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Biomedical subjects

R T Krediet

Publications and source records attributed to R T Krediet.

At least 19 recordsLinked to original sources

Quality of life in patients on chronic dialysis: self-assessment 3 months after the start of treatment. The Necosad Study Group.

The aim of the present multicenter study was to assess quality of life of Dutch dialysis patients 3 months after the start of chronic dialysis treatment. The quality of life was compared with the quality of life of a general population sample, and the impact of demographic, clinical, renal function, and dialysis characteristics on patients' quality of life was studied. New end-stage renal disease (ESRD) patients who were started on chronic hemodialysis or peritoneal dialysis in 13 dialysis centers in The Netherlands were consecutively included. Patients' self-assessment of quality of life was measured by the SF-36, a 36-item Short Form Health Survey Questionnaire encompassing eight dimensions: physical functioning, social functioning, role-functioning physical, role-functioning emotional, mental health, vitality, bodily pain, and general health perceptions. One hundred twenty hemodialysis and 106 peritoneal dialysis patients completed the SF-36. Quality of life of hemodialysis and peritoneal dialysis patients was substantially impaired in comparison to the general population sample, particularly with respect to role-functioning physical and general health perceptions. Mean role-functioning physical and general health perceptions scores of the hemodialysis patients corresponded with the lowest scoring 8% and 12%, respectively, of the reference group. Mean role-functioning physical and general health perceptions scores of the peritoneal dialysis patients corresponded with the lowest scoring 10% and 12%, respectively, of the reference group. Hemodialysis patients showed lower levels of quality of life than peritoneal dialysis patients on physical functioning, role-functioning emotional, mental health, and pain. However, on the multivariate level, we could only demonstrate an impact of dialysis modality on mental health. A higher number of comorbid conditions, a lower hemoglobin level, and a lower residual renal function were independently related to poorer quality of life. The variability of the SF-36 scores explained by selected demographic, clinical, renal function, and dialysis characteristics was highest for physical functioning (29.7%). Explained variability of the other SF-36 dimensions ranged from 6.9% for general health perceptions to 15.4% for vitality. We conclude that quality of life of new ESRD patients is substantially impaired. Comorbid conditions, hemoglobin, and residual renal function could explain poor quality of life only to a limited extent. Further research exploring determinants and indices of quality of life in ESRD patients is warranted. From a clinical perspective, we may conclude that quality of life should be considered in the monitoring of dialysis patients.

Adolescent

Longitudinal follow-up of CA125 in peritoneal effluent.

Mesothelial changes occur during peritoneal dialysis. CA125 provides a way to study the mesothelial cells in the in vivo situation. In the present study longitudinal changes of CA125 were analyzed. In addition, the appearance of CA125 in peritoneal effluent and day-to-day variability were studied. CA125 was measured in the effluent of five stable CAPD patients during four hour dwells with 1.36% glucose, with 3.86% glucose and with 7.5% icodextrin. In addition, CA125 was determined on six consecutive days in four hour effluents of three patients and appearance rates (AR) were calculated. Longitudinal follow-up was performed in 31 patients in whom three to seven yearly observations had been made. Linear appearance of CA125 was present in all dwells. No difference was found between the appearance rates of CA125 with 3.86% glucose, compared to either 1.36% glucose or icodextrin. Mean day-to-day coefficient of variation was 6.4% for CA125 AR, but a wide variation existed in stable CA125 values among patients (mean 22.1, range 2 to 48 U/ml). A negative trend with duration of CAPD was present in the longitudinal study. A mean decrease of 2.2% per year could be calculated, but substantial interindividual differences existed. Sudden decreases of CA125 AR were found in five patients. Possible causes were found in all of them and included a severe or recurrent peritonitis, and temporary cessation of peritoneal dialysis. In one patient a sudden decrease preceded the manifestation of peritoneal sclerosis. It can be concluded that CA125 can be used for the in vivo follow-up of the mesothelium in peritoneal dialysis patients. The appearance of CA125 in effluent is linear in time and not influenced by the initial lysis of mesothelial cells. A gradual loss of mesothelial cells is likely to occur, although interindividual variability is substantial. An acceleration of the process may be caused by severe peritonitis and perhaps by temporary cessation of peritoneal dialysis. A sudden decrease in CA125 may be an alarming sign for the development or manifestation of peritoneal sclerosis.

