Doble Ciego , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Trastornos del Crecimiento/etiología , Humanos , Hipercalcemia/etiología , Lactante , Masculino , Estudios Prospectivos , Resultado del TratamientoRESUMEN
The Growth Failure in Children With Renal Diseases Study, a double-blind, multicenter clinical trial with 108 children entered into the control period over 4.3 years of patient enrollment (December 1984 to April 1989), is being extended for 3 years (December 1988 to December 1991) to provide the time needed to accrue additional patients, aged between 1 1/2 and 10 years, with glomerular filtration rates of 20 to 75 ml/min/1.73 m2. The study design of randomization to two treatment arms (1,25-dihydroxyvitamin D vs dihydrotachysterol) requires a total of 108 patients with a minimum of 6 months of treatment to test the long-term effectiveness and safety of 1,25-dihydroxyvitamin D, an essential part of the therapeutic regimen for children with chronic renal insufficiency. The frequent longitudinal assessments of nutrition and growth in children with chronic renal insufficiency can better define the natural history of renal disease and its influence on growth. Similar data in the treatment period will define the impact of treatment with 1,25-dihydroxyvitamin D3 versus dihydrotachysterol on this natural history. Linear growth must be observed long enough (6 to 12 months minimum) to permit valid quantitation and comparison of the two vitamin D treatment arms, the multiple confounding variables that affect growth (e.g., steroid therapy, diabetes mellitus, prior vitamin D treatment) must be rigorously excluded or controlled, and the assignment of patients to the two groups must be random. These controls--sufficient study duration, sufficient patient numbers, and randomization--should eliminate extraneous sources of variation, including seasonal periodicity. This carefully developed, double-blind clinical trial with multiple participating centers and an effective organizational structure is coming close to achieving the goals of the study. An explosion of data regarding the natural history of chronic renal insufficiency and its treatment with vitamin D metabolites will be forthcoming at the conclusion of the study.
Asunto(s)
Trastornos del Crecimiento/prevención & control , Fallo Renal Crónico/tratamiento farmacológico , Niño , Preescolar , Método Doble Ciego , Femenino , Tasa de Filtración Glomerular , Trastornos del Crecimiento/etiología , Humanos , Hipercalcemia/epidemiología , Incidencia , Lactante , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/fisiopatología , Masculino , Estudios Multicéntricos como AsuntoRESUMEN
Saralasin acetate, a competitive inhibitor of angiotensin II, was administered as a continuous infusion to two pediatric patients for 8 and 13 days, respectively, to control hypertension. Both patients had become refractory to parenterally administered antihypertensive medications and had an ileus that precluded drug treatment orally. Both patients had a reduction in blood pressure of 30% in response to intravenous infusion of saralasin as a diagnostic test. In the patient with renal failure, neither saralasin nor ultrafiltration was effective alone, but blood pressure was controlled when their use was combined. In these two patients the continuous infusion of saralasin proved to be an effective means for blood pressure control and was unassociated with any recognized adverse effects.
Asunto(s)
Angiotensina II/análogos & derivados , Hipertensión/tratamiento farmacológico , Saralasina/uso terapéutico , Niño , Femenino , Humanos , Hipertensión/terapia , Lactante , Infusiones Parenterales , Masculino , Saralasina/administración & dosificación , Saralasina/efectos adversos , UltrafiltraciónRESUMEN
The adherence of circulating phagocytes to glass was studied in 15 children with acute poststreptococcal glomerulonephritis and in 27 healthy adults, 21 healthy children, and 14 children with normocomplementemic renal disease. The phagocytic adherence to glass in the patients with hypocomplementemic PSGN differed significantly from that of the control groups (p=less than 0.001). There was a positive correlation of phagocyte adherence with plasma C3 but not with plasma C4, C3, properdin factor B, severity of illness, or drugs administered. In addition, the adherence defect was present in two normocomplementemic PSGN patients. The defect gradually resolved in all patients with clinical improvement: it was useful as an index of recovery. The in vitro addition of functional C3 to whole blood produced the adherence defect in normal subjects and failed to correct the defect in patients with PSGN. It was postulated that a fragment of activated complement may have blocked a membrane receptor on these phagocytes and interfered with their adherence to glass.
Asunto(s)
Glomerulonefritis/inmunología , Fagocitos/inmunología , Infecciones Estreptocócicas/inmunología , Adolescente , Adulto , Reacciones Antígeno-Anticuerpo , Niño , Preescolar , Complemento C3/análisis , Complemento C4/análisis , Femenino , Formazáns , Glomerulonefritis/etiología , Humanos , Técnicas In Vitro , Masculino , Fagocitos/enzimología , Infecciones Estreptocócicas/complicacionesRESUMEN
The serum complement profiles of four patients with shunt nephritis indicated classical pathway activation of the complement system. The presence of mixed cryoglobulins was correlated with disease activity and the cryoglobulins were shown to be complement reactive. Antisera to two of the cryoglobulins recognized antigens of the infecting organism, and a specific bacterial antibody was identified in one cryoglobulin, giveing evidence that the cryoglobulins contained immune complexes. Bacterial antibody without detectable antigen was demonstrable in the sera indicating antibody excess. Renal morphology demonstrated mesangial proliferation and interposition with subendothelial and mesangial deposits. Parallels are drawn with active lupus nephritis.