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B Lindholm

Publications and source records attributed to B Lindholm.

At least 73 records · Page 4Linked to original sources
PubMed1999

Physiological saline is not a biocompatible peritoneal dialysis solution.

UNLABELLED: We have previously demonstrated that daily exposure to dialysis fluid results in significantly increased peritoneal lymphatic flow. In this study, we investigated if daily intraperitoneal infusion of saline (isotonic, glucose free) could cause similar changes. METHODS: Sixteen male SD rats received daily infusion (i.p.) of 20 ml saline for ten days (Saline group). Twenty-four hours after the last infusion, a 4 hour dwell study using 25 ml 3.86% glucose dialysis solution with frequent dialysate and blood sampling was done in each rat as well as in rats which did not receive daily infusion (Control, n=8). Radiolabeled human albumin (RISA) was added to the solution as an intraperitoneal volume marker. Radioactivity, glucose, urea, sodium, and potassium were measured for each sample. In a separate study, the RISA absorption to peritoneal tissue was also determined. RESULTS: The net ultrafiltration was significantly decreased in the daily infusion group (p<0.05). However, the apparent volume at 3 minutes of the dwell was markedly increased; this was due to a significant increase in the RISA binding (1.5-12.0% in the Saline group vs. 0.45-1.12% in the Control group) to peritoneal tissues as assessed by measurement of RISA recovery at 3 min of the dwell. This resulted in a significant overestimation both of the intraperitoneal volume (IPV) at 3 min and the (apparent) fluid absorption rate (as estimated by the transport of RISA out of peritoneal cavity): 0.087+/-0.026 ml/min in the Saline group vs. 0.052+/-0.007 ml/min in the Control group, p<0.001. The direct lymphatic flow as estimated by the clearance of RISA to plasma (which should not be affected by the RISA binding) also increased markedly (0.021+/-0.005 ml/min in the Saline group vs. 0.008+/-0.001 ml/min in the control group). There was no significant difference in the D/P values for small solutes (urea, sodium, potassium, urate) and D/D0 for glucose between the two groups. CONCLUSIONS: 1) Daily infusion of physiological saline into peritoneal cavity may increase the peritoneal lymphatic flow; 2) The significant (apparent) increase in IPV shortly after infusion may suggest increased RISA binding to peritoneal tissues (which may be related to the damage of the tissues, and results in overestimation of the peritoneal fluid absorption rate); 3) Saline is not a biocompatible peritoneal dialysis solution, and should therefore not be used as a control or flush solution.

Absorption↗
PubMed1999

Alterations in water and solute transport with time on peritoneal dialysis.

Peritoneal ultrafiltration capacity and small-solute transport characteristics seem to be relatively stable in most patients treated with PD for up to 3 years. However, in patients treated with PD for 4 years or more, there is a tendency towards increasing diffusive transport for small solutes as well as a tendency towards decreasing net UF, whereas the peritoneal protein clearances seem to be reduced or stable. Loss of UFC is a well-known complication during long-term PD treatment, and the risk for loss of UFC may be as high as 50% after 6 years on PD. Several different mechanisms of UFC loss have been reported. In particular, the most common mechanism for loss of UFC is increased diffusive transport resulting in rapid glucose absorption and thus rapid loss of the osmotic driving force. Also reported as causes of UFC loss have been: reduced efficiency of the osmotic agent (perhaps owing to decreased transcellular water transport); loss of peritoneal surface area with slow solute transport owing to fibrosis and the formation of adhesions (during the late stage of sclerosing peritonitis); and increased peritoneal fluid absorption. In individual patients, a combination of several mechanisms may be involved in the apparent UFC failure.

Animals↗
PubMed1999

Intraperitoneal addition of hyaluronan improves peritoneal dialysis efficiency.