CA-125 Antigen

The nitric oxide donor nitroprusside intraperitoneally affects peritoneal permeability in CAPD.

Nitroprusside is a nitric oxide (NO) donor. To investigate effects of nitroprusside i.p. on peritoneal permeability and perfusion, standard peritoneal permeability analyses were performed. Ten stable CAPD patients were studied twice within one week with glucose based dialysate (1.36% Dianeal) with and without addition of nitroprusside 4.5 mg/liter. Mass transfer area coefficients (MTAC) of CO2 were calculated to estimate peritoneal blood flow. Nitrate, a stable metabolite of NO, and cGMP, a second messenger of NO synthesis, were measured in plasma and dialysate. The MTACs of low molecular weight solutes were greater with nitroprusside (NP) compared to the control dwell (C): creatinine median 14.1 (NP) versus 9.9 ml/min (C), urea 21.7 (NP) versus 18.5 ml/min (C) and urate 10.5 (NP) versus 8.6 ml/min (C) (P < 0.05 for all). This points to an increased effective peritoneal surface area with nitroprusside. Furthermore, the restriction coefficient for the low molecular weight solutes decreased from 1.28 (C) to 1.23 (NP) (P = 0.02), suggesting some effect also on the size selectivity to these solutes. The effect of nitroprusside on the clearances of serum proteins was more pronounced. The increase with nitroprusside was 34% for beta 2-microglobulin, 70% for albumin, 77% for IgG and 143% for alpha 2-macroglobulin. This reduction in size selectivity was reflected in a decrease in the restriction coefficient for macromolecules from 2.29 (C) to 1.86 (NP), P < 0.01. This implies an increase in the intrinsic permeability of the peritoneal membrane. Kinetic modeling, using computer simulations, was done to analyze these effects in terms of the pore theory, using a convection model and a diffusion model for the transport of macromolecules. Nitroprusside led to an increase of both the large pore radius and the small pore radius and of the unrestricted area over diffusion distance. These effects were more pronounced with the diffusion model. The MTAC CO2 was not different: NP 76.9 and C 84.1 ml/min. MTACs of nitrate were not greater than expected on the basis of the molecular weight during both dwells. The dialysate/plasma (D/P) ratio of cGMP was greater after addition of nitroprusside: 0.36, range 0.21 to 0.77 (C) and 0.74, 0.23 to 2.50 (NP), P = 0.02. With nitroprusside the D/P ratio of cGMP was greater than expected on the basis of its molecular weight (P < 0.001). This points to local generation of cGMP after the addition of nitroprusside, induced by NO. No differences were found in the dialysate concentrations of the prostaglandins (PG) PGE2 and 6-keto-PGF1 alpha and thromboxane B2 after addition of nitroprusside. The transcapillary ultrafiltration rate and the net ultrafiltration rate during four hours were not different with nitroprusside. In conclusion, nitroprusside i.p. increased the effective peritoneal surface area and the intrinsic permeability, but the peritoneal blood flow did not change. The greater than expected D/P ratios of cGMP point to local generation of cGMP with nitroprusside, induced by NO.

Adult

IgG glycation and function during continuous ambulatory peritoneal dialysis.

