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Biomedical subjects

B Lindholm

Publications and source records attributed to B Lindholm.

At least 55 records · Page 3Linked to original sources
PubMed2000

Elevated serum levels of soluble adhesion molecules predict death in pre-dialysis patients: association with malnutrition, inflammation, and cardiovascular disease.

BACKGROUND: Atherosclerotic cardiovascular disease, malnutrition, and increased levels of pro-inflammatory cytokines are common features in patients with chronic renal failure, and contribute to the high mortality rate observed in these patients. A diverse group of soluble cellular adhesion molecules (CAM) (sVCAM-1, sICAM-1 and sE-selectin) are expressed on the surface of vascular endothelial cells in response to pro-inflammatory cytokines and may play an important role in the atherogenic process. METHODS: Serum levels of sVCAM-1, sICAM-1 (n=87) and sE-selectin (n=71) were analysed in a cohort of 88 patients (50+/-1 years) with chronic renal failure. The presence of malnutrition (subjective global assessment (SGA) and serum albumin), inflammation (C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha), and serum hyaluronan), and cardiovascular disease (CVD) were assessed at a time-point close to the start of dialysis treatment (GFR 7+/-1 ml/min). Blood lipid parameters were also assessed. RESULTS: Significant correlations were observed between Log high-sensitivity CRP (hsCRP) and sVCAM-1 (R=0.39; P<0.01) and sICAM-1 (R=0.47; P:<0.001) levels but not between Log hsCRP and sE-selectin levels in 60 patients examined with a hsCRP assay. Also serum concentrations of Log hyaluronan correlated significantly to sVCAM-1 (R=0.34; P<0.01) and sICAM-1 (R=0.29; P<0.05) levels. Malnourished patients (SGA>1) had elevated serum concentrations of sVCAM-1 (1436+/-94 vs. 1105+/-53 ng/ml; P<0.01) compared to well-nourished patients (SGA 1). Patients with clinical signs of CVD (n=26) had elevated serum levels of sICAM-1 (282+/-18 vs. 242+/-9 ng/ml; P<0.05) compared to 61 patients without signs of CVD. Plasma Log lipoprotein (a) (Lp(a)) levels correlated significantly with sVCAM-1 (R=0.30; P<0.01). Survival analysis by the Cox regression model showed that elevated sICAM-1 was, independent of age, SGA, CVD, and Log CRP, significantly related to an increased mortality rate. CONCLUSIONS: Elevated serum concentrations of soluble adhesion molecules are found in pre-dialysis patients who are malnourished, inflamed, and have signs of cardiovascular disease. These data also suggest that sICAM-1 is an independent predictor of mortality in pre-dialysis patients. Further studies are needed to determine if inflammation causes accelerated atherogenesis via effects on soluble adhesion molecules or if elevated serum levels of soluble adhesion molecules are merely markers of endothelial activation in patients with chronic renal failure.

Adult↗
PubMed2000

Kinetic modeling of fluid and solute transport in peritoneal dialysis.

Mathematical models for fluid and solute transport during peritoneal dialysis are described. A model for the transport of the so-called volume marker enables the correct estimation of the kinetics of the intraperitoneal dialysate volume as well as the rate of peritoneal fluid absorption. On the basis of these estimations, the solute transport components (diffusion, convective solute transport with ultrafiltrate and peritoneal solute absorption) may be separated within the net solute transport using a modified version of the Babb-Randerson-Farrell (BRF) model. The diffusive mass transport coefficient and sieving coefficient are given by the model. A simplified method for the estimation of the diffusive mass transport coefficient during the so-called isovolemia period is also described and compared to the BRF modeling. The three-pore model and the distributed model, which describe the structure-function relationship for the peritoneum, are also addressed.

Dialysis Solutions↗
PubMed2000

Effect of dialysate composition on the apoptosis and proliferation of human peritoneal mesothelial cells and protein expression of Fas and c-Myc.

