Mechanisms underlying sCD40 production in hemodialysis patients

CD40 and its ligand (CD40L) regulate several cellular functions, including T and B-cell activation. The soluble form of CD40 (sCD40) antagonizes CD40/CD40L interaction. Patients undergoing hemodialysis (HD) present elevated sCD40 serum levels, which underlying molecular mechanisms are unknown.We studied sCD40 serum and urinary levels, CD40 membrane and gene expression and membrane shedding in HD, uremic not-HD patients (UR) and healthy subjects (N).We found that in HD sCD40 serum levels were higher than UR and N, being significantly elevated in anuric patients, and that sCD40 correlated to renal function in UR subjects, who presented also a reduced sCD40 urinary excretion rate. HD and UR presented reduced CD40 membrane and gene expression. The concentration of TNF-α converting enzyme (TACE), responsible for CD40 cleavage was not different between HD and N. Therefore the reduced renal clearance is the main cause of elevated sCD40 levels in HD. This finding could have relevant clinical implications.

► Soluble form of CD40 (sCD40) is a natural antagonist of CD40/CD40L interaction.
► Patients with renal failure present elevated sCD40 serum levels.
► The loss of renal function is the main cause of sCD40 elevation in hemodialysis.
► The reduction of sCD40 could have important biological and clinical implications.