BACKGROUND: It has been shown that hyaluronan (HA) can decrease peritoneal fluid absorption. It is not known, however, how various molecular weights and various concentrations of hyaluronan affect peritoneal fluid absorption rate. METHODS: A study of 4-hour dwells, with frequent dialysate and blood sampling, was performed in male Sprague-Dawley rats (6-7 rats in each group) with 131I albumin as an intraperitoneal volume marker. Each rat was infused intraperitoneally with 25 mL of 1.5% glucose solution alone or 1.5% glucose solution containing hyaluronan at various molecular weights (MW-85 kD, 280 kD, 500 kD, and 4 MD) or containing hyaluronan of MW 500 kD at various concentrations (0.01%, 0.05%, 0.1%, 0.5%). Two additional groups were infused with 40 mL of 1.36% glucose dialysate alone or 1.36% glucose dialysate with 0.01% hyaluronan (MW 500 kD) to test the effect of hyaluronan when high dialysate fill volume was used. RESULTS: Addition of 0.01% hyaluronan significantly decreased peritoneal fluid absorption rate (K(E)) (by 22%, p < 0.01). The decrease was more marked with hyaluronan at high MW or high concentration, or with high dialysate fill volume. The net ultrafiltration tended to be higher in all hyaluronan groups compared to their control groups except in the 4 MD group; this difference was mainly due to a lower K(E) in all the hyaluronan groups. The direct lymphatic flow was significantly decreased in the 0.5% HA group. The transcapillary ultrafiltration rate (Qu) was significantly lower in the 4 MD group as compared to the control group. No difference in Qu was found between the other groups as compared to their control groups. CONCLUSIONS: (1) Intraperitoneal addition of hyaluronan may increase net peritoneal fluid removal, mainly because hyaluronan decreases peritoneal fluid absorption rate. The decrease was more marked when high dialysate fill volume was used, indicating that intraperitoneal addition of hyaluronan can prevent the decreased net ultrafiltration caused by an increase in dialysate fill volume. (2) The decrease in peritoneal fluid absorption rate may be both MW-dependent and concentration-dependent: that is, a higher MW as well as a higher concentration of hyaluronan result in a more marked decrease in peritoneal fluid absorption rate. (3) Low concentrations of high MW hyaluronan may also decrease Qu. However, Qu did not decrease when high concentrations of hyaluronan were used despite a significant decrease in peritoneal fluid absorption rate.

Absorption↗
PubMed1999

A simple and fast method to estimate peritoneal membrane transport characteristics using dialysate sodium concentration.

BACKGROUND: The peritoneal equilibration test (PET) is widely used to classify a patient's peritoneal transport characteristics. However, PET is laborious and the prediction of fluid removal based on PET is generally poor. It is believed that osmosis by glucose occurs partially through transcellular water channels, resulting in sieving of sodium and decrease of dialysate sodium concentration when using hypertonic glucose dialysate. OBJECTIVE: In this study, we investigated the possibility of using dialysate sodium concentration to classify the patient's peritoneal transport characteristics. METHODS: A 6-hour dwell study with frequent dialysate and plasma sampling was performed in 46 patients using 2 L of 3.86% glucose dialysate with 131I-albumin as an intraperitoneal volume (IPV) marker. The peritoneal transport of sodium, creatinine, glucose, and fluid was evaluated. RESULTS: The dialysate sodium concentration at 240 min (D(Na240)) significantly correlated with D/P creatinine (r = 0.76, p < 0.001) and D/D0 glucose (r = -0.83, p < 0.001) at 240 min of the dwell (better than dialysate sodium concentration at any other time of the dwell). DNa240 also significantly correlated with IPV at 240 min of the dwell (r = -0.61, p < 0.001)(better than D/P creatinine and D/D0 glucose). There were significant correlations between D(Na240) and the sodium-sieving coefficient (r = 0.71, p < 0.001) and the diffusive mass transfer coefficient for sodium (r = 0.50, p < 0.001). When using D(Na240) to divide the patients into four groups, as in the PET method, no significant difference was found between the two methods. CONCLUSION: Using 3.86% glucose solution, D(Na240) can be used instead of D/P creatinine to classify patients into different transport groups. D(Na240) provides a better prediction of peritoneal fluid transport and reflects both the diffusive and convective transport properties of the membrane. As only one dialysate sample (and no blood sample) is needed, D(Na240) may offer important clinical advantages compared with PET.

Biological Transport↗
PubMed1999

Peritoneal fluid kinetics: comparison between polyglucose solution and albumin solution.

