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Biomedical subjects

B Lindholm

Publications and source records attributed to B Lindholm.

At least 37 records · Page 2Linked to original sources
PubMed2001

Acute effects of peritoneal dialysis solutions on appetite in non-uremic rats.

BACKGROUND: Standard peritoneal dialysis (PD) solutions may contribute to anorexia in PD patients due to the peritoneal absorption of glucose from the dialysate, abdominal discomfort and other factors. New PD solutions containing alternative osmotic agents, neutral pH and bicarbonate as buffer were recently developed. To test the effect of these solutions on appetite, we investigated how intraoral (IO) intake of sucrose via an IO cannula was influenced by intraperitoneal (IP) infusion of different PD solutions in an appetite model in rats. METHODS: The IO intake was measured in male Wistar rats after an IP dwell of 30 and 120 minutes with the following PD solutions: 1.36%, 2.27% and 3.86% glucose based and lactate buffered solutions (D); 1.36%, 2.27% and 3.86% glucose based and bicarbonate/lactate buffered solutions (P); 7.5% icodextrin based solution (E); 1.1% amino acid-based solution (N); and, 2.5% glucose-based lactate-buffered solution (GB), using sham injection (injection without infusion) as control. Prior to the tests, rats were provided with an IO cannula, and were trained for two weeks until the rate of IO intake had stabilized. RESULTS: The D and N solutions inhibited IO intake. For the D solutions, the degree of appetite suppression was higher with the higher concentration of glucose. P 3.86%, but not P 1.36% and P 2.27% solutions, inhibited the IO intake. However, a comparison of the degree of appetite inhibition between D and P showed less inhibition with P 1.36%, 2.27% and 3.86% solutions than with corresponding D solutions. The E solution did not seem to suppress appetite. Finally, no significant difference in IO intake was found between rats given GB 2.5% and D 2.27%. CONCLUSIONS: In this appetite model in rats, the measurement of IO intake after the IP infusion of different dialysis solutions showed that (1) N and D solutions may reduce appetite, and for the D solutions the degree of appetite inhibition was related to the dialysate concentrations of glucose; (2) the P solutions had less impact on appetite than the D solutions; (3) the E solution had no impact on appetite during the short dwells of 30 and 120 minutes. The demonstrated differences between the different solutions appear to be due to different concentrations, and type, of nutrients used as osmotic agent (glucose, amino acids, icodextrin) or buffer (lactate), although differences in dialysate pH, tonicity and concentration of glucose degradation products also may be important. The present studies suggest a possible positive effect on appetite by using bicarbonate/lactate buffered solutions instead of lactate buffered solutions.

Administration, Oral↗
PubMed2001

Kinetic studies of dipeptide-based and amino acid-based peritoneal dialysis solutions.

BACKGROUND: Dipeptide-based peritoneal dialysis solutions may have potential advantages compared with the glucose or amino acid-based solutions. Dipeptides may hydrolyze in the peritoneal cavity, generating constituent amino acids and thereby increasing the osmolality of the dialysate. Dipeptides can also be a valuable source of amino acids, which are poorly soluble in water, such as tyrosine. METHODS: Dwell studies in rats were performed during four hours with dipeptide solutions containing five dipeptides (Gly-His, Ala-Tyr, Thr-Leu, Ser-Phe, Val-Lys), 8, or 16 mmol/L of each dipeptide (low or high dipeptide group). Dwell studies were also performed with a 1.1% amino acid solution (Nutrineal(R)). The model of dipeptide hydrolysis (hydrolysis rate, KH), diffusive (rate constant, KBDD) and convective transport as well as transport of constituent amino acids consisted of mass balance equations, written for each dipeptide and amino acid. RESULTS: Peritoneal volume with the amino acid solution decreased much faster than that with the high and low dipeptide solutions. KH for all dipeptides did not differ between the high and low dipeptide groups. In the low dipeptide group, KH was 0.004 +/- 0.004 mL/min (mean +/- SD) for Gly-His (the lowest) and 0.088 +/- 0.048 mL/min for Thr-Leu (the highest). KBDD was higher than KH for all dipeptides, the average being 0.2 +/- 0.05 mL/min. CONCLUSIONS: Dipeptides are hydrolyzed in the peritoneal cavity, generating constituent amino acids. However, the hydrolysis rate appears to be several times lower than the dipeptide diffusive transport rate from dialysate to blood. Due to the higher molecular weight and intraperitoneal generation of amino acids, the dipeptide-based solutions provide more sustained ultrafiltration than the amino acid solution. The plasma concentration of amino acids at 60 minutes, in relation to the dose of amino acids delivered between 0 and 60 minutes, is considerably higher during the dwells with amino acid-based solution than during dwells with the dipeptide-based solutions.

