Night-time activation of the intrarenal renin-angiotensin system due to nocturnal hypertension is associated with renal arteriosclerosis in normotensive IgA nephropathy patients

Intrarenal renin-angiotensin system (RAS) activation plays an important role in the development of hypertension and renal damage. However, the association between daytime and night-time intrarenal RAS activation and renal structural damage in normotensive IgA nephropathy patients is unclear. We investigated the relationships between urinary angiotensinogen (U-AGT) excretion, which reflects intrarenal RAS activity, and renal structural damage (i.e., endocapillary and mesangial cell hypercellularity, arteriolar hyalinosis and arteriosclerosis levels, and global glomerulosclerosis and tubulointerstitial fibrosis percentages) in 27 normotensive IgA nephropathy patients (age 39.2 ± 13.6 years, 10 men and 17 women, estimated glomerular filtration rate (eGFR) 74.0 ± 17.3 ml/min/1.73 m , urinary protein excretion 0.58 ± 0.50 g/day, and U-AGT excretion 64.9 ± 100.6 μg/day). The arteriosclerosis level had a significant positive association with the daytime and night-time U-AGT excretion levels. By contrast, the endocapillary and mesangial cell hypercellularity and arteriolar hyalinosis levels and global glomerulosclerosis and tubulointerstitial fibrosis percentages did not correlate with the daytime and night-time U-AGT excretion levels. The daytime and night-time U-AGT excretion levels were higher in patients with arteriosclerotic changes than in patients without these changes. Multiple linear regression analysis revealed that the arteriosclerosis levels had a significant positive association with the U-AGT excretion levels at night after adjusting for age, sex, body mass index, and the eGFR. However, when diastolic BP was added as an independent variable, the relationship between U-AGT excretion and arteriosclerosis at night disappeared. In normotensive IgA nephropathy patients, intrarenal RAS activation at night due to nocturnal hypertension may be associated with arteriosclerosis.