Serum total renin, an independent marker of the activity and severity of retinopathy in patients with IDDM

Abstract

Background/aims. Recent studies have demonstrated marked renin and prorenin concentration gradients between ocular tissues and blood, and local expression of the renin-angiotensin system (RAS) in the eye. The authors determined whether serum total renin, which mostly consists of prorenin, is a marker of the activity and severity of diabetic retinopathy independent of other microvascular complications. Methods. Total renin concentrations (TRC) were measured with a time resolved immunofluorometric assay in 38 patients with IDDM (age 34 (SD 7) years, duration of disease 22 (7) years, serum creatinine 95 (15) μmol/l, urinary albumin excretion rate (UAER) 207 (829) μg/min, HbA(1c) 8.5% (1.2%)), and in 13 matched normal subjects. All subjects were carefully characterised with respect to the presence and severity of retinopathy (RP score), nephropathy, and neuropathy using seven different tests of autonomic neuropathy. Results. Serum TRC was on average twofold higher in IDDM (396 (SE 211) ng/l) than in normal subjects (201 (88) ng/l, p < 0.001). It was nearly twofold higher in patients with preproliferative or active proliferative retinopathy requiring careful follow up or therapy (TRC 596 (268) ng/l, n = 11) compared with those with quiescent proliferative retinopathy after laser treatment (TRC 338 (183) ng/l, p < 0.01, n = 5); moderately severe non-proliferative retinopathy (337 (106) ng/l, p < 0.01, n = 13), no retinopathy, or only minimal non-proliferative retinopathy (270 (43) ng/l, p < 0.001, n = 9). In multiple linear regression analysis, RP score (p < 0.01), but not the UAER or any index of autonomic neuropathy, was an independent determinant of serum TRC, and explained 32% of its variation (R = 0.57, p < 0.005). Conclusions. Serum TRC in patients with diabetic retinopathy is increased independent of renal function and autonomic neuropathy, especially in those with severe active changes requiring careful follow up or treatment. These findings support the idea that diabetic retinopathy is the most important determinant of serum TRC in patients with IDDM, and that TRC is produced when retinopathy is active.