To investigate the effect of dialysate composition on apoptosis and proliferation of human peritoneal mesothelial cells (HPMCs) in vitro, HPMCs were cultured from human omental tissue. The cells were exposed for three days to culture medium containing: (1) 3.86% glucose, (2) 1.36% glucose, (3) 1.75 mmol/L Ca++, (4) 1.25 mmol/L Ca++, or (5) no additions (control). Apoptosis and proliferative cell nuclear antigen (PCNA) were measured by terminal deoxynucleotidyl transferase (TdT)-mediated in situ end-labelling and immunohistochemistry. Protein expression of Fas and of c-Myc were measured by flow cytometry. Apoptotic cells were significantly increased in the high glucose group compared to control (137 +/- 47 cells per field unit vs 63 +/- 30 cells per field unit, p < 0.01), but did not vary in the low glucose and low calcium groups versus control (76 +/- 25 cells per field unit and 77 +/- 31 cells per field unit, respectively, vs 63 +/- 30 cells per field unit, p > 0.05). Cells with positive expression of PCNA were increased in the high calcium group versus control (366 +/- 101 cells per field unit vs 186 +/- 76 cells per field unit, p < 0.01). However, the expression of PCNA was significantly more inhibited in the high glucose group than in the control group (158 +/- 52 cells per field unit vs 186 +/- 76 cells per field unit, p < 0.05). Expression of Fas was stimulated by high glucose (41% +/- 16% vs 25% +/- 8% in the control group, p < 0.05). High glucose and high calcium also up-regulated the expression of c-Myc, but only the high glucose group showed significant difference from control (39% +/- 10% vs 24% +/- 8%, p < 0.05). Our data suggest that: (1) Peritoneal dialysate could induce apoptosis of HPMCs in vitro, the degree of apoptosis depending on concentration of glucose. (2) High calcium stimulates PCNA expression by HPMCs and high glucose inhibits expression of PCNA. (3) Genes associated with apoptosis (Fas, c-Myc) might play an important role in triggering apoptosis of HPMCs.

Apoptosis↗
PubMed2000

Phospholipids in dialysate and the peritoneal surface layer.

Dialysate concentration of phospholipids has been used to monitor peritoneal membrane status. However, we recently found that the peritoneum has a surface layer in which phospholipids may be the main constituent. Therefore, in this study, we compared the phospholipids composition of peritoneal dialysate and of the peritoneal surface in rats. Eight male Sprague-Dawley rats were used in the study. Five rats received an intraperitoneal injection of 25 mL 4.25% glucose dialysis solution. After four hours, the rats were killed, and the dialysate was drained completely. Then 20 mL of Folch solution was infused into the peritoneal cavity for 30 seconds and drained completely. The other three rats received the Folch solution without dialysis. The effluent and Folch solution were then processed for phospholipids analysis using high performance thin-layer chromatography (HPTLC). The total phospholipids content was ten times higher in the surface layer than in the dialysate effluent. In the effluent, four clearly different components were seen: lysophosphatidylcholine (LPC), sphingomyelin (SM, 29%), phosphatidylcholine (PC, 66%), and phosphatidylinositol (PI, 4.5%). However, in the surface layer, as well as LPC, SM (20.6%), PHC (47%), and PI (6.3%), two additional components were seen, phosphatidylserine (PS, 17.1%) and phosphatidylethanolamine (PE, 8.9%). The quantity of phospholipids in the peritoneal surface of non dialyzed rats was similar to the total quantity of phospholipids (in effluent and in the peritoneal surface) of dialyzed rats. Our results suggest that: (1) a surface layer is present on the peritoneum; this layer could well be extracted by Folch solution; and, with appropriate incubation time, one can separate the surface layer without damaging the mesothelial cells; (2) the composition of phospholipids in the effluent is different from that in the peritoneal surface layer, which contains membrane phospholipids (PS and PE); (3) shielding from the peritoneal surface may be the main reason for the presence of phospholipids in the dialysate.

Animals↗
PubMed2000

Comparison of three chronic dialysis models.

