The Role Of Genetic Hypertension

As discussed elsewhere in this text, hypertension is one of the most important predictors of the onset and progression of nephropathy in patients with diabetes. While there are many environmental influences on blood pressure, hypertension also comes under significant genetic control. A number of studies have demonstrated that blood-pressure traits appear to segregate with the risk of nephropathy in patients with diabetes.41,42 The concept that genetic hypertension may predispose to accelerated nephropathy is clearly demonstrated in the spontaneously hypertensive rat, a model of polygenetic (essential) hypertension. When compared to normotensive diabetic rats, hypertensive diabetic rats have an earlier and more rapid rise in urinary albumin excretion and increased glomerular basement-membrane thickness.43

However, the evidence for the role of human genetic hypertension in determining the susceptibility to diabetic nephropathy is less clear. Some studies have suggested that parental hypertension increases the risk of nephropathy in both type 1 and type 2 diabetes.21,22,44 Diabetic patients with a positive family history of hypertension are also more likely to develop nephropathy than patients without familial hypertension.42 Seen another way, systolic and diastolic blood pressures are greater in the parents of diabetic patients with

Figure 4.3 Increased diabetic glomerulosclerosis in the Apo E 'knock-out' mouse [D] compared to control (c57/b16) mouse without diabetes [C]. Normal glomerular architecture in the Apo E knockout [B] and control mice [A] without diabetes is shown by comparison.

(Pictures Courtesy of Dr Karin Jandeliet-Dahm, unpublished data.) [Stained with periodic acid Schiff reagent (PAS), 400x magnification.]

nephropathy than in the parents of diabetic subjects without proteinuria. These data could suggest that inherited traits that contribute to the development of hypertension also influence the development of nephropathy in the setting of hyperglycaemia. However, it is more likely that the traits that determine hypertension (and subsequent risk of nephropathy) are multifactorial. Moreover, at least in type I diabetes, the susceptibility trait appears to be related to the subsequent development of hypertension in offspring rather than nephropathy in itself.44

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