Amino Acids↗
PubMed2001

Intraperitoneal atrial natriuretic peptide increases peritoneal fluid and solute removal.

BACKGROUND: Atrial natriuretic peptide (ANP) is a hormone with well-known diuretic and vasodilating properties. Recently it was reported that ANP could increase the peritoneal fluid formation and increase peritoneal solute clearance. This study investigated the effect of ANP on peritoneal fluid and solute transport characteristics. METHODS: Eighteen male Sprague-Dawley rats were divided into three groups. A four-hour dwell study using 25 mL 2.27% glucose dialysis solution with 50 microg/kg ANP (N = 6, H-ANP) or 5 microg/kg ANP (N = 6, L-ANP) or without ANP (N = 8, control) and frequent dialysate and blood sampling was done in each rat. Radiolabeled human albumin (RISA) was added to the solution as an intraperitoneal volume marker. RESULTS: The intraperitoneal volume was significantly higher in the H-ANP group as compared with the control group and the L-ANP group. The drainage volume was 26.2 +/- 1.1, 25.5 +/- 0.7, and 29.8 +/- 0.8 mL for the control, L-ANP, and H-ANP groups, respectively (P < 0.01). This was related to significant differences in the peritoneal fluid absorption rates (K(E); estimated as the RISA elimination coefficient): 39 +/- 3, 38 +/- 3, and 19 +/- 4 microL/min, and in the direct lymphatic absorption rate (K(EB); estimated as the clearance of RISA from dialysate to blood): 7 +/- 1, 6 +/- 1, and 4 +/- 1 microL/min for the control, L-ANP, and H-ANP groups, respectively (all P < 0.01). No differences were found in the intraperitoneal volume, K(E), and K(EB) between the control group and the L-ANP group. The diffusive mass transport coefficient (K(BD)) for urea, sodium, potassium, and total protein did not differ among the three groups. However, the glucose D/D(0) was significantly higher, and the K(BD) for glucose was significantly lower in the H-ANP group as compared with the other two groups. Solute clearances (+175% for sodium and +26% for potassium) were significantly increased in the H-ANP group, mainly as a result of the increased fluid removal in this group. CONCLUSIONS: Our results suggest that ANP may decrease peritoneal fluid absorption (by 51%, partially because of decreasing the direct lymphatic absorption), resulting in a significant increase in peritoneal fluid removal and small solute clearances. While the basic diffusive permeability of the peritoneal membrane was not changed, the peritoneal glucose absorption was retarded by adding ANP to peritoneal dialysate, perhaps through interaction of ANP with glucose metabolism.

Analysis of Variance↗
PubMed2001

Effects of methionine loading on plasma and erythrocyte sulphur amino acids and sulph-hydryls before and after co-factor supplementation in haemodialysis patients.

BACKGROUND: Hyperhomocysteinaemia, which is potentially atherogenic, is common in chronic haemodialysis (HD) patients but the reason for this is not yet known. The methionine (Met) loading test (MLT) is used to test the capacity of homocysteine (Hcy) disposal by the trans-sulphuration pathway and thus may provide information on the metabolism of sulphur amino acids. The availability of vitamin B(6) and folic acid, as co-factors for Hcy metabolism may affect the response to MLT. In the present study, we compared the effect of Met loading on plasma and erythrocyte (RBC) sulphur amino acids and sulph-hydryls before and after co-factor supplementation in healthy subjects and HD patients. METHODS: In 10 HD patients and 10 healthy subjects the effect of Met loading, 0.1 g/kg BW, on plasma and RBC methionine metabolites was studied over 7 h, before and after 4 weeks supplementation with high daily doses of vitamin B(6) (200 mg) and folic acid (15 mg). RESULTS: MLT before vitamin supplementation in HD patients, compared to the healthy subjects, caused significantly greater increases in plasma Hcy levels (43+/-12 vs 15+/-5 micromol/l), cysteinesulphinic acid (CSA) (1.34 vs 0.36 micromol/l) and gamma-glutamylcysteine (0.98+/-0.83 vs -01+/-0.42 micromol/l) and no decline in plasma cysteine (Cys) (0.5+/-33.9 vs -31+/-26 micromol/l), but no significant differences in plasma taurine, cysteinylglycine, and glutathione concentrations. In RBCs there was a small increase in Hcy levels and a more marked increase in Tau levels, with no difference between the healthy subjects and HD patients. Vitamin supplementation in pharmacological doses failed to correct the abnormal responses to MLT in the HD patients. CONCLUSIONS: Oral methionine loading in HD patients leads to higher accumulation of Hcy and other Met metabolites in plasma and RBCs than in healthy subjects, indicating impaired metabolism of sulphur amino acids via the trans-sulphuration pathway. Supplementation with high doses of vitamin B(6) and folic acid does not correct this impairment, suggesting that it most probably is not due to lack of these co-factors.

