Biomedical subjects

Abelardo Aguilera

Publications and source records attributed to Abelardo Aguilera.

At least 19 recordsLinked to original sources

PubMed2007

Brain activation in uremic anorexia.

This article reviews current knowledge about mechanisms responsible for uremic events, especially those that involve the central nervous system (CNS). Anorexia is a frequent complication of the uremic syndrome that contributes to malnutrition in patients on dialysis. Uremic anorexia has been associated with many factors. Traditionally, anorexia in dialysis patients has been regarded as a sign of uremic toxicity; therefore, 2 hypotheses have been proposed: the "middle molecule" and "peak concentration" hypotheses; both of these remain unproved. Recently, our group has proposed the tryptophan-serotonin hypothesis, which is based on a disorder in the amino acid profile that may be acquired when the patient is in uremic status. It is characterized by low concentrations of large neutral and branched chain amino acids in the cerebrospinal fluid. This situation permits a high level of tryptophan transport across the blood-brain barrier and enhances the synthesis of serotonin (the final target responsible for inhibiting appetite). The role of inflammation in the genesis of anorexia-malnutrition is also emphasized. In summary, in the CNS, factors associated with uremic anorexia include high levels within the cerebrospinal fluid of proinflammatory cytokines, leptin, and free tryptophan and serotonin (hyperserotoninergic-like syndrome), along with deficiency of neural nitric oxide (nNO) and disorders in various receptors such as melanocortin receptor-4 (MC4-R). Uremic anorexia is a complex complication associated with malnutrition and high levels of morbidity and mortality. Several uremia-acquired disorders in the CNS such as high cerebrospinal fluid levels of anorexigen substances and disorders in appetite regulator receptors may explain the lack of appetite.

Amino Acids↗

PubMed2006

Epithelial-to-mesenchymal transition of the mesothelial cell--its role in the response of the peritoneum to dialysis.

Peritoneal membrane fibrosis, ranging from mild inflammation to severe sclerosing peritonitis, is one of the complications of peritoneal dialysis (PD). In parallel with fibrosis, the peritoneum shows a progressive increase of capillaries and vasculopathy, involved in increased small solute transport across the membrane and ultrafiltration failure. Glucose and glucose degradation products from PD solutions are responsible of stimulating transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF) production by mesothelial cells (MCs). TGF-beta is a potent pro-fibrotic factor and inducer of epithelial-to-mesenchymal transition (EMT) of the MC. Local production of VEGF by transitional MC appears to play a central role in the processes leading to peritoneal angiogenesis. This review addresses the mechanism involved in peritoneal structural alteration by dialysis and points to the EMT of MC as the initiating mechanism of peritoneal injury. Information from multiple origins about TGF-beta and VEGF is integrated into EMT process in a comprehensive manner. Regulation and new targets for inhibition of EMT or its deleterious effects are discussed.

Epithelial Cells↗

PubMed2006

Serum ghrelin concentrations in patients with chronic renal failure undergoing dialysis.

BACKGROUND: Ghrelin is a recently discovered protein hormone mainly synthesized in the gastric endocrine cells. This hormone not only is a potent growth hormone secretagogue but also is involved in the regulation of food ingestion and energy metabolism. Derangements in ghrelin secretion in patients with chronic renal failure (CRF) have not been fully evaluated. OBJECTIVE: Our aim has been to quantify serum concentrations of total ghrelin in a group of patients with CRF on chronic therapy with both haemodialysis (HD) and peritoneal dialysis (PD) in comparison with a group of patients on conservative management (predialysis). PATIENTS AND MEASUREMENTS: We studied 68 CRF patients treated by HD (n = 30, 16 men, age 61.2 +/- 1.8 years) and PD groups (n = 38, 21 men, age 54.4 +/- 1.7 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of ghrelin, leptin, insulin, IGF I and GH were measured in all subjects. RESULTS: Patients undergoing HD showed similar concentrations of ghrelin in comparison with the control group (9491 +/- 787 vs 9280 +/- 918 pg/ml, NS). However, PD patients exhibited baseline ghrelin concentrations significantly lower than those found in patients on conservative management (3230 +/- 216 pg/ml, P < 0.0001). Men and women showed similar serum ghrelin levels in both HD (9845.9 +/- 1071 vs 9085 +/- 1194 pg/ml) and PD patients (3214 +/- 297 vs 3250 +/- 324 pg/ml). Hypertension and diabetes mellitus did not influence ghrelin levels. Serum GH levels were positively correlated with serum ghrelin concentrations in both HD (r = 0.46, P < 0.05) and PD (r = 0.53, P < 0.001) patients; however, no relationships between ghrelin, leptin, insulin and IGF I were found. CONCLUSIONS: These results suggest that PD is accompanied by a striking decrement in baseline ghrelin concentrations in comparison with values found both in HD and control patients. Further studies are necessary to determine mechanisms involved in ghrelin regulation in uraemic patients.