IgG in dialysate may have an important role in anti-infection mechanisms during continuous ambulatory peritoneal dialysis (CAPD). As Fc fragment oligosaccharidic chains are crucial for IgG effector functions, we have tested the hypothesis that IgG glycation might occur during CAPD and modify IgG properties. Purified normal IgG was incubated with glucose solutions of different concentrations and pH. Separation of glycated IgG was performed by affinity chromatography. Complement activation (C3c deposition) and phagocytosis by polymorphonuclear leucocytes (PMN) were studied in vitro using Staphylococcus aureus Wood (STAW) as antigen. In addition, we compared the percentages of glycated IgG in IgG purified from sera and dialysates of 12 CAPD patients. The percentage of glycated IgG after in vitro incubation of normal IgG with glucose solutions was directly proportional to glucose concentrations, incubation time and pH. Glycated IgG anti-STAW induced a higher C3c deposition than non-glycated IgG anti-STAW (C3c/IgG (mean +/- SD) 0.96 +/- 0.06 vs 0.79 +/- 0.08; P = 0.027). PMN phagocytosis was not affected by IgG glycation. The percentages of glycated IgG in dialysates of CAPD patients were greater than those in corresponding sera (5.38 +/- 2.36% vs 4.56 +/- 2.47%; P = 0.006). It is concluded that IgG glycation may take place in the peritoneal cavity during CAPD and lead to enhanced complement activation. This could explain the high degree of complement activation previously described in dialysate of CAPD patients and might theoretically result in a reduction of complement factors available in dialysate for adequate anti-infection mechanisms.

Adolescent

Clearance ratios of amylase isoenzymes and IgG subclasses: do they reflect glomerular charge selectivity?

The clearance ratios of endogenous plasma proteins with the same size but a different charge, such as the amylase isoenzymes and the immunoglobulin (Ig) G subclasses, have been used to assess glomerular charge selectivity in man. These proteins are, however, subject to tubular reabsorption. In this study we measured the IgG subclass/IgG clearance ratios for IgG1 (pI 8.0-9.5), IgG2 (pI 7.0-7.5) and IgG4 (pI < 6) in 6 healthy volunteers. Our results suggested a selective influence of tubular reabsorption: the IgG1/IgG clearance ratio was 0.68 +/- 0.14 (mean +/- SD) and lower than IgG2/IgG (2.02 +/- 1.06, p < or = 0.01). IgG4/IgG was 0.89 +/- 0.39. In addition, we studied the clearance ratios of pancreatic (PA, pI 7.0) and salivary amylase (SA, pI 5.9-6.4) and of IgG1 and IgG2 in 8 patients with minimal change nephrotic syndrome (MCNS), 11 patients recovering from acute tubular necrosis (ATN) and 9 healthy volunteers (controls). In MCNS glomerular charge selectivity is lost, while in recovering ATN tubular function is severely disturbed. The PA/SA clearance ratio was 3.25 +/- 0.89 in controls, reflecting intact glomerular charge selectivity. In MCNS patients the PA/SA clearance ratio had decreased to 1.21 +/- 0.23 (p < or = 0.001). In ATN patients the PA/SA clearance ratio was reduced as well: 1.55 +/- 0.41 (p < or = 0.001), although the aselective nature of the proteinuria and the modest albuminuria indicated intact glomerular charge selectivity. The IgG1/ IgG2 clearance ratio was 0.54 +/- 0.15 in controls, again suggesting preferential tubular reabsorption of IgG1. In MCNS patients the IgG1/IgG2 clearance ratio was 0.16 +/- 0.10 (p < or = 0.001); this probably reflects the relatively increased glomerular sieving of IgG2 when glomerular charge selectivity is lost. In ATN patients the IgG1/IgG2 clearance ratio was 1.07 +/- 0.47 (p < or = 0.001), which suggests a partial loss of preferential reabsorption of IgG1. It was concluded that the PA/SA clearance ratio is influenced by loss of tubular function and therefore does not reflect glomerular charge selectivity specifically. The IgG1/IgG2 ratio cannot be used to assess glomerular charge selectivity either because of the interference of selective tubular reabsorption of the subclasses. These findings put the assessment of glomerular charge using endogenous proteins in a new light and bring forward the necessity to interpret these ratios with the utmost cautiousness.

Adult

Predicting mortality in intensive care patients with acute renal failure treated with dialysis.

