IgA nephropathy with early kidney disease is associated with increased arterial stiffness and renin–angiotensin system activity

Abstract

IgA nephropathy is associated with increased cardiovascular risk, though whether this is due to loss of kidney function or proteinuria is unclear. For this study 10 normotensive IgA nephropathy subjects with early kidney disease (41±5 yrs, glomerular filtration rate (GFR) 87±9 ml/min, proteinuria 720±300 mg/d) and 10 gender- and blood pressure-matched healthy controls (36±1 yrs, estimated GFR 102±5 ml/min, proteinuria 70±6 mg/d) were studied in high-salt balance. Blood pressure and arterial stiffness, expressed as pulse wave velocity and aortic augmentation index, were measured at baseline and in response to 60 min of angiotensin II (AngII) infusion. At baseline, IgA nephropathy subjects demonstrated similar pulse wave velocity (8.6±0.7 vs. 8.0±0.4 m/s, p=0.5) but increased aortic augmentation index (12.6±3.1 vs. 1.8±4%, p=0.04) and a trend towards increased circulating renin-angiotensin system (RAS) components (plasma renin activity, 0.55±0.18 vs. 0.21±0.05 ng/l/s, p=0.08; angiotensin II, 25±5 vs. 16±1 ng/l, p=0.08) compared with controls. However, despite similar baseline blood pressure values (p=0.8), IgA nephropathy was associated with reduced arterial sensitivity to AngII challenge (Δmean arterial pressure: 19±4 vs. 29±1 mm Hg, p=0.05; Δpulse wave velocity: -0.06±0.6 vs. 1.5±0.3 m/s, p=0.07) compared with controls, even after multivariate analysis. Even in the setting of early kidney disease, IgA nephropathy is associated with increased arterial stiffness and decreased angiotensin II responsiveness, a marker of increased RAS activity.