The chronic peritoneal dialysis model is important for understanding the pathophysiology of peritoneal transport and for studying biocompatibility of peritoneal dialysis solutions. In this study, we compared three different chronic peritoneal dialysis models. A peritoneal catheter was placed in 23 male Sprague-Dawley rats, 12 of which had an intact omentum (model 1) and 11 of which received an omentectomy (model 2). Seven other rats, without a catheter, received a daily intraperitoneal injection (model 3). Each rat received a daily infusion of 25 mL of 3.86% glucose dialysis solution either through the catheter (models 1 and 2) or through injection (model 3) for 4 weeks. Then, a 4-hour dwell study using 3.86% glucose solution with an intraperitoneal volume marker and frequent dialysate and blood sampling was performed in each rat. The intraperitoneal volume was significantly lower in all the dialysis groups as compared to a control group (n = 6) in which the rats had no chronic dialysate exposure. The peritoneal fluid absorption rate, as well as the direct lymphatic absorption rate, was significantly higher in the three dialysis groups as compared to the control group. In general, no significant differences were seen in any of the parameters among the three dialysis models. Owing to catheter obstruction, three rats in model 1 and four rats in model 2 were lost during dialysis. Histological examination showed no significant differences among the three dialysis groups. Our results suggest that omentectomy may not be necessary in the chronic peritoneal dialysis model when using dialysate infusion and no drainage. Based on the present study, we think that perhaps model 1 may be the method of choice to test new peritoneal dialysis solutions. However, owing to its simplicity, model 3 could also be used if great care is taken to avoid puncturing the intestine or injecting into the abdominal wall.

Absorption↗
PubMed2000

Biocompatibility of new peritoneal dialysis solutions: clinical experience.

The successful development of peritoneal dialysis (PD) during the last two decades has been made possible by using well-established glucose-based solutions with lactate as buffer. On the other hand, awareness has been increasing about the potentially negative effects of the high concentrations of glucose and lactate, and the low pH of conventional PD solutions. This awareness has prompted an intensive effort to search for and test alternative solutions. As a result, three new, more biocompatible solutions-containing either less glucose or less lactate--are available. Amino acid-based solution uses amino acids instead of glucose as the osmotic agent; it is indicated for treatment of malnutrition. The higher pH and absence of glucose in this solution may prevent alterations of the peritoneal membrane caused by acidity and high glucose concentrations. Bicarbonate/lactate-buffered solution contains a physiologic concentration of bicarbonate and a reduced concentration of lactate; it also has a physiologic pH and markedly reduced levels of glucose degradation products (GDPs). Icodextrin-based solution contains icodextrin as the osmotic agent; it is indicated for long dwells, delivering sustained ultrafiltration for more than 16 hours. This iso-osmolar glucose-free solution may reduce peritoneal membrane alterations caused by glucose or the hyperosmolality (or both) of conventional solutions. Clinical experience of the new solutions is now extensive, and their efficacy and safety are well documented. It therefore seems appropriate to state that we have entered a new era of PD therapy. Each of the new solutions may be less damaging to the peritoneal membrane than conventional solution. In addition, they permit better management of malnutrition and fluid status, and may thus help to improve PD patient survival. Although the effects of each of these new solutions have been well described, clinical documentation of the combined use of these new biocompatible PD solutions is still insufficient. However, the results of studies are expected, during the coming years, to support the combined use of the new solutions as the preferred standard practice for PD.

Amino Acids↗
PubMed2000

Biocompatibility of new peritoneal dialysis solutions: what can we hope to achieve?