Existing prognostic methods were compared in their ability to predict mortality in intensive care unit (ICU) patients on dialysis for acute renal failure (ARF). The clinical goal of this study was to determine whether these models could identify a group of patients where dialysis would provide no benefit because of a near 100% certainty of death even with dialysis treatment. This retrospective cohort study included 238 adult patients who received a first dialysis treatment for ARF in the ICU. This study examined the performance of seven general ICU mortality prediction models and four mortality prediction models developed for patients with ARF. These models were assessed for their ability to discriminate mortality form survival and for their ability to calibrate the observed mortality rate with the expected mortality rate. The observed in hospital mortality was 76% for our patient group. Areas under the receiver operating characteristic curve ranged from 0.50 to 0.78. With the Acute Physiology and Chronic Health Evaluation (APACHE) III and the Liano models, the observed mortality in the highest quintiles of risk were 97% and 98%. In conclusion, although none of the models examined in this study showed excellent discrimination between those patients who died in hospital and those who did not, some models (APACHE III, Liano) were able to identify a group of patients with a near 100% chance of mortality. This indicates that these models may have some use in supporting the decision not to initiate dialysis in a subgroup of patients.

Acute Kidney Injury

Markers of peritoneal mesothelial cells during treatment with peritoneal dialysis.

Loss of peritoneal mesothelial cells and decrease of mesothelial cell mass have been described in peritoneal dialysis (PD) patients. Longitudinal follow-up in individual PD patients cannot be performed by serial peritoneal biopsies. Markers of mesothelial integrity, measured in the effluent, may therefore be a valuable approach to detect changes in the mesothelium in vivo. In the present study, markers that are known to be produced by mesothelial cells were followed in individual patients: cancer antigen 125 (CA125), phospholipids (PHL), and hyaluronan (HA). CA125 is considered to be a reflection of mesothelial cell mass or stable mesothelial cell turnover. Appearance rates (AR) were determined in the effluents of 30 PD patients on a yearly basis. Median AR (range) were: CA125: 111 U/min (10-610), PHL: 15 mg/min (3-46), HA: 666 mg/min (135-6200). Cross sectionally, the AR for CA125 was negatively related to duration of PD (r = -0.47, p < 0.0001) and weakly related to peritonitis incidence (r = -0.20, p < 0.05). Patients treated with PD for more than 4 years had lower CA125 appearance than patients treated less than 4 years (p < 0.0004). HA was also related to the incidence of peritonitis, but positively (r = 0.32, p < 0.004). PHL were not related to either parameter. A significant negative trend with time of PD treatment was observed for CA125 only [mean regression coefficient (t) -3.75, SD 1.2]. No trend in time of PD treatment could be detected for HA and PHL. These data indicate a gradual loss of mesothelial cell mass during PD by the decrease of CA125 with time. The lack of a decrease in HA and its positive relation to incidence of peritonitis suggest an additional release of HA by cells other than the mesothelial cells, such as fibroblasts and leukocytes. Alternatively, an activation of (mesothelial) cells with duration of PD and possibly with increased peritonitis incidence cannot be excluded. The relation between PHL and duration of PD suggested by others was not confirmed in this study. PHL are probably released by a number of different cells, and therefore changes in PHL cannot be used as a reflection of changes in mesothelial cell mass. It is concluded that CA125 is the most specific marker for the follow-up of mesothelial cell mass in vivo.

Biomarkers

Differences in fluid and solute transport between diabetic and nondiabetic patients at the onset of CAPD.

Loss of transcapillary ultrafiltration (TCUF) can occur during continuous ambulatory peritoneal dialysis (CAPD) and may be caused by exposure to the high glucose concentrations in the dialysate, leading to glycation of water channels in the endothelial cells of the peritoneal microvessels. If this hypothesis is correct, diabetic patients should have lower TCUF rates at the onset of CAPD than nondiabetic controls. Such a difference should disappear during longer-duration CAPD because of the continuous glucose exposure in both groups, induced by the high glucose concentrations in the dialysate. Therefore, the standard peritoneal permeability analysis of 11 diabetic (mean age 48 years, range 33-70 years) and 11 nondiabetic patients (mean age 49 years, range 36-69 years) matched for sex, age, and duration of CAPD were studied shortly after the onset of CAPD treatment (mean duration 162 vs 131 days) and one year later. No differences were found in solute transport or protein clearances between the two groups at the onset of CAPD. The TCUF rate was lower in the diabetic patients: 0.9 mL/min (0.09-2.25) versus 1.51 mL/min (0.97-2.44), p = 0.01. The other parameters of fluid transport were not different. The mean osmotic pressure gradient, exerted by albumin and glucose, was 1.72 mmHg in the diabetic patients and 5.44 mmHg in the controls (p = 0.0004). No differences were found in peritoneal permeability, including TCUF, after one year between the two groups. In conclusion, the TCUF rate was lower in diabetic patients compared to nondiabetics only shortly after the onset of CAPD. These results suggest that long-term exposure to high glucose concentrations in diabetics prior to CAPD may cause changes in capillary wall aquaporins, similar to long-term exposure to high glucose concentrations in the dialysate in CAPD.