Adult↗
PubMed2001

Association between inflammation and changes in residual renal function and peritoneal transport rate during the first year of dialysis.

BACKGROUND: Peritoneal transport rate, a major determinant of peritoneal dialysis (PD) patient survival, increases in most patients starting on PD, while in other patients peritoneal transport rate may decline. Although several factors may contribute to changes in peritoneal transport rate, inflammation is known to be associated with a high peritoneal transport rate, and residual renal function (RRF), which often declines after start of PD, may also be related to inflammation. Therefore, we hypothesized that changes in peritoneal transport rate during patients' first year on PD and declining RRF may be linked with inflammation. METHODS: A total of 76 PD patients (40 males, mean age 56.8+/-14.1 years), who underwent two peritoneal equilibration tests at a mean of 0.4 months and 1 year after beginning PD, were included in the study. Based on the change in dialysate to plasma creatinine concentration ratio at 4-h dwell (D/P Cr) during first year on PD, the patients were divided into decreased or unchanged (group DUC; n=22) and increased (group I; n=54) groups. RESULTS: Initially, group I had a lower proportion of high transporters and more often high serum C-reactive protein (sCRP, > or =10 mg/l) and lower RRF compared with the DUC group. In group I, serum albumin and RRF decreased significantly and dialysate protein loss and glucose absorption increased significantly during the first year on PD. When patients were divided into two groups based on median change in RRF (1.9 ml/min), patients with a decrease in RRF >1.9 ml/min during first year on PD had a higher proportion of high sCRP, higher D/P Cr, and higher changes in D/P Cr compared to patients with a decrease in RRF < or =1.9 ml/min. Patients with elevated sCRP at one year included a higher proportion of patients who had high sCRP at the start of PD, higher increase in D/P Cr, lower serum albumin, lower RRF, and more decrease in RRF during first year on PD compared with patients having normal sCRP. RRF was inversely correlated with changes in D/P Cr during the first year on PD (r=-0.28, P=0.02). Multiple regression analysis revealed that the only factors affecting changes in D/P Cr were high sCRP and a low RRF. CONCLUSIONS: Our preliminary short-term study suggests that changes in peritoneal transport rate during patients' first year on PD may be linked with inflammation and declining residual renal function. Inflammation and residual renal function were identified as the only independent factors determining peritoneal transport rate during the first year on PD. It is possible that inflammation may cause both an increase in peritoneal transport rate and a decline in residual renal function, or that the decline in residual renal function and the increase in peritoneal transport rate may induce or aggravate inflammation. Further studies are needed to confirm these findings.

Adult↗
PubMed2001

Effects of intraperitoneal heparin on peritoneal transport in a chronic animal model of peritoneal dialysis.

BACKGROUND: Heparin has anti-inflammatory effects and is often added to the peritoneal dialysis fluid to prevent fibrin formation. Conjugation of heparin to the surface of biomaterials has been shown to improve its biocompatibility. In this study, we describe for the first time an experimental chronic peritoneal dialysis model with repeated dwell studies in non-uraemic rats and evaluate the effect of addition of heparin to glucose-based peritoneal dialysis fluid on peritoneal fluid and solute transport. METHODS: Wistar male rats, weighing 340+/-15 g, with implanted peritoneal catheters were infused during 1 month, twice per day with 20 ml of Dianeal 1.36%+antibiotics (AB; n = 10) or Dianeal 1.36%+antibiotics+heparin 2500 U/l (HAB; n = 9). After 10 (DS 1) and 30 days (DS 2), a dwell study was performed in rats with free access to drinking water, by infusing 30 ml of Dianeal 3.86%. Dialysate samples were obtained at 0, 2, 30, 60, 120 and 240 min. Blood samples were drawn before and at the end of the dwell. Radiolabelled serum albumin was used as macromolecular volume marker. RESULTS: Peritoneal volumes during DS 1 were significantly greater for the HAB group as compared with the AB group. No differences in ultrafiltration were found during DS 2 for HAB vs AB. However, peritoneal volumes were significantly higher for DS 2 compared with DS 1 in the AB group. The amount of glucose absorbed over time did not differ between the solutions, while fluid absorption tended to be lower in the HAB group. CONCLUSIONS: Heparin may improve peritoneal fluid transport possibly due to better healing and reduced peritoneal inflammation as shown in this novel animal model of chronic peritoneal dialysis with repeated dwell studies.

