1. The effect of the plasma protein concentration on renal function remains controversial. Most, but not all, experimental studies suggest that a reduced plasma protein concentration perfusing the kidney may reduce tubular sodium reabsorption. Hypoproteinaemic disease states are usually associated with sodium retention, which is not always volume-dependent.
2. We induced a 21% and 24% reduction in plasma total protein and plasma albumin, respectively, in unanaesthetized sheep by acute extracorporeal plasmapheresis. Arterial pressure did not change, and changes in circulatory volume were minimised by infusion of crystalloid to maintain pulmonary artery occlusion pressure, measured using a Swann-Ganz pulmonary artery catheter.
3. After plasmapheresis, there was no significant change in creatinine clearance, sodium excretion, plasma renin activity or urinary kallikrein excretion.
4. After plasmapheresis, there was a significant reduction in plasma osmolality, increase in urine osmolality and fall in free water clearance.
5. The results suggest that in the absence of detectable changes in circulating volume or arterial pressure, acute hypoproteinaemia is associated with significant changes in renal water handling, but has no direct effect on sodium excretion or on renal release of renin and kallikrein.