Biomedical subjects

Rafael Selgas

Publications and source records attributed to Rafael Selgas.

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

Inherent high peritoneal transport and ultrafiltration deficiency: their mid-term clinical relevance.

BACKGROUND: High peritoneal transport has been associated with poorer outcome in peritoneal dialysis (PD) patients, but not necessarily because of PD-dependent conditions. Our primary objective was to analyse the influences of baseline peritoneal small solute transport and ultrafiltration (UF) capacity on patient and technique survival, after adjusting for comorbid conditions. A secondary objective was to determine whether high transport was associated with basal comorbidity. METHODS: In this prospective observational patient/technique survival study, we followed 410 patients who started PD. At the baseline, we collected data to define comorbidities, tally the Charlson index, determine the baseline mass transfer area coefficients (MTAC) of urea and creatinine, net UF, plasma albumin and residual renal function (RRF). No data other than the information on patient and technique survival were recorded after baseline. RESULTS: The mean follow-up was 33 +/- 28 months. Dropouts during the study were due to renal transplantation in 140 cases, death in 142 cases and transfer to haemodialysis (HD) in 77 cases. Patients with inherent UF deficiency, high transport rate or both were not significantly different in the survival analysis from the rest. In the Cox hazards analysis, only age, Charlson index and a lower RRF were the significant mortality risk factors. None of the baseline parameters studied was a predictor of technique failure. High transporter patients had lower plasma albumin and UF capacity, comorbidity and more frequent liver diseases than the rest. Moderate to severe liver disease (n = 14) was significantly associated with the inherent high transport status, but was never accompanied by UF failure (UFF). UFF patients showed higher RRF, creatinine-MTAC and age. CONCLUSIONS: Neither the high transport nor the inherent UFF status has any influence on patient and technique survival. The inherent high small solute transport status is associated with hypoalbuminaemia and a greater comorbidity index. The Charlson index, age and lower RRF are the only independent predictors of mortality. Technique dropout is not predicted by any of the variables studied at the baseline.

Aged↗

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↗

PubMed2006

Mast cell quantification in normal peritoneum and during peritoneal dialysis treatment.

CONTEXT: Mast cells (MCs) have been implicated in fibrogenesis, angiogenesis, and immunity against bacteria. These 3 mechanisms participate in the peritoneal pathology secondary to peritoneal dialysis (PD) treatment. Despite their potential relevance to PD-related pathology, few studies have focused on MCs. OBJECTIVE: To evaluate possible variations in the number of MCs during PD treatment. DESIGN: A quantitative study of tissue MCs in normal and pathologic peritoneum. Parietal peritoneal biopsies were collected from 4 groups: (1) normal controls (n = 9), (2) uremic non-PD patients (n = 16), (3) uremic patients on PD (n = 26), and (4) non-renal patients with inguinal hernia (n = 20). MCs were evaluated using immunohistochemistry for the detection of tryptase. The total number of cross sections of vessels per peritoneal field was examined in 22 of the 26 peritoneal biopsies of PD patients. RESULTS: PD tissue samples showed fibrosis, mesothelial cell loss, and variable hyalinizing vasculopathy. The number of MCs was similar in normal controls and non-PD uremic patients (mean +/- SE: 7.13 +/- 0.67 and 7.74 +/- 0.74 MCs/mm2, respectively). Peritoneal dialysis patients showed a reduction (4 +/- 0.38 MCs/mm2, P < .001), whereas hernia sac samples showed an increase (10.59 +/- 3.48 MCs/mm2). MC reduction showed no correlation with time on dialysis, fibrosis, number of vessels, or previous episodes of peritonitis. CONCLUSIONS: The peritoneum of patients receiving PD treatment shows a reduction of MCs. Despite such a reduction, fibrosis takes place, suggesting that MCs do not play a critical role in fibrosis genesis. Mast cell loss may be a contributory factor to peritonitis episodes in PD patients.

Adult↗

PubMed2006

Peritoneal transport in peritoneal dialysis patients is not affected by transitorily successful renal transplantation.

Patients returning to peritoneal dialysis (PD) from failed renal transplantation are recognized to be inflamed, and this situation might produce a high peritoneal solute transport status. We wanted to determine if a period of time with a kidney allograft induces a change in peritoneal function. We studied 19 PD patients who had been living with a graft for a mean of 47 +/- 39 months. We studied their peritoneal function upon starting PD (baseline), immediately before transplantation (pre-Tx), and after returning to PD when the graft failed (post-Tx). We analyzed the peritoneal mass transfer coefficients for urea (U-MTAC) and creatinine (Cr-MTAC), the dialysate-to-plasma ratio of creatinine (D/P-Cr), and net ultrafiltration (UF). We observed no significant differences in the various variables pre-Tx and post-Tx. The U-MTAC post-Tx was significantly lower than at PD baseline (25.9 +/- 8 mL/min vs. 20.2 +/- 5 mL/min, p = 0.03). The U-MTAC and Cr-MTAC post-Tx were not correlated with months on a graft or with MTAC values at baseline. In inherent high transporters (Cr-MTAC > or = 11.5 mL/min at baseline, n = 8), we observed a significant reduction in Cr-MTAC post-Tx (15.2 +/- 2 mL/min vs. 10.2 +/- 4 mL/min, p = 0.03). Three of these patients remained high transporters post-Tx. We conclude that peritoneal function upon reinitiating PD after transplantation is similar to function in the pre-transplantation phase; and that a high peritoneal transport status is more prevalent at first initiation onto PD than at return after transplantation, suggesting that inherently high transport is almost exclusively a feature of an intact, predialysis peritoneum.

