Familial, hemodynamic and metabolic factors in the predisposition to diabetic kidney disease.

Proteinuric diabetic patients have an increased risk of cardiovascular disease and almost always have hypertension. In the early stages of diabetic renal disease (microalbuminuria) when renal function is well preserved, systemic arterial blood pressure is already elevated compared to insulin-dependent diabetic patients without microalbuminuria. Prospective studies have shown that normoalbuminuric patients who progress to microalbuminuria have higher blood pressures (albeit within the normal range) than those who persistently remain normoalbuminuric. Parents of insulin-dependent diabetic patients with nephropathy have a higher prevalence of hypertension and cardiovascular disease compared to those of patients without nephropathy. Moreover, diabetic nephropathy clusters within families. Erythrocyte sodium-lithium countertransport activity, the most consistent marker for essential hypertension and its cardiorenal complications, is elevated in diabetic patients with nephropathy and in their non-diabetic parents. These data suggest that a familial predisposition to arterial hypertension and cardiovascular disease increases the risk for the development of nephropathy and its associated cardiovascular complications in insulin-dependent diabetes. Arterial hypertension is a state of insulin resistance and diabetic patients susceptible to nephropathy have been found to be less insulin sensitive. Preventive strategies of diabetic kidney disease in the future will have to take into account its metabolic hemodynamic and familial basis.