Despite the bioincompatibility of the "old", standard, high glucose, lactate-buffered peritoneal dialysis (PD) solutions, PD is itself a highly successful dialysis modality with patient survival equivalent to that of hemodialysis (HD) during the initial 3 - 5 years of dialysis therapy. Nevertheless, PD technique survival is often limited by infectious complications and alterations in the structure and function of the peritoneal membrane. These local changes also have a negative impact on patient survival owing to systemic effects such as those often seen in patients with high peritoneal transport rate and loss of ultrafiltration (UF) capacity. Patient mortality remains unacceptably high in both HD and PD patients, with most premature deaths being associated with signs of malnutrition, inflammation, and atherosclerotic cardiovascular disease (MIA syndrome). These systemic signs are likely to be influenced by PD solutions both directly and indirectly (via changes in the peritoneal membrane). New, biocompatible PD solutions may have favorable local effects (viability and function of the peritoneal membrane) and systemic effects (for example, on MIA syndrome). Amino acid-based solution [Nutrineal (N): Baxter Healthcare Corporation, Deerfield, IL, U.S.A.] may improve nutritional status as well as peritoneal membrane viability. Bicarbonate/lactate-buffered solution [Physioneal (P): Baxter Healthcare Corporation] may ameliorate local and systemic effects of low pH, high lactate, and high glucose degradation products. Icodextrin-based solution [Extraneal (E): Baxter Healthcare SA, Castlebar, Ireland] may improve hypertension and cardiovascular problems associated with fluid overload and may extend time on therapy in patients with loss of UF capacity. The positive effects of each of these new, biocompatible solutions have been demonstrated in several studies. It is likely that the combined use of N, P, and E solutions will produce favorable synergies in regard to both local effects (peritoneal viability) and systemic effects (less malnutrition, inflammation, and fluid overload). Solution combination is an exciting area for clinical study in the coming years. Furthermore, dialysis fluid additives such as hyaluronan, which protects and improves the function of the peritoneal membrane, may further improve PD solutions. The new, biocompatible PD solutions represent an entirely new era in the evolution of the PD therapy; they are likely to have markedly positive effects on both PD technique and PD patient survival in coming years.

Amino Acids↗
PubMed1999

[Strong connection between malnutrition, inflammation and arteriosclerosis. Improved treatment of renal failure if underlying factors are attacked].

Malnutrition, inflammation and atherosclerotic cardiovascular disease occur at high prevalence, and often concomitantly, in conjunction with chronic renal failure. Several features of malnutrition (e.g., increased oxidative stress, increased plasma levels of fibrinogen, Lp(a), and inflammation) may all, alone or in concert, increase the risk of cardiovascular disease. Recent findings suggest malnutrition and hypoalbuminaemia in chronic renal failure to be largely the consequence of such factors as heart failure, chronic infection and inflammation, that simultaneously trigger the development of atherosclerotic cardiovascular disease. Central to this scenario is the involvement of proinflammatory cytokines which may cause muscle wasting, hypoalbuminaemia, anorexia, and accelerated atherosclerosis. It is unlikely that the high mortality due to atherosclerotic disease among patients with chronic renal failure can be substantially reduced unless new treatment strategies are developed which address the complex relationships that exist between malnutrition, inflammation and cardiovascular disease.

Arteriosclerosis↗
PubMed1999

High serum hyaluronan indicates poor survival in renal replacement therapy.

Atherosclerotic cardiovascular disease (CVD), malnutrition, and inflammation are common clinical features of chronic renal failure and are associated with increased mortality. Elevated levels of C-reactive protein (CRP) and cytokines are commonly observed in dialysis patients and have been shown to predict mortality. Serum hyaluronan previously has been used as a marker of an inflammatory reaction, irrespective of its cause. We have determined serum levels of albumin and hyaluronan, as well as the prevalence of malnutrition (subjective global assessment, 2 to 4), inflammation (CRP >/= 10 mg/L), and overt CVD in a cohort of 97 predialysis patients (52 +/- 13 years). Moreover, we determined the outcome of these patients 29 +/- 11 months after the basal measurement of hyaluronan. Serum levels of hyaluronan (median) were markedly elevated in predialysis patients with signs of malnutrition (127.1 v 50.5 ng/mL; P < 0.0001), inflammation (130.1 v 55.0 ng/mL; P < 0.0001) and CVD (118.8 v 56.0 ng/mL; P < 0.001). The levels of log hyaluronan correlated significantly to log CRP (R = 0.35; P < 0.001), serum albumin (R = -0.40; P < 0.0001), CVD (R = 0.36; P < 0.001), and age (R = 0.40; P < 0.0001), respectively. Survival analysis by the Cox regression model showed that elevated hyaluronan levels were, independent of CVD, CRP, and age, significantly related to an increased mortality rate. The current study showed that markedly elevated serum hyaluronan levels are found in predialysis patients with malnutrition, inflammation, and CVD and that serum hyaluronan is a risk predictor of poor survival in dialysis.

