Lack of effect of clinical doses of cyclosporin A on erythrocyte Na+/K+-ATPase activity

Cyclosporin A (CsA) may exert its cytotoxic effects by altering the activit y of different plasma membrane transport systems. Although CsA may act at t he gene level, it has been also suggested that it can directly alter transp ort processes at the plasma membrane. To examine th is possibility in a phy siological context, we determined Na+/K+-ATPase activity in erythrocytes fr om two groups of subjects receiving CsA treatment: group I consisted of kid ney transplant patients, and group II comprised patients with steroid-resis tant idiopathic nephrotic syndrome. Group I patients showed a marked decrea se (35%) in the activity of the Na+/K+-ATPase in erythrocytes immediately a fter surgery, before the initiation of CsA treatment. The activity remained low 2 days after the introduction of CsA, but had recovered to the origina l (pre-surgery) value I month later. Group II patients showed the same patt ern of erythrocyte Na+/K+-ATPase activity as those in group I. When the blo od CsA levels from all patients were plotted against the corresponding eryt hrocyte Na+/K+-ATPase transport activity, a significant linear correlation was found. Higher levels of CsA in the blood were correlated significantly with increased Na+/K+-ATPase activities. The blood sodium concentration was also correlated positively with both erythrocyte Na+/K+-ATPase activity an d blood CsA concentration. Thus CsA treatment is not associated with inhibi tion of the Na+/K+-ATPase in erythrocytes.