[Changing the frequency of administration of darbepoetin alfa (from weekly to fortnightly) maintains the haemoglobin levels in patients undergoing peritoneal dialysis]. / El cambio en la frecuencia de administración de darbepoetin alfa (de semanal a quincenal) mantiene los niveles de hemoglobina en pacientes en diálisis peritoneal.

SUMMARY BACKGROUND: Less frequent dosing regimens during anemia treatment could benefit Peritoneal Dialysis (PD) patients. We investigated the effectiveness of darbepoetin alfa dosed every-other-week (Q2W) for maintaining hemoglobin (Hb) levels (11-13 g/dL). PATIENTS AND METHODS: One hundred and nine PD patients from 14 centers participated in an 8-month observational, prospective study. Patients (Hb 11-13 g/dL) receiving weekly (QW) darbepoetin alfa switched to Q2W dosing at the investigator's discretion. Doses were adjusted according to published guidelines. RESULTS: Sixty-nine percent (75 out of 109) of patients switched to Q2W dosing. Thirty-three percent maintained the g/week, equivalent to twice the previous mean weekly dose (26.1-25.8 g/week, QW dose). Forty-seven percent received a dose reduction (35.8-20.2 equivalent to the previous QW dose). More patients in the maintenance dose group 11 g/dL than those receiving a reduced weekly dose (80% vs. had Hb levels 51.4%, respectively, p = 0.0236). During the Q2W phase, the mean Hb level ranged from 12.0-12.5 g/dL for the maintenance dose group and 11.5-12.0 g/dL for the reduced dose group. From the switch to the end of the study, the mean (SD) change in Hb was -0.7 g/dL (0.98 g/dL, p = 0.0557) and -0.6 g/dL (1.6 g/dL, p = 0.1296) for the maintenance and reduced dose groups, respectively. The Q2W darbepoetin alfa was well tolerated. Only a single treatment-related adverse event (polycythemia) occurred. CONCLUSION: The majority of PD patients receiving QW darbepoetin alfa can be effectively switched to Q2W and still maintain their Hb level.

Epithelial-to-mesenchymal transition of mesothelial cells is an early event during peritoneal dialysis and is associated with high peritoneal transport.

Ultrafiltration (UF) failure is a consequence of long-term peritoneal dialysis (PD). Fibrosis, angiogenesis, and vasculopathy are causes of this functional disorder after 3-8 years on PD. Epithelial-to-mesenchymal transition (EMT) of mesothelial cell (MC) is a key process leading to peritoneal fibrosis with functional deterioration. Our purpose was to study the peritoneal anatomical changes during the first months on PD, and to correlate them with peritoneal functional parameters. We studied 35 stable PD patients for up to 2 years on PD, with a mean age of 45.3+/-14.5 years. Seventy-four percent of patients presented loss of the mesothelial layer, 46% fibrosis (>150 microm) and 17% in situ evidence of EMT (submesothelial cytokeratin staining), which increased over time. All patients with EMT showed myofibroblasts, while only 36% of patients without EMT had myofibroblasts. The number of peritoneal vessels did not vary when we compared different times on PD. Vasculopathy was present in 17% of the samples. Functional studies were used to define the peritoneal transport status. Patients in the highest quartile of mass transfer area coefficient of creatinine (Cr-MTAC) (>11.8 ml min(-1)) showed significantly higher EMT prevalence (P=0.016) but similar number of peritoneal vessels. In the multivariate analysis, the highest quartile of Cr-MTAC remained as an independent factor predicting the presence of EMT (odds ratio 12.4; confidence interval: 1.6-92; P=0.013) after adjusting for fibrosis (P=0.018). We concluded that, during the first 2 PD years, EMT of MCs is a frequent morphological change in the peritoneal membrane. High solute transport status is associated with its presence but not with increased number of peritoneal vessels.

[Theoretical bases for the proposal of a randomized, controlled, open label clinical trial to assess the efficacy of adding bemiparin to the icodextrin solution in patients on peritoneal dialysis with peritoneal transport disorders [FRIAT-BEM-2005-01]]. / Bases teóricas para la propuesta de un ensayo clínico aleatorizado, controlado y abierto, para evaluar la eficacia de la adición de bemiparina a la solución de icodextrina en pacientes en diálisis peritoneal con trastornos del transporte peritoneal [FRIAT-BEM-2005-01].