Adult

Restriction coefficients of low molecular weight solutes and macromolecules during peritoneal dialysis.

The intrinsic permeability of the peritoneal membrane can be functionally represented by the restriction coefficient (RC). The RC can be calculated as the exponent of the power relation between the mass transfer area coefficients (MTACs) of various solutes and their free diffusion coefficients in water. When the RC = 1.0, transport is determined by free diffusion only, as is expected for low molecular weight (LMW) solutes. A RC > 1.0 suggests that transport is restricted by the peritoneal membrane in a size-selective way, as has been found previously for macromolecules (MM). RCLMW can be calculated using the MTACs of urea, creatinine, urate, and beta 2-microglobulin, whereas RCMM can be calculated from clearances of beta 2-microglobulin, albumin, IgG, and alpha 2-macroglobulin. RCLMW and RCMM were determined in 108 peritoneal dialysis (PD) patients. In 36 patients, 3 or more (range 3-13) observations for RCLMW during a period of at least 2 years were available. RCMM were analyzed when present in the same patients. The median cross sectional values (n = 108) were: RCLMW: 1.22 (range 0.75-2.18) and RCMM: 2.30 (range 1.86-3.27). RCLMW was not correlated with time on PD, neither cross sectionally (r = -0.07, NS) nor after analysis of trend (mean regression coefficient t = 0.26, SD = 0.07). For RCMM a positive correlation with duration of PD was demonstrated (cross sectionally r = -0.18, p = 0.02, analysis of trend: t = 2.27, SD = 0.11, n = 27). Both RCs were not interrelated (r = -0.18, NS). The absence of a relation between both RCs suggests that LMW solutes and MM are transported by different pathways. The mean value of 1.22 for the RCLMW illustrates that the transport of LMW solutes is mainly by free diffusion, through the small-pore system. MM, which have to pass through the large-pore system, are restricted by the peritoneal membrane in a size-selective way, as shown by the high value of the RCMM. The lack of a correlation between the RCLMW and duration of PD indicates that no systematic changes occur in the small pores of the peritoneal vessels. In contrast, the increase of RCMM with duration of PD suggests restrictive changes at the level of the large-pore system.

Biological Transport

Production of IL-1 beta and TNF-alpha by peritoneal macrophages depends on the bacterial species and the inoculum.

Peritoneal macrophages (PMs) are very potent producers of proinflammatory stimuli, such as interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha. After contact with invading micro-organisms, PMs produce different cytokines, both pro- and anti-inflammatory. Therefore, they are crucial in the regulation of inflammatory events. The aim of this study was to investigate whether the production of IL-1 beta and TNF-alpha is dependent on the bacterial species used. PMs were harvested from spent peritoneal dialysis effluent and subsequently stimulated with five strains of bacteria in two different concentrations. After 24 hours of stimulation, supernatants were harvested and analyzed for both IL-1 beta and TNF-alpha content. IL-1 beta was measured with a commercial ELISA, and TNF-alpha was determined with a bioassay. Both the IL-1 beta and the TNF-alpha production were species-dependent. One strain of Staphylococcus aureus and one strain of Staphylococcus epidermidis induced a markedly higher response in both IL-1 beta and TNF-alpha than the other species. This response was also dose-dependent, and this holds true for all species. In conclusion, the IL-1 beta and TNF-alpha response by PMs is both species- and dose-dependent.

Dialysis Solutions

Peritoneal transport characteristics with glucose polymer based dialysate.