Adult↗

PubMed2005

Mesenchymal conversion of mesothelial cells as a mechanism responsible for high solute transport rate in peritoneal dialysis: role of vascular endothelial growth factor.

BACKGROUND: During peritoneal dialysis (PD), the peritoneum is exposed to bioincompatible dialysis fluids that cause epithelial-to-mesenchymal transition of mesothelial cells, fibrosis, and angiogenesis. Ultrafiltration failure is associated with high transport rates and increased vascular surface, indicating the implication of vascular endothelial growth factor (VEGF). Sources of VEGF in vivo in PD patients remain unclear. We analyzed the correlation between epithelial-to-mesenchymal transition of mesothelial cells and both VEGF level and peritoneal functional decline. METHODS: Effluent mesothelial cells were isolated from 37 PD patients and analyzed for mesenchymal conversion. Mass transfer coefficient for creatinine (Cr-MTC) was used to evaluate peritoneal function. VEGF concentration was measured by using standard procedures. Peritoneal biopsy specimens from 12 PD patients and 6 controls were analyzed immunohistochemically for VEGF and cytokeratin expression. RESULTS: Nonepithelioid mesothelial cells from effluent produced a greater amount of VEGF ex vivo than epithelial-like mesothelial cells (P < 0.001). Patients whose drainage contained nonepithelioid mesothelial cells had greater serum VEGF levels than those with epithelial-like mesothelial cells in their effluent (P < 0.01). VEGF production ex vivo by effluent mesothelial cells correlated with serum VEGF level (r = 0.6; P < 0.01). In addition, Cr-MTC correlated with VEGF levels in culture (r = 0.8; P < 0.001) and serum (r = 0.35; P < 0.05). Cr-MTC also was associated with mesothelial cell phenotype. VEGF expression in stromal cells, retaining mesothelial markers, was observed in peritoneal biopsy specimens from high-transporter patients. CONCLUSION: These results suggest that mesothelial cells that have undergone epithelial-to-mesenchymal transition are the main source of VEGF in PD patients and therefore may be responsible for a high peritoneal transport rate.

Adult↗

PubMed2005

Serum concentrations of leptin, adiponectin and resistin, and their relationship with cardiovascular disease in patients with end-stage renal disease.

BACKGROUND AND OBJECTIVE: High levels of some adipocytokines have been reported in patients with chronic renal failure, but little information is available on adipocytokine concentrations in uraemic patients under different modalities of therapy. Our aims were (1) to quantify the serum concentrations of leptin, adiponectin and resistin in uraemic patients on peritoneal dialysis (PD) and haemodialysis (HD), in comparison with patients on conservative management, and (2) to study the relationships between adipocytokine levels and previous atherosclerotic vascular disease. PATIENTS AND MEASUREMENTS: We studied 82 dialysis patients treated by PD (n = 44, 23 males and 21 females, mean age 54.4 +/- 1.8 years) or HD (n = 38, 22 males and 16 females, age 60.8 +/- 1.6 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of leptin, adiponectin and resistin were measured in all subjects. Information on vascular disease (cerebral vascular, peripheral vascular and heart disease) was obtained from a detailed medical history. RESULTS: PD patients showed significantly higher serum leptin concentrations [median (interquartile range), 28.7 (13.0-71.9) microg/l] than those found in patients on HD [9.7 (4.7-31.9) microg/l, P < 0.01] or in conservative management [5.9 (4.3-38.6) microg/l, P < 0.05]. Adiponectin concentrations were similar in the three groups of patients (mean +/- SEM, 48.0 +/- 4.5 mg/l in PD, 57.7 +/- 4.4 mg/l in HD, and 44.4 +/- 7.0 mg/l in controls, NS). Patients treated by both PD and HD exhibited resistin concentrations significantly higher than those found in controls (26.3 +/- 0.99 and 27.5 +/- 1.4 microg/l, respectively, vs. 17.3 +/- 1.0 microg/l, P < 0.001). Leptin concentrations were positively correlated with body mass index (BMI) (r = 0.287, P < 0.01) and adiponectin levels were negatively related to BMI (r = -0.416, P < 0.001) and the homeostatic model assessment (HOMA-R) index (r =-0.216, P < 0.05). Leptin, adiponectin and resistin levels in patients with previous vascular events were similar to those found in patients without these complications. Logistic regression analysis did not demonstrate any relationship between serum adipocytokine concentrations and the presence of vascular disease of any type. A significant relationship between resistin and heart disease [odds ratio (OR) 1.80 (1.03-3.15), P = 0.039] was found when analysing subgroups of patients. CONCLUSIONS: These data suggest that leptin levels are higher in PD patients, and resistin levels are higher in PD and HD patients in relation to patients on conservative management, whereas adiponectin concentrations are similar in the three groups. These results do not support the presence of a clinically relevant relationship between adipocytokines and previous episodes of vascular disease in the whole population or in patients classified in subgroups, with the only exception of a relationship between resistin levels and heart disease.