Multiple investigations performed on peritoneal pathophysiology during peritoneal dialysis (PD) suggest that intraperitoneal heparin might modify most of the causes of membrane deterioration. The actions described favouring this idea are: 1) Peritoneal Chronic inflammation alters peritoneal function and hepraine has anti-inflammatory properties. 2) Peritoneal fibrosis related to peritoneal dialysis or traumatic injury may be avoided or limited with heparin. 3) Heparine induces tPA synthesis by mesothelial cells, which represents a potentiation of fibrinolytic action. 4) Heparine, specifically low-molecular weight heparin, inhibits angiogenesis. 5) Intraperitoneal heparin favors the removal of advanced glycosilation end products in PD. 6) Animal models and clinical studies with small series of patients have demonstrated an improvement of peritoneal function with intraperitoneal heparine use. 7) Until now, no adverse effects of the intraperitoneal heparin use have been found. In consequence, it is a plausible hypothesis to consider that intraperitoneal heparin may favourably modify peritoneal function in patients under peritoneal dialysis.

[Renal infarction and acute renal failure induced by cocaine]. / Infarto renal e insuficiencia renal aguda por consumo de cocaína.

We describe the case of a 36 year old man, habitual consumer of cocaine, who after the inhaled cocaine consumption develops acute renal failure secondary to massive left and segmental right renal infarction. Although the most frequent complications associated to cocaine consumption are of cardiovascular and neurological nature, the kidney can be frequently affected.

[Monitoring on-line treated water and dialysate quality]. / Monitorización de la calidad del agua tratada <> y del líquido de diálisis (LD).

INTRODUCTION: On line-treated water has been designed to obtain ultrapure water. This quality of water is obviously necessary to obtain ultrapure dialysate, although this is not the only condition. To keep the quality of the process, is necessary the continuous monitoring of the water treatment, dialysate and haemodialysis machines. METHOD: After the installation of a water treatment with these characteristics, we developed a protocol to follow up its quality. The measures included in the protocol were: a) Microbiologic, endotoxin and chemical controls of the water on different stage: before and at the end of the treatment, pre-treatment and network of distribution. The chemical analysis included analytical and colorimetric measures. b) Control of specific mechanical functions of the facilities. c) Microbiologic and endotoxin analysis of the dialysate produced by haemodialysis machines. d) Control and maintenance of haemodialysis machines, according to the technical indications. RESULTS: We analyse the initial five years of water treatment with the aim to evaluate quality parameters and efficiency. We explain the reasons of the modifications introduced in the system. During this period we have not any episodes of global or partial contamination. We refer here some incidents related with the quality of raw water supply before the treatment, but in any case it was necessary neither to stop the water supply or to reduce the water quality. We observed a persistent contamination of one haemodialysis monitor due to the port used to get the samples. CONCLUSIONS: On line-treated water is at present the most appropriate system to obtain high quality water for haemodialysis. The process must be continuously monitored through specific protocols developed to evaluate the raw water's characteristics and the treated water.

Myofibroblastic differentiation in simple peritoneal sclerosis.

OBJECTIVE: To analyze the presence of myofibroblasts in a series of peritoneal dialysis (PD) patients with simple sclerosis and non-PD, uremic patients. Since there is a close correlation between active fibrosis and myofibroblastic differentiation we wanted to test if myofibroblasts are present in uremic, non-PD peritoneal samples. To determine if there are correlations between myofibroblastic presence and other functional and morphologic peritoneal parameters. METHODS: Biopsies were collected from three patient groups: 1) Normal control samples (n = 15) of parietal and visceral peritoneum 2) non-PD uremic patients (n = 16); and 3) uremic patients on PD (n = 32). Peritoneal morphologic and functional parameters and immunohistochemical expression of alfa-smooth muscle actin was analyzed in each case. Vascular endothelial growth factor (VEGF), bcl-2 anti-apoptotic protein, and progesterone receptor was evaluated in a subset of cases. RESULTS: Myofibroblasts were present in 56.3% of the patients with PD-related simple sclerosis. In most cases they were distributed in the upper submesothelial area. None of the biopsies from normal controls and uremic, non-PD patients showed myofibroblasts. Within the group of PD patients, myofibroblasts showed no correlation with time on dialysis, urea/creatinine MTAC, episodes of peritonitis, submesothelial thickening, hyalinizing vasculopathy or mesothelial status. In a subset of PD patients VEGF expression was observed in submesothelial fibroblastic cells. No expression of progesterone receptor or bcl-2 was observed. CONCLUSIONS: Myofibroblasts are a reliable and simple indicator of fibrosis since they appear in early stages of PD treatment and in patients with minor morphologic anomalies. They are not exclusive of patients with sclerosing peritonitis, ultrafiltration loss or long standing treatment. Their absence in non-PD, uremic patients suggest that uremia-related fibrosis takes place without a significant participation of myofibroblasts.

