Altered synthesis of renin in patients with insulin-dependent diabetes: plasma prorenin as a marker predicting the evolution of nephropathy

Abstract

Plasma active renin (PARC) and plasma total renin (PTRC) were measured in 72 patients with childhood-onset IDDM and 37 control subjects in the supine posture. The diabetic patients were divided into three groups: group A, 55 patients with normoalbuminuria; group B, 11 patients with microalbuminuria; and group C, 6 patients with overt proteinuria. The levels of PTRC were 125 ± 51, 240 ± 124 and 580 ± 285 ng/l in groups A, B and C, respectively; all of which were significantly higher than 114 ± 33 ng/l in the control subjects. On the other hand, the ratios of plasma active to total renin, ARC/TRC, were 18.1 ± 12.5, 10.7 ± 6.7, and 2.9 ± 1.4% in groups A, B and C, respectively; all of which were in turn significantly lower than 24.8 ± 8.7% in the control subjects. Among the diabetic groups, PTRC became higher and ARC/TRC became lower in conjunction with the degree of albuminuria. The acute increments of PARC and PTRC during a standing load test were subsequently observed in 7 patients of group A, 5 of group B, 4 of group C, 13 patients with non-diabetic glomerulonephritis, and 6 control subjects. The ratios of increments of PARC to that of PTRC, ΔARC ΔTRC , were 48.3 ± 22.3, 35.1 ± 10.4 and 8.4 ± 8.1% in groups A, B, C, respectively; all of which were significantly lower than 84.2 ± 48.6% in the control subjects. Patients with non-diabetic glomerulonephritis showed, to a lesser degree, low ratio of ΔARC ΔTRC (60.4 ± 37.9%) in conjunction with higher level of PTRC (249 ± 89 ng/l). This level of PTRC was significantly higher than 116 ± 29 in the control subjects and 170 ± 64 ng/l in group A. The levels of PARC were relatively maintained until overt diabetic nephropathy occurred. These findings suggest that patients with IDDM may have an altered synthesis of renin with the lowered conversion rate of prorenin to the active one as early as in the normoalbuminuric stage. Although the mechanism of high PTRC and low ARC/TRC in diabetic nephropathy may relate to the glomerular hyperfiltration through chronic activation of tubuloglomerular feedback loop, the precise events remain to be clarified. We propose a prospective study to see whether ARC/TRC along with PTRC can be a functional marker predicting the evolution of diabetic nephropathy.