Adiponectin↗

PubMed2005

Epithelial to mesenchymal transition as a triggering factor of peritoneal membrane fibrosis and angiogenesis in peritoneal dialysis patients.

Peritoneal fibrosis (or sclerosis) is a complication of peritoneal dialysis (PD) and includes a wide spectrum of peritoneal structural changes, ranging from mild inflammation to severe sclerosing peritonitis and encapsulating-sclerosing peritonitis. In parallel with fibrosis, the peritoneum shows a progressive increase in capillary number (angiogenesis) and vasculopathy, which are involved in both the elevation of small solute transport across the peritoneal membrane and ultrafiltration failure. The most important substances from the PD solutions responsible for peritoneal deterioration are glucose and glucose degradation products, which stimulate transforming growth factor (TGF)beta and vascular endothelial growth factor (VEGF) production by mesothelial cells (MCs). TGFbeta is a potent pro-fibrotic factor and induces epithelial-mesenchymal transition (EMT) of the MC. Local production of VEGF during PD appears to play a central role in the processes leading to peritoneal neo-angiogenesis and functional decline. This review discusses the mechanisms implicated in peritoneal structural alteration and points to EMT of MC as the protagonist and initiator of peritoneal membrane injury, through an increment of the submesothelial fibroblast population. We also propose possible mechanisms of regulation and new targets for inhibition of EMT.

Epithelium↗

PubMed2004

Immunohistochemical characterization of fibroblast subpopulations in normal peritoneal tissue and in peritoneal dialysis-induced fibrosis.

Peritoneal fibrosis is one of the most common morphological changes observed in continuous ambulatory peritoneal dialysis (CAPD) patients. Both resident fibroblasts and new fibroblast-like cells derived from the mesothelium by epithelial-to-mesenchymal transition are the main cells involved fibrogenesis. In order to establish markers of peritoneal impairment and pathogenic clues to explain the fibrogenic process, we conducted an immunohistochemical study focused on peritoneal fibroblasts. Parietal peritoneal biopsies were collected from four patient groups: normal controls ( n = 15), non-CAPD uremic patients ( n = 17), uremic patients on CAPD ( n = 27) and non-renal patients with inguinal hernia ( n = 12). To study myofibroblastic conversion of mesothelial cells, alpha-smooth muscle actin (SMA), desmin, cytokeratins and E-cadherin were analyzed. The expression of CD34 by fibroblasts was also analyzed. Fibroblasts from controls and non-CAPD uremic patients showed expression of CD34, but no myofibroblastic or mesothelial markers. The opposite pattern was present during CAPD-related fibrosis. Expression of cytokeratins and E-cadherin by fibroblast-like cells and alpha-SMA by mesothelial and stromal cells supports that mesothelial-to-myofibroblast transition occurs during CAPD. Loss of CD34 expression correlated with the degree of peritoneal fibrosis. The immunophenotype of fibroblasts varies during the progression of fibrosis. Myofibroblasts seem to derive from both activation of resident fibroblasts and local conversion of mesothelial cells.

Adult↗

PubMed2004

Effect of recombinant human erythropoietin on inflammatory status in dialysis patients.

Under normal conditions, inflammatory status is regulated by a complex equilibrium between plasma and intracellular mediators. This equilibrium is broken in patients receiving dialysis, which can lead to chronic inflammation causing deleterious consequences on their organs and systems. During recent years, substances that can inhibit the effects of inflammation have been sought. The results of these investigations have produced controversial data on the effects of recombinant human erythropoietin (epoetin) and, in this review, the effects of epoetin on the inflammatory status of dialysis patients are discussed. Aspects discussed include biomarkers of inflammation, and the relationships between epoetin, growth factors, endothelial dysfunction, endothelial fibrinolytic capacity, endothelial damage and oxidative stress. Relationships between epoetin and inflammation in non-uraemic patients are also addressed, as are associations between the malnutrition-inflammation-atherosclerosis syndrome and endothelial dysfunction. It is concluded that although epoetin administration in non-uraemic rats has been shown to have an anti-inflammatory and cytoprotective effect, the mechanisms responsible for regulating inflammation in uraemia are very complex and partially contradictory. The changes in pro-thrombotic and pro-atherogenic factors in dialysis patients require further study to evaluate all the factors implicated in the atherogenic process.

