No abstract

Renin, prorenin, and immunoreactive renin were present in vitreous and subretinal fluid of eyes from subjects with and without diabetic retinopathy. Renin substrate, albumin, transferrin, and immunoglobin G were also found in these ocular fluids. In many samples renin levels were close to the detection limit of the assay. The levels of renin substrate, albumin, transferrin, and immunoglobulin G varied widely among ocular fluid samples, but in each individual sample the levels were, relative to each other, similar to those in plasma. In contrast, the prorenin level in ocular fluid was up to 100 times higher than expected on the basis of the plasma protein content of ocular fluid. Moreover, there was little difference in prorenin concentrations between samples with low and high plasma protein contents. Prorenin, relative to albumin and other plasma proteins, was higher in vitreous fluid from eyes with proliferative diabetic retinopathy complicated by traction retinal detachment than in eyes of nondiabetic subjects with spontaneous retinal detachment. It appears that prorenin (and possibly renin) in ocular fluid is controlled by an active and specific process, possibly local synthesis within the eye. In view of the vascular actions of angiotensin II, an intraocular renin-angiotensin system may play a role in diabetic retinopathy.

GHD men receiving GH treatment have a mortality rate not different from the background population. In women, after exclusion of high-risk patients, mortality was not different from the background population except for CVD. Mortality due to malignancies was not elevated in adults receiving GH treatment. Next to gender, the heterogeneous etiology is of influence on mortality in GHD adults with GH treatment.

Plasma prorenin is abnormally high, whereas renin is normal or even low, in many patients with long-standing diabetes mellitus complicated by microvascular disease. Nephropathy or autonomic neuropathy has been put forward as a cause. We found that in 223 consecutive diabetics prorenin correlated positively with serum creatinine, the presence of macroalbuminuria (greater than 250 mg/L), and the presence of diabetic retinopathy, particularly the proliferative type. This correlation did not depend on the presence of neuropathy or whether the patient was receiving insulin. It was also independent of sex, age, duration of diabetes, blood pressure, and blood levels of glucose and hemoglobin-A1c. The association between elevated prorenin and retinopathy remained significant after adjustment for creatinine and the presence of macroalbuminuria. Of the whole group of diabetics 94 consecutive patients were assessed for the presence of microalbuminuria (30-300 mg/24 h). Independently of the presence of micro- or macroalbuminuria, the mean level of prorenin was not above normal in the patients without retinopathy and was 2-3 times normal in those with proliferative retinopathy. Thus, retinopathy appears to be a more important determinant of abnormally high prorenin than nephropathy. In addition, the renal vein to artery ratio of prorenin in 7 diabetics with both advanced nephropathy and proliferative retinopathy was not elevated, despite the high peripheral venous prorenin level and the impaired renal perfusion. Thus, the abnormally high prorenin level in these patients could not be explained by abnormal secretion by the kidneys. Finally, prorenin was not high in 16 nondiabetics with loss of sympathetic activity due to chronic autonomic neuropathy, which indicates that in the absence of diabetes, this type of autonomic failure is not sufficient to cause the high prorenin levels seen in diabetics. Our findings are evidence that abnormally high plasma prorenin levels in diabetics are not an immediate consequence of altered glucose metabolism. This abnormality is related to the development of microvascular disease in the eye and kidney and is at least in part due to decreased clearance of prorenin from the circulation, increased production from extrarenal sources, or both.

The incidence of secondary intracranial tumors and mortality did not differ between IRR and non-IRR patients. However, a CVE was found significantly more frequently in IRR men but not in women. Further research into the long-term effects of cranial radiotherapy seems mandatory. The potential risks of radiotherapy have to be taken into account when radiotherapy is considered in NFPA patients, and long-term follow-up is recommended.