GENETICS OF DIABETIC NEPHROPATHY

Diabetic nephropathy is a clinical syndrome characterized by persisten t albuminuria, a relentless decline in GFR, raised arterial blood pres sure, and increased relative mortality for cardiovascular diseases. Di abetic nephropathy is a leading cause of end-stage renal failure, The pathogenesis of diabetic nephropathy is multifactorial, with contribut ions from metabolic abnormalities, hemodynamic alterations, and variou s growth factors and genetic factors. Epidemiologic and family studies have demonstrated that only a subset of the patients develop this com plication, that family clustering of nephropathy is present, and that ethnicity plays an important role in the risk of developing this kidne y disease. Short stature and low birth weight are both associated with increased risk of developing diabetic nephropathy, supporting the hyp othesis that genetic predisposition or factors operating in utero, in early childhood, or both contribute to the development of diabetic nep hropathy. Studies elucidating phenotypic markers such as parenteral hy pertension and systemic blood pressure elevation have yielded conflict ing results, The contribution from elevated blood pressure only plays a minor role in the majority of the patients developing diabetic nephr opathy. The majority of the studies have demonstrated increased sodium /lithium countertransport activity in insulin-dependent diabetes melli tus patients with nephropathy, whereas studies of this phenotypic mark er in parents of patients with and without nephropathy have yielded co nflicting results, Recently, studies of genetic markers involved in th e regulation of blood pressure and levels of cardiovascular risk facto rs have been conducted, Several studies have demonstrated that the del etion polymorphism in the angiotensin-l-converting enzyme acts as a ri sk factor for cardiovascular disease in diabetic patients. However, a meta-analysis does not support the suggestion that this factor plays a ny role for the initiation of diabetic nephropathy. Similar negative r esults have been obtained in relation to polymorphisms of the genes en coding for angiotensinogen and the angiotensin II Type 1 receptor, How ever, studies in diabetic and non-diabetic glomerulopathies have clear ly demonstrated a deleterious effect of the deletion polymerphism in t he angiotensin-converting enzyme on the progression of kidney function .