Role of glomerular filtration rate in controlling blood pressure early in diabetes

Perhaps the most obvious, and least contentious, examples of hypertension caused by the kidneys are renal artery stenosis and diabetic nephropathy, because there are readily identifiable, physical limitations in the ability of the kidneys to excrete sodium in each case. The former is characterized by a global restriction in renal perfusion, and the latter is characterized more specifically by glomerular injury and reduced glomerular filtration rate (GFR), but in each case there must be an increase in arterial pressure to maintain salt and water balance.1–3 Thus, in long-standing diabetes, types 1 and 2, a progressive decline in GFR is matched by a reciprocal increase in arterial pressure, which enables maintenance of sodium balance and body fluid volume homeostasis at the expense of deleterious adverse effects of chronic hypertension.4

In this framework, decreased GFR in diabetic nephropathy is responsible for imparting a chronic sodium-retaining influence on the kidneys, and hypertension is the counterbalancing natriuretic influence required to maintain sodium balance and sustain life. It, therefore, becomes curious that the early stages of diabetes are characterized by increased GFR and sodium balance, yet blood pressure is normal rather than low. For sodium balance to be maintained at normal blood pressure in the face of the chronic natriuretic influence of elevated GFR, there must be a concurrent sodium-retaining influence. If not, then the natriuretic effect of increased GFR would act unopposed and result in the maintenance of sodium balance at a lower blood pressure, similar to the effect of a diuretic. However, the presence of an underlying salt-retaining influence has been difficult to realize conceptually because of the increase in absolute sodium excretion in diabetes and because normal blood pressure typically does not spur research interest. This review focuses on how sodium balance is maintained at the onset of diabetes with normal blood pressure and increased GFR and how disruption of the mechanisms that sustain that balance influence blood pressure.