lactoferrin and Kidney-Failure--Chronic

Degranulation of polymorphonuclear leukocytes (PMNL) occurs during extracorporeal circulation. A degranulation-inhibiting protein identical to angiogenin was recently isolated from high-flux dialyzer ultrafiltrate. This protein inhibits the release of lactoferrin and metalloproteinases from PMNL in vitro. In the present study, we investigated end-stage renal disease patients undergoing regular hemodialysis treatment with either high-flux dialyzers (n = 51) or low-flux dialyzers (n = 44), and chronically uremic patients undergoing hemodiafiltration (n = 30). Hemodialysis therapy with low-flux polysulfone or cellulose triacetate membranes caused no or only minimal reduction (

Topics: Adult; Aged; Aged, 80 and over; Azo Compounds; Cell Degranulation; Cellulose; Extracorporeal Circulation; Female; Humans; Kidney Failure, Chronic; Lactoferrin; Leukocyte Elastase; Male; Membranes, Artificial; Middle Aged; Neutrophils; Polymers; Renal Dialysis; Ribonuclease, Pancreatic; Sulfones

At the concentrations used in haemodialysis and in a dose-dependent way, unfractionated heparin (UFH) and, to a lesser degree, a low-molecular-weight heparin (LMWH) stimulate polymorphonuclear cells (PMN) in vitro, and could act in synergy with the stimulatory effect of dialysis membranes in vivo. To examine this hypothesis, we studied the effects of different heparin types and regimens on blood PMNs during haemodialysis sessions.. Ten haemodialysed patients were studied during regular dialysis sessions on a cellulose triacetate membrane (CT 110 G; 1.10 m(2); Baxter), with four different random heparin protocols: one high-UFH regimen (HHR) at 90 IU/kg body-weight (b.w.) and one low-UFH regimen (LHR) at 50 IU/kg b.w., and with a LMWH (nadroparin calcium) at 85 (HHR) or 45 (LHR) IU/kg b.w. Blood granulocytes, platelet counts, and plasma granulocyte degranulation products (elastase, lactoferrin) were measured serially during 4 h dialysis sessions.. After 10 min, the reduction in PMNs with UFH was 29.5% for HHR (P<0.01) and 28.5% for LHR (P<0.01), and only 16.8 and 18.6% with LMWH (NS), significantly higher for HHR with UFH than with LMWH (P<0.01). At 60 min, the elastase increase with HHR was greater, 61% with UFH (P<0.01) and 37.8% with LMWH (P<0.01), significantly higher than LHR for UFH (P<0.05) or LMWH (P<0.05). The overall decrease in platelets (with LMWH P<0.01) and the overall increase in lactoferrin (P<0.001) were not different between heparinization procedures.. Under a conventional heparin regimen, the PMN variation during the course of the dialysis session suggests a more biocompatible effect of LMWH over UFH. In addition, the variation of elastase favours the lower dose, whatever the type of heparin. Heparin type and dose should therefore be considered in studies addressing biocompatibility in haemodialysis: a low dose of LMWH may be viewed as a better biocompatible treatment with regard to leukocyte stimulation.

Topics: Adult; Aged; Anticoagulants; Biocompatible Materials; Cell Degranulation; Chemical Fractionation; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Kidney Failure, Chronic; Lactoferrin; Leukocyte Count; Male; Middle Aged; Neutrophils; Pancreatic Elastase; Platelet Count; Renal Dialysis

Multiple dysfunctions of polymorphonuclear leukocytes (PMNLs) contribute significantly to the increased morbidity and mortality among patients with end-stage renal disease. In the present study, we measured the PMNL content of beta(2)-microglobulin (beta(2)m) and lactoferrin in different states of renal insufficiency and after kidney transplantation. PMNLs were lysed ultrasonically and, after centrifugation, both proteins were assayed in the supernatant by enzyme-linked immunosorbent assay technique. Despite marked differences in plasma beta(2)m levels, no significant difference in PMNL content of beta(2)m and lactoferrin could be shown among the groups analyzed. There was also no correlation between plasma beta(2)m level and PMNL beta(2)m content. In control subjects, as well as in renal allograft recipients with a well-functioning graft, PMNL beta(2)m level correlated positively with PMNL lactoferrin level (pooled data, r = 0.55; P < 0.001; n = 55). Both proteins are considered to colocalize in peroxidase-negative PMNL granules. However, no correlation was found in the azotemic and uremic patient groups. Standard immunofluorescence staining of control PMNLs showed a cytoplasmic granular distribution of both granule proteins. However, in PMNLs of uremic patients, lactoferrin shifted to a perinuclear localization. PMNLs obtained from uremic individuals failed to elicit an increase in lactoferrin release after stimulation with the chemotactic peptide f-Met-Leu-Phe compared with PMNLs obtained from healthy volunteers. These data indicate abnormalities in uremic patients of PMNL granule lactoferrin content and release that are reversible after successful renal transplantation.

