Na⁺-K⁺ pump in chronic renal failure

This review summarizes the evidence for the defect in Na⁺-K⁺ pump in chronic renal failure, considers the role of various factors in causing this defect, and discusses the clinical implications thereof. Intracellular Na is elevated in erythrocytes, leukocytes, and muscle cells from some patients with chronic renal failure (CRF). Recent evidence suggests that this elevation of cell Na may be, in large part, a consequence of decreased number of Na⁺-K⁺ pump units per cell. Maintenance dialysis over a period of weeks ameliorates the defect in intracellular Na⁺, and this improvement is contemporaneous with an increase in the number of Na⁺-K⁺ pump sites per cell. In erythrocytes with normal cell Na⁺, acute hemodialysis increases the rate of Na⁺ and K⁺ transport. Many factors such as the presence of retained toxic metabolite or circulating inhibitor in the uremic plasma, or biochemical changes produced by acute hemodialysis, may explain this finding. In cells with high cell Na⁺, the pump-mediated K⁺ transport is normalized at the expense of a raised cell Na⁺. The decreased muscle membrane potential in uremic subjects has been attributed to a decreased activity of Na⁺-K⁺ pump. Enzymatic Na⁺-K⁺-ATPase activity of the uremic erythrocyte, leukocyte, sarcolemma, and intestines is also decreased. We discuss the role of hormonal abnormalities and circulating inhibitors, which may cause an acute inhibition of the pump and of other factors such as K⁺ depletion, which may cause more chronic alterations. The implications of alteration of Na⁺ and K⁺ pump transport and raised cell Na⁺ on other non-pump-mediated transport pathways are discussed. Raised cell Na⁺ may be a marker for the adequacy of maintenance dialysis in patients with end-stage renal failure.