IMMUNE DYSFUNCTION IN UREMIA

Among uremic patients on hemodialysis and continuous ambulatory perito neal dialysis treatment infectious complications leading to a high inc idence of morbidity and mortality are a well documented problem. Polym orphonuclear leukocytes (PMNLs) are the main cells of the unspecific d efence system during bacterial infections. There is a number of partly interdependent factors responsible for the diminished PMNL functions (chemotaxis, phagocytosis, intracellular killing by proteolytic enzyme s and toxic oxygen radicals) found in uremia: iron overload, elevated levels of intracellular calcium and hemodialysis treatment pel se has been shown to be involved in altered PMNL functions. Uremic toxins are circulating plasma factors accumulating in the serum of uremic patien ts. They are thought to play a crucial role in inhibiting the unspecif ic immune defence. A number of uremic toxins has already been purified and characterized. In our laboratory, a granulocyte inhibiting protei n (GIP) with homology to immunoglobulin light chains has been isolated . We could show that free immunoglobulin light chains per se are able to interfere with essential PMNL functions. A GIP with homology to bet a 2-microglobulin was also isolated from dialysis patients. Angiogenin was purified from uremic patients as a PMNL degranulation inhibiting protein and complement factor D was shown to adversely affect PMNL fun ctions. A modified form of ubiquitin isolated from peritoneal dialysis patients interferes with PMNL chemotaxis. Furthermore, p-cresol was i dentified as a uremic solute that impairs the respiratory burst activi ty of PMNL. There is also increased clinical evidence for profound def ects in the specific immune defence in uremia, such as the high suscep tibility to viral infections in uremic patients, the deficient respons es of their T lymphocytes, and the significantly depressed specific an tibody responses.