Altered Na⁺‐K⁺ ATPase activity in uraemic adolescents

Abstract

The Na(+)-K+ ATPase enzyme plays an essential role in the regulation of cell composition and volume. Enzyme activity itself is regulated by substrate availability and several hormones. In adult uraemic patients red blood cell Na(+)-K+ ATPase activity is decreased. However, it is unknown if children with uraemia exhibit the same phenomenon. Therefore, in the present study we examined whether endogenous digoxin-like factors (EDLF) and physicochemical membrane properties play a role in the regulation of erythrocyte Na(+)-K+ ATPase activity in uraemic children and adolescents. Healthy age-matched children were used as controls. Enzyme activity was measured in detergent-pretreated red blood cells and erythrocyte ghosts. Na(+)-K+ ATPase activity (2204 +/- 538 nmol Pi ml erythrocyte-1 h-1 in detergent pretreated erythrocytes; 204 +/- 56 nmol Pi mg protein-1 h-1 in ghosts) in adolescents with uraemia was lower compared to controls (3245 +/- 362 nmol Pi ml erythrocyte-1 h-1; 266 +/- 37 nmol Pi mg protein-1 h-1, p < 0.001, p < 0.05, respectively). Plasma levels of EDLF were elevated in uraemic patients (0.30 +/- 0.05 versus 0.21 +/- 0.04 ng ml-1, p < 0.01). Furthermore, the membrane lipid component was decreased in patients with uraemia, while the cholesterol/phospholipid ratio and membrane fluidity were similar in both groups. No correlation was found between the decrease in Na(+)-K+ ATPase and the increase in EDLF concentration and altered membrane lipid components. Our results demonstrate, that similar to the findings of adults, the activity of Na(+)-K+ ATPase is diminished in uraemic adolescent patients, and that uraemia-associated elevation in EDLF and altered membrane components do not play a role in the down-regulation of Na(+)-K+ ATPase. Therefore other factors (presence of other inhibitors and/or reduced number of enzyme molecules) should contribute to the lower activity of the Na(+)-K+ pump.

Monitoring cardiovascular changes during hemodialysis in children

“…This study supports earlier findings of decreased Na + /K + ATP-ase activity in uremic patients [1,2,5,8]. Several investigators have demonstrated increased levels of Na + pump inhibitors in CRF [7,9,10]. We have also found an elevated EDLF plasma level in uremia.…”

“…P placed above the control values shows the results of the Mann-Whitney U test for unpaired data between the control group and the starting value of the chronic renal failure (CRF) group used in emission mode, after careful washout followed by hemolysis of the erythrocyte suspension. The EDLF level was determined by fluorescence polarization immunoassay using an Abbot TDX automatic system and Abbot Digoxin II kits as described previously [7].…”

“…Plasma of blood samples treated with lithium-heparin anticoagulant was separated for determination of EDLF. The erythrocyte Na + /K + ATP-ase activity was measured as described previously [7], using a Boehringer UV Phosphor kit on a Hitachi 704 automated system. One unit of Na + /K + ATP-ase activity was expressed as 1 µmol P/l erythrocyte per hour.…”

“…In addition to the above-mentioned factors, the role of circulating toxic materials is repeatedly raised [5,6,7]. Among others the endogenous digoxin-like factor (EDLF) accumulates during the course of CRF, exerting an inhibitory action on the sodium-potassium ATP-ase (Na + /K + ATP-ase).…”

Postasphyxial Reoxygenation Reduces the Activity of Na⁺/K⁺-ATPase in the Erythrocytes of Newborn Piglets

“…As a result of hypoxic stress and following reoxygenation, lipid peroxidation is enhanced with the alteration of cell membrane structure. The Na + /K + -ATPase molecules are integral membrane proteins, so the alteration of its environment would be expected to alter its function [17]. Additionally, as the result of hypox- Table 1.…”