ENDOTHELIAL FUNCTION OF CONDUIT AND RESISTANCE ARTERIES IN NEPHROTIC RANGE PROTEINURIA

Abstract

OBJECTIVE: To test the hypothesis that endothelial dysfunction occurs in nephrotic range proteinuria primarily as a consequence of dyslipidaemia. METHODS: Brachial artery and forearm microcirculatory endothelial function was compared among patients with nephrotic range proteinuria (NRP, n = 14 ), primary hyperlipidaemia (HL, n = 15) and normal controls (NC, n = 16). Endothelial function was studied by measuring post-ischaemic flow-mediated dilatation (FMD) of the brachial artery using high resolution ultrasonography. Endothelium-independent, glyceryl trinitrate (GTN) mediated brachial artery vasodilatation was also measured. Basal and post-ischaemic blood flow of the forearm microcirculation was measured using venous-occlusion strain gauge plethysmography. RESULTS: Serum creatinine was similar among groups. The proteinuric group had a mean albumin of 27.6g/L(1.8) and 24-hour urinary protein excretion of 6.3g(1.3). Plasma lipids and lipoproteins were not statistically different between the NRP and HL groups. Brachial artery FMD was significantly lower in the NRP and HL groups compared with the controls (NRP 4.7%(1.3)*, HL 4.9%(0.7)* and NC 8.3%(0.6), *p = 0.012 vs. NC); GTN mediated dilatation and basal and post-ischaemic forearm blood flow were not statistically different among the three groups. CONCLUSION: Patients with nephrotic range proteinuria have endothelial dysfunction of conduit arteries in the peripheral circulation, similar to that observed in patients with primary hyperlipidaemia. This suggests dyslipoproteinaemia is the principal cause of endothelial dysfunction of conduit arteries in nephrotic range proteinuria. Confirmation of this should be sought with an intervention trial of lipid-regulating therapy.