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Biomedical subjects

M Haag-Weber

Publications and source records attributed to M Haag-Weber.

At least 19 recordsLinked to original sources
PubMed1999

Ultrasonography of the catheter tunnel in peritoneal dialysis patients: what are the indications?

The importance of sonography for the early detection and follow-up of tunnel infections in peritoneal dialysis patients is well documented, whereas other indications are less clear. We investigated indications and outcome of 738 ultrasound examinations of the peritoneal dialysis catheter tunnel. Indications for tunnel sonography included routine screening (27%), exit-site infection without peritonitis (24.1%), follow-up of tunnel infection (29.5%), clarification of questionable results (7.5%), pain in the course of the catheter tunnel (1.8%), peritonitis without (5.3%) and with (2.0%) exit-site infection, search for foci (2.2%), and recurrent peritonitis (0.7%). No positive sonographic results were obtained during routine screening or in patients with fever or elevated C-reactive protein levels showing no clinical signs of exit-site infection. Sonographic examinations were positive in 1 of 13 patients with pain in the course of the catheter tunnel, in 1 of 39 cases of peritonitis not associated with exit-site infection, in 12 of 15 patients with peritonitis and simultaneous exit-site infection, and in 2 of 5 patients with recurrent peritonitis. Questionable results were detected in 15 of 178 patients with exit-site infection, in 15 of 199 routine examinations, in 2 of 16 examinations of patients with elevated C-reactive protein levels or fever, and in 2 of 15 cases of peritonitis and simultaneous exit-site infection. All but two of these questionable results had to be rated as negative during further follow-up. We conclude that tunnel sonography is indicated in patients with exit-site infection (including cases with simultaneous peritonitis), for follow-up of tunnel infections, and for estimating the prognosis of these infections. Furthermore, tunnel sonography should be performed in patients with recurrent peritonitis. Tunnel sonography is not indicated for routine screening, search for foci, in cases of peritonitis without exit-site infection, or in patients with pain in the course of the catheter tunnel showing no other clinical signs of exit-site infection.

C-Reactive Protein↗
PubMed1999

Tidal peritoneal dialysis for home-treated patients: should it be preferred?

Tidal peritoneal dialysis (TPD) was introduced to increase the efficacy of peritoneal dialysis. We measured peritoneal clearances of small solutes and beta2-microglobulin, peritoneal protein loss, and efficacy of ultrafiltration in 30 patients during TPD and intermittent peritoneal dialysis (IPD) with low-dialysate flow (1.7 L/h) and, in addition, in 17 of these patients using a high-dialysate flow (3 L/h). Using a low-dialysate flow, patients with low/low average peritoneal transport rates showed significantly better peritoneal creatinine and urea nitrogen clearances during IPD compared with TPD, whereas there was no difference between these two treatment modalities in high/high average transporters. With high-dialysate flow, peritoneal clearances of creatinine and urea nitrogen were similar between TPD and IPD independent of peritoneal transport type. Clearances of phosphate and beta2-microglobulin were similar between TPD and IPD independent of dialysate flow or peritoneal transport type. Increasing the dialysate flow rate led to a significant increase in small-solute clearances, but not beta2-microglobulin clearances, in both peritoneal transport types. Total peritoneal protein and albumin losses were similar between TPD and IPD only with low-dialysate flow. However, using a high-dialysate flow, total protein losses tended to increase in both transport types during IPD compared with TPD. In conclusion, up to a dialysate flow of 3 L/h, TPD did not provide better small-solute or middle-molecule clearances compared with IPD. Moreover, using a low-dialysate flow, IPD was superior to TPD in low/low average transporters.

Adult↗
PubMed1999

Iron status and iron supplementation in peritoneal dialysis patients.