Absorption↗
PubMed2001

Hyperhomocysteinemia in chronic renal failure patients: relation to nutritional status and cardiovascular disease.

A moderate increase in plasma total homocysteine (tHcy) is considered to be an independent risk factor for cardiovascular disease (CVD) in the general population. Almost all chronic renal failure (CRF) patients have plasma concentration of tHcy that is elevated 3 to 4 times above normal. The prevalence of CVD, diabetes mellitus, malnutrition and hypoalbuminemia is high in CRF patients. Previous investigations have focused on the role of vitamin status on plasma tHcy in CRF patients, but little information exists on the influence of nutritional status and hypoalbuminemia on plasma tHcy in CRF, although a substantial fraction of tHcy (>70%) is protein-bound, mainly to albumin. Our study in patients with end-stage renal disease showed that more than 90% of the patients had elevated plasma tHcy levels, which were higher in patients with normal nutritional status than in malnourished patients. Moreover, plasma tHcy was inversely correlated with subjective global nutritional assessment (high values denote malnutrition) and positively correlated with serum albumin and protein intake. Hence, it seems likely that serum-albumin is a strong determinant of plasma tHcy in CRF patients and this may contribute to the lower tHcy levels in malnourished patients. Patients with diabetes mellitus had lower serum-albumin and plasma tHcy than non-diabetic patients, irrespective whether they were malnourished or not. Patients with CVD had lower (although still elevated) plasma tHcy levels than those without CVD. An explanation may be that the prevalence of diabetes mellitus, malnutrition and hypoalbuminema, i.e. factors that decrease tHcy, was higher in patients with CVD, which may explain why they had less elevated values. Assuming that hyperhomocysteinemia carries an independent risk of CVD, this implies that almost all CRF patients are exposed to this risk. CRF patients with CVD had a higher prevalence of malnutrition, hypoalbuminemia and diabetes mellitus, which was associated with a lower plasma Hcy level. This may explain why plasma tHcy was lower (although still abnormally high) in patients with CVD than in patients without CVD. The lower tHcy levels in CVD patients do not contradict the assumption that hyperhomocysteinemia is a risk factor for CVD since almost all patients are exposed to this risk, and other factors might be present that confound the relationship between the absolute tHcy levels and CVD. Our findings imply that nutritional status and serum albumin, as well as the presence of diabetes mellitus, should be taken into consideration when evaluating tHcy as a risk factor for CVD in CRF patients.

Cardiovascular Diseases↗
PubMed2001

Peritoneal dialysis solutions disturb the balance of apoptosis and proliferation of peritoneal cells in chronic dialysis model.