Animals↗

PubMed2004

Growth hormone, IGF-I and its binding proteins (IGFBP-1 and -3) in adult uraemic patients undergoing peritoneal dialysis and haemodialysis.

OBJECTIVE: The GH/IGF axis is altered in chronic renal failure (CRF). CRF patients usually show normal or high serum concentrations of GH and IGF-I, whereas all IGF binding proteins (IGFBP-1 to -6), except IGFBP-5, considerably increase with declining renal function. The aims of the present study were to quantify serum concentrations of GH, IGF-I, IGFBP-1 and IGFBP-3 in a group of patients with CRF, and determine whether there were differences according to the type of dialysis, that is, peritoneal dialysis (PD) and haemodialysis (HD). DESIGN: A cross-sectional study in the setting of a dialysis unit of a general hospital. PATIENTS AND MEASUREMENTS: We studied 108 dialysis patients treated by PD (n = 54, 32 males and 22 females, mean age 61.0 +/- 1.4 years) or HD (n = 54, 31 males and 23 females, age 62.6 +/- 1.5 years). A group of 42 healthy subjects of similar age, sex and body mass index (BMI) served as the control group. Baseline serum concentrations of GH, insulin, IGF-I, IGFBP-1 and IGFBP-3 were measured in all patients and control subjects. RESULTS: Fasting serum concentrations of IGF-I and its binding proteins (IGFBP-1 and IGFBP-3) were significantly higher in dialysis patients than in subjects with normal renal function. IGF-I (248.9 +/- 23.4 vs. 205.5 +/- 15.5 micro g/l, NS), IGFBP-3 (5.6 +/- 0.4 vs. 5.5 +/- 0.2 mg/l, NS) and IGFBP-1 (36.1 +/- 5.9 vs. 44.1 +/- 6.5 micro g/l, NS) concentrations were similar in both groups of dialysis (PD vs. HD) patients. However, GH (2.3 +/- 0.3 vs. 1.1 +/- 0.1 micro g/l, P < 0.001) and insulin (40.4 +/- 4.5 vs. 30.1 +/- 3.1 micro U/ml, P < 0.05) levels were significantly higher in the PD group than in the HD group. Both groups of dialysis patients showed significantly higher levels of insulin than healthy subjects (14.7 +/- 1.9 micro U/ml, P < 0.0001 and P < 0.01 for PD and HD, respectively). In both groups of dialysis patients, IGF-I correlated inversely with IGFBP-1 (PD group r = -0.46, P = 0.0006; HD group r = -0.57, P = 0.0001) and directly with IGFBP-3 (PD group r = 0.44, P = 0.001; HD group r = 0.73, P = 0.001). No correlation between insulin and IGFBP-1 was found in any of the groups studied. CONCLUSIONS: These findings demonstrate that adult dialysis patients have elevated IGF-I, IGFBP-1 and IGFBP-3 serum concentrations compared with subjects with normal renal function. Only GH and insulin show statistically significant differences in relation to type of dialysis. Finally, the negative correlation between IGF-I and IGFBP-1 and the positive correlation between IGF-I and IGFBP-3 are maintained in both groups of adult dialysis patients.

Analysis of Variance↗

PubMed2004

Ghrelin plasma levels and appetite in peritoneal dialysis patients.

Anorexia-associated malnutrition is a severe complication that increases mortality in peritoneal dialysis (PD) patients. Ghrelin is a recently-discovered orexigenic hormone with actions in brain and stomach. We analyzed, in 42 PD patients, the possible relationship between ghrelin and appetite regulation with regard to other orexigens [neuropeptide Y (NPY), NO3] and anorexigens [cholecystokinin (CCK), leptin, glucose-dependent insulinotropic peptide (GIP), tumor necrosis factor alpha (TNFalpha)]. All orexigens and anorexigens were determined in plasma. Eating motivation was evaluated using a visual analog scale (VAS). The patients were divided into three groups: those with anorexia (n = 12), those with obesity associated with high intake (n = 12), and those with no eating behavior disorders (n = 18). A control group of 10 healthy volunteers was also evaluated. Mean plasma levels of ghrelin were high (3618.6 +/- 1533 mg/mL), with 36 patients showing values above the normal range (< 2600 mg/mL). Patients with anorexia had lower ghrelin and NPY levels and higher peptide-C, CCK, interleukin-1 (IL-1), TNFalpha, and GIP levels than did the other patients. Patients with anorexia also had an early satiety score and low desire and pleasure in eating on the VAS and diet survey. We observed significant positive linear correlations between ghrelin and albumin (r = 0.43, p < 0.05), prealbumin (r = 0.51, p < 0.05), transferrin (r = 0.4, p < 0.05), growth hormone (r = 0.66, p < 0.01), NO3 (r = 0.36, p < 0.05), and eating motivation (VAS). At the same time, negative relationships were observed between blood ghrelin and GIP (r = -0.42, p < 0.05), insulin (r = -0.4, p < 0.05), leptin (r = -0.45, p < 0.05), and creatinine clearance [r = -0.33, p = 0.08 (nonsignificant)]. Ghrelin levels were not related to Kt/V or to levels of CCK and cytokines. Ghrelin plasma levels are elevated in PD patients. Uremic patients with anorexia show relatively lower ghrelin plasma levels than the levels seen in obese patients or in patients with normal appetite. The role of ghrelin in appetite modulation is altered in uremic PD patients, and that alteration is possibly associated with disorders in insulin and growth hormone metabolism.

