Peritoneal dialysis and kidney transplant. A two-way ticket in an integrated renal replacement therapy model.

BACKGROUND: Peritoneal dialysis (PD) seems to be a good option to initiate renal replacement therapy (RRT), but patients with graft failure choose PD less frequently than incident patients (de novo). OBJECTIVE: To describe patient movements between PD and kidney transplantation (TX) and risk factors for failure of the PD technique. METHOD: Multicentre observational study of patients starting PD between 2003 and 2009 with follow-up up until January 2010. Survival analysis based on switching from PD to HD as an event using Kaplan-Meier (KM) and forward, stepwise Cox proportional hazards models. Hazard ratio and 95% confidence intervals (HR [CI]) are shown. MAIN VARIABLE: Switch from PD to HD. Two-group comparison: PD post transplant (post-TX) patients (76) compared to pure incident PD (de novo-PD) patