The angiotensin-converting enzyme gene and its inhibition in diabetic nephropathy

The pathogenesis of diabetic nephropathy is multifactorial, with contributions from metabolic abnormalities, hemodynamic alterations, various growth factors, and genetic factors. Recently, studies of genetic markers involved in the regulation of blood pressure and levels of cardiovascular risk factors have been conducted. Several studies have demonstrated that the deletion polymorphism in the angiotensin-I-converting enzyme (ACE) gene acts as a risk factor for cardiovascular disease in diabetic patients. However, the present meta-analysis does not support the suggestion that this factor plays any role in the initiation of diabetic kidney disease. Studies suggest that albuminuria is not only a marker of kidney disease but also a risk factor in the pathogenesis of glomerulopathies and that reduction in albuminuria during ACE inhibition predicts a diminished progression in diabetic nephropathy. ACE inhibitors postpone progression to diabetic nephropathy in normotensive patients with insulin-dependent or non-insulin-dependent diabetes with persistent microalbuminuria. Long-term antihypertensive treatment with ACE inhibitors, frequently combined with diuretics, reduces albuminuria, protects kidney function, and enhances survival in hypertensive patients with insulin-dependent diabetes with diabetic nephropathy. The deletion polymorphism in the ACE gene reduces the long-term beneficial effect of ACE inhibition on progression of diabetic nephropathy.