Dialysate fluids containing glucose polymers as osmotic agent are different from the conventional solutions, because they are iso-osmotic to plasma and produce transcapillary ultrafiltration (TCUF) by colloid osmosis. To investigate the effects on fluid and solute kinetics, a comparison was made between a 7.5% glucose polymer based dialysate (icodextrin) and 1.36% and 3.86% glucose based dialysate in 10 stable CAPD patients. In each patient three standard peritoneal permeability analyses (SPA) were done with the osmotic agents and concentrations mentioned above. Dextran 70 was added to the glucose solutions to calculate fluid kinetics. In the glucose polymer SPAs fluid kinetics were calculated from the dilution and disappearance of dextrin. The TCUF rate with icodextrin was closer to that obtained with 3.86% glucose than to 1.36% glucose. Extrapolation of the fluid profiles revealed sustained ultrafiltration with icodextrin. TCUF increased linearly in time in the icodextrin tests, whereas a hyperbola best described the glucose profiles. The effective lymphatic absorption rate with icodextrin was similar to the glucose based solutions. Mass transfer area coefficients of low molecular weight solutes with icodextrin were also similar to the values obtained with glucose, as was D/P creatinine. A positive correlation was present between the MTAC creatinine and the TCUF rate with icodextrin (r = 0.66, P = 0.05), which was absent in the glucose SPAs. This suggests that in patients with a larger effective peritoneal surface area, more ultrafiltration can be achieved by glucose polymer solutions. Clearances of beta 2-microglobulin (beta 2m) were higher with icodextrin than with 3.86% glucose and 1.36% glucose dialysate (P < 0.05). No differences were found for the larger serum proteins albumin, IgG and alpha 2-macroglobulin. Initial D/PNa-->was higher (0.96) with icodextrin than with the glucose based solutions (0.92), due to the higher Na+ concentration of icodextrin, and it remained unchanged during the dwell. In contrast, D/PNa+ of 1.36% glucose increased during the dwell, whereas D/PNa+ decreased with 3.86% glucose until 60 minutes, followed by a subsequent increase. The ultrafiltration coefficient (UFC) of the total peritoneal membrane was assessed using 3.86% glucose (0.18 +/- 0.04 ml/min/mm Hg), and the UFC of the small pores was assessed using icodextrin (0.06 +/- 0.008 ml/min/mm Hg). The difference between these represented the UFC through the transcellular pores, which averaged 50.5% of the total UFC, but with a very wide range (0 to 85%). An inverse relation existed between the duration of CAPD treatment and the total ultrafiltration coefficient (r = -0.68, P < 0.04), which could be attributed to a lower UFC of the transcellular pores in long-term patients (r = -0.66, P < 0.05), but not to the UFC of the small pores (r = -0.48, NS). The TCUFRo-60 min through the transcellular pores correlated with the sodium gradient, corrected for diffusion, in the first hour of the dwell (r = 0.69, P < 0.04), indicating that both parameters indeed measure transcellular water transport. It can be concluded that the glucose polymer solution induced sustained ultrafiltration and had no effect on peritoneal membrane characteristics. In addition, the results of the present study support the hypothesis that the glucose polymer solutions exerts its osmotic pressure across intercellular pores with radii of about 40 A. This leads to increased clearances of low molecular weight proteins such as beta 2m that are transported through these pores without sieving of Na+. The latter, as found during 3.86% glucose dialysate, is probably caused by transcellular water transport. The transcellular water transport accounted for 50% of the total ultrafiltration with glucose based dialysis solutions. It was lower in long-term CAPD patients.

Adult

Ingestion of Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli by human peritoneal mesothelial cells.

In the present study we examined whether mesothelial cells can ingest and digest bacteria. The results showed that all strains were ingested. Ingested staphylococci proliferated abundantly, and only a few were digested. Escherichia coli, however, was digested during the first 8 h, whereafter the mesothelial cells disintegrated and proliferation of bacteria could be observed. The clinical implications of these findings are discussed.

Cells, Cultured

Cytokine patterns in the effluent of continuous ambulatory peritoneal dialysis: relationship to peritoneal permeability.