Effects of rapamycin on the epithelial-to-mesenchymal transition of human peritoneal mesothelial cells.

The preservation of the peritoneal membrane is crucial for long-term survival in peritoneal dialysis. Epithelial-to-mesenchymal transition (EMT) is a process demonstrated in mesothelial cells (MC), responsible for negative peritoneal changes and directly related to PD. EMT enables neovascularization and fibrogenic capabilities in MC. Vascular endothelial growth factor (VEGF) is the mediator for neo-vascularization. Rapamycin is a potent immunosuppressor with antifibrotic action in renal allografts and has a demonstrated anti-VEGF effect. We performed this study with the hypothesis that rapamycin may regulate the EMT of MC. MC from human omentum were cultured. When mesothelial cells reached confluence, some of them were stimulated with r-TGF-beta (1 ng/mL) to induce EMT, co-administered with rapamycin (0.2, 2, 4, 20 and 40 nM). Other groups of cells received similar doses of rapamycin or r-TGF-beta, separately. Cells were analyzed at 6, 24, 48 hours and 7 days. As markers of EMT we included alfa -SMA, E-cadherin and snail nuclear factor by quantitative RT-PCR. EMT markers and regulators demonstrated the following changes with rapamycin: E-cadherin (a protective gene for EMT) increased 2.5-fold relative to controls under 40 nM, at 24h. Importantly, rapamycin inhibited snail expression induced by TGF-beta at 6h, whereas TGF-beta increased snail 10-fold. At day 7, rapamycin showed no anti-EMT properties. An important decrease in alfa -SMA expression by MC after rapamycin addition was observed. In conclusion, rapamycin shows a mild protective effect on EMT, as it increases E-cadherin and decreases alfa -SMA expression. Consequently, rapamycin might partially regulate the epithelial-to-mesenchymal transition of mesothelial cells.

Vascular endothelial growth factor (VEGF) levels in peritoneal dialysis effluent.

BACKGROUND: Long-term peritoneal dialysis (PD) patients who develop peritoneal ultrafiltration failure have an abnormally large number of capillaries and sclerotic changes in peritoneal biopsy. Peritoneal vascular endothelial growth factor (VEGF) production has been suggested to explain the higher levels in peritoneal effluent than in plasma. The high effluent VEGF levels have been related to peritoneal changes consisting of increased permeability to small molecules. To further analyze the relationship between peritoneal neoangiogenesis induced by VEGF and peritoneal transport, we studied peritoneal effluent VEGF levels in active PD patients. METHODS: VEGF levels were determined in serum and plasma, and in peritoneal effluent (PE) after 4, 8 and 15 h dwell times. RESULTS: PE VEGF levels were 58.6+/-33.7 pg/mL, with a mean VEGF D/P ratio of 0.45+/-0.29 (range 0.06-0.93). In low-transport patients (n = 7) this ratio did not differ from high-average ones (n=5) (0.48+/-0.3 and 0.41+/-0.1, NS). In multivariate analysis, the VEGF D/P ratio showed no correlation with the independent variables included in this study. VEGF levels were higher in 15 h than in 8 h effluent; so the VEGF D/P ratios were higher as well. Regression analysis showed a direct correlation between PEVEGF levels and dwell time (r: 0.57, p = 0.03), but not between VEGF D/P ratio and dwell time. PEVEGF levels directly correlated with effluent protein content. Regression analysis showed no correlation between PEVEGF levels and age, time on PD, days of peritonitis, urea and creatinine-mass transfer coefficients, ultrafiltration capacity, and accumulated glucose dose. Multivariate regression analysis showed correlation only between PEVEGF levels and dwell time, but not with the other independent variables. CONCLUSIONS: This study confirms that VEGF is present in fresh PE from PD patients at levels that suggest local production and filtration from plasma. Peritoneal effluent VEGF levels are not significantly associated with peritoneal functional parameters and background, and seem to be influenced by ultrafiltration in a dilution process. We believe that the role of VEGF in peritoneal pathophysiology is part of a complex relationship involving multiple peritoneal structures and other growth factors, including local counteracting factors for VEGF that regulate neoangiogenesis.

