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 nonproliferative 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. (Br J Ophthalmol 1998;82:939-944) The aspartyl protease renin is the rate liming enzyme in the formation of the vasoactive octapeptide angiotensin II.

Angiotensin II and Its Receptor Subtypes in the Human Retina

“…18,25,27,62 Plasma prorenin is increased with the onset of PDR in diabetic patients, 63,64 and serum total renin (prorenin and renin) is two times higher in insulin-dependent diabetic patients than in normal subjects, 65 suggesting that the RAS may be activated in patients with PDR. In diabetic patients with PDR, the prorenin concentrations in vitreous is 100 times the level expected on the basis of the plasma protein content of ocular fluid.…”

“…In diabetic patients with PDR, the prorenin concentrations in vitreous is 100 times the level expected on the basis of the plasma protein content of ocular fluid. 65 Ang II levels are significantly higher in the vitreous of patients with PDR compared with nondiabetic persons, and/or diabetic patients without retinopathy. 18 Activation of the intraocular RAS may lead to enhanced intraocular Ang II, which, in view of its effects on growth, may contribute to the development of PDR.…”

Hyperreninemia Characterizing Women with Polycystic Ovary Syndrome Improves after Metformin Therapy

“…Binding of renin/prorenin to its common receptor leads to increased renin activity [10][11][12] , increased plasminogen activator inhibitor-1 production [9,13] and in-duces cellular hypertrophy and vascular fibrosis [10,[14][15][16] . These findings suggest that renin/prorenin plays an important role in the development of end-organ damage in the hyperreninic state, and in diabetics, high total renin levels have been considered as an index of microvascular dysfunction [17,18] .…”

Adherence to diabetic eye examination guidelines in Australia: the National Eye Health Survey

“…The renin-angiotensin system is widely expressed in the eye [180][181][182] . Gene expression of renin, angiotensinogen and angiotensin-converting enzyme (ACE) have been demonstrated 182 with production by vascular endothelial and retinal pigment epithelial cells 183 .…”

“…The renin-angiotensin system is expressed in the eye [180][181][182] , including expression of ACE 182;183 . Patients with DR have elevated levels of intraocular and serum ACE, prorenin and angiotensin II, which are correlated with disease severity 180;181;184 .…”