PLASMA PRORENIN AS AN EARLY MARKER OF NEPHROPATHY IN DIABETIC (IDDM) ADOLESCENTS

We studied a group of 50 adolescents, average age 16 years, with diagn osed IDDM present for about seven years. Twenty-five had microalbuminu ria (MA) averaging 111.0 +/- 34.0 (SEM) mu g/min albumin excretion rat e versus 6.7 +/- 7.4 mu g/min in the 25 without MA. In other respects, such as sex ratio, age, body mass index, duration of IDDM, hemoglobin A1c, and normotensive systolic, diastolic and mean blood pressures (B P), these subgroups were closely matched. We compared them with a cont rol group of 39 normotensive adolescents, of whom 18 were carefully ma tched siblings of the IDDM subjects with MA and 21 were similarly matc hed siblings of the IDDM non-MA subjects. Plasma renin concentration w as determined by a direct radioimmunoassay method (Sanofi-Pasteur) and found to be virtually the same in the control and IDDM adolescents as a whole. There was also no real difference between the MA and non-MA subgroups. In contrast, plasma prorenin was significantly higher in th e combined IDDM group (197.5 +/- 9.3 vs. control, 134.0 +/- 7.9 pg/ml, P < 0.0001). It was also higher in the MA subgroup than in the non-MA subgroup (226.4 +/- 13.6 vs. 168.5 +/- 10.1 pg/ml, P < 0.001). Intere stingly, the 18 control siblings matching the MA subgroup had higher p lasma prorenin than the 21 control siblings matching the non-MA subgro up (P < 0.001), suggesting a familial predisposition that precedes det ectable diabetes and nephropathy. Our findings confirm and extend repo rts by other workers that elevated plasma prorenin is associated with incipient nephropathy, manifested by MA. The exclusive renal origin of this prorenin, its role in plasma, and the mechanism responsible for its elevation in IDDM with MA, are yet to be demonstrated, as is the g eneral applicability of these findings to different populations of dia betics, with a higher incidence and severity of complications.