The present study investigated variation in apoptosis and proliferation, and the balance between apoptosis and proliferation, for peritoneal mesothelial cells (MCs) after exposure to peritoneal dialysis solution (PDS) in vivo. We implanted 32 male Sprague-Dawley rats (4 groups; n = 8 in each group) with catheters and intraperitoneally infused the animals with 20 mL Dianeal 1.36%, 2.27%, or 3.86% (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.) PDS twice daily for eight consecutive weeks, using saline as a control. At the end of the eighth week, samples of peritoneal membrane were fixed and sliced. Expression of apoptosis was checked with TUNEL kits (Boehringer Mannheim, Mannheim, Germany), and expression of proliferative cell nuclear antigen (PCNA) was checked by immunohistochemistry [streptoavidin-biotin-peroxidase complex (SABC) method]. The ratio of MC apoptosis to proliferation was measured from the same slices using the dual-stain combination of TUNEL and SABC. Cells positive for apoptosis and PCNA were counted for all samples by light microscopy in 50 consecutive grids (10 x by 40). Peritoneal dialysis solution was found to significantly induce MC apoptosis as compared with control at the end of the eighth week. The degree of apoptosis was proportional to the concentration of glucose in the PDS. The 1.36% PDS, but not the 2.27% or 3.86%, significantly stimulated the expression of PCNA. The degree of PCNA expression was negatively related to the glucose concentration of the PDS. The MC apoptosis: PCNA ratio was significantly higher for 3.86% and 2.27% PDS than for the control, but no significant difference was seen between 1.36% PDS and control. We conclude that glucose-based PDS may induce apoptosis and disturb the balance of MC apoptosis and proliferation, and that 1.36% PDS damages the balance less than does 2.27% or 3.86% PDS. These effects may be partly due to pH, calcium, hyperosmolality, and glucose degradation products (GDPs). Loss of balance between MC proliferation and apoptosis--induced by unphysiologic PDS--may be one of the major causes of peritoneal membrane failure during long-term continuous ambulatory peritoneal dialysis.

Animals↗
PubMed2001

Loss of phospholipids asymmetry in red blood cells contributes to anemia in uremic patients.

Anemia is common in dialysis patients. Change in phospholipids asymmetry in red blood cells (RBCs) may affect the removal of RBCs from the circulation and thus shorten the lifespan of RBCs. In the present study, we investigated phospholipids asymmetry in RBCs in uremic patients and its relationship with anemia. We studied 34 continuous ambulatory peritoneal dialysis (CAPD) patients (age: 51 +/- 15 years), 73 hemodialysis (HD) patients (age: 48 +/- 12 years), 8 pre-dialysis renal-failure patients (age: 42 +/- 21 years), and 16 healthy controls (age: 32 +/- 9 years). All patients were clinically stable. Phospholipids asymmetry as measured by phosphatidylserine exposure was determined by a flow-cytometric annexin V-binding assay. Hemoglobin levels were 93 +/- 20 g/L, 83 +/- 17 g/L, 78 +/- 21 g/L, and 145.8 +/- 12.5 g/L for CAPD patients, pre-dialysis patients, HD patients, and healthy controls respectively. Phosphatidylserine exposure in RBCs was significantly higher in uremic patients as compared with healthy controls, especially in HD patients--whose values were significantly higher than values seen in CAPD patients and pre-dialysis patients. No significant difference was seen in RBC phosphatidylserine exposure between pre-dialysis patients and CAPD patients. Cells positive for annexin V binding were 1.58%, 1.40%, 2.11%, and 0.71% for CAPD patients, pre-dialysis patients, HD patients, and healthy controls respectively. Significant reverse correlations were seen between annexin V and hemoglobin (r = -0.381, p < 0.001), and between annexin V and hematocrit (r = -0.355, p < 0.001). Our results suggest that (1) anemia is common in our uremic patients, especially in HD patients; and (2) anemia in uremic patients may be partly related to the loss of phospholipids asymmetry in RBCs.

Adult↗
PubMed2001

Methods to improve the preservation of peritoneal tissues.

Peritoneal mesothelial cells are easily detached during conventional tissue processing, which may result in artifacts in peritoneal tissue examination. Therefore, in the present study, we investigated several methods to improve the preservation of the anterior parietal peritoneal tissues. Peritoneal tissue from the anterior abdominal wall was taken from each of 5 rats killed for the experiment. Tissue samples were immediately treated by one of these methods: (1) fixed with 10% formaldehyde; (2) fixed with Bouin's solution; (3) fixed with Helly's solution. After fixation, the samples were dehydrated with one of (a) ethanol, 1 hour in each step; (b) ethanol, 15 minutes in each step; or (c) tertiarybutyl alcohol. Five sections were taken from each tissue and stained with hematoxylin and eosin. The quality of tissue fixation was evaluated by image analysis. Peritoneal mesothelial cells were well preserved after fixation with Helly's solution or Bouin's solution. With 10% formaldehyde, about 40% of the mesothelial cells were lost. Dehydration with ethanol--especially long-duration dehydration--increased the loss. However, dehydration with tertiarybutyl alcohol avoided the increased loss of mesothelial cells. The submesothelial extracellular matrix was well preserved with Bouin's solution, but not with the other fixatives. Our results suggest that fixation with formaldehyde and dehydration with ethanol results in significant loss of peritoneal mesothelial cells and submesothelial extracellular matrix in peritoneal tissues. Fixation with Bouin's solution and dehydration with tertiary-butyl alcohol may be a better method of preserving peritoneal tissue.

