SERUM TOTAL RENIN, AN INDEPENDENT MARKER OF THE ACTIVITY AND SEVERITYOF RETINOPATHY IN PATIENTS WITH IDDM

Background/aims-Recent studies have demonstrated marked renin and pror enin concentration gradients between ocular tissues and blood, and loc al expression of the renin-angiotensin system (RAS) in the eye. The au thors determined whether serum total renin, which mostly consists of p rorenin, is a marker of the activity and severity of diabetic retinopa thy independent of other microvascular complications. Methods-Total re nin concentrations (TRC) were measured with a time resolved immunofluo rometric assay in 38 patients with IDDM (age 34 (SD 7) years, duration of disease 22 (7) years, serum creatinine 95 (15) mu mol/l, urinary a lbumin excretion rate (UAER) 207 (829) mu g/min, HbA(1c) 8.5% (1.2%)), and in 13 matched normal subjects. All subjects were carefully charac terised with respect to the presence and severity of retinopathy (RP s core), nephropathy, and neuropathy using seven different tests of auto nomic neuropathy. Results-Serum TRC was on average twofold higher in I DDM (396 (SE 211) ng/l) than in normal subjects (201 (88) ng/l, p<0.00 1). It was nearly twofold higher in patients with preproliferative or active proliferative retinopathy requiring careful follow up or therap y (TRC 596 (268) ng/l, n=ll) compared with those with quiescent prolif erative 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 nonproliferative reti nopathy (270 (43) ng/l, p<0.001, n=9). In multiple linear regression a nalysis, RP score (p<0.01), but not the UAER or any index of autonomic neuropathy, was an independent determinant of serum TRC, and explaine d 32% of its variation (R=0.57, p<0.005). Conclusions-Serum TRC in pat ients with diabetic retinopathy is increased independent of renal func tion and autonomic neuropathy, especially in those with severe active changes requiring careful follow up or treatment. These findings suppo rt the idea that diabetic retinopathy is the most important determinan t of serum TRC in patients with IDDM, and that TRC is produced when re tinopathy is active.