TGF-beta gene expression is a potential mechanism of the renoprotective effect of renin-angiotensin blockade. Perindopril causes a reduction in expression of transforming growth factor-beta-1 (TGF-beta-1) in kidneys of patients with type 2 diabetes and nephropathy. The ACE inhibitor may thereby protect the diabetic kidney against damage caused by TGF-beta.
"Over the past several years, experimental evidence consistently has suggested a key role for TGF-beta in the pathogenesis of the extracellular matrix accumulation that characterizes diabetic nephropathy and closely correlates with declining renal function," write Dr. Robyn Langham and colleagues at the University of Melbourne and St. Vincent’s Hospital in Fitzroy, Victoria, Australia.
"The renoprotective mechanisms of ACE inhibition independent of blood pressure changes in type 2 diabetes have been demonstrated in a number of other small studies … that showed less fibrosis in ACE inhibitor-treated patients that paralleled a slower progression of proteinuria," Dr. Langham stated that, "The numbers involved and the stratification at randomization were insufficient, however, to draw the conclusion that ACE inhibition was renoprotective."
To investigate possible molecular mechanisms, the researchers extracted RNA from renal biopsies of 12 patients in the Diabiopsies study, a randomized, placebo-controlled, 2-year trial of perindopril, 4 mg/day, in patients with type 2 diabetes and nephropathy.
Renal biopsies were taken at enrollment and again 2 years later in the six patients on perindopril and the six on placebo.
TGF-beta-1 expression was reduced 83% in patients on perindopril but there was no change in placebo-treated patients after 2 years. There was no change in TGF-beta receptor II in either group of patients.
This is the It is the first study "to demonstrate TGF-beta gene reduction with ACE inhibitor therapy in human kidney tissue, confirming the results of animal studies and indirect urine analysis studies of many years," Dr. Langham commented.
"It further strengthens the argument that abrogation of TGF-beta gene expression is a potential mechanism of the renoprotective effect of renin-angiotensin blockade, but because of the limited size of the original study, it is difficult to extrapolate to hard and fast clinical implications," she concluded.
Diabetes Care 2006;29:2670-2675.
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Diabetes Test Helping the Endangered African Black Rhinos Stave off Extinction: Victoria University is leading an international project testing the belief that high sugar levels in female black rhinos is causing a disproportionate number of male births. About 71 per cent of black rhinos born in captivity are male. The captive black rhino population could be extinct within 10 to 15 years unless the sex imbalance was fixed. "We believe that female embryos in rhinos are more vulnerable than males to excess glucose in the mother. "Moving the rhinos to zoos or game reserves seems to increase glucose levels by either increased stress from the move or better nutrition available to the mothers in resource-rich reserves or in captivity." It seemed female embryos had higher mortality rates if their pregnant mothers were stressed, or fed a sugar-rich diet, Dr Linklater said. Blood glucose is being checked with Accu-Chek test strips. Dr Linklater said if the study discovered that excess blood glucose was the cause of the calf sex imbalance, it would change the way rhinos were cared for in captivity.
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