Animals↗
PubMed2001

Increased peritoneal membrane permeability is associated with abnormal peritoneal surface layer.

OBJECTIVES: We recently showed that the peritoneal surface layer may be an important barrier in modulating peritoneal membrane permeability. In the present study, we investigated the relationship between an increased peritoneal transport rate and the peritoneal surface layer. METHODS: Male Sprague-Dawley rats (n = 8) received intraperitoneal injections of 4.25% glucose dialysate daily for 1 week. Forty-eight hours after the last injection, a 4-hour dwell study using 25 mL 4.25% glucose dialysate was performed in each rat. The results were compared with those from control rats that received no intraperitoneal injections (n = 8). The peritoneal fluid and small-solute transport characteristics were evaluated. The peritoneal surface layer was studied using an electron microscope. The phospholipids content of the dialysate was also evaluated. RESULTS: Peritoneal fluid removal was significantly reduced in the daily injection group (30.6 +/- 1.3 mL) as compared with the control group (38.2 +/- 0.6 mL). The peritoneal fluid absorption rate and small-solute transport rate were also significantly higher in the daily injection group as compared with the control group. The amounts of phospholipids in the dialysate were significantly lower in the daily injection group--especially the quantity of phosphatidylcholine. However, lysophosphatidylcholine increased significantly in the daily injection group. Electron microscopy showed that the peritoneal surface layer was almost completely gone in the daily injection group, but that a dense and thick (average 4 microm) peritoneal surface layer was present on the top of the mesothelial cells in the control group. CONCLUSIONS: Our results suggest that daily injection of hypertonic glucose dialysate significantly increased the peritoneal transport rate. The increased peritoneal transport rate was associated with a significant reduction in the peritoneal surface layer and the phospholipids content of the dialysis effluent.

Animals↗
PubMed2001

Effect in a rat model of heparinized peritoneal dialysis catheters on bacterial colonization and the healing of the exit site.

We performed a prospective, double-blind, randomized study to evaluate whether stable surface heparinization of silicone peritoneal dialysis (PD) catheters prevents bacterial colonization or biofilm formation and improves healing of the exit site. Heparinized catheters were implanted in 20 Sprague-Dawley rats (group H) and non heparinized catheters in another 20 (group C). The PD catheters, constructed of silicon tubing with two polyester cuffs, were patterned after the standard Tenckhoff catheter. A covalent multipoint method of attachment onto polymeric surfaces was used for stable, permanent chemical immobilization of heparin on the PD catheter. Dialysis exchanges (25-mL instillation volume) were performed twice daily for 4 weeks through the permanent catheter. Prophylactic antibiotics were not used. The exit sites were evaluated at 2-week intervals. The extent of biofilm coverage on the intraperitoneal portion of the catheter (obtained at the end of the experiment) was assessed, and sonicated fluid from the catheter tip was cultured for evaluating bacterial colonization of the catheter. Exit-site scores in group H were lower than in group C (p = 0.052) at the end of week 4. Bacterial colonization tended to be less common in group H [2 of 12 catheters (17%)] than in group C [8 of 15 catheters (53%); p = 0.058], but the extent of biofilm, the peritonitis rate, and the inflammation score of tissue adjacent to the cuff were not different between the groups. Those data suggest that heparinized PD catheters can be a practical approach to the prevention of bacterial colonization and can improve healing of the exit site.

Animals↗
PubMed2001

The effect of icodextrin-based solutions on peritoneal transport in rats undergoing chronic peritoneal dialysis.

BACKGROUND: We evaluated the effect of icodextrin on peritoneal permeability and inflammation in an experimental chronic peritoneal dialysis (PD) model with repeated dwell studies (DSs) in non uremic rats. METHODS: Male Wistar rats with implanted peritoneal catheters were infused twice daily for 3 weeks with 20 mL Dianeal 3.86% (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.) (n = 11) or icodextrin 7.5% (n = 12). After 10 days (DS1) and 21 days (DS2), a 4-hour DS using 30 mL icodextrin solution was performed in conscious animals. Radioiodinated serum albumin (RISA) was used as a macromolecular volume marker. Blood samples were drawn before the start of the dwell and at its end. RESULTS: We observed a steady increase in intraperitoneal volume (IPV) versus dwell time (0-240 minutes) during DS1 and DS2 in both groups. No significant differences in peritoneal permeability to solutes were observed between the groups. However, in both groups, IPV volume was significantly higher during DS2 after the 4-hour dwell time [IPV icodextrin: 34.4 +/- 1.4 mL (DS1), 35.4 +/- 1.1 mL (DS2), p < 0.002; IPV Dianeal: 34.2 +/- 0.9 mL (DS1), 35.2 +/- 0.7 mL (DS2), p < 0.01]. CONCLUSION: Changes of peritoneal permeability seen during in vivo experimental models of chronic peritoneal dialysis in rats with repeated dwell studies are comparable to results obtained in humans on continuous ambulatory peritoneal dialysis (CAPD).