Adult↗

PubMed2004

Treatment of anorexia and malnutrition in peritoneal dialysis patients with megestrol acetate.

Anorexia and malnutrition are common complications and powerful predictors of morbidity and mortality in peritoneal dialysis (PD) patients. Megestrol acetate (MA) is a progestogen that has been demonstrated to increase appetite and weight in patients with cancer or acquired immunodeficiency syndrome. To determine whether MA might benefit PD patients, we treated 32 patients with 160 mg MA daily. Treatment lasted a mean of 5.93 +/- 5.12 months (range: 1 - 23 months). In 68.8% of the patients, appetite improved. Weight gain was statistically significant starting in the third month (initial weight: 66.5 +/- 11.4 kg; weight at third month: 68 +/- 10.4 kg; p < 0.05). We observed a nonsignificant increase in serum albumin at the third treatment month (initial serum albumin: 3.44 +/- 0.27 g/L; serum albumin at third month: 3.54 +/- 0.27 g/L; p = 0.45). No side effects were observed. Our experience suggests that treatment with 160 mg MA daily in PD patients leads to an increase in appetite, serum albumin, and weight gain in most patients, with no negative side effects.

Anorexia↗

PubMed2003

Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells.

BACKGROUND: During continuous ambulatory peritoneal dialysis, the peritoneum is exposed to bioincompatible dialysis fluids that cause denudation of mesothelial cells and, ultimately, tissue fibrosis and failure of ultrafiltration. However, the mechanism of this process has yet to be elucidated. METHODS: Mesothelial cells isolated from effluents in dialysis fluid from patients undergoing continuous ambulatory peritoneal dialysis were phenotypically characterized by flow cytometry, confocal immunofluorescence, Western blotting, and reverse-transcriptase polymerase chain reaction. These cells were compared with mesothelial cells from omentum and treated with various stimuli in vitro to mimic the transdifferentiation observed during continuous ambulatory peritoneal dialysis. Results were confirmed in vivo by immunohistochemical analysis performed on peritoneal-biopsy specimens. RESULTS: Soon after dialysis is initiated, peritoneal mesothelial cells undergo a transition from an epithelial phenotype to a mesenchymal phenotype with a progressive loss of epithelial morphology and a decrease in the expression of cytokeratins and E-cadherin through an induction of the transcriptional repressor snail. Mesothelial cells also acquire a migratory phenotype with the up-regulation of expression of alpha2 integrin. In vitro analyses point to wound repair and profibrotic and inflammatory cytokines as factors that initiate mesothelial transdifferentiation. Immunohistochemical studies of peritoneal-biopsy specimens from patients undergoing continuous ambulatory peritoneal dialysis demonstrate the expression of the mesothelial markers intercellular adhesion molecule 1 and cytokeratins in fibroblast-like cells entrapped in the stroma, suggesting that these cells stemmed from local conversion of mesothelial cells. CONCLUSIONS: Our results suggest that mesothelial cells have an active role in the structural and functional alteration of the peritoneum during peritoneal dialysis. The findings suggest potential targets for the design of new dialysis solutions and markers for the monitoring of patients.

Cell Movement↗

PubMed2003

Gastrointestinal and pancreatic function in peritoneal dialysis patients: their relationship with malnutrition and peritoneal membrane abnormalities.