Biomarkers↗
PubMed1999

Do ACE-inhibitors suppress tumour necrosis factor-alpha production in advanced chronic renal failure?

OBJECTIVES: The serum levels of the catabolic cytokine TNF-alpha are often raised in malnourished chronic heart failure patients as well as in chronic renal failure (CRF) patients. Angiotensin-converting enzyme (ACE) inhibitors are often used in these patients and may decrease TNF-alpha and IL-1beta levels in vitro and in vivo. The aim of this study was to find out whether CRF patients with ongoing ACE-inhibitor treatment have lower TNF-alpha levels. DESIGN: Cross-sectional study. SETTING: Tertiary Referral Center and University Hospital. SUBJECTS: Ninety-six predialysis patients (mean age 52 +/- 1 years) with advanced CRF (glomerular filtration rate 7 +/- 1 mL min-1). MAIN OUTCOME MEASURES: Plasma levels of TNF-alpha, subjective global assessment of nutritional status and data on ongoing antihypertensive treatment (ACE-inhibitors, beta blockers, calcium channel blockers and angiotensin II (AII) receptor blockers). RESULTS: Patients treated with ACE-inhibitors (n = 44) had significantly lower plasma TNF-alpha levels (18.5 +/- 1.2 vs. 26.6 +/- 2.2 pg mL-1; P < 0.01) and were less frequently malnourished, relative to 52 patients not treated with ACE-inhibitors. No significant difference in TNF-alpha levels were observed when comparing patients with or without treatment with beta, calcium channel, or AII receptor blockers, respectively. CONCLUSIONS: The present data suggest that the use of ACE-inhibitors is associated with lower plasma TNF-alpha and CRP levels as well as a lower prevalence of malnutrition in patients with advanced CRF. Further studies are needed to establish if there is a casual relationship between these findings and, if so, the molecular mechanism(s).

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Hyaluronan decreases peritoneal fluid absorption: effect of molecular weight and concentration of hyaluronan.

BACKGROUND: We have recently shown that the addition of hyaluronan to peritoneal dialysis solution could decrease the peritoneal fluid absorption rate, possibly through decreasing peritoneal tissue hydraulic conductivity. The physical-chemical properties of hyaluronan were found to be both molecular weight and concentration dependent. In this study, we investigated the effects of different molecular weight as well as different concentrations of hyaluronan on the peritoneal fluid kinetics. METHODS: A four-hour dwell study was performed in 48 male Sprague-Dawley rats (6 rats in each group) with 131I albumin (RISA) as an intraperitoneal volume marker. Each rat was intraperitoneally injected with 25 ml of 1.36% glucose dialysate alone (control) or with 0.01% hyaluronan (HA) with different molecular weights [85,000 (HA85K group), 280,000 (HA280K group), 500,000 (HA500K group), and 4,000,000 (HA4M group) molecular wt] or with a different concentrations of hyaluronan [(molecular wt 500,000); 0.01% (0.01% HA group), 0.05% (0.05% HA group), 0.1% (0.1% HA group), and 0.5% (0.5% HA group) hyaluronan]. RESULTS: The peritoneal fluid absorption rate (as assessed by the RISA elimination rate, KE) was significantly decreased in the HA500K and H4M groups as well as in all the different concentration groups (with molecular wt 500,000) as compared with the control group, resulting in significantly higher net fluid removal in these groups (except for the H4M group) as compared with the control group. In the 0.5% HA group (but not in the other hyaluronan groups), the direct lymphatic absorption (KEB) was also significantly decreased. The transcapillary ultrafiltration rate (Qu) was significantly lower in the HA4M group as compared with the control group but significantly higher in the 0.05% HA (and tended to be higher in the 0.1% HA group) as compared with the other groups. No difference in Qu was found between the 0.5% HA group as compared with the control group, despite a more marked decrease in KE in this group as compared with the H4M group. There were no significant differences in KE, Qu, and net fluid removal between the HA85K and HA280K groups and the control group. CONCLUSIONS: Our results suggest that (a) the addition of hyaluronan to dialysate could decrease peritoneal fluid absorption and thus increase the net ultrafiltration; this effect appears to be both size dependent and concentration dependent. (b) High molecular weight fraction of hyaluronan may also decrease the transcapillary Qu by decreasing tissue hydraulic conductivity. (c) A higher concentration of hyaluronan in dialysate resulted in a more marked decrease in peritoneal fluid absorption (absorption to peritoneal tissues as well as direct lymphatic absorption), possibly through both decreasing tissue hydraulic conductivity and increasing fluid viscosity. (d) Decreasing tissue hydraulic conductivity by adding a high concentration of hyaluronan to dialysate does not decrease the transcapillary ultrafiltration, possibly because the osmotic effect of hyaluronan may counterbalance the decrease in transcapillary ultrafiltration because of the decrease in tissue hydraulic conductivity.