Topics: Adult; beta 2-Microglobulin; Cell Degranulation; Cell Nucleus; Chemotactic Factors; Cytoplasmic Granules; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique, Direct; Humans; Kidney Failure, Chronic; Kidney Transplantation; Lactoferrin; Middle Aged; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Transplantation, Homologous; Uremia

Advanced glycation endproducts (AGEs), structural components of beta-amyloid plaques and neurofibrillary tangels, have been implicated in the pathogenesis of Alzheimer's disease. AGE levels, measured by fluorescence, and their precursor molecules such as glucose and its Amadori product, fructosylamine, were measured to examine the question whether the reported increased level of AGEs in the brain is reflected in an increase in AGE-associated parameters in peripheral blood. Lactoferrin, proposed to play an important role in the interaction of AGEs with their receptors, was determined by ELISA. All AGE-associated parameters showed trends to lower values in patients with Alzheimer's disease compared with non-demented controls. Albumin and total iron were not significantly different between the groups. In contrast to diabetes and renal failure, where high levels of AGEs and their precursors are present in tissue as well as in peripheral blood, elevated CNS AGE levels in patients with Alzheimer's disease are manifested without detectable peripheral changes.

Topics: Aged; Alzheimer Disease; Blood Glucose; Enzyme-Linked Immunosorbent Assay; Glycated Hemoglobin; Glycation End Products, Advanced; Humans; Iron; Kidney Failure, Chronic; Lactoferrin; Middle Aged; Reference Values; Renal Dialysis; Serum Albumin; Spectrometry, Fluorescence

The authors investigated in patients with renal disease the lactoferrin content in duodenal aspirate. The aspirate was obtained after previous stimulation of the pancreas with pancreozymin. Lactoferrin estimation is described in the literature as a sensitive examination of changes of exocrine pancreatic secretion. The authors provided evidence that by assessing lactoferrin it is possible to detect initial changes of reduced exocrine pancreatic capacity already in subjects who are on the waiting list of chronic intermittent haemodialyzation programmes (CHIDP); maximum increase of the lactoferrin content in the duodenal aspirate corresponds with the severity of chronic renal failure. Transplantation of the kidneys leads to normalization of the amount of lactoferrin secreted by the pancreas which is evidence of normalization of pancreatic secretion. In patients with chronic renal failure lactoferrin is a sensitive marker of developing uraemic pancreatopathy.

Topics: Humans; Intestinal Secretions; Kidney Failure, Chronic; Kidney Transplantation; Lactoferrin; Pancreatic Diseases; Renal Dialysis

The present study was devised to investigate, whether reduction of membrane surface area would contribute to enhanced dialyzer membrane compatibility. Therefore, 10 hemodialysis patients were dialyzed with three different cuprophan dialyzers, displaying membrane surface areas of 0.9 m2, 1.2 m2, and 1.8 m2. As an index of biocompatibility release of granulocyte elastase and secretion of granulocyte lactoferrin were determined by enzyme-linked immunoassays. With the three cuprophan membranes, marked leukopenia occurred 15 min after the start of hemodialysis, without significant distinction between the different membranes. On the other hand, the release of leukocyte elastase was strictly dependent on the membrane surface area. Thus, at the end of dialysis, plasma levels of elastase were as follows: 0.9 m2: 255 +/- 51; 1.2 m2: 356 +/- 65; 1.8 m2: 471 +/- 56 ng/ml. The magnitude of secretion of leukocytic lactoferrin was also dependent on membrane surface area. Therefore, the increment during dialysis was 300% with the 1.2 m2 membrane compared to 650% using a 1.8 m2 dialyzer. Based upon these data, we concluded that, using measurements of granulocyte degranulation as an index of biocompatibility, reduction of membrane area resulted in a marked improvement of membrane compatibility.

Topics: Adult; Aged; Biocompatible Materials; Cellulose; Humans; Kidney Failure, Chronic; Kidneys, Artificial; Lactoferrin; Leukocyte Count; Membranes, Artificial; Middle Aged; Pancreatic Elastase; Uremia

In 20 patients suffering from chronic renal failure treated by hemodialysis (CRFH) the pure pancreatic juice (PPJ) collected via endoscopic cannulation of the papilla was studied. PPJ was collected during 20 minutes in 1 minute samples. Secretin and pancreozymin (CCK-PZ) were given as boluses respectively at the beginning and at the 10th minute of the test. Volumes, total protein and bicarbonate concentrations, total protein and bicarbonate outputs, Lactoferrin (LF) levels were measured. The results observed in patients were compared to those of ten subjects free of any organic disease. The volume of PPJ was significantly more important in CRFH than in controls. Bicarbonate and protein concentrations were not significantly modified. Protein output was not significantly more important in CRFH at the exception of the 12th sample. Bicarbonate output was not significantly increased at the exception of the 9th and the 11th samples. LF level was more than 0.03% of total proteins in 4 CRFH.

Topics: Adult; Bicarbonates; Cholecystokinin; Female; Humans; Kidney Failure, Chronic; Lactoferrin; Male; Middle Aged; Pancreas; Pancreatic Juice; Proteins; Renal Dialysis; Secretin