Biochemical definition of the uremic syndrome and possible therapeutic implications.

Renal failure is characterized by the progressive decline in the capacity of the kidneys to eliminate toxic solutes. In parallel, the “uremic syndrome” is depicted by a functional disturbance of enzymes, organelles, cells, and organs. This leads to an overall malaise that ultimately ends in coma and death unless artificial kidney treatment (dialysis) is started (1). The current conception of dialysis is highly aspecific. Emphasis has been on the elimination of small, water-soluble compounds such as creatinine and urea; however, the toxicity of the latter substances is still debatable. Uremic biological fluids are in fact complex mixtures containing innumerable interfering compounds that are the basis of the “uremic syndrome.” The uremic toxin probably does not exist (2). Despite several decades of study, the pathophysiology of the uremic syndrome remains i l l defined. The possibilities in this domain have been improved recently by the introduction of new techniques for biochemical and biological evaluation and for separation and identification of the contents of complex biological fluids. The latter steps were made possible by the introduction of high-performance liquid chromatography (HPLC). In our laboratory, a stepwise strategy has been developed whereby complex uremic mixtures (sera or ultrafiltrates) are fractionated in several fractions (eluates). By evaluating the effect of uremic biological fluids on functional systems that are known to be disturbed in renal failure, we can pursue a fractionation of these biological fluids to identify the responsible compounds. This approach has already enabled us to identify the sub-