Absorption↗
PubMed1999

High peritoneal residual volume decreases the efficiency of peritoneal dialysis.

BACKGROUND: Wide variation in peritoneal residual volume (PRV) is a common clinical observation. High PRV has been used in both continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis to minimize the time of a dry peritoneal cavity and to achieve better dialysis. However, the impact of PRV on peritoneal transport is not well established. In this study, we investigated the effect of PRV on peritoneal transport characteristics. METHODS: Peritoneal effluents were collected in 32 male Sprague-Dawley rats after a five-hour dwell with 1.36% glucose solution. Forty-eight hours later, a four hour dwell using 25 ml of 3.86% glucose solution and frequent dialysate and blood sampling was done in each rat with 125I-albumin as a volume marker. Before the infusion of the 3.86% glucose solution, 0 (control), 3, 6, or 12 ml (8 rats in each group) of autologous effluent (serving as PRV) was infused to the peritoneal cavity. RESULTS: After subtracting the PRV, the net ultrafiltration was significantly lower in the PRV groups as compared with the control group: 13.4 +/- 0.5, 12.0 +/- 1.0, 11.7 +/- 1.7, and 8.9 +/- 0.4 ml for 0, 3, 6, and 12 ml PRV groups, respectively (P < 0.001). The lower net ultrafiltration associated with higher PRV was due to (a) a significantly lower transcapillary ultrafiltration rate (Qu) caused by a lower osmotic gradient, and (b) a significantly higher peritoneal fluid absorption rate (KE) caused by an increased intraperitoneal hydrostatic pressure. No significant differences were found in the diffusive mass transport coefficient for small solutes (glucose, urea, sodium, and potassium) and total protein, although the dialysate over plasma concentration ratios values were higher in the high-PRV groups. The sodium removal was significantly lower in the PRV groups as compared with the control group (P < 0.01). CONCLUSION: Our results suggest that a high PRV may decrease net ultrafiltration through decreasing the Qu, which is caused by a decreased dialysate osmolality, and increasing the KE caused by an increased intraperitoneal hydrostatic pressure. The high volume of PRV also decreased the solute diffusion gradient and decreased peritoneal small solute clearances, particularly for sodium. Therefore, a high PRV may compromise the efficiency of dialysis with a glucose solution.

Animals↗
PubMed1999

Effect of blood perfusion on diffusive transport in peritoneal dialysis.

