Endocrine control of skeletal development in man.

to produce intracellular oedema: this should be minimal when a twin-coil ultrafiltration artificial kidney (Aoyama and Kolff, 1957) is used, because this machine can effectively remove water at a rate of 800 ml./hour. Anima! experiments (Alexander et al., 1961) have shown that intravenous infusions of urea, similar to those used to decrease brain bulk at craniotomy (Stubbs and Penny-backer, 1960), produce a significant transitory increase of plasma volume which is believed to reflect withdrawal of fluid from body tissues as a result of a generalized blood-tissue osmotic gradient. To postulate that reversal of such a process in uraemic patients treated by haemo-dialysis, especially when a high rate of urea clearance is achieved and the plasma protein concentration is low. could produce a reversed osmotic gradient should therefore cause little surprise. Indeed, the development of cerebral oedema, which has been observed on occasion during haemodialysis, together with the gradual restitution of the neurological state which begins shortly after haemodialysis is stopp,d, can be reasonably attributed to urea-concentration differences in the intracellular and extracellular compartments and their subsequent spontaneous equilibration. The cause of the delayed uirea diffusion remains obscure: it is possible that a specific non-diffusible urea moiety exists in such circumstances (Blackmore and Elder, 1961), but expansion of the extracellular compartment physically affecting urea transfer might also be significant. Summary Intracellular concentrations of urea were determined in muscle biopsies taken from 19 unselected patients with acute renal failure immediately after haemodialysis on a rotating-coil artificial kidney. The values were compared with corresponding plasma urea values of venous blood samples withdrawn at the time of the biopsies and were found to be significantly greater in 14 instances and less in 5. Post-dialysis hourly rates of rise of plasma urea concentration were determined in 14 unselected patients and the average time taken for equilibration with the respective pre-dialysis hourly rates of rise was found to be 15 hours. The observations suggest that haemodialysis on a rotating-coil artificial kidney may sometimes, as a result of delayed diffusion of urea across cell membranes, be followed by an intracellular/extracellular urea concentration ratio greater than unity. A raised intracellular/extracellular urea concentration ratio, by producing an osmotic gradient, could rationally explain the development of cerebral oedema during haemodialysis, its gradual spontaneous regression when haemodialysis is stopped, and the well-recognized temporary accelerated rate of rise of the plasma urea concentration during the first post-dialysis day. Exhaustive studies at the …