Renal disease and hypertension in non–insulin-dependent diabetes mellitus

Abstract

Recent epidemiologic data demonstrate a dramatic increase in the incidence of end-stage renal disease (ESRD) in patients with non-insulin-dependent diabetes mellitus (NIDDM), thus dispelling the mistaken belief that renal prognosis is benign in NIDDM. Currently, the leading cause of ESRD in the United States, Japan, and in most industrialized Europe is NIDDM, accounting for nearly 90% of all cases of diabetes. In addition to profound economic costs, patients with NIDDM and diabetic nephropathy have a dramatically increased morbidity and premature mortality. NIDDM-related nephropathy varies widely among racial and ethnic groups, genders and lifestyles; and gender may interact with race to affect the disease progression. While the course of insulin-dependent diabetes mellitus (IDDM) progresses through well-defined stages, the natural history of NIDDM is less well characterized. NIDDM patients with coronary heart disease have a higher urinary albumin excretion rate at the time of diagnosis and follow-up. This greater risk may also be associated with hypertension and hyperlipidemia, and genes involved in blood pressure are obvious candidate genes for diabetic nephropathy. Hyperglycemia appears to be an important factor in the development of proteinuria in NIDDM, but its role and the influence of diet are not yet clear. Tobacco smoking can also be deleterious to the diabetic patient, and is also associated with disease progression. Maintaining euglycemia, stopping smoking and controlling blood pressure may prevent or slow the progression of NIDDM-related nephropathy and reduce extrarenal injury. Treatment recommendations include early screening for hyperlipidemia, appropriate exercise and a healthy diet. Cornerstones of management should also include: (1) educating the medical community and more widely disseminating data supporting the value of early treatment of microalbuminuria; (2) developing a comprehensive, multidisciplinary team approach that involves physicians, nurses, diabetes educators and behavioral therapists; and (3) intensifying research in this field.

Altered Gene Expression Related to Glomerulogenesis and Podocyte Structure in Early Diabetic Nephropathy of db/db Mice and Its Restoration by Pioglitazone

“…iabetic nephropathy is the leading cause of end-stage renal disease in the U.S., Japan, and most of Europe (1). Clinical features of diabetic nephropathy are development of albuminuria followed by persistent proteinuria and, later, reduction of glomerular filtration rate (2).…”

The vasopeptidase inhibitor AVE7688 ameliorates Type 2 diabetic nephropathy

“…Pharmacological blockade of the renin angiotensin aldosterone system by either inhibition of angiotensin converting enzyme (ACE) or blockade of the angiotensin II receptor has clinically proven its ability to delay the progression of diabetic nephropathy [3,4,5,6,7,8]. The novel vasopeptidase inhibitors could be of therapeutic value in a variety of nephropathies, based on their potential to increase tissue concentrations of bradykinin and the organoprotective natriuretic peptides through inhibition of neutral endopeptidase in addition As a result of its dramatically increasing incidence, Type 2 diabetes has become the leading single cause of end stage renal disease in most industrialized countries [1]. Urinary excretion of albumin has been estab-to ACE [9].…”

Combined antioxidant and COMT inhibitor treatment reverses renal abnormalities in diabetic rats.

“…Diabetic nephropathy is commonly associated with systemic hypertension, and it is well established that hypertension increases the rate of progression of renal dysfunction (2)(3)(4). The etiology of hypertension is multifactorial, but sodium retention and salt sensitivity may be important primary causal factors (5,6).…”