The immune system in uremia and during its treatment

Infectious complications are frequent and often lethal in patients with uremia. Serious alterations in neutrophil function, e.g., phagocytosis, mononuclear cell activation, cytokine production, complement activation, T-cell function, and adhesion molecule expression, have been documented in uremic patients. Uremia per se is a cause of some of these derangements, but much evidence now exists that blood-membrane interaction during dialysis is responsible for many of these abnormalities. This is particularly true when bio-incompatible cellulose-based membranes are used. In many of these patients, newly described granulocyte inhibitory proteins (GIP) can be demonstrated. These two proteins, GIP I and II (28 kD and 9.5 kD, respectively, in molecular weight), block effective bacterial killing, chemotaxis, and oxygen metabolism. It appears that GIP I is a member of the lightchain family, and GIP II is the advanced glycosilation end product of beta 2-microglobulin. Another inhibitory protein, degranulation inhibitory protein (DIP), has been isolated. This protein is 14 kD in molecular weight, and is identical to the angioplastic factor angiogenin. DIP levels are significantly elevated in patients undergoing dialysis. Much still needs to be learned about the interactions of these inhibitory proteins with other soluble inflammatory mediators and, in particular, cytokines. It is clear, however, that profound derangements in immune function take place during uremia and dialytic therapy. Such derangements are likely to play an important role in determining the rate of recovery of renal function and the patient's ability to respond to septic insults. Further insights into the pathogenesis of uremic-dialytic immune dysfunction are already yielding improved patient management and decreased infection rates.