Impaired endothelium-dependent vascular responses of retinal and intrarenal arteries in patients with type 2 diabetes.

Endothelial dysfunction has been implicated in the pathogenesis of diabetic microangiopathies such as retinopathy and nephropathy as well as macrovascular diseases. The aim of the current study was to determine whether endothelial function in the retinal and renal arteries is impaired in type 2 diabetes mellitus. We examined the effects of an intravenous infusion of L-arginine and a sublingual administration of nitroglycerin on the brachial, retinal, and interlobar arterial hemodynamics in 20 type 2 diabetic patients (10 with normoalbuminuria and 10 with microalbuminuria) and 10 aged-matched control subjects. Despite no difference in the nitroglycerin-induced vascular response of the brachial or retinal artery among the 3 groups, the L-arginine-induced vascular response of each artery was significantly lower in both the normoalbuminuric and microalbuminuric patients than in the control subjects and the microalbuminuric patients showed the lowest value among the 3 groups (P<0.01, each artery, respectively). The L-arginine-induced vascular response of each artery was significantly correlated with HbA1c levels (brachial artery, r=0.617, P=0.0003; retinal artery, r=0.599, P=0.0005; interlobar artery, r=0.636, P=0.0002). In addition, stepwise multiple regression analysis of all subjects showed that HbA1c level was an independent determinant for the L-arginine-induced vascular response of each artery. The results showed that the endothelium-dependent vascular responses of the retinal and intrarenal arteries as well as the brachial artery were impaired in diabetic patients before the clinical manifestation of diabetic nephropathy, and suggest that endothelial dysfunction in these arteries is associated with hyperglycemia in these patients.

A case of membranous glomerulonephritis associated with gastric cancer.

We describe a patient with gastric cancer and membranous glomerulonephritis (MGN). The patient, a 61-year-old male, was admitted to our Hospital in May, 1996, because of proteinuria and hyperlipidemia persisting for a year. Laboratory examination filled the criteria of nephrotic syndrome and renal biopsy revealed MGN of stage II. Prednisolone therapy (40 mg/day p.o.) was started, followed by a gradual decrease in proteinuria from 4.5 g/day to 0.1 g/day. Endoscopic examination was performed because of stomach-ache revealed advanced gastric cancer of Borrmann 4. Desiring for a conservative therapy, he was discharged and moved to a hospice. In literature review, MGN is the most frequent lesion among various glomerular diseases associated with malignancy, such as the lung, stomach, and colon, particularly at an elderly ages, and sometimes antedates the detection of malignancy, as in the present case. In several cases with MGN, immune-complexes composed of tumor antigens, such as carcino-embryonic antigen, and antibodies have been reported to deposit in basement membrane of glomeruli, causing MGN. In the renal and gastric cancer tissues of the present case, the presence of three novel tumor-associated antigens, Span-1, Thomsen-Friedenreich antigen (T antigen) and F1 alpha antigen, was examined, using a immuno-peroxidase method. Although none of these three antigens were immuno-stained in the renal tissue, clinical course and literature review suggest that MGN in this patient seems to be associated with gastric cancer, which may have produced MGN-causing tumor antigens other than the three antigens. It should be emphasized that malignancy should be carefully and routinely examined in patients with MGN, particularly at elderly ages.