Prevalence of TT virus in serum and peripheral mononuclear cells from a CAPD population.

BACKGROUND: A novel virus named TT virus (TTV) has been isolated recently from patients with posttransfusional hepatitis of unknown etiology. The prevalence of TTV in several groups at risk has been reported, however, there is no information about the prevalence of TTV in patients on continuous ambulatory peritoneal dialysis (CAPD) without blood transfusions or hemodialysis antecedents. OBJECTIVE: To study the incidence of TTV in serum and peripheral blood mononuclear cells (PBMC) of CAPD patients. DESIGN: TTV DNA was detected by polymerase chain reaction, using primers from the open reading frames (ORF) 1 and 2, in serum and PBMC from 22 CAPD patients who had not received blood transfusions or hemodialysis therapy prior to CAPD. As controls, sera from 20 patients with chronic viral hepatitis (10 with HBV and 10 with HCV) and 20 healthy donors were included in the study. RESULTS: TTV DNA was detected in the serum of 5 of 22 (22.7%) CAPD patients with both sets of primers. Four of the 5 (80%) patients with TTV DNA in their serum were TTV positive in their PBMC with primers from ORF1 and ORF2. Five of 20 (25%) patients with chronic viral hepatitis (2 patients with HBV and 3 with HCV) and 4 of 20 (20%) healthy donors were TTV DNA positive in serum. No relation was found between TTV infection and the underlying kidney disease, previous surgery, and abnormal alanine aminotransferase levels. CONCLUSION: We have found a relatively high prevalence of TTV that is similar to that found in healthy donors and in patients with chronic viral hepatitis.

Risk factors responsible for ultrafiltration failure in early stages of peritoneal dialysis.

OBJECTIVE: To define risk factors for ultrafiltration failure (UFF) during early stages of peritoneal dialysis (PD). DESIGN: Retrospective analysis of a group of patients whose peritoneal function was prospectively followed. SETTING: A tertiary-care public university hospital. PATIENTS: Nineteen of 90 long-term PD patients required a peritoneal resting period to recover UF capacity: 8 had this requirement before the third year on PD (early, EUFF group) and 11 had a late requirement (LUFF group). The remaining 71 patients, those with stable peritoneal function over time, constituted the control group. MAIN OUTCOME MEASURES: Peritoneal UF capacity under standard conditions (monthly) and small solute peritoneal transport (yearly). RESULTS: None of the conditions appearing at the start of PD or during the observation period could be definitely identified as the cause of UFF. There were no differences in characteristics between the EUFF group and the other two groups, except for the higher prevalence of diabetes in the EUFF group. Residual renal function (RRF) declined in all three groups during the first 2 years, with rapid loss during the third year in the EUFF group. This rapid loss in RRF was coincident with UFF. Peritoneal solute and water transport at baseline was similar in the three groups. After 2 years on PD, individuals in the EUFF group showed a significantly lower UF and higher creatinine mass transfer coefficient values than those in the LUFF group. Diabetic patients in the control group showed remarkable stability in UF capacity over time. During the second year on PD, requirement for increases in dialysate glucose concentration was 3.4 +/- 0.5% in the LUFF group, but as high as 25.5 +/- 24.2% in the EUFF group. The accumulated days of active peritonitis (APID, days with cloudy effluent) were similar for the three groups after 1, 2, and 3 years on PD. Interestingly, diabetic patients in the control group showed an APID index significantly lower than the overall EUFF group. Diabetics in the control group also had significantly lower APID versus nondiabetics in the control group (p = 0.016). CONCLUSIONS: Our findings suggest that certain patients develop early UFF type I. Diabetic state and a higher glucose requirement to obtain adequate UF suggest that glucose on both sides of the peritoneal membrane could be responsible. The mechanisms for this higher requirement remain to be elucidated. The identification of a larger cohort of these early UFF patients should lead to a better exploration of the primary pathogenic mechanisms.

Icodextrin effluent leads to a greater proliferation than glucose effluent of human mesothelial cells studied ex vivo.