Iron deficiency represents an important problem in peritoneal dialysis patients, especially during erythropoietin therapy. A combination of serum ferritin, transferrin saturation, and/or the percentage of hypochromic red cells should be used to assess iron status in peritoneal dialysis patients. Primarily, oral iron supplementation should be the preferred therapy. However, most of the studies using oral substitution in erythropoietin-treated peritoneal dialysis patients show a progressive decline of serum ferritin. Therefore, parenteral iron supplementation is required in part of the patients, and the intravenous route should be preferred in these cases. Intravenous iron therapy is recommended if serum ferritin falls below 100 microg/liter and should be stopped if the serum ferritin level is more than 650 microg/liter. The optimal form of intravenous iron supplementation is still unclear. Injections once to three times per week restrict the patients' flexibility, but application of higher doses in longer intervals may lead to an impairment of neutrophil functions, probably connected to a higher risk of infection. We treated 17 stable peritoneal dialysis patients with 100 or 200 mg iron saccharate monthly over a period of six months and found an increase of transferrin saturation (from 12.1+/-1.6 to 20.9+/-2.4%, P = 0.026), serum ferritin (from 100.4+/-32.0 to 372.4+/-54.6 microg/liter, NS) and hematocrit (from 32.0+/-0.8% to 35.1+/-0.9%, P = 0.099). The required erythropoietin dosage could be reduced significantly (from 148.4+/-30.3 to 69.4+/-19.5 U/kg/week, P = 0.025). Side effects occurred in 0.9% after application of 100 mg and in 5.9% after injection of 200 mg iron saccharate. The incidence of catheter infections and peritonitis was the same in the period before and after the start of treatment. Further studies are needed to find the most suitable regime of iron supplementation for peritoneal dialysis patients.

Administration, Oral↗
PubMed1998

New criteria for management of catheter infections in peritoneal dialysis patients using ultrasonography.

Catheter-related infection is one of the most important causes of technical dropout in peritoneal dialysis patients. Both the type of cultured organism and the extent of inflammation are well known prognostic factors for the outcome of these infections. From December 1994 to November 1996, 96 catheter-related infections without simultaneous peritonitis occurred in 49 of 86 peritoneal dialysis patients treated in this study. During the observation period, only single-cuff catheters were used. Staphylococcus aureus was the most common organism cultured (51%). Involvement of the tunnel was diagnosed by sonography in 57.1% of all Staphylococcus aureus cases, but only in 26.1% of Staphylococcus epidermidis-related exit-site infections. Ten of the 96 catheter-related infections (10.4%) resulted in catheter loss. Catheter removal was necessary only in cases of deep tunnel infection caused by Staphylococcus aureus. The number of gram-negative catheter infections was too small to allow conclusive analysis. Although sonography of the catheter tunnel is now well established in the early diagnosis of tunnel infections, no clear guidelines exist for management of these infections. In this study, patients with deep tunnel infection who did not require catheter removal showed a significant decline of the hypoechogenic area around the cuff (from 7.02 +/- 0.70 to 3.75 +/- 1.04 mm, P < 0.002) 2 wk after initiation of therapy. No significant decline was observed in patients who later lost their catheters. On the basis of these data, it is concluded that in cases of exit-site and superficial tunnel infection, conservative treatment should be performed. In cases of deep tunnel infection without peritonitis caused by Staphylococcus aureus, antibiotic treatment should be started and sonographic examination should be performed every second week. If the hypoechogenic area around the cuff decreases (> 30%), conservative treatment should be prolonged. In cases without sonographic improvement (< 30%) 2 wk after therapy, catheter removal is recommended.

Abdominal Abscess↗
PubMed1998

New strategies to prevent Staphylococcus aureus infections in peritoneal dialysis patients.

The importance of Staphylococcus aureus as etiological agent for catheter-related infections and peritonitis in peritoneal dialysis patients is well established. To evaluate groups at risk of developing Staphylococcus aureus infections, nasal and exit-site cultures were performed in 76 peritoneal dialysis patients monthly over a period of 3 yr. The risk of Staphylococcus aureus catheter infection was significantly higher in diabetic (group 1) and immunosuppressed (group 2) patients compared with nondiabetic and nonimmunosuppressed (group 3) patients. In diabetic patients, Staphylococcus aureus-positive nasal cultures were more frequent than positive cultures taken from the bland exit-site (73.3% versus 60.0%). On the other hand, both positive and negative exit-site cultures had a better prognostic value for Staphylococcus aureus catheter infection compared with nasal cultures. In immunosuppressed patients, both nasal and exit-site carriages were associated with a very high risk of Staphylococcus aureus catheter infection, but nasal swabs were far more often positive than swabs from the bland exit-site (72.7% versus 25.0%). However, the risk of infection was also high for non-nasal and non-exit-site carriers in this group. In nondiabetic and nonimmunosuppressed patients, the risk of Staphylococcus aureus catheter infection was increased only if two or more positive nasal cultures were detected. It is concluded that in diabetic patients, antibiotic prophylaxis should be performed in all Staphylococcus aureus exit-site carriers. All immunosuppressed patients should be treated prophylactically. In contrast, in nondiabetic and nonimmunosuppressed patients, prophylactic treatment should be considered only in nasal carriers with two or more positive cultures. The overall low peritonitis rate does not influence this prevention strategy.

