Comparison of intrarenal renin-angiotensin system activity in diabetic versus non-diabetic patients with overt proteinuria

Abstract

AimThe intrarenal renin-angiotensin system (RAS) has been reported to be activated in chronic proteinuria patients. This study aimed to compare intrarenal RAS activity between diabetic nephropathy (DN) and non-diabetic nephropathy (NDN) patients with overt proteinuria. MethodsA multicenter, cross-sectional study was conducted in 116 patients with overt proteinuria (urinary protein/creatinine ratio [uPCR]>1mg/mg Cr). To estimate intrarenal RAS activity we measured urinary excretion of angiotensinogen (uAGT) and renin (uRenin) in patients with DN (n=38) and NDN (n=78). ResultsBoth natural logarithms of uAGT/urinary creatinine (ln[uAGT/uCr]) and uRenin (ln[uRenin/uCr]) levels were significantly higher in patients with DN compared with those with NDN (ln[uAGT/uCr]: 4.161.13 in DN vs. 3.521.21 in NDN, P=0.007; ln[uRenin/uCr]: 5.66 +/- 1.60 in DN vs. 4.29 +/- 1.48 in NDN, P<0.001), when estimated glomerular filtration rate (eGFR) and uPCR showed no significant difference between the two groups. In a subgroup analysis, according to amount of proteinuria, both uAGT and uRenin were higher in DN in patients with subnephrotic-range proteinuria (uPCR<3.5mg/mg Cr). However, in patients with nephrotic-range proteinuria (uPCR3.5mg/mg Cr), only uRenin was higher in DN compared to NDN. In a multiple regression analysis, diabetes showed independent association with uRenin. ConclusionConsistently elevated uRenin in DN, regardless of the amount of proteinuria, indicates that intrarenal RAS activity may be higher in DN compared to NDN in patients with overt proteinuria. Summary at a Glance Clinical study on 116 subjects with proteinuria documenting increased urinary excretion of renin and angiotensinogen among patients with diabetes compared to non-diabetics. Plasma renin and angiotensinogen levels did not differ between the two groups suggesting the enhanced role of intra-renal RAS activity among patients with diabetes and proteinuria.