OBJECTIVE: To compare the effect of glucose (Glu) and icodextrin (Ico) dialysate on in vitro culture of mesothelial cells (MC) from peritoneal dialysis (PD) patients. DESIGN: Prospective, controlled comparative study on the effects of two PD solutions. SETTING: A tertiary-care public university hospital. PATIENTS: Sixteen PD patients regularly using Glu dialysate were asked to collect an 8-hour dwell peritoneal effluent on 2 different days, with an interval shorter than 7 days. In the first collection, 2.27% Glu solution and in the last, 7.5% Ico solution was infused. Human MC were isolated from the nocturnal peritoneal effluent bags and grown ex vivo. MAIN OUTCOME MEASURES: Mesothelial cell proliferative capacity ex vivo. RESULTS: Mesothelial cells were present in all patient dialysates except that of a single patient's Glu dialysate. The number of MC drained was similar with both solutions. After the initial culture reached confluence, MC were identified in 14 and 12 patients receiving Ico and Glu, respectively. However, in 1 patient using Ico and in 2 using Glu, the MC count at this stage was so low that further subculture could not be performed. Cells from Ico-derived solutions exhibited a higher degree of proliferation than cells from Glu-derived solutions. The morphology of MC was also different. Cells from drained effluent were typical in 11 patients using Glu solution in contrast with 14 patients using Ico. At confluence, the percentages of typical appearance were 50% and 92.9% (p < 0.05) in Glu and Ico respectively. CONCLUSIONS: Mesothelial cells taken from icodextrin effluent show a greater proliferation ex vivo than those taken from glucose effluent.

Helicobacter pylori infection: a new cause of anorexia in peritoneal dialysis patients.

OBJECTIVE: Helicobacter pylori (HP) infection has frequently been found in dialysis patients. Chronic infections induce overproduction of pro-inflammatory substances. Inflammation has been associated with cachexia and anorexia. We explored the relationship between HP infection, anorexia, and malnutrition in peritoneal dialysis (PD) patients. PATIENTS AND METHODS: The study included 48 clinically stable PD patients divided into four groups: HP+ with anorexia (group I, n = 12); HP+ without anorexia (group II, n = 4); HP- with anorexia (group III, n = 5); and HP- without anorexia (group IV, n = 27). Infection with HP was diagnosed by breath test. Anorexia was evaluated using a personal interview and an eating motivation scale (VAS). The VAS included five questions that are answered before and after eating. The questions concern desire to eat, hunger, feeling of fullness, prospective consumption, and palatability. Biochemical markers of nutrition and inflammation were also determined. RESULTS: At baseline, group I showed lower scores for desire to eat, hunger sensation, prospective consumption, and palatability. They also showed lower lymphocyte counts, prealbumin, transferrin, serum albumin, normalized equivalent of protein-nitrogen appearance (nPNA), and residual renal function (RRF). In addition, the same group showed higher levels of C-reactive protein (CRP) and more sensation of fullness than the remaining groups. In the entire series, we found significant linear correlations between the following markers of nutrition and certain questions on the VAS: albumin with before-lunch desire to eat (r = 0.38, p < 0.05), and prealbumin with before-lunch hunger (r = 0.41, p < 0.05) and after-lunch hunger (r = -0.35, p < 0.05). Negative linear correlations were found between albumin and fullness before lunch (r = -0.45, p < 0.01), and between prealbumin and before-lunch desire to eat (r = -0.39, p < 0.05). Negative linear correlations were also seen between CRP and albumin (r = -0.35, p < 0.05) and between CRP and prealbumin (r = -0.36, p < 0.05). Similarly, CRP showed a negative correlation with before-lunch desire to eat (r = -0.38, p < 0.05) and afterlunch desire to eat (r = -0.45, p < 0.01). After HP eradication, group I showed a significant increase in markers of nutrition and in VAS scores for almost all questions. Simultaneously, they showed a decrease in CRP level. Significant differences were also found in lymphocyte count (1105 +/- 259.4 cells/mm3 vs 1330.8 +/- 316 cells/mm3, p < 0.05), nPNA (0.9 +/- 0.16 g/kg/day vs 1.07 +/- 0.3 g/kg/day, p < 0.05), prealbumin (26.7 +/- 6.5 mg/dL vs 33.9 +/- 56.6 mg/dL, p < 0.01), albumin (3.48 +/- 0.3 g/dL vs 3.67 +/- 0.35 g/dL, p < 0.05), CRP (1.16 +/- 1.14 mg/dL vs 0.88 +/- 1.2 mg/dL, p < 0.054), before-lunch desire to eat (56.6 +/- 6.8 vs 72.2 +/- 4, p < 0.001), after-lunch desire to eat (5.4 +/- 2.6 vs 12.3 +/- 2, p < 0.01), hunger before lunch (55.4 +/- 5.4 vs 73.1 +/- 4.6, p < 0.001), hunger after lunch (5.8 +/- 2.9 vs 11 +/- 4, p < 0.01), fullness before lunch (36.6 +/- 10.3 vs 18.7 +/- 8.8, p < 0.001), consumption after lunch (5 +/- 4.7 vs 17.5 +/- 18, p < 0.05), and palatability (61 +/- 5.3 vs 74.1 +/- 4.1, p < 0.001). CONCLUSION: Infection with HP is associated with anorexia, inflammation, and malnutrition in PD patients. Eradication of HP significantly improves this syndrome. Residual renal function seem to have a protective effect on appetite preservation. The present study supports the hypothesis of the involvement of inflammation in the pathogenesis of malnutrition in PD patients.