BACKGROUND: Diffusive transport between blood and dialysate during peritoneal dialysis is evaluated in clinical and experimental studies by the diffusive mass transport coefficient, KBD. This global parameter depends on the local diffusive characteristics of the blood capillary wall (permeability) and the tissue, as well as on the density and distribution of capillaries within the tissue. It also depends on the rate of delivery (or washout) of solutes from the tissue with blood flow, that is, on the rate of tissue perfusion. However, the role of blood perfusion in peritoneal transport has not been theoretically evaluated. METHODS: The relationship between the local characteristics of the peritoneal tissue and the global diffusive mass transport coefficient was studied using a new extended version of the distributed model for peritoneal transport, which included the effect of tissue perfusion and capillary surface area on the blood-tissue transport. RESULTS: The solute concentration profiles within the tissue were found to depend on the solute penetration depth, which is equal to the square root of the ratio of the solute diffusivity in tissue to the solute clearance from the capillary bed to tissue. It was shown that KBD might be interpreted as the dialysance of a capillary bed of a characteristic size that would be immersed directly in dialysate. A definition of the effective peritoneal blood flow (EPBF; the blood flow within the tissue layer) was formulated, and it was shown that EPBF depends on the local transport characteristics for the solute. Assuming typical values of the model parameters (known from physiological studies), the values of KBD and EPBF for urea, creatinine, glucose, and CO2 were calculated and compared with the measured values with good qualitative agreement. The transient initial increase of KBD values observed at the beginning of the peritoneal dialysis dwell was interpreted as a transient sixfold increase in tissue perfusion and a twofold increase in the capillary surface area. CONCLUSION: The distributed model can be useful as a theoretical tool for detailed physiological interpretations of changes in peritoneal transport associated with changes in peritoneal microcirculation and structure of the interstitium.

Ascitic Fluid↗
PubMed1999

Effects of high-dose folic acid and pyridoxine on plasma and erythrocyte sulfur amino acids in hemodialysis patients.

In this investigation, sulfur amino acids (sAA) and sulfhydryls were determined in the plasma and erythrocytes (RBC) of 10 uremic patients on regular hemodialysis (HD) treatment and 10 healthy subjects, before and after supplementation with 15 mg/d of folic acid and 200 mg/d of pyridoxine for 4 wk. The basal total plasma concentrations of homocysteine (Hcy), cysteine (Cys), cysteinylglycine (Cys-Gly), gamma-glutamylcysteine (gamma-Glu-Cys), glutathione (GSH), and free cysteinesulfinic acid (CSA) were significantly higher in HD patients when compared to healthy subjects, whereas methionine (Met) and taurine (Tau) concentrations were the same in the two groups. HD patients showed significantly higher RBC levels of Hcy and Cys-Gly, whereas the RBC concentrations of Met, Cys, Tau, and GSH were not different from those in the healthy subjects. The plasma concentrations of sAA and sulfhydryls differed compared with RBC levels in the healthy subjects and HD patients. In both groups, supplementation with high doses of folic acid and pyridoxine reduced the plasma Hcy concentration. In addition, increased plasma concentrations of Cys-Gly and GSH were found in the HD patients and of CSA in the healthy subjects. After vitamin supplementation, the RBC concentrations of Hcy, Cys, and GSH increased and that of Tau decreased in healthy subjects. The only significant finding in RBC of HD patients was an increase in GSH levels after supplementation. This study shows several RBC and plasma sAA and sulfhydryl abnormalities in HD patients, which confirms earlier findings that RBC and plasma pools play independent roles in interorgan amino acid transport and metabolism. Moreover, high-dose supplementation with folic acid and pyridoxine significantly reduced Hcy levels, but did not restore the sAA and sulfhydryl abnormalities to normal levels. The increase that was observed in GSH after vitamin supplementation may have a beneficial effect in improving blood antioxidant status in uremic patients. Finally, the findings of elevated plasma Cys levels correlating to the elevated plasma Hcy levels in the presence of elevated plasma CSA levels, both before and after vitamin supplementation, led to the hypothesis that a block in decarboxylation of CSA is linked to hyperhomocysteinemia in end-stage renal failure.

Adult↗