Cytokines are pluripotent pleiotropic agents that have received widespread attention over the last few years. Not surprisingly, the have also been studied in the context of continuous ambulatory peritoneal dialysis. Cytokines play a central role in this treatment modality for uremic patients, because these inflammatory mediators act upon the biological dialysis membrane, i.e. the peritoneum, while simultaneously they participate in host defense mechanisms. This review describes which cytokines are present in dialysate, whether there is support for intraperitoneal release, and under which circumstances. If focuses particularly on the relationship between cytokines in peritoneal effluent and peritoneal permeability to macromolecules. In addition, the presence of prostanoids in dialysate and their role in the local regulation of peritoneal permeability are discussed, because cyclooxygenase products are tightly linked to cytokine networks.

Animals

Fluid kinetics in CAPD patients during dialysis with a bicarbonate-based hypoosmolar solution.

The magnitude of transcapillary backfiltration by the colloidosmotic pressure within the peritoneal capillaries compared to the effective lymphatic absorption was investigated in continuous ambulatory peritoneal dialysis patients. This was done during a 4-hour dwell period, using a hypoosmolar dialysis fluid (280 mosm/kg H2O) in 8 patients and compared to 5 of these patients using a 1.36% glucose (GS; 324 mosm/kg H2O). The low molecular weight solute transport did not differ between the two solutions. The intraperitoneal dextran 70 concentration increased during the dwell with the hypoosmolar dialysis fluid (from 770 to 945 mg/l; p = 0.000002) and decreased with the GS (from 859 to 719 mg/l; p = 0.007). With the GS the transcapillary ultrafiltration was directed towards the abdominal cavity during the dwell period. With the hypoosmolar fluid, the transcapillary ultrafiltration was continuously directed towards the circulation. In this solution, the magnitude of transcapillary backfiltration due to colloidosmotic pressure within the peritoneal capillaries was 0.4 +/- 0.1 ml/min. In conclusion, intraperitoneal markers can be used in continuous ambulatory peritoneal dialysis patients for determination of effective lymphatic absorption and transcapillary fluid passage in both transport directions.

Adult

Identification of the major chemokines that regulate cell influxes in peritoneal dialysis patients.

To investigate which members of the recently discovered family of chemotactic cytokines (chemokines) are important in leukocyte recruitment to a bacterial inflammation site, four different chemokines in the effluent of peritoneal dialysis patients suffering from acute bacterial peritonitis were measured. The presence of two neutrophil-attracting chemokines, interleukin-8 and human melanoma growth-stimulating activity (huGRO alpha), and two monocyte-attracting members of the chemokine superfamily, monocyte chemotactic protein-1 (MCP-1) and regulated on activation normal T cell expressed and secreted (RANTES), was investigated in patient effluents just before, during, and after a peritonitis episode. This was studied in seven peritonitis effluents of five patients by using chemokine-specific enzyme-linked immunosorbent assays. Cell populations in the dialysates were differentiated on cytocentrifuge preparations. The contribution of the detected chemokines to neutrophilic and monocytic cell influxes in the inflamed peritoneal cavity was analyzed by correlating concentrations of chemokines to the relevant cell numbers present in the dialysates of these patients. The detection of the neutrophil-attracting chemokine interleukin-8 during peritonitis was in accordance with other studies. Moreover, a second neutrophil chemoattractant, huGRO alpha, was identified in vivo. Both were elevated during inflammation (P < 0.02) and contributed significantly to the neutrophilic cell influx (P < 0.05). One of the monocyte-attracting chemokines, RANTES, could not be detected in any of the effluents, whereas the other, MCP-1, was significantly elevated during peritonitis (P < 0.02). In contrast to the other chemokines measured, MCP-1 concentration was relatively high in steady-state peritoneal dialysates. An absolute correlation between dialysate MCP-1 concentration and the number of macrophages in these effluents was absent. However, in a 48-well chemotaxis assay, monocyte migration toward peritonitis, as well as steady-state patient dialysates, could be blocked with antibodies to MCP-1. It was concluded, therefore, that MCP-1 is the most important monocyte chemoattractant in peritoneal dialysis steady-state and peritonitis patients; whereas, besides interleukin-8, huGRO alpha was identified as a major neutrophil-attracting chemokine in the peritonitis situation.

Acute Disease