Peritoneal kinetics of cancer antigen 125 in peritoneal dialysis patients: the relationship with peritoneal outcome.

Cancer antigen 125 (CA125) is a mesothelial product that has been directly related with mesothelial bulk in peritoneal dialysis (PD) patients. Here, we evaluate CA125 levels in peritoneal effluent over time on PD, and relate them to changes in peritoneal function. We analyzed 27 peritoneal kinetic studies in 20 stable PD patients. Three patients dropped out of PD for peritoneal membrane failure after the last kinetic study, and six patients required a peritoneal rest period as treatment for membrane failure type I. We recorded the standardized daily ultrafiltration capacity, net ultrafiltration during the kinetic study, peritoneal mass transfer coefficients, time from onset of PD, and incidence of peritonitis prior to the study. A linear increase in CA125 levels over time was observed, and a strong correlation appears among the levels at different dwell times (r: 0.85-0.98, p < 0.05). At 180 minutes, the mean CA125 concentration was 48.5 +/- 39.7 U/mL. We observed significant differences in CA125 levels in effluent between the group of patients who later required a peritoneal rest period and the group of stable patients (27.7 +/- 26.3 U/mL vs 55.7 +/- 41.5 U/mL respectively, p < 0.05). Patients who left PD showed lower CA125 levels in effluent (31.4 +/- 30.6 U/mL vs 52.3 +/- 41.1 U/mL, p < 0.1). No correlation was seen between CA125 levels in effluent and time on PD, episodes of peritonitis, accumulated days of peritoneal inflammation, ultrafiltration capacity, or urea and creatinine mass transfer coefficients (MTCs). In conclusion, we believe that serial determinations of peritoneal effluent CA125 levels may help in the early identification of patients who show abnormal responses to peritoneal dialysis or its complications.

Effect of bicarbonate/lactate peritoneal dialysis solutions on human mesothelial cell proliferation ex vivo.

Peritoneal membrane suffers structural and functional changes over time on peritoneal dialysis (PD)--in part, owing to the dialysis solutions currently used. Low pH seems to be an important element associated with solution bioincompatibility. Bicarbonate-containing fluids open new perspectives on this issue. The present study compared the effects of bicarbonate/lactate (Bic/Lac) solution (25 mmol/L bicarbonate, 15 mmol/L lactate) and lactate (Lac) solution (40 mmol/L lactate) on mesothelial cell (MC) growth in culture. Eight stable PD patients were asked to collect peritoneal effluent from an 8-hour dwell on two separate days, within an interval shorter than one week. For the first dwell, Lac solution was infused; for the second dwell, Bic/Lac solution was instilled. Human MCs were isolated from the effluent, seeded in 25-cm2 tissue culture flasks, and grown ex vivo. Morphology of the cells was also evaluated. In all effluents, MCs were present in mean amounts of 26,939 +/- 21,267 cells (Bic/Lac) and 25,986 +/- 15,286 cells [Lac, p = nonsignificant (NS)]. Morphology of the MCs was similar with both solutions (87.5% typical). After initial culture, MCs from 6 patients using Bic/Lac (75%) and 3 patients using Lac (37.5%) reached confluence. At this time, the number of MCs from the 3 patients who showed MC growth with both solutions was slightly higher with Bic/Lac-buffered fluid (Lac: 1,154,125 +/- 213,333 cells; Bic/Lac: 1,198,291 +/- 806,713 cells). To summarize: 3 patients showed MC growth under both solutions; 3 patients showed MC growth only under Bic/Lac solution; and 2 patients showed no MC growth at all. After cells were seeded in 24-well plates, the MC growth curve was performed in 4 cases of Bic/Lac solution use and in 3 cases of Lac solution use. Although no significant differences were observed between the solutions, the final number of MCs obtained was higher with Bic/Lac solution use. In conclusion, MCs released into peritoneal effluent under bicarbonate/lactate-buffered peritoneal dialysis solution are associated with a greater ex vivo proliferation capacity than those released under lactate solution in the same patient. This finding may demonstrate better biocompatibility for Bic/Lac solution.

