Lipoprotein Metabolism in the Nephrotic Syndrome in Man

The aim of this thesis was to characterise the abnormalities of plasma lipoprotein metabolism which occur in the nephrotic syndrome in man. Both quantitative and qualitative changes in plasma lipoproteins were documented in a series of 45 consecutive patients with heavy proteinuria. Patients with proteinuria less than the nephrotic range (<3g/24 hours) did not have any significant elevations in cholesterol concentrations compared to controls but there was a relationship between urinary albumin loss and blood cholesterol. Primary hyperlipidaemia was not associated with increased urinary albumin losses. The duration and magnitude of postprandial lipaemia following an oral fat load were not significantly greater in a group of nephrotic subjects compared to controls. However, both groups showed a high degree of interindividual variation. The lipoproteins isolated in the d< 1.006g/mL fraction following an oral fat load did not differ in composition between the two groups. Post-heparin lipase activities were not significantly different. The transfer of apolipoprotein B along the delipidation cascade from very low to low density lipoproteins was investigated using radioiodinated lipoproteins. Overall, apoB synthesis in nephrotic syndrome was not greater than in controls although the range in the nephrotic group was wide (up to four times normal). There was a significant increase in the production of apoB into the smaller, triglyceride-poor VLDL2 density interval. Both VLDL1 and VLDL2 were cleared from the plasma at slower rates in the nephrotic syndrome. There was a modest increase in apoB transfer to LDL. Studies of LDL metabolism revealed a consistent defect in fractional catabolism of LDL by the receptor-mediated pathway. LDL production was closely related to proteinuria and only rose when this exceeded 10g/day. Inhibition of cholesterol synthesis with simvastatin produced dramatic falls in total and LDL-cholesterol in these subjects. Metabolic studies revealed a heterogeneous response with a majority of patients demonstrating increased catabolism of LDL but some showing reduced synthesis. Two serious and potentially worrying adverse events were witnessed during simvastatin therapy. Particles corresponding to both HDL and LDL were isolated form urine collected from nephrotic subjects. The significance of this is uncertain but justified the corrections made for urinary LDL losses in the metabolic studies and gives credence to the suggestion that filterd lipoproteins may be nephrotoxic. The results of these studies are compared with the relatively few previous reports of lipoprotein metabolism in human nephrotic syndrome and the extensive literature on animal work. In man, catabolic defects appear to be at least as important as increases in lipoprotein production in the genesis of the hyperlipidaemia. However, some of the data is difficult to reconcile. Reasons for conflicting observations are discussed and areas requiring further research are highlighted

Birth outcome in relation to licorice consumption during pregnancy.

A role for glucocorticoids is suspected in the etiology of low birth weight. The authors tested whether maternal consumption of glycyrrhizin (an inhibitor of cortisol metabolism) in licorice affects birth weight in humans. A sample of 1,049 Finnish women and their healthy singleton infants was studied in 1998. Glycyrrhizin intake was calculated from detailed questionnaires on licorice consumption. Glycyrrhizin exposure was grouped into three levels: low ( or =500 mg/week; n = 110). Birth weight and gestational age (from ultrasound measurements) were obtained from hospital records. Babies with heavy exposure to glycyrrhizin were not significantly lighter at birth, but they were significantly more likely to be born earlier: The odds ratio for being born before 38 weeks' gestation was 2.5 (95% confidence interval: 1.1, 5.5; p = 0.03). Although the effect of heavy glycyrrhizin intake on mean duration of gestation was small (2.52 days) when expressed as an effect on the mean, this shift to the left of the distribution of duration of gestation was sufficient to double the risk of being born before 38 weeks. The association remained in multivariate analyses. In conclusion, heavy glycyrrhizin exposure during pregnancy did not significantly affect birth weight or maternal blood pressure, but it was significantly associated with lower gestational age