1. Central and peripheral haemodynamics, circulating blood volume and plasma renin activity (PRA) were investigated under resting conditions in 97 patients with chronic nonuraemic renal parenchymatous disease and without anaemia. For comparison a group of 17 healthy subjects was used.
2. An initial abnormality appeared in 12 out of 32 normotensive renal patients. It consisted of a markedly increased circulating blood volume, raised cardiac output, low total peripheral and forearm vascular resistance, hyperfusion of the forearm and increased venous distensibility. PRA was slightly (but insignificantly) higher in these hyperkinetic subjects with relaxed peripheral vessels than in the other 20 normotensive renal patients who did not differ haemodynamically from the control subjects.
3. Fifteen out of 47 renal patients with a mild or moderate hypertension (stage I–II WHO) were hyperkinetic. However, in these there was no compensatory vasodilatation in response to the high cardiac output: forearm blood flow was normal and venous distensibility below that of the control subjects. Blood volume was normal. Plasma renin activity (PRA) was the same as in the normotensive renal patients.
4. The difference between stage I–II and stage III was due entirely to a rise in total peripheral vascular resistance.
5. A re-examination of these patients 2-8 years after they had been first studied revealed that 11 out of the 12 originally hyperkinetic normotensive renal patients were now hypertensive compared with only one-half of the originally normokinetic normotensive renal subjects.
6. It is concluded that an inability of the diseased kidney to control volume homoeostasis leads to hypervolaemia, which raises cardiac output in the renal patients whilst still normotensive. As long as the arterioles adjust to the high output and the capacitance system to the high volume, blood pressure remains normal. When this adaptation of the periphery ceases, blood pressure rises, normalizing (possibly through a pressure diuresis) blood volume. PRA does not correlate with any of these changes and only in advanced renal hypertension may its rise partly contribute to the maintenance of high blood pressure without being its cause.