BACKGROUND: Malnutrition is frequent in peritoneal dialysis (PD) patients, but the contribution of gastrointestinal (GI) dysfunction has not been well established. METHODS: We studied GI function in 49 stable PD patients to ascertain its relationship with malnutrition. After an overload fat diet, fecal fat, sugar, starch and nitrogen, intestinal protein permeability (alpha(1)-antitrypsin fecal clearance [C-alpha(1)-AT]), fecal chymotrypsin (CT), GI hormones and gastrin, pepsinogen I and II, cholecystokinin (CCK), gastrin releasing peptide (GRP), and neuropeptide Y (NPY) were measured. Vasoactive intestinal polypeptide (VIP), substance P (SP), and tumor necrosis factor (TNF-alpha) and biochemical nutritional markers were evaluated. RESULTS: All patients showed high fecal sugar. Elevated fecal nitrogen was found in 21 patients, 6 with high C-alpha(1)-AT. High fecal starch levels appeared in 21, fat in 20, and low fecal CT in 39 patients. These determinations showed inverse relation with nutritional markers. Increased fecal C-alpha(1)-AT values were associated with lower serum albumin. Fecal CT values showed a negative linear correlation with serum albumin and were inversely associated with retinol-binding protein, normalized protein nitrogen appearance, and serum iron. High plasma levels of pancreatic stimulating hormones were found: gastrin, CCK, and VIP. These levels were higher in patients with a worse pancreatic exocrine function. Higher values of other GI hormones, gastrin, pepsinogen I and II, CCK, GRP, and TNF-alpha. Normal concentrations of NPY, VIP, and PS were observed. CONCLUSION: GI abnormalities (malabsorption, maldigestion, pancreatic dysfunction, and protein losing enteropathy) are present in an important number of PD patients. These features are negatively associated to nutrition.

Adult↗

PubMed2003

Clinical experience with tamoxifen in peritoneal fibrosing syndromes.

Peritoneal sclerosis is one of the most important complications of peritoneal dialysis (PD) treatment. Encapsulating peritoneal sclerosis (EPS) represents the most advanced stage of that disease and has a high mortality. No therapy of choice has been established for sclerosing peritonitis, although many have been proposed, with variable results. Tamoxifen has been successfully used in the treatment of patients with fibrosing diseases, mainly retroperitoneal fibrosis. Our purpose in the present study was to investigate whether treatment with tamoxifen in PD patients with peritoneal sclerosis has a beneficial effect. Among more than 450 patients treated in our program since 1980, 23 were diagnosed with peritoneal sclerosis. Of those 23.9 were treated with tamoxifen [20 mg every 12 hours: tamoxifen group (TG)] for a mean period of 14.5 +/- 7 months (range: 6-30 months). The other 14 patients received no treatment and were considered the control group (CG). Both groups were similar in demography and peritoneal antecedents. Follow-up was longer in CG than in TG (mean: 47 months vs. 29 months), but the difference did not reach statistical significance. Mild thrombopenia in 1 patient was the only toxic effect observed with the use of tamoxifen. In CG, 4 patients developed EPS and died--3 of them during the first 6 months after diagnosis. No patient treated with tamoxifen developed EPS. Overall mortality was significantly higher in CG (71% vs. 22%, p = 0.03). Although follow-up was longer in CG, half the patients in that group died during the first 2 years after diagnosis. Our experience suggests that treatment with tamoxifen of patients diagnosed with peritoneal sclerosis diminishes the related complications and significantly reduces mortality, at least in the short- to mid-term. However, a prospective therapeutic trial is required to confirm our results.

Adult↗

PubMed2003

Malnutrition-inflammation syndrome is associated with endothelial dysfunction in peritoneal dialysis patients.

Endothelial dysfunction with atherosclerosis is a recognized complication of uremic patients. The hypoalbuminemia of peritoneal dialysis (PD) patients can induce a hypercoagulable and atherogenic state. In this study, we investigated the role played by malnutrition-inflammation syndrome on endothelial function markers in PD patients. We measured markers of nutrition [normalized protein catabolic rate (nPCR), albumin, prealbumin, insulin-like growth factor 1 (IGF-1), transferrin, and cholesterol], markers of endothelial damage and function [tissue-type plasminogen activator (tPA), thrombomodulin (TM), von Willebrand factor (vWF), and NO3 (representing NO)], markers of a coagulable state [fibrinogen and plasminogen activator inhibitor 1 (PAI-1)], markers of inflammation [tumor necrosis factor alpha (TNF alpha) and C-reactive protein (CRP)], and other endothelial injury factors [lipoprotein(a) [Lp(a)] and homocysteine]. We also performed an endothelial stimulation test consisting of right-arm venous occlusion (VO) for 10 minutes. The patients were divided into four groups according to their clinical atherosclerotic score (CAS). We studied 45 clinically stable PD patients. At baseline, statistically significant negative linear correlations were found between albumin and age (r = -0.54, p < 0.05), albumin and vWF post-VO (r = -0.54, p < 0.05), and albumin and TM (r = -0.36, p < 0.05), which are endothelial damage markers and prothrombotic factors. A positive linear correlation was seen between albumin and NO3 post-VO (r = 0.48, p < 0.05), indicating a high vasodilatation capacity. C-Reactive protein and TNF alpha showed a positive linear correlation (r = 0.5, p < 0.01). Similarly, TNF alpha showed a positive linear correlation with cardiovascular risk markers such as fibrinogen (r = 0.79, p < 0.01), PAI-1 (r = 0.44, p < 0.05), and homocysteine (r = 0.37, p < 0.05). Creatinine clearance showed a negative linear correlation with TM (r = -0.36, p < 0.05). Patients with albumin < 4 g/dL showed a lower tPA ratio, lower NO3, and a higher CRP, TNF alpha, and Lp(a) than did patients with albumin > 4 g/dL [tPA ratio: 2.1 +/- 1.56 (n = 29) vs. 2.6 +/- 2.3 (n = 16), p < 0.05; NO3: 47 +/- 27 micrograms/mL vs. 69 +/- 33 micrograms/mL, p < 0.05; CRP: 1.8 +/- 3 mg/dL vs. 1.1 +/- 1.6 mg/dL, p < 0.05; TNF alpha: 44.4 +/- 16 pg/mL vs. 36.6 +/- 21.4 pg/mL, p < 0.05; Lp(a): 55 +/- 39 mg/dL vs. 33 +/- 21 mg/dL, p < 0.05]. Patients with a worse CAS showed higher homocysteine levels and lower albumin values. Those relationships were maintained in both periods of the study. We found no relationships between dialysis dose and endothelial function markers. In conclusion, malnutrition-inflammation syndrome may contribute to endothelial dysfunction and, consequently, to prothrombotic and proatherogenic processes in PD patients.