Polyglucose (PG) solution has been shown to be capable of inducing peritoneal ultrafiltration despite its hypo-osmolality. However, the mechanism of osmosis by PG is not clear. In this study, we compared the fluid kinetics of albumin (ALB) solution (thought to be an ideal solution that should induce ultrafiltration through colloid osmosis) and PG solution. A 4-hour dwell study with frequent sampling was conducted in Sprague-Dawley rats (six rats in each group). The study used 25 mL of dialysate buffer, 10% ALB dialysis solution, 15% ALB dialysis solution, 20% ALB dialysis solution, or 7.5% PG solution, with 131I albumin as an intraperitoneal volume marker. All solutions were prepared by adding ALB or PG to a base dialysis solution (without osmotic agent). The initial osmolality values of the five solutions were 250 mOsm/kg, 284 mOsm/kg, 300 mOsm/kg, 320 mOsm/kg, and 280 mOsm/kg, and the dialysate drainage volumes at 4 hours were 17.0 +/- 0.8 mL, 22.4 +/- 0.8 mL, 25.4 +/- 0.6 mL, 27.3 +/- 0.9 mL, and 26.3 +/- 0.6 mL (buffer, 10% ALB, 15% ALB, 20% ALB, and 7.5% PG groups, respectively). The higher initial osmolality in the ALB groups was partially due to the sodium content in the ALB powder. The intraperitoneal volume was decreasing in the 10% ALB group, rather stable in the 15% ALB group, but slowly increasing in the 20% ALB group. In the PG group, intraperitoneal volume decreased initially and then started to increase after 2 hours. This pattern was closely related to the increase in the dialysate osmolality (to higher than plasma level). At 4 hours, the dialysate osmolality was significantly higher (and higher than plasma level) in the PG group as compared to all the ALB groups. No differences in peritoneal fluid absorption rate were observed among the four treatment groups. In the 15% ALB and 20% ALB groups, the transcapillary ultrafiltration rate (Qu) was lower in the later part of the dwell than in the initial part of the dwell; in the PG group, the opposite pattern was observed. Our results suggest that the osmosis of albumin dialysis solution is different from the osmosis of polyglucose solution. Polyglucose solution induces net ultrafiltration only when the dialysate osmolality increase to higher than plasma level, suggesting that degradation of polyglucose may be important for effective ultrafiltration.

Albumins↗
PubMed1999

Vasodilatation by intraperitoneal addition of nitroprusside is not a model for high peritoneal transport.

It has been suggested that the peritoneal capillary is the major determinant for peritoneal fluid transport and that an increase in the number of peritoneal capillaries may be the reason for an increased peritoneal transport rate. In this study, we investigated the impact on peritoneal fluid and solute transport of vasodilatation (which may increase the number of perfused capillaries) by intraperitoneal addition of nitroprusside. A 4-hour dwell was performed in four groups of Sprague-Dawley rats (4-8 rats in each group) with 131I albumin as an intraperitoneal volume marker. Nitroprusside at concentrations of 0% (control), 0.0005%, 0.001%, and 0.002% was added to the 3.86% glucose solution before intraperitoneal infusion. Net ultrafiltration (NUF) was 13.2 +/- 0.6 mL, 14.5 +/- 0.7 mL, 13.4 +/- 0.9 mL, and 6.3 +/- 2.0 mL for the control group and the 0.0005%, 0.001%, and 0.002% nitroprusside groups, respectively. No significant differences in peritoneal fluid absorption rate (KE) were observed among the four groups. The intraperitoneal volume, transcapillary ultrafiltration rate (Qu), and peritoneal small-solute transport rate (glucose and urea) as assessed by diffusive mass transfer coefficient were significantly higher or tended to be higher in the 0.0005% nitroprusside group as compared to control. However, with further increase in the dose of nitroprusside, these parameters started to decrease as compared to the 0.0005% nitroprusside group, and NUF was significantly lower in the 0.002% nitroprusside group, conceivably suggesting a reduction in blood flow owing to the systemic effects of nitroprusside. Our study showed that: (1) a low dose of nitroprusside increased the peritoneal small-solute transport rate, but did not decrease peritoneal transcapillary ultrafiltration rate; (2) although a high dose of nitroprusside decreased peritoneal fluid removal, the decrease was not due to an increased small-solute transport rate, but more likely to a significant drop in peritoneal blood flow; (3) vasodilatation by nitroprusside did not change peritoneal fluid absorption rate. Overall, vasodilatation does not seem to produce a pattern of peritoneal fluid kinetics similar to that seen in high transporters, who have a higher peritoneal transport rate, lower transcapillary ultrafiltration rate, and higher peritoneal fluid absorption rate.

Animals↗
PubMed1998

Malnutrition, cardiac disease, and mortality: an integrated point of view.