Adult↗
PubMed1997

Immune dysfunction in uremia.

Among uremic patients on hemodialysis and continuous ambulatory peritoneal dialysis treatment infectious complications leading to a high incidence of morbidity and mortality are a well documented problem. Polymorphonuclear leukocytes (PMNLs) are the main cells of the unspecific defence system during bacterial infections. There is a number of partly interdependent factors responsible for the diminished PMNL functions (chemotaxis, phagocytosis, intracellular killing by proteolytic enzymes and toxic oxygen radicals) found in uremia: iron overload, elevated levels of intracellular calcium and hemodialysis treatment per se has been shown to be involved in altered PMNL functions. Uremic toxins are circulating plasma factors accumulating in the serum of uremic patients. They are thought to play a crucial role in inhibiting the unspecific immune defence. A number of uremic toxins has already been purified and characterized. In our laboratory, a granulocyte inhibiting protein (GIP) with homology to immunoglobulin light chains has been isolated. We could show that free immunoglobulin light chains per se are able to interfere with essential PMNL functions. A GIP with homology to beta 2-microglobulin was also isolated from dialysis patients. Angiogenin was purified from uremic patients as a PMNL degranulation inhibiting protein and complement factor D was shown to adversely affect PMNL functions. A modified form of ubiquitin isolated from peritoneal dialysis patients interferes with PMNL chemotaxis. Furthermore, p-cresol was identified as a uremic solute that impairs the respiratory burst activity of PMNL. There is also increased clinical evidence for profound defects in the specific immune defence in uremia, such as the high susceptibility to viral infections in uremic patients, the deficient responses of their T lymphocytes, and the significantly depressed specific antibody responses.

B-Lymphocytes↗
PubMed1996

Are granulocyte inhibitory proteins contributing to enhanced susceptibility to infections in uraemia?

Infectious complications are still a major cause of morbidity and mortality in patients undergoing regular dialysis treatment. This increased morbidity and mortality of patients with uraemia has been attributed to the dysfunction of polymorphonuclear leukocytes (PMNLs). Uraemia contributes to impaired PMNL function by means of disarrangements in cellular biochemistry and biology. Reduced chemotaxis, adherence, oxidative activity, and glucose consumption in response to phagocytic challenge have been reported. Several compounds present in uraemic serum have been isolated and characterized to inhibit the biological activity of PMNLs. A first granulocyte inhibitory protein (GIP I) responsible for the PMNL dysfunction in uraemia has been isolated and characterized. The polypeptide, with a molecular weight of 28 000 Da, inhibits the uptake of deoxyglucose, chemotaxis, oxidative metabolism, and intracellular bacterial killing by PMNLs. A second granulocyte inhibitory protein (GIP II), with a molecular weight of 9500 Da, has been isolated from plasma ultrafiltrates obtained from haemodialysis patients. It interferes with similar functions of PMNLs. GIP I displays homology with light chain protein and GIP II with beta 2-microglobulin, respectively. Both proteins were also isolated from peritoneal dialysis effluents. Isolated kappa and lambda light chain monomers and dimers from haemodialysis and peritoneal dialysis patients also inhibit several PMNL functions. Recently, a PMNL degranulation inhibiting protein (DIP) was purified from plasma ultrafiltrates obtained from patients undergoing regular haemodialysis therapy. DIP shows homology with angiogenin and inhibits spontaneous as well as stimulated PMNL degranulation. These proteins may explain at least in part the enhanced susceptibility to infections in haemodialysis and peritoneal dialysis patients.