Adult↗

PubMed2002

Effects of short-term recombinant human growth hormone therapy on plasma leptin concentrations in dialysis patients.

BACKGROUND: Hyperleptinaemia is a well-known biochemical feature found in uraemic patients. However, little is known about the hormonal regulation of leptin in chronic renal disease. Recent studies have shown that circulating leptin levels are modified by treatment with recombinant human growth hormone (rhGH), by recombinant insulin-like growth factor I (rhIGF I), or by a combination of rhIGF I plus rhGH in patients with chronic renal failure. We performed a prospective study to assess plasma leptin concentrations in a group of dialysis patients both before and during short-term rhGH therapy. METHODS: We studied eight dialysis patients (four haemodialysis (HD) and four on continuous ambulatory peritoneal dialysis (CAPD); three female, five male; mean age 63.9 +/- 3.1 years). All patients were instructed to maintain a stable diet (35 kcal/kg/day and 1 g protein/kg/day ideal body weight) and were treated with rhGH (0.2 IU/kg/day s.c.) for 4 weeks. Blood samples were taken at 0, 2, 4, and 8 weeks for determination of leptin, GH, and IGF I. Serum insulin concentrations were assessed at 0 and 4 weeks. RESULTS: Mean plasma leptin concentrations were elevated (36.2 +/- 12.8 ng/ml) at study outset and increased progressively throughout the 4 weeks of rhGH therapy (43.7 +/- 13.5 ng/ml (2 weeks, NS) and 70.6 +/- 18.4 ng/ml (4 weeks, P<0.0001)). These values returned to baseline levels (38.0 +/- 12.0 ng/ml, NS) at 1 month after rhGH withdrawal. rhGH therapy was accompanied by the development of direct correlations between leptin and IGF I concentrations at 2 weeks (r=0.86, P<0.01), and with correlations between leptin and IGF I (r=0.84, P<0.01) and between leptin and insulin (r=0.88, P<0.01) after 4 weeks of rhGH administration. CONCLUSION: These results confirm the presence of high circulating plasma leptin in dialysis patients and show that these levels are further increased by exogenous rhGH administration. The increase in plasma leptin after rhGH therapy may be related to the rhGH-induced changes in insulin in these patients.

Aged↗

PubMed2002

Effects of human recombinant erythropoietin on inflammatory status in peritoneal dialysis patients.