Malnutrition and hypoalbuminemia, which are prevalent in patients with end-stage renal disease (ESRD), are strong predictors of increased mortality. However, cardiovascular disease predominates among direct causes of death, whereas malnutrition appears to be of minor importance in this respect. Reports in the literature demonstrate that cardiac failure may cause malnutrition and that infection/inflammation may predispose to atherosclerosis as well as to catabolism and hypoalbuminemia. Proinflammatory cytokines, generated in response to cardiac failure, infection, and other inflammatory stimuli, appear to play a pivotal role by causing muscle wasting, hypoalbuminemia, and anorexia as well as reduced cardiac contractility and atherosclerotic vascular disease. We hypothesize that this scenario also applies to ESRD patients, in whom congestion, hypertension, cardiac failure, and ischemic cardiovascular disease are common. Malnutrition rarely may be the direct cause of death, except in elderly dialysis patients, but may contribute to a poor prognosis by aggravating pre-existing heart failure and increasing the susceptibility to infections.

Age Factors↗
PubMed1998

Experimental models in peritoneal dialysis: a European experience.

BACKGROUND: The development of adequate animal models is important for the in vivo study of selected aspects of peritoneal dialysis (PD) that cannot be evaluated by an in vitro model, such as peritoneal membrane transport, the influence of local defense mechanisms, and for testing new osmotic agents and their biocompatibilities. METHODS: Our experience with animal models for PD, including the acute Stockholm model in non-uremic rats, the acute and chronic Amsterdam model in non-uremic rats, and the chronic Gent model in uremic rats, is described. RESULTS: The Stockholm model proved to be useful in understanding the normal physiology of peritoneal transport, and for testing new dialysis solutions and their biocompatibilities. It is a rather simple and inexpensive model, and thus is suitable for screening new solutions and additives. The Amsterdam model permits the study of chemokines and mesothelial cell regeneration in vivo, and is applied in a model of chronic peritonitis. The results of the Gent model suggest that chronic peritoneal dialysis in uremic rats is feasible for at least eight weeks. This model is, however, very laborious, time consuming, and expensive. CONCLUSION: Further improvement of the technique and increase of the dialysis dose should result in a better and more realistic model for peritoneal dialysis. It is hoped that in the future these models will be useful to test the effects of long-term intraperitoneal application of different dialysis solutions and additives in uremic animals.

Animals↗
PubMed1998

Hyaluronan prevents the decreased net ultrafiltration caused by increased peritoneal dialysate fill volume.

In the present study, we investigated (1) the effect of an increase in dialysate fill volume on peritoneal fluid and solute transport using a 1.36% glucose solution, and (2) the effect of intraperitoneal administration of hyaluronan on peritoneal transport characteristics when different fill volumes were used. A four-hour dwell study with frequent dialysate and blood sampling was performed in 26 male Sprague-Dawley rats with 131I albumin as the intraperitoneal volume marker. Each rat was injected intraperitoneally with 25 ml (group Con25, N = 6) or 40 ml (group Con40, N = 7) of 1.36% glucose dialysis solution alone or 25 ml (group HA25, N = 6) or 40 ml (Group HA40, N = 7) of 1.36% glucose dialysis solution with 0.01% hyaluronan. The peritoneal transport of fluid, glucose, urea, and total protein as well as the intraperitoneal hydrostatic pressure (IPP) with different fill volumes were evaluated. We found that IPP and peritoneal fluid absorption rate significantly increased with the increase in fill volume (P < 0.01), and therefore the net ultrafiltration volume was significantly lower in the Con40 group compared to the Con25 group despite a higher transcapillary ultrafiltration rate in the Con40 group. The addition of hyaluronan to dialysate significantly (P < 0.01) decreased the peritoneal fluid absorption rate (by 22% in HA25 vs. Con25 and by 29% in HA40 vs. Con40) and thus significantly increased the net peritoneal fluid removal. The diffusive mass transport coefficients for glucose, urea and total protein did not differ between the Con25 and Con40 groups or between the two hyaluronan groups as compared to their respective control groups. The peritoneal clearance of urea increased significantly in the high fill volume group (by 58% in Con40 vs. Con25) and in the two hyaluronan groups (by 21% in HA25 vs. Con25 and by 16% in HA40 vs. Con40). We conclude that: (1) An increase in dialysate fill volume using 1.36% glucose dialysis solution results in higher intraperitoneal hydrostatic pressure and higher peritoneal fluid absorption rate, and therefore lower net ultrafiltration. (2) Intraperitoneal addition of hyaluronan significantly decreases the peritoneal fluid absorption rate, and the decreasing effect is even more marked when a high fill volume is used. (3) Small solute clearances increase markedly with increases in fill volume, and then further increase by adding hyaluronan to the dialysate due to the increase in drainage volume. Thus, intraperitoneal administration of hyaluronan during a single peritoneal dialysis exchange may significantly increase the peritoneal fluid and solute removal by decreasing peritoneal fluid absorption, and may thereby prevent the decreased net ultrafiltration caused by an increase in dialysate fill volume.

