Release of granulocyte neutral proteinases in patients with acute and chronic renal failure

In uremic intoxication proteolytic activity in plasma and striated muscle is enhanced. To get further insight into the underlying mechanisms the neutral proteinases of polymorphonuclear (PMN) leukocytes were investigated in patients with acute and chronic renal failure. The following studies were performed: 1. Neutral proteolytic activity of PMN neutrophils in blood smears (according to Klessen, 1978). 2. Serum levels of elastase alpha 1 proteinase inhibitor complex (Neumann et al., 1981). In about half of the patients with chronic renal insufficiency on dietary treatment the proteolytic activity of PMN leukocytes (halo formation are due to digestion of erythrocytes and plasma) was reduced. The serum concentration of elastase alpha 1 proteinase inhibitor complex was normal in most subjects, but increased in 3 patients with the highest serum creatinine levels (greater than 13 mg/dl). In the patients with acute renal failure (ARF) of various origin (postoperatively, septicemia, pancreatitis or dye induced) halo formation was either reduced or absent. Serum elastase alpha 1 proteinase inhibitor was increased in 5/6 patients by a factor of two to four. Also in the 15 patients on regular hemodialysis treatment halo formation was substantially reduced, while the serum levels of elastase alpha 1 proteinase inhibitor complex was slightly increased. The finding of reduced proteolytic activity of PMN neutrophils in uremia is probably due to an enhanced release of proteinases into the circulation as indicated by the elevated serum levels of elastase alpha 1 proteinase inhibitor complex in some patients. The release of proteinases might be in part due to the effect of "uremic toxins". In the RDT patients the contact of the blood with the dialyzer (cuprophane) membrane might be an additional factor. In the patients with ARF the underlying disease (infection, shock, trauma) contributes to the release of proteinases. These disturbances may be harmful for the patient, if the blood concentration or function of the most important proteinase inhibitors (alpha 1 proteinase inhibitor, alpha 2 macroglobulin) is reduced.