Animals↗
PubMed2001

Peritoneal dialysis solutions.

After several decades of experience of peritoneal dialysis therapy, we now understand the peritoneal membrane and the causes of its changes during long-term dialysis much better. Several new, more biocompatible solutions are available in clinic today, and the outcome of peritoneal dialysis therapy is expected to be further improved. However, limitations with the currently available peritoneal dialysis solutions still exist, and continual efforts are needed to develop solutions that are more efficient and more membrane-friendly. With the better understanding of the role of fluid balance in peritoneal dialysis, we believe that development of peritoneal dialysis fluid that protects the peritoneal surface layer (and thus the integrity of the peritoneum, thereby improving peritoneal fluid removal) may be an area of research in the near future.

Amino Acids↗
PubMed2000

Effect of peritonitis on peritoneal transport characteristics: glucose solution versus polyglucose solution.

BACKGROUND: Peritonitis is a common clinical problem and contributes to the high rate of technique failure in continuous ambulatory peritoneal dialysis treatment. The present study investigated the effect of peritonitis on peritoneal fluid and solute transport characteristics using glucose and polyglucose (icodextrin) solutions. METHODS: A four-hour dwell was performed in 32 Sprague-Dawley rats (8 rats in each group), with 131I albumin as an intraperitoneal volume marker. Peritonitis was induced by an intraperitoneal injection of 2 mL lipopolysaccharide (100 microg/mL phosphate-buffered saline) four hours before the dwell. Each rat was intraperitoneally infused with 25 mL of 3.86% glucose [glucose solution control group (Gcon) and glucose solution peritonitis group (Gpts)] or 7.5% icodextrin solution [icodextrin solution control group (Pgcon) and icodextrin peritonitis group (PGpts)]. RESULTS: Net ultrafiltration was significantly lower (by 44%) in the Gpts as compared with the Gcon group, but was significantly higher (by 138%) in the PGpts as compared with the PGcon group. The peritoneal fluid absorption rate, including the direct lymphatic absorption rate, was significantly increased (by 78%) in the Gpts group as compared with the Gcon group. However, the total fluid absorption did not differ between the PGpts and the PGcon groups. The dialysate osmolality decreased much faster in the Gpts group as compared with the Gcon group, resulting in significantly lower (by 9%) transcapillary ultrafiltration in the Gpts group. In contrast, the dialysate osmolality increased faster in the PGpts group as compared with the PGcon group, resulting in higher (by 40%) transcapillary ultrafiltration in the PGpts group. The in vitro increase in dialysate osmolality was also higher in the PGpts group as compared with the PGcon group. The solute diffusive transport rates were, in general, increased in the two peritonitis groups as compared with their respective control groups. CONCLUSIONS: Our results suggest the following: (1) Peritonitis results in decreased net ultrafiltration using glucose solution caused by (a) decreased transcapillary ultrafiltration and (b) increased peritoneal fluid absorption. (2) Ultrafiltration induced by the icodextrin solution appears to be related to the increase in dialysate osmolality (mainly because of the degradation of icodextrin). (3) Peritonitis results in increased degradation of icodextrin and a faster increase in dialysate osmolality and therefore better ultrafiltration, whereas the fluid absorption rate does not change. (4) Peritonitis results in increased peritoneal diffusive permeability.

Animals↗
PubMed2000

Fat tissue accumulation during peritoneal dialysis is associated with a polymorphism in uncoupling protein 2.