Cytokines↗
PubMed1996

Dysfunction of polymorphonuclear leukocytes in uremia.

There is increased incidence of infectious complications in uremic patients, indicating impairment of cellular host defense in these patients. Several reports confirm metabolic and functional abnormalities of polymorphonuclear leukocytes (PMNL) including altered adherence to endothelial cells, altered generation of reactive oxygen species, altered release of microbial enzymes, impaired chemotaxis, phagocytosis, intracellular killing of bacteria, altered carbohydrate metabolism, and/or impaired ATP formation. Several studies report on correlations between PMNL dysfunction, especially phagocytosis and oxidative burst, and ferritin content. Deferoxamine therapy improved PMNL function. Chronic renal failure is a state of increased cytosolic calcium. Increased cytosolic calcium is associated with several alterations of PMNL function and metabolism, which improve by normalization of cytosolic calcium either by calcium channel blockers or by lowering of elevated parathyroid hormone. Each hemodialysis session using bioincompatible membranes triggers neutrophil activation, evidenced by overexpression of adhesion molecules, elevation of cytosolic calcium, release of PMNL granular enzymes, and generation of reactive oxygen species. Several studies claim that this results in chronic downregulation of phagocyte function. Several granulocyte inhibitory compounds have been isolated and characterized from uremic serum. The uremic retention product p-cresol depresses respiratory burst activity. The following granulocyte inhibitory peptides could be isolated from dialysis patients: granulocyte inhibitory protein I and II with homology to light chain proteins and beta 2-microglobulin, degranulation inhibitory protein I and II being identical to angiogenin and complement factor D, and immunoglobulin light chains. These proteins inhibit PMNL function in nanomolar concentrations.

Calcium↗
PubMed1995

Verapamil reverses abnormal [Ca2+]i and carbohydrate metabolism of PMNL of dialysis patients.

The basal levels of cytosolic calcium ([Ca2+]i) of polymorphonuclear leukocytes (PMNL) are elevated in hemodialysis (HD) patients, and this abnormality has been implicated in the dysfunction of the PMNL of these patients. The elevated [Ca2+]i appears to be due to PTH-induced entry of calcium into PMNL, an action that may be prevented by calcium channel blockers. We examined [Ca2+]i and carbohydrate metabolism of PMNL of normal subjects and of HD patients before, after eight to nine weeks of verapamil therapy (120 mg/day), and after eight to ten weeks of discontinuation of verapamil treatment. In HD patients, the basal levels of [Ca2+]i of PMNL are elevated and their glucose uptake, the activity of total and active forms of glycogen synthetase, and glycogen content are reduced compared to values in normal subjects (P < 0.01). These derangements were normalized after verapamil therapy and re-emerged after discontinuation of treatment with verapamil despite no change in blood levels of PTH. The results indicate that the elevation in [Ca2+]i of PMNL and the consequent derangements in carbohydrate metabolism of these cells are treatable with a calcium channel blocker. The data assign a valuable role for calcium channel blockers for the amelioration of some aspects of cell dysfunction of uremia.

Aged↗
PubMed1995

Effect of immunoglobulin light chains from hemodialysis and continuous ambulatory peritoneal dialysis patients on polymorphonuclear leukocyte functions.

Circulating plasma factors accumulating in the serum of uremic patients have the potential to inhibit essential functions of polymorphonuclear leukocytes (PMNL). As a consequence, these factors can contribute to the increased risk for bacterial infections generally found in uremic patients. Free immunoglobulin light chains that are present in the serum of healthy adults at low levels appear in the serum of uremic patients at significantly higher levels. Therefore, kappa and lambda light chains in their monomeric and dimeric forms were isolated from hemodialysis and continuous ambulatory peritoneal dialysis patients and their potential to inhibit essential PMNL functions in in vitro assays was tested. It was found that all isolates tested were able to inhibit deoxyglucose uptake, a measure for the state of activation of PMNL, as well as chemotaxis. In contrast, free immunoglobulin light chains had no influence on the phagocytotic functions of PMNL. It was concluded that free immunoglobulin light chains are able to act as uremic toxins by interfering with essential PMNL functions and that their serum levels and fate during the treatment of uremic patients should be taken into consideration.