Adult↗

PubMed2006

Risk of technique failure and death in fungal peritonitis is determined mainly by duration on peritoneal dialysis: single-center experience of 24 years.

Fungal peritonitis (FP) is an infrequent cause of peritonitis in peritoneal dialysis (PD), but it has high morbidity and mortality. We analyzed the experience with FP in a single PD unit over a 24-year period. We identified 671 episodes of peritonitis that occurred in 496 patients during the study period. Of these episodes, 23 (3.4%) were FP episodes occurring in 21 patients. In the FP episodes, the patients' mean time on PD was 29.2 +/- 27 months. In 5 episodes, the patients had experienced a peritonitis episode within the preceding month, and in 11 episodes, the patients had used antibiotics within the preceding month. The FP diagnosis was made a mean of 3.17 +/- 3 days after the diagnosis of peritonitis, and in 1 patient, the diagnosis was made after death. Candida spp. were isolated in 82.6% of patients. In 91.3%, the peritoneal catheter was removed. After the FP diagnosis, 15 patients dropped out of PD, but in only 8 patients (34.7%) was drop-out related to FP. In 4 patients, drop-out occurred because of peritoneal membrane failure, and 4 patients (17.4%) died. Time on PD was significantly higher in the group of patients that dropped out of PD because of the FP (45.7 +/- 31 months vs. 19 +/- 18 months, p = 0.02). Fungal peritonitis is a rare cause of peritonitis in PD patients, but it is associated with high morbidity and mortality. Longer time on PD is the main factor in technique failure and mortality.

Antifungal Agents↗

PubMed2006

Serum albumin levels, an additional factor implicated in hyperparathyroidism outcome in peritoneal dialysis: a prospective study with paired bone biopsies.

Renal osteodystrophy encompasses several histologic subtypes, all of which can undergo change over time. In peritoneal dialysis (PD) patients, we studied bone histology and the factors influencing any changes over 1 year In 44 PD patients, we collected two paired bone biopsies (at baseline and after 12 months) and biochemical and treatment data (at baseline and every 3 months). Of the 44 original patients, 24 completed the study. Of these 24 patients, 19 were initially diagnosed with adynamic bone lesion (ABL). After 1 year, 12 still had ABL; the other 7 had changed to high turnover bone lesion (HTBL). Another 5 patients were initially diagnosed with HTBL. Among these, 4 still had HTBL at 1 year; 1 had changed to ABL. In patients who changed to HTBL from ABL, serum albumin had increased to 4.2 +/- 0.3 g/dL at month 12 from 3.7 +/- 0.4 g/dL at baseline (p < 0.05). In patients who still had ABL, serum albumin did not change. Additionally, the percentage increase in serum albumin over the study was higher in HTBL patients than in ABL patients (0.1408 +/- 0.139 g/dL vs. -0.0076 +/- 0.113 g/dL, p = 0.009). A lower likelihood of diabetes (p = 0.033) and a higher serum albumin [area under the curve: 0.822; 95% confidence interval (CI): 0.651 to 0.993] identified a HTBL diagnosis at 12 months. Older age increased the probability of changing to ABL (OR: 1.2935; 95% CI: 1.03 to 1.67; p= 0.02). Bone lesions can change over time, and this change is associated with age, diabetes, and serum albumin. A change to HTBL was associated with improvement in serum albumin. Protein status is possibly a factor influencing bone lesion outcome.

Biopsy, Needle↗

PubMed2005

Factors influencing peritoneal transport parameters during the first year on peritoneal dialysis: peritonitis is the main factor.

BACKGROUND: Studies on the evolution of peritoneal transport during the first year of peritoneal dialysis (PD) are scarce and their results are contradictory. The aim of the present study was to analyse the evolution of peritoneal transport and residual renal function during the first year on PD, and to determine the factors that may influence them. METHODS: We studied 249 patients on continuous ambulatory PD with glucose exchange solutions (117 men, 132 women, mean age 51.9+/-16 years) 59 of whom had diabetes (25 type I). At baseline and after 1 year, we determined the mass transfer coefficients of urea (U-MTAC) and creatinine (Cr-MTAC), net ultrafiltration and residual renal function. RESULTS: Residual renal function decreased significantly during the first year (from 3.9+/-2.8 to 2.4+/-2.2 ml/min, P<0.001). Both U-MTAC and Cr-MTAC decreased after 1 year [U-MTAC from 22.7+/-7.8 to 20.7+/-6.6 ml/min (P<0.001), Cr-MTAC from 10.5+/-5.3 to 10.1+/-4.6 ml/min (NS)]. The ultrafiltration capacity increased significantly (from 923+/-359 to 987 U 341 ml/4 h, P<0.001). The evolution of MTAC values was independent of age, sex, diabetes and amount of hypertonic glucose used. When patients were grouped according to their initial Cr-MTAC, we observed a tendency toward normalization of the parameters of peritoneal function. Patients with peritonitis (n = 88) showed a first year increase in Cr-MTAC, which was significantly higher than in patients without peritonitis (11.1+/-5 vs 9.5+/-4.2, P<0.01). Ultrafiltration decreased in patients with more than four accumulated days of peritonitis (from 1062+/-447 to 1024+/-340 ml/4 h, NS); it increased in patients without peritonitis. CONCLUSIONS: The peritoneal transport parameters tended toward normalization during the first year on PD, mainly with a decrease of small solute transport and an increase of ultrafiltration capacity. This evolution is independent of age, gender, diabetes and higher exposure to glucose in PD solutions. Peritonitis was the only independent factor that affected peritoneal function during the first year on peritoneal dialysis.

Adolescent↗

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