RESUMEN
It has been suggested that the glomerular basement membrane restricts the passage of large molecules only, the barrier to filtration of smaller molecules being at the level of the epithelial slit pore. This hypothesis was investigated by measuring glomerular permeability to (125)I-labeled polydisperse polyvinyl pyrrolidone (PVP) in 16 children with idiopathic nephrotic syndrome (INS) and in 6 children of comparable age who had no evidence of renal disease. Studies were performed in the patients with INS before, during, and after treatment with steroids. PVP in blood and urine samples was separated according to molecular size by solumn chromatography, to permit the calculation of permeability to inert macromolecules of sizes ranging from 8,000 mol wt. In untreated INS, glomerular permeability to molecules > 40 A was normal; permeability to smaller molecules was markedly reduced, frequently to 20% or less of normal. There was an average decrease in inulin clearance (C(in)) of 24%. Glomerular permeability and C(in) returned to normal in INS treated with steroids only when proteinuria disappeared. The results support the concept, derived from studies with ultrastructural tracers, that the final barrier to filtration may be at the level of the epithelial slit pore. Thus fusion of the epithelial foot processed with obliteration of the slit pores was associated with impaired passage of smaller molecules of PVP into the urine. Reversal of the pathologic abnormality resulted in return of permeability to normal. The decreased C(in) seen in INS may not reflect true glomerular filtration rate, but may result from restricted passage of inulin molecules (mol wt 5,000) through the epithelial slit pore.
Asunto(s)
Glomérulos Renales/fisiopatología , Síndrome Nefrótico/fisiopatología , Adolescente , Ácidos Aminohipúricos , Membrana Basal/metabolismo , Niño , Preescolar , Cromatografía en Gel , Células Epiteliales , Epitelio/patología , Epitelio/fisiopatología , Tasa de Filtración Glomerular , Humanos , Lactante , Inulina , Radioisótopos de Yodo , Glomérulos Renales/fisiología , Sustancias Macromoleculares , Peso Molecular , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/metabolismo , Síndrome Nefrótico/patología , Permeabilidad , Povidona/metabolismo , Prednisona/uso terapéutico , Proteinuria/tratamiento farmacológico , Proteinuria/etiologíaRESUMEN
Serial determinations, using plasma fibrinogen gel chromatography as well as standard methodology, demonstrated that six children with severe glomerulonephritis, characterized on renal biopsy by glomerular necrosis and crescent formation, had persistent evidence of intravascular coagulation. Based on these observations, therapy with anticoagulants and azathicoagulants and azathioprine was instituted for one year; treatment with anticoagulants was continued for a second year. Anticoagulant therapy was initiated with heparin, followed by oral anticoagulation with phenindione and dipyridamole. In contrast to our earlier experience with similar patients, each of the present patients improved. Urinalyses returned to normal and glomerular filtration rates to near normal values in all patients at the end of the treatment period and have remained so for up to 3.9 years since treatment has been completed. Post-treatment biopsies showed remarkable improvement, with virtually no glomerulosclerosis even in patients who had had a high incidence of glomerular crescents before treatment. It is suggested that the therapeutic regimen favorably influenced the natural history of disease and that plasma fibrinogen chromatographic findings may be helpful in selecting patients likely to benefit from the use of anticoagulant therapy.
Asunto(s)
Anticoagulantes/uso terapéutico , Coagulación Intravascular Diseminada/etiología , Glomerulonefritis/complicaciones , Inmunosupresores/uso terapéutico , Enfermedad Aguda , Adolescente , Anticoagulantes/efectos adversos , Azatioprina/uso terapéutico , Niño , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/tratamiento farmacológico , Coagulación Intravascular Diseminada/orina , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/uso terapéutico , Tasa de Filtración Glomerular/efectos de los fármacos , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis/orina , Heparina/farmacología , Heparina/uso terapéutico , Humanos , Inmunoglobulina G , Inmunosupresores/efectos adversos , MasculinoRESUMEN
Eight patients with severe glomerulonephritis and an average inulin clearance of 21.7 ml/min/1.73 m2 body surface were treated with high-dosage intravenous methylprednisolone, 30 mg/kg given over a one-hour period on each of six alternate days. The mean inulin clearance rate doubled after this "pulse" therapy. In the six patients treated early in the course of their disease, GFR increased to a mean of 100.2 ml/min/1.73 m2 during the follow-up period extending for up to three years and was accompanied by clinical improvement. These observations suggest that "pulse" methylprednisolone may be beneficial in treating some patients with potentially life-threatening severe glomerulonephritis.