BACKGROUND: Patients with nephrotic range proteinuria have a marked increase in the risk of cardiovascular disease. Qualitative and quantitative changes in lipids and lipoproteins contribute to this increased risk with an abundance of atherogenic triglyceride (TG) rich apolipoprotein B containing lipoproteins. TG rich lipoproteins predominate postprandially and are associated with increased risk of coronary heart disease (CHD). Omega-3 fatty acids derived from fish oils have been shown to have beneficial effects on lipids and lipoproteins in patients without proteinuria.

METHODS: 17 patients with nephrotic range proteinuria and 17 age and sex matched controls were studied. Postprandial lipaemia was assessed in patients and controls, before and after 8 weeks treatment with 4 g daily of omega-3 fatty acids (Omacor). A standard fat load (90 g) was administered and blood sampling was performed in the fasting state and at 2, 4, 6 and 8h after the fat load. Chylomicrons and VLDL(1) density fraction was isolated from plasma by density ultracentrifugation. Postprandial chylomicron and VLDL(1) triglyceride concentrations were measured and quantified using the incremental area under the curve (AUC) method.

RESULTS: Baseline postprandial chylomicron TG AUC was greater in patients compared with controls: median 18.5 mmol/lh (interquartile range 8.9-32.6) vs 9.3 mmol/lh (4.8-14.4) p=0.05. Following treatment patient chylomicron AUC fell [mean reduction 6.8 mmol/lh (95% CI 0.1-13.6) p=0.05]. No significant reduction in chylomicron AUC was observed in the controls [mean reduction 3.9 mmol/lh (95% CI -3.6 to 11.5)]. As a result, following 8 weeks treatment with omega-3 fatty acids, patient and control chylomicron AUC were no longer significantly different [patients 13.5 mmol/lh (7.4-22.9), controls 7.2 mmol/lh (4.6-14.5) both median and IQR, p=nsd]. VLDL(1) TG AUC did not differ at baseline between patients and controls. Furthermore, there was no significant effect on VLDL(1) AUC following treatment in either group.

CONCLUSIONS: We have shown that there is an excess of postprandial chylomicron density fraction in patients with nephrotic range proteinuria, which is reduced by treatment with omega-3 fatty acids. We suggest that this would be an ideal therapy in combination with statins for this high risk group of patients.

Key Words:
Nephrotic Range Proteinuria, Postprandial Lipaemia, Lipemia, Omega-3 Fatty Acids, PUFAs