Animals↗
PubMed1998

Factors predicting malnutrition in hemodialysis patients: a cross-sectional study.

Signs of protein-energy malnutrition are common in maintenance hemodialysis (HD) patients and are associated with increased morbidity and mortality. To evaluate the nutritional status and relationship between various parameters used for assessing malnutrition, we performed a cross-sectional study in 128 unselected patients treated with hemodialysis (HD) thrice weekly for at least two weeks. Global nutritional status was evaluated by the subjective global nutritional assessment (SGNA). Body weight, skinfold thicknesses converted into % body fat mass (BFM), mid-arm muscle circumference, hand-grip strength and several laboratory values, including serum albumin (SA1b), plasma insulin-like growth factor I (p-IGF-I), serum C-reactive protein (SCRP) and plasma free amino acids, were recorded. Dose of dialysis and protein equivalence of nitrogen appearance (nPNA) were evaluated by urea kinetic modeling. The patients were subdivided into three groups based on SGNA: group I, normal nutritional status (36%); group II, mild malnutrition (51%); and group III, moderate or (in 2 cases) severe malnutrition (13%). Clinical factors associated with malnutrition were: high age, presence of cardiovascular disease and diabetes mellitus. nPNA and Kt/V(urea) were similar in the three groups. However, when normalized to desirable body wt, both were lower in groups II and III than in group I. Anthropometric factors associated with malnutrition were low body wt, skinfold thickness, mid-arm muscle circumference (MAMC), and handgrip strength. Biochemical factors associated with malnutrition were low serum levels of albumin and creatinine and low plasma levels of insulin-like growth factor 1 (IGF-1) and branched-chain amino acids (isoleucine, leucine and valine). The serum albumin (SAlb) level was not only a predictor of nutritional status, but was independently influenced by age, sex and SCRP. Plasma IGF-1 levels also reflected the presence and severity of malnutrition and appeared to be more closely associated than SAlb with anthropometric and biochemical indices of somatic protein mass. Elevated SCRP (> 20 mg/liter), which mainly reflected the presence of infection/inflammation and was associated with hypoalbuminemia, was more common in malnourished patients than in patients with normal nutritional status, and also more common in elderly than in younger patients. Plasma amino acid levels, with the possible exception of the branched-chain amino acids (isoleucine, leucine, valine), seem to be poor predictors of nutritional status in hemodialysis patients.

Adult↗
PubMed1998

Increased peritoneal permeability is associated with decreased fluid and small-solute removal and higher mortality in CAPD patients.

BACKGROUND: Recent studies suggest that increased peritoneal membrane permeability is associated with higher morbidity and mortality in peritoneal dialysis patients. It is not known, however, whether the difference in clinical outcome among different peritoneal transport groups is due to differences in peritoneal fluid and solute removal. In the present study, we compared the peritoneal fluid and solute transport and clinical outcome in CAPD patients with high (H), high-average (H-A), low-average (L-A) and low (L) peritoneal transport patterns. DESIGN: A 6-h dwell study was performed in 46 patients with frequent dialysate and plasma samples using 2 l of 3.86% glucose dialysate with 131I albumin as an intraperitoneal volume marker. The patients were divided into four transport groups according to their D/P of creatinine at 240 min. RESULTS: The results showed that high transporters had significantly lower peritoneal fluid and small-solute removal but high glucose absorption and high protein loss during a 6-h exchange. The serum albumin was lower and blood pressure and triglycerides were higher in high transporters compared with the other groups. Two-year patient survival from the start of CAPD treatment was significantly lower for high transporters (64, 85, 90 and 100% for H, H-A, L-A and L respectively, P < 0.01). The 1-year patient survival from the dwell study was also significantly lower in high transporters (16, 63, 90 and 100% for each group, P<0.01). CONCLUSION: Our results suggest that high transporters remove less fluid and small solutes and have higher protein loss and increased glucose absorption. These alterations may contribute to fluid overload, malnutrition and lipid abnormalities that perhaps contribute to the increased mortality among the high transporters.

Adult↗
PubMed1998

Factors contributing to catabolism in end-stage renal disease patients.

