Hypotension is frequently encountered during hemodialysis (HD). One of the main factors of the HD-induced hypotension is acute reduction of circulating plasma volume by water removal, which is induced by the poor plasma refilling from the extravascular space into vessels. The determinants of plasma refilling, however, have not been clearly identified. Recently, we devised a mathematical model of water transport in HD patients, which can estimate the plasma-refilling coefficient (Kr) during HD. In the present study, we evaluated the factors determining plasma refilling by using this model. In 13 patients undergoing regular HD, the changes of Kr during HD were calculated from the model. Levels of ANP, cGMP, cAMP, endothelin, angiotensin II and vasopressin were measured before and after HD. Kr fell from 750.4 ± 558.0 to 112.8 ± 81.9 ml/mm Hg/h during HD. The rate of water removal during HD showed no significant correlation with the changes of Kr. Among the hormones and nucleotides measured here, plasma ANP level and cGMP were significantly correlated with Kr (r = 0.78, p < 0.01 and r = 0.62, p < 0.01, respectively). Our findings suggest that severe reduction in the level of serum ANP during HD, which is induced by water removal, plays some role in HD-induced hypotension through the attenuation of plasma refilling in HD patients.

During hemodialysis therapy, a large amount of water is removed from the patient’s blood in a short time; however, blood pressure remains stable in most patients. As water is removed, the circulating serum proteins become more concentrated, resulting in a marked increase in the driving force which pulls water from the extravascular space into the blood vessels, by a process called plasma refilling. However, since a method for studying plasma refilling has not previously been proposed, it is not known what determines the plasma refilling capacity of hemodialysis patients. To evaluate the plasma refilling capacity of patients, we propose here a method for calculating an index of plasma refiling capacity, which we have called the plasma-refilling coefficient (Kr). In 14 patients receiving maintenance hemodialysis therapy, total serum protein was measured before hemodialysis, and hematocrits were measured hourly during hemodialysis. From the changes in the hematocrits, we estimated the changes in the circulating plasma volume and in the intracapillary oncotic pressure at each time point. The water removal rate was also measured hourly. From these values, we calculated Kr. An averaged volume of 2,692 ± 219 ml of water was removed from each patient resulting in a decrease in the estimated circulating blood volume, while the hematocrit and the estimated intracapillary oncotic pressure increased gradually. Kr calculated after 1 h of hemodialysis varied widely between patients, 140.3-1,744.2 ml/mm Hg/h, and decreased gradually as water removal continued. The average Kr of 14 patients was 698.9 ± 15.2 ml/mm Hg/h at the beginning of water removal, and it decreased to 405.3 ± 75.4,203.9 ± 39.5,130.2 ± 20.5 and 93.9 ± 14.3 each hour thereafter. The index of plasma refilling proposed in this paper is useful for examining capillary water permeability and the degree of plasma refilling in hemodialysis patients.

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