Exploring the opinion of CKD patients on dialysis regarding end-of-life and Advance Care Planning.

Advance care planning (ACP) and the subsequent advance directive document (ADD), previously known as "living wills", have not been widely used in Spain. The Ethics Group from the Spanish Society of Nephrology has developed a survey in order to investigate the opinion of dialysis patients regarding the ADD and end-of-life care. Patients received documentation explaining ACP and filled out a survey about their familiarity with and approval of the ADD. Seven hospital dialysis centres participated in the study for a total of 416 active dialysis patients. Questionnaires were distributed to 263 patients, 154 of which answered (69.2% completed them without assistance). The rates for ADD implementation (7.9%) and designation of a representative person (6.6%) were very low. Most of the patients clearly expressed their wishes about irreversible coma, vegetative state, dementia and untreatable disease. More than 65% did not want mechanical ventilation, chronic dialysis, tube feeding or resuscitation if cardiorespiratory arrest occurred. They reported that an ADD could be done before starting dialysis but most thought that it should be offered only to those who requested it (65% vs 34%). In conclusion, patients have clear wishes about end-of-life care, although these desires had not been documented due to the very low implementation of the ADD.

[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.

[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.

[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.

[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.

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.

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.

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.

[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.

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.