[Influence of different pharmacological agents in the ex vivo proliferation of mesothelial cells obtained from the peritoneal effluent of patients treated with peritoneal dialysis]. / Influencia de factores exógenos en la capacidad de proliferación ex vivo de las células mesoteliales obtenidas de efluente de pacientes tratados con diálisis peritoneal crónica.

UNLABELLED: Mesothelial cells (MC) are the first peritoneal membrane barrier in contact with dialysate. The aim of this study was to analyze the in vitro capacity of different pharmacological agents to modify the ex vivo proliferation of MC obtained from the peritoneal effluent of patients treated with peritoneal dialysis (PD). MATERIAL AND METHODS: Thirty cultures of MC taken from nocturnal peritoneal effluent were performed. After identification, MC are subcultured in 24 multi-well plates, adding the different exogenous agents. Proliferative capacity and cell morphology were estimated on day 16th of culture. The agents evaluated were insulin, IGF-1, tamoxifen, labetalol, carvedilol, enalapril and losartan. RESULTS: Insulin shows a dose-dependent effect on MC growth, with a limit that is stimulated by the addition of fetal bovine serum (FBS). Concentrations higher than 100 micrograms/ml, are not associated with further growth, even with cell damage. In contrast, the wide range of IGF-1 dose used did not affect to MC proliferation. Tamoxifen causes negative effects on MC growth just a very high doses, not resembling doses in clinical practice. Labetalol does not modify MC proliferation used under therapeutic calculated range. However, concentrations higher than 40 micrograms/ml showed a negative influence on growth, behaving as lethal doses that over 100 micrograms/ml. The addition of FBS attenuates this effect. These effects were very similar to that caused by carvedilol addition. Enalapril and losartan act as antiproliferative agents for MC. This effect is potentiated with angiotensin II, reaching lethal concentrations increasing the dose. In conclusion, mesothelial cell growth ex vivo taken from nocturnal peritoneal effluent on PD patients is an useful tool to explore the effects of any pharmacological agent on the biology of the cell of the peritoneum. The agents used had any influence in the proliferation capacity of mesothelial cells.

Comparisons of hemodialysis and CAPD in patients over 65 years of age: a meta-analysis.

This meta-analysis had the aim of studying the available studies on comparison between Hemodialysis and Peritoneal Dialysis in the elderly. The final objective was to reach, if possible, evidence for potential differences. In the case that no differences could be demonstrated, contribute to accept that HD and PD are similar techniques to be offered to elderly people requiring dialysis. The question formulated was this: Do we have adequately contrasted data on results for survival, hospitalization rate, quality of life and morbidity on hemodialysis and peritoneal dialysis in the elderly (more than 65 years old)? As data sources we selected eight papers that compared the general results of these two dialysis techniques. Different elements were considered in this selection because none reached the two first levels in the hierarchy of sources of evidence, and only two reached the third level--that of prospective studies; this is because an oral presentation of data has been included in a meta-analysis. Another four papers--uni- or multicenter retrospective studies compared the results obtained with PD and HD. The remaining two papers--reports from nationwide registries that compare of mortality rates, adjusted for co-morbid conditions and age, present specific results on groups of elderly patients. Three papers compare particular aspects of the two techniques, including nutritional status, psychiatric and psychosocial aspects and rehabilitation, in this case comparing PD with home hemodialysis patients. Finally, we have included the opinions of healthy elderly people on dialysis issues. This meta-analysis of these different studies suggests that the mortality and hospitalization rate of elderly people treated by PD is similar to that of similar people treated by HD. In consequence, we have no reasons to select either therapy on behalf of the patient. The nephrologist should consider and inform the patient and family about the relative advantages and disadvantages of both techniques and tailor dialysis technique choice to the specific individual to assure the best results. Local circumstances should also be considered.