RESUMEN
A genetic mendelian autosomal recessive condition of deficiency of lecithin- cholesterol acyltransferase (LCAT) can produce two different diseases: one highly interesting nephrologic picture of complete enzymatic deficiency (lecithin:cholesterol acyltransferase deficiency; OMIM ID #245900; FLD), characterized by the association of dyslipidemia, corneal opacities, anemia and progressive nephropathy; and a partial form (fish eye disease; OMIM ID #136120; FED) with dyslipidemia and progressive corneal opacities only. The diagnosis of FLD falls first of all under the competence of nephrologists, because end-stage renal disease appears to be its most severe outcome. The diagnostic suspicion is based on clinical signs (corneal opacities, more severe anemia than expected for the degree of chronic renal failure, progressive proteinuric nephropathy) combined with histology obtained by kidney biopsy (glomerulopathy evolving toward sclerosis with distinctive lipid deposition). However, the final diagnosis, starting with a finding of extremely low levels of HDL-cholesterol, requires collaboration with lipidology Centers that can perform sophisticated investigations unavailable in common laboratories. To be heterozygous for a mutation of the LCAT gene is one of the monogenic conditions underlying primary hypoalphalipoproteinemia (OMIM ID #604091). This disease, which is characterized by levels of HDL-cholesterol below the 5th percentile of those of the examined population (<28 mg/dL for Italians), has heritability estimates between 40% and 60% and is considered to be a predisposing condition for coronary artery disease. Nevertheless, some monogenic forms, and especially those associated with LCAT deficiency, seem to break the rule, confirming once more the value of a proper diagnosis before drawing prognostic conclusions from a laboratory marker. As in many other rare illnesses, trying to discover all the existing cases will contribute to allow studies broad enough to pave the way for further therapies, in this case also fostering the production by industries of the lacking enzyme by genetic engineering. Epidemiological studies, although done on selected populations such as hypoalphalipoproteinemia patients on dialysis and with the effective genetic tools of today, have been disappointing in elucidating the disease. Spreading the clinical knowledge of the disease and its diagnostic course among nephrologists seems to be the best choice, and this is the aim of our work.
Asunto(s)
HDL-Colesterol/sangre , Enfermedades Renales/diagnóstico , Enfermedades Renales/genética , Deficiencia de la Lecitina Colesterol Aciltransferasa/diagnóstico , Deficiencia de la Lecitina Colesterol Aciltransferasa/genética , Fosfatidilcolina-Esterol O-Aciltransferasa/genética , Anemia/etiología , Biomarcadores/sangre , Biopsia , HDL-Colesterol/metabolismo , Opacidad de la Córnea/etiología , Enfermedad de la Arteria Coronaria/prevención & control , Progresión de la Enfermedad , Dislipidemias/etiología , Ingeniería Genética , Heterocigoto , Humanos , Italia/epidemiología , Enfermedades Renales/enzimología , Enfermedades Renales/patología , Enfermedades Renales/terapia , Fallo Renal Crónico/genética , Fallo Renal Crónico/patología , Deficiencia de la Lecitina Colesterol Aciltransferasa/complicaciones , Deficiencia de la Lecitina Colesterol Aciltransferasa/enzimología , Deficiencia de la Lecitina Colesterol Aciltransferasa/epidemiología , Deficiencia de la Lecitina Colesterol Aciltransferasa/terapia , Mutación , Proteinuria/etiología , Factores de Riesgo , Resultado del TratamientoRESUMEN
Previous studies have suggested that endothelins could be involved in the pathogenesis of target organ damage in diabetes. The aim of this study was to evaluate the possible protective effect of Bosentan, an antagonist of endothelin receptor, on the kidney of diabetic rats. The study comprised a control group of 10 WKY rats and a group of 22 WKY rats in which diabetes was induced by streptozotocin i.v.; 10 rats were the control group. Diabetic rats received insulin and mean blood glucose was approximately mS 400 mg/dl throughout the study; they were divided into two groups: 11 rats received Bosentan 100 mg/kg/die by gastric gavage and 11 received vehicle for 1 month. Twenty-four hour urine collection was performed before and at the end of the study. Urinary protein excretion rate was expressed as microg urinary protein/mg urinary creatinine. The renal collagen I, fibronectin, and TGFbeta were evaluated by means of immunochemistry. The statistical analysis of the results demonstrates that Bosentan has prevented the increase in urinary protein excretion and that of renal immunoreactive collagen I, fibronectin, and TGFbeta induced by diabetes without reducing blood pressure. This study suggests a new clinical application for the antagonists of endothelin receptors.