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K Iso

Publications and source records attributed to K Iso.

25 records · Page 2Linked to original sources

Long-term effect of epalrestat, an aldose reductase inhibitor, on the development of incipient diabetic nephropathy in Type 2 diabetic patients.

The aim of the present study was to elucidate the long-term effect of epalrestat, an aldose reductase inhibitor (ARI), on renal function in patients with type 2 diabetes mellitus showing microalbuminuria. Patients were allocated to two groups (cases and controls) matched for age, BMI, and the extent of urinary albumin excretion (UAE). Thirty-five type 2 diabetic patients presenting microalbuminuria were included in this study: cases were treated with epalrestat (150 mg/day) for 5 years. No significant changes were found in blood pressure, HbA1c, and total cholesterol in either group during the observation period. In the control group, UAE increased significantly (P<.01) from 82+/-12 mg/g Cr at the baseline to 301+/-111 mg/g Cr at the end of the study, while UAE remained unchanged, 81+/-15 mg/g Cr at the baseline and 87+/-19 mg/g Cr at the end of the study, in the epalrestat-treated group. Reciprocal creatinine measured by an enzyme assay decreased significantly (P<.01) in both groups; however, the reduction rate in the epalrestat-treated group was significantly (P<.05) smaller than that in the control group. These results suggest the potential usefulness of ARIs in preventing the progression of incipient diabetic nephropathy in patients with type 2 diabetes mellitus.

Albuminuria↗

Protective effects of a small dose of captopril on the reduction of glomerular basement membrane anionic sites in spontaneously hypertensive rats with streptozotocin-induced diabetes.

Angiotensin-converting enzyme (ACE) inhibitors have been used in several clinical trials to slow a progressive decline in glomerular function in patients with diabetic nephropathy independent of their effects on blood pressure. The purpose of this study was to clarify the mechanisms(s) through which an ACE inhibitor, captopril, exerts its protective effect on renal function using spontaneously hypertensive rats (SHR) with streptozotocin (STZ)-induced diabetes. Male SHRs were made diabetic by intravenous injection of STZ (45 mg/kg). One hundred or 25 mg/kg of captopril was administered daily for 4 weeks to them. Urine albumin excretion (UAE) rate was markedly increased in diabetic SHRs, while captopril treatment resulted in a significant suppression of UAE in diabetic SHRs, independent of both its daily dose and effects on blood pressure as well as glycemic control. Examination by electron microscope revealed that the number of anionic sites (AS) in the lamina rara externa per 1000 nm of glomerular basement membrane (GBM) was significantly decreased (22.9+/-0.2 to 16.1+/-0.3, p < 0.001), after induction of diabetes, whereas, significant recovery (18.2+/-0.1, p < 0.001) could be obtained even by the smaller dose (25 mg/kg) of captopril which did not exert either antihypertensive or antidiabetic effect on diabetic SHRs. Thus, we demonstrate here the direct evidence that captopril, an ACE inhibitor, can protect against damage on GBM of diabetic SHR without controlling blood pressure as well as blood glucose level.

Albuminuria↗