BACKGROUND: Chronic treatment with peritoneal dialysis (PD) is a unique long-term metabolic procedure entailing a continuous 24-hour supply of glucose absorbed from the dialysis fluid. One common and important side effect of this treatment is weight gain and accumulation of body fat stores. However, not all patients accumulate body fat mass during PD, and the reason for this is not clear. Recently, two new mitochondrial uncoupling proteins (UCP2 and UCP3) have been found to have thermogenic properties that suggest involvement in the control of metabolic efficiency in humans. Moreover, recent results suggest that a polymorphism in the UCP2 gene may contribute to adipose tissue accumulation through its effects on energy metabolism. It could therefore be speculated that genetic differences in the metabolic rate might contribute to the differences in the accumulation of fat tissue during PD. METHODS: Genotyping of a polymorphism in the 3' untranslated region of exon 8 of UCP2 was performed in 41 patients (53 +/- 2 years) with chronic renal failure for whom we had prospective data on body composition (as estimated by dual-energy x-ray absorptiometry) following PD. In addition, indices of dialysis adequacy, peritoneal glucose absorption, and urea kinetics were followed (3 to 6 times per year in each patient) during treatment with PD. The degree of physical activity was assessed before the start of PD. RESULTS: Twenty patients with the deletion/deletion UCP2 genotype had a significant increase in body weight (3.0 +/- 0.8 vs. -1.0 +/- 1.1 kg, P < 0.01) and body fat mass (3.8 +/- 0.9 vs. 0.8 +/- 1.0 kg, P < 0.05) during PD, compared with 19 patients with an insertion/deletion UCP2 genotype. On the other hand, no significant differences in indices of dialysis adequacy, peritoneal glucose absorption, urea kinetic parameters, or degree of physical activity were observed when comparing patients who accumulated or lost fat tissue during PD. CONCLUSIONS: As most patients with the deletion/deletion UCP2 genotype acquired fat tissue during PD, the present results suggest that the UCP2 polymorphism contributes to variations in body composition. Thus, variations in UCP2 production or activity may be factors contributing to adipose tissue accumulation in a subgroup of patients treated with PD. It is possible that the polymorphism has a similar effect in the general population.

Adipose Tissue↗
PubMed2000

Hyperhomocysteinemia, nutritional status, and cardiovascular disease in hemodialysis patients.

BACKGROUND: Hyperhomocysteinemia, cardiovascular disease (CVD), and malnutrition are common in patients with end-stage renal disease (ESRD). This study was designed to assess possible relationships between total plasma homocysteine (tHcy), nutritional status, and ischemic CVD. METHODS: We performed a cross-sectional study in 117 unselected patients on maintenance hemodialysis (HD) treatment, among whom there was a high prevalence of malnutrition (56%), as assessed by the subjective global nutritional assessment (SGNA), and a high prevalence of CVD (60%), and prospectively, we followed-up the overall mortality for four years. RESULTS: The level of tHcy was elevated in 95% of the HD patients, and that of total plasma cysteine (tCys) was also significantly elevated, while the plasma concentrations of methionine (Met), serine (Ser), and taurine (Tau) were significantly lower than those in healthy controls. The 65 patients who were malnourished according to the SGNA score had significantly lower levels of serum albumin (SAlb), plasma IFG-1 (p-IGF-1), tHcy, tCys, and Met than the 52 patients with normal nutritional status, whereas the levels of Ser, Tau, plasma folate, and vitamin B12 were similar in the two groups. The prevalence of malnutrition was 30% in the 47 patients without CVD and was significantly higher (70%, P < 0.001) in the 70 patients with CVD, who also had lower tHcy, SAlb, plasma IGF-1, serum creatinine (SCr), and blood hemoglobin. The tHcy levels were positively correlated with SAlb, Met, tCys, and SCr. Stepwise, multiple-regression analysis showed that tCys, SAlb, and normalized protein equivalent of nitrogen appearance (nPNA), an indicator of protein intake, were independent predictors of tHcy. The patients with tHcy <24 micromol/L (median value) had a significantly worse four-year survival than those with a higher tHcy (> or =24 micromol/L). CONCLUSIONS: Our results demonstrate that most of HD patients have grossly elevated tHcy levels, but that the absolute level appears to be dependent on nutritional status, protein intake, and SAlb. The results also suggest that the lower tHcy levels in patients with CVD than in those without CVD may be related to the higher prevalence of malnutrition and hypoalbuminemia in the CVD patients. This is also in accordance with our observation that the patients with lower tHcy had a worse survival rate than those with higher tHcy, considering that malnutrition is a strong risk factor for mortality and that CVD is the most common cause of death in ESRD patients.

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