| [ Summary ] |
Dialysis membranes in the 1960's, when chronic hemodialysis treatments were begun, were regenerated cellulose membranes. During that decade target substances for removal in the blood of uremic patients were small molecules, such as urea, creatinine, and guanidine compounds. In the 1970's, "middle molecular substances", those with molecular weights ranging from 300 to 5,000 daltons, were considered to be uremic toxins. Hemodiafiltration was developed in order to increase the removal amounts of middle molecular toxins, and separation and identification of such substances in uremic serum were actively attempted by many researchers worldwide. Inhibitory peptides of erythropoiesis and neurotoxic polyols were detected in uremic ultrafiltrates. In that decade, it was a development policy for dialysis membranes to not allow protein leakage across the membranes. In the 1980's, new dialysis membranes, by which considerable amounts of low molecular weight proteins (LMWP) such as beta2-microglobulin were removable as readily as with glomerular filtration, were developed. In LMWP physiologically active substances such as cytokines, complement factor D, proteases and protease inhibitors exist in uremic serum. |