alpha-chymotrypsin and Uremia

To evaluate pancreatic exocrine function in uremia, 25 patients undergoing regular hemodialysis without clinical evidence of pancreatic disease and 25 healthy control subjects were studied by fecal elastase 1 and chymotrypsin. Abdominal ultrasonography and measurement of serum lipase, calcium, phosphate, and parathormone were also carried out. Fecal elastase was significantly lower (P < 0.001) in patients than in controls. Abnormally low values were found in 12/25 patients of whom six had values <100 microg/g. Fecal chymotrypsin was significantly lower (P < 0.05) in patients than in controls, with lower than normal values found in 10/25 patients. Fecal elastase was not related to the serum calcium, phosphate, or parathormone levels or to the period of dialysis. In patients serum lipase was normal or slightly elevated (<300 units/liter), and there was no evidence of pancreatic disease at ultrasound examination. The results lend further support to the existence of pancreatic function impairment in a significant number of patients with renal failure despite the absence of clinical and morphological evidence of pancreatic disease.

Topics: Aged; Aged, 80 and over; Chymotrypsin; Feces; Female; Humans; Male; Middle Aged; Pancreatic Elastase; Pancreatic Function Tests; Pancreatitis; Reference Values; Renal Dialysis; Uremia

The uremic state is characterized by subnormal platelet aggregation. Fibrinogen fragments, usually absent in normal human blood, but present in uremic plasma, may play a role in uremic platelet dysfunction.. To examine this hypothesis, we investigated the availability and function of fibrinogen receptors [glycoprotein (GP) IIb-IIIa] on uremic and normal platelets, as well as the effect of fragments obtained from chymotrypsin digestion of human fibrinogen on normal platelets. The availability of fibrinogen receptors was examined using anti-GP IIb-IIIa antibodies and flow cytometry, whereas receptor function was assessed by the receptor's ability to mediate fibrinogen binding and platelet aggregation.. Platelet aggregation and the availability of GP IIb-IIIa were lower in uremic patients when compared with normal controls. Flow cytometric analysis showed that fibrinogen fragments decreased the binding of anti-CD61, an activation-independent anti-GP IIIa monoclonal antibody, to resting normal platelets. These fragments also reduced the binding of PAC-1, an activation-dependent anti-GP IIb-IIIa monoclonal antibody, to adenosine diphosphate (ADP)-activated normal platelets. In addition, the binding of radiolabeled fibrinogen to activated normal platelets and platelet aggregation in response to ADP were both decreased by fibrinogen fragments.. These findings suggest that fibrinogen fragments impair platelet function by occupying fibrinogen receptors prior to cell activation, thus preventing the binding of intact fibrinogen to platelets after subsequent stimulation. These observations also suggest a plausible mechanism by which endogenous fibrinogen fragments present in uremic plasma may contribute to platelet dysfunction.

Topics: Adenosine Diphosphate; Antibodies, Monoclonal; Blood Platelets; Chymotrypsin; Fibrinogen; Humans; Male; Peptide Fragments; Platelet Activation; Platelet Aggregation; Platelet Glycoprotein GPIIb-IIIa Complex; Reference Values; Uremia

Sera from chronically uremic and normal individuals were subjected to gel filtration with Sephadex G-25 and the same fraction of both was infused into rats with a decreased nephron population to determine the effects on sodium excretion. Sodium excretion rate and fractional sodium excretion increased slightly with the normal fractions; but the increase in both functional parameters produced by the uremic fractions was substantially and significantly greater. The natriuresis could not be explained by associated changes in glomerular filtration rate (GFR), para-aminohippurate (PAH) clearance, filtration fraction, hematocrit, or blood pressure. The possibility thus exists that the inhibitor affected some component part of the transepithelial sodium transport system. The elution characteristics of the fraction plus certain of its physicochemical properties suggest that the inhibitor of sodium reabsorption by the rat nephron may be identical with the inhibitor of PAH uptake by kidney slices and the inhibitor of transepithelial sodium transport by the frog skin and toad bladder previously found in the serum of chronically uremic patients.

Topics: Adolescent; Adult; Aminohippuric Acids; Animals; Anura; Biological Assay; Blood; Chronic Disease; Chymotrypsin; Female; Glomerular Filtration Rate; Humans; Inulin; Kidney Tubules; Middle Aged; Natriuresis; Pronase; Rats; Skin Absorption; Uremia; Urinary Bladder

An inhibitor of transepithelial sodium transport was found in a low molecular weight fraction obtained from serum of patients with far advanced chronic renal disease. In 18 nondialyzed patients, the mean inhibition of short circuit current (SCC) was 24.9 +/-2.2% (SE). With a comparable fraction from 11 normal subjects. SCC decreased by only 5.3 +/-1.5%. There was significantly greater inhibition with the serum fractions of patients with end stage renal disease being maintained on chronic hemodialysis than in the normal control group; but the degree of inhibition in the dialyzed population was significantly less than that observed in the nondialyzed chronically uremic patients. The inhibition of SCC produced by the serum fractions of a group of seven patients with acute renal failure was not significantly different from the control group despite the presence of high grade uremia in the former. The inhibitory fraction has characteristics identical with the uremic serum fraction which previously has been shown to inhibit p-aminohippurate (PAH) uptake by rabbit kidney cortical slices. With gel filtration through Sephadex G-25, the active fraction appears after the major peaks of substances as small as urea and sodium; hence it may have been retarded on the column. But its ultrafiltration characteristics suggest that its molecular weight may be less than 1000. The inhibitory capability was not destroyed by boiling, freezing, or digestion with chymotrypsin or pronase. Neither methylguanidine nor guanidinosuccinic acid in concentrations well above those present in the serum of uremic patients inhibited sodium transport in the frog skin. The data suggest that there is an inhibitor of sodium transport in the serum of patients with chronic uremia. The role of this material in the regulation of sodium excretion in uremia as well as its possible role as a uremic toxin are subjects of both theoretical and practical interest.

Topics: Acute Kidney Injury; Animals; Anura; Biological Transport; Chemical Phenomena; Chemistry; Chromatography, Gel; Chymotrypsin; Cold Temperature; Guanidines; Hot Temperature; Humans; Kidney Failure, Chronic; Molecular Weight; Peptide Hydrolases; Potentiometry; Renal Dialysis; Skin; Sodium; Succinates; Uremia