Immunologic defects and vaccination in patients with chronic renal failure.

Patients with chronic renal failure suffer from defective host defenses which are directly the result of the renal impairment, in addition to those dependent on the primary illness leading to the renal failure. The mechanisms underlying the defective responses in phagocytic cells, lymphocytes and antigen processing are likely due to either failure to adequately eliminate suppressive compounds by the defective kidneys or to improper metabolic processing of the factors by the damaged renal parynchema. That some of the defects are reversed by transplantation and not dialysis suggests that renal parenchymal metabolic activities may be involved, although it is also possible that functioning glomerular cells are capable of filtering substances that membranes are not currently capable of eliminating. The current strategy for dealing with the immunodeficiency appears to be totally based on developing means to circumvent the defective function. The other approach, correction of the impaired function, cannot be even considered until the mechanisms underlying the defective function of the cells involved in defenses are better delineated. It seems possible that one or a few compounds are pivotal in altering the function of all the affected cell lines, since, with only a small amount of effort, it is possible to relate the dysfunction to abnormal cell membrane functions in phagocytic cells, dendritic cells and lymphocytes. Until the biochemical basis of the dysfunction of all the cell types affected are better defined, such exercises cannot be translated into better management of patients with chronic renal failure. Proper function of host defenses requires that appropriate cells can properly respond to threats to host viability. For the cells of the immune system (phagocytes and lymphocytes) this means that their response to regulatory molecules be appropriate, that their mobility be normal, that their adherence to substrates be preserved, and that they can generate the appropriate response to the challenge. For neutrophils, for example, it is necessary that they recognize and mobilize appropriately to chemotactic stimuli, that they be able to adhere to and migrate through endothelial lining, that their phagocytic activity be sufficient, and that they can kill and degrade endocytosed particles and generate appropriate secretions. Similar lists of requirements for good function can be generated for any cell type in the immune defense system. Uremia, as well as currently available treatments for uremia, directly or indirectly alters the function of all phases of appropriate immune cell function. Defective host responses in uremia have been recognized for decades and there has been considerable effort in the past decade to better define the extent and mechanisms of impaired defenses. Despite the multitude of major defects in humoral, cellular, and inflammatory processes, uremic patients who are cared for today, although they remain at higher risk of serious infectious complications, can and do maintain a good quality of life, with most remaining free of major infections for years and decades.