Treatment with recombinant human erythropoietin (rHuEPO) in dialysis patients has been associated with improvement of nutritional and immune status through an increase of cytokine production [such as tumor necrosis factor alpha (TNF alpha)]. The high cytokine production can be a double-edged sword owing to the relationship of cytokines with the systemic inflammatory process, which has been associated with many complications of uremic status. Our aim was to analyze the medium-long term effects of rHuEPO treatment on uremic inflammatory markers. We studied 45 peritoneal dialysis (PD) patients divided in two groups: a rHuEPO group (40-70 subcutaneous units/kg weekly) and a control group (no rHuEPO). The treated group was analyzed in four periods. Period 1 (rHuEPO-1) included 24 patients who had been using rHuEPO at long-term. Period 2 (rHuEPO-2; n = 21) looked at the patients 2 months after rHuEPO withdrawal. Period 3 (rHuEPO-3; n = 19) looked at the patients after 2 months under rHuEPO therapy. Period 4 (rHuEPO-4; n = 17) looked at the patients after 4 months on rHuEPO treatment. With the reintroduction of rHuEPO, we observed a progressive, statistically significant (p < 0.05), and temporary increase in TNF alpha plasma levels, from 44 +/- 24 pg/mL (rHuEPO-2) to 76.8 +/- 25 pg/mL (rHuEPO-3), and then to 83 +/- 27 pg/mL (rHuEPO-4). But in the long term, TNF alpha decreased [33.5 +/- 10 pg/mL (rHuEPO-1)]. Similarly, albumin increased in the short term (3.73 +/- 0.5 g/dL to 4 +/- 0.5 g/dL, and then to 4 +/- 0.43 g/dL), and then decreased (3.8 +/- 0.44 g/dL). The normalized protein catabolic rate (nPCR) increased from 1 +/- 0.2 g/kg daily to 1.12 +/- 0.3 g/kg daily (rHuEPO-4). Long term, nPCR decreased to 1.06 +/- 0.3 g/kg daily. Leptin initially increased (60.1 +/- 48 ng/mL to 42.8 +/- 22 ng/mL, and then to 38 +/- 18.2 ng/mL); it also increased in the long term (62 +/- 50.9, p < 0.05). At baseline, we found a significant positive linear correlation (p < 0.05) between TNF alpha and leptin (r = 0.52), TNF alpha and C-reactive protein [(CRP) r = 0.4], CRP and leptin (r = 0.49), fibrinogen and CRP (r = 0.78, p < 0.01), fibrinogen and leptin (r = 0.37), and leptin and body mass index [(BMI) r = 0.67]. In conclusion, rHuEPO induces a temporary, non inflammatory immune hyperactivity mediated by TNF alpha, without the adverse effects associated with that cytokine. By decreasing leptin, rHuEPO could increase food intake and improve the nutritional status of PD patients. At baseline, we confirm the existence of a chronic inflammatory process in uremia.

Adult↗

PubMed2002

True deficiency of antioxidant vitamins E and A in dialysis patients. Relationship with clinical patterns of atherosclerosis.

Atherosclerosis is an important cause of morbidity and mortality in peritoneal dialysis (PD) patients. Oxidative stress plays a role in the pathogenesis of uremic atherosclerosis. Although antioxidant substances (vitamins A and E) are elevated in the plasma of dialysis patients, intracellular and clinical signs of hypovitaminosis are frequently found. Recently, the importance of vitamin/carrier complexes as a marker of vitamin bioavailability has been demonstrated. In the present study, we analyzed vitamin A and E bioavailability, measured as vitamin/carrier complexes, and the relationship of those measurements with clinical atherosclerosis status in PD patients. We studied 45 patients (15 men, 30 women), who were divided into four groups according to clinical atherosclerotic score (CAS). Five cases were scored as CAS grade 1 (low CAS); 9 as CAS-2; 18 as CAS-3; and 13 as CAS-4. Vitamins A and E and their carriers [prealbumin and retinol binding protein (vitamin A), and cholesterol and triglycerides (vitamin E)] were determined. Plasma levels of vitamin A were low in 5 patients, normal in 7 patients, and high in 33 patients. By correcting the values for the carrier levels, we created three groups: 24 patients showed low vitamin A/carrier complex (5 from the low plasma vitamin A group, 6 from the normal-value group, and 13 from the high-value group); 11 patients were in the group with normal vitamin A/carrier (1 from the normal plasma vitamin A group, and 10 from the high-value group); and 10 patients were in the group with high vitamin A/carrier. The vitamin A/carrier complex showed a statistically significant, negative linear correlation with CAS and with serum iron. Low vitamin E plasma levels were found in 1 patient, normal levels in 28 patients, and high levels in 16 patients. When those values were corrected using the carrier values, three groups were also created. The group with low vitamin E/carrier complex contained 24 patients (1 from the low-value group, 22 from the normal-value group, and 1 from the high-value group). The group with normal vitamin E/carrier complex contained 21 patients (15 from the group with high vitamin E values, and 6 from the normal-value group). By univariate logistic regression analysis, significant associations between CAS and vitamin E plasma levels, vitamin E/carrier, age, and serum albumin were found. In the multiple logistic regression analysis, we confirmed that vitamin E/carrier complex, age, and serum albumin showed independent associations with CAS, but not with vitamin-only plasma levels. Our results in PD patients show a vitamin/carrier complex disorder that results in elevated vitamin mobilization from pool and target cells. Our results and the findings of other researchers about intracellular vitamin A and E deficiencies may change the traditional concept of hypervitaminosis A and E in uremic patients.

Adult↗