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Deproteinized plasma from patients with renal failure had an inhibitory effect on Na,K ATPase activity measured in vitro by a linked-enzyme assay. No inhibitory effect was observed with plasma from normal subjects or from patients undergoing chronic ambulatory peritoneal dialysis. The inhibition of Na,K ATPase whether measured by the linked-enzyme assay or by 86Rb uptake in guinea pig aortic strips was decreased acutely by a single hemodialysis treatment, but was unaffected during a time-control study or ultrafiltration. Changes in Na,K ATPase activity and in Rb uptake were correlated, indicating that the presence of the enzyme inhibitor in uremic plasma was associated with depressed Na pump activity. Change in inhibition of Na,K ATPase activity did not correlate with change in body weight. Dialysis in vitro against a membrane of molecular weight 3,500 cut-off decreased the inhibitory effect of uremic plasma on Na,K ATPase. It was concluded that a dialyzable, low-molecular-weight Na,K ATPase inhibitor circulates in uremia but has no demonstrable role in volume homeostasis.
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