Chemotaxis↗
PubMed1995

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.

Acute Kidney Injury↗
PubMed1994

Impaired cellular host defence in peritoneal dialysis by two granulocyte inhibitory proteins.

Bacterial and fungal peritonitis is associated with a high risk of morbidity and mortality in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Impaired cellular host defence in the peritoneal cavity underlies this risk. Two granulocyte inhibitory proteins with a molecular weight of 28,000 dalton (GIP I) and about 9500 dalton (GIP II) with homology to light-chain proteins and beta 2-microglobulin, respectively, were isolated from peritoneal dialysis effluents. In vitro, both granulocyte inhibitory proteins inhibit PMNL glucose uptake, phagocytosis and intracellular killing of bacteria. The IC50 of GIP I or GIP II required for inhibition of half-maximal FMLP-induced or PMA-stimulated PMNL function was found to be in the nanomolar range, suggesting very specific inhibition. These data may explain, at least in part, defective local cellular host defence in CAPD patients.

Cytokines↗
PubMed1994

Studies of biocompatibility of different dialyzer membranes: role of complement system, intracellular calcium and inositol-triphosphate.

PMNLs are activated during extracorporeal circulation. The aim of this cross-over biocompatibility study was to investigate the role of complement system, intracellular calcium [Ca2+]i and inositol-triphosphate (IP3) on PMNL degranulation during hemodialysis (HD) with following membranes: polyamide, hemophane and cuprophane. In a second study the effect of complement system, intracellular calcium and IP3 on lactoferrin release during HD with polysulfone and polymethylmethacrylate (PMMA) was also investigated. HD with cuprophane leads to the highest formation of terminal complement component (TCC) followed by PMMA and hemophane. There was a strong correlation between maximal arterial TCC formation and procentual increase of plasma lactoferrin during hemodialysis treatment with all membranes. Both HD with PMMA and hemophane leads to a significant increase of resting [Ca2+]i after 30 minutes of HD. Lowest TCC formation and lowest rise in [Ca2+]i were observed with polysulfone and polyamide. Procentual and absolute increase of [Ca2+]i did also correlate with maximal TCC formation during HD using PMMA, hemophane, polyamide and polysulfone. Since cuprophane induces an initial drop of PMNLs, these cells could not be isolated during HD with cuprophane membranes. Resting PMNL IP3 values were similar before and 30 minutes after begin of hemodialysis and comparable with all membranes used. These data indicate that TCC and intracellular calcium are important signals for PMNL degranulation during HD with cuprophane, PMMA and hemophane. However, mild degranulation of specific PMNL granules can also occur in the absence of significant change in TCC, [Ca2+]i or IP3 levels during HD with polyamide or polysulfone.

Biocompatible Materials↗
PubMed1994

Effect of calcium channel blockers on intracellular calcium accumulation.

Protection against acute renal failure by calcium channel blockers include radiocontrast agent, cyclosporin, aminoglycosides, amphotericin B, cisplatin nephrotoxicity, and ischaemia-induced toxicity. Calcium overload occurs in ischaemic cells. The type of calcium channel blocker influences the potential effect on protection against nephrotoxicity. A number of growth factors and hormones induce cellular activation by increasing calcium concentrations. Calcium channel blockers interfere with activation of different cell types, e.g. decrease platelet aggregation, macrophage activation, platelet-activating factor release and also proliferative response of vascular smooth muscle and mesangial cells. Uraemia is also a state of calcium accumulation. Increase of intracellular calcium [Ca2+]i in PMNLs is associated with deactivation. Treatment with calcium channel blockers normalizes elevated PMNL [Ca2+]i and improves functional parameters of PMNLs. Normalization of enhanced [Ca2+]i of PMNLs can also be achieved with effective 1,25(OH)2 vitamin D3 therapy by lowering PTH. Uraemia is also a state of insulin resistance. Elevated levels of [Ca2+]i in insulin target cells diminish sensitivity to insulin at the postbinding site. Therapeutic manoeuvres preventing the increase of cytosolic calcium may improve insulin resistance.

Acute Kidney Injury↗