End-stage renal disease (ESRD) patients, whether they are treated with hemodialysis or continuous ambulatory peritoneal dialysis, frequently suffer from protein-energy malnutrition, which is associated with increased morbidity and mortality. The protein requirements in dialysis patients are increased compared to those of healthy individuals and nondialyzed patients with chronic renal failure. The intake of protein and energy is frequently reduced because of the underlying disease, comorbidity, psychosocial factors, and uremic anorexia (underdialysis). There are several factors in ESRD patients that may enhance protein catabolism and increase protein requirements, such as low energy intake, amino acid abnormalities, metabolic acidosis, endocrine abnormalities (insulin resistance, hyperglucagonemia, hyperparathyroidism, insensitivity to growth hormone and insulin-like growth factor-1, cardiac failure, infection and inflammation, anemia, and physical inactivity. The dialytic procedures per se may enhance protein catabolism due to dialytic losses of protein and amino acids and, in hemodialysis, an inflammatory response to blood-dialyzer interaction. The relative importance of the various factors which cause anorexia and stimulate protein catabolism is still not well understood.

Acidosis↗
PubMed1998

Amphotericin B does not increase peritoneal fluid removal.

Intraperitoneal use of amphotericin B (AmB) has been reported to increase ultrafiltration during short peritoneal dwell in rabbits. In this study, we investigated the effect of AmB on peritoneal fluid kinetics in rats. A 4 hour dwell using 25 mL of 2.27% glucose dialysis solution without AmB (control, n = 6), with 1 mg/kg (L-AmB, n = 6) or with 10 mg/kg AmB (H-AmB, n = 6), and with frequent dialysate and blood sampling was done in Sprague-Dawley rats. 131I-albumin was added to the solution as an intraperitoneal (i.p.) volume marker. There was no difference in the drainage volumes measured at 4 hours of the dwell (26.2 +/- 1.1 mL, 26.0 +/- 1.5 mL, and 26.0 +/- 1.1 mL for the control, L-AmB, and H-AmB groups, respectively.) However, the i.p. volumes were higher at 60 minutes, 90 minutes, and 120 minutes of the dwell in the H-AmB group as compared to the other two groups (1 to 1.5 mL higher, all P < 0.05). There were no differences in the peritoneal fluid absorption rate (KE) and the lymphatic flow rate (KEB) between the three groups. The D/D0 for glucose and dialysis-over-plasma concentration ratio (D/P) values for urea, sodium, and total protein, as well as the diffusive mass transport coefficient (KBD) values for these solutes did not differ among the three groups. However, the D/P as well as the KBD values for potassium were significantly higher in the H-AmB and L-AmB groups as compared to the control group, resulting in significantly higher potassium clearances among the two AmB groups as compared to the control group. Our results suggest that i.p. use of AmB did not increase peritoneal fluid removal after 4 hours of dwell in rats. Although the basic membrane permeability may not be altered by AmB, the higher D/P and KBD values as well as the higher clearances for potassium in the AmB groups may suggest a local release of potassium due to the cytotoxic effect of AmB. The contribution of water release from local cells to the increase in i.p. volume in the H-AmB group cannot be ruled out.

Absorption↗
PubMed1997

Uremic serum enhances scavenger receptor expression and activity in the human monocytic cell line U937.

The macrophage scavenger receptor (SR) plays a leading role in atherogenesis, but little is known about the relevance of SR to atherosclerosis in uremia. In this study, the impact of uremic serum on SR expression and activity was examined in the human monocytic cell line U937. The cells were cultured with serum from ten healthy subjects, ten hemodialysis (HD) and ten continuous ambulatory peritoneal dialysis (CAPD) patients. SR mRNA expression was examined using reverse transcriptase-polymerase chain reaction followed by Southern blot. SR protein amount was evaluated by ligand blot. SR activity was analyzed by cellular uptake of fluorescently labeled acetylated low-density lipoprotein using flow cytometry. Uremic serum dose-dependently enhanced SR activity primarily by increasing the amount of receptor protein. Heat-inactivated uremic serum had a stimulatory effect, but ultrafiltrate of uremic serum, which included molecules with a molecular weight less than ten kDa, had no effect. The serum levels of macrophage-colony stimulating factor (M-CSF), an activator of SR, were fourfold higher in uremia and significantly correlated with SR activity in cells treated with uremic serum. Pre-treatment of uremic serum with a neutralizing antibody to M-CSF abolished the effect of uremic serum on SR activity. In conclusion, uremic serum contains a factor(s) that enhances SR expression and activity in U937 cells. Elevated M-CSF in uremic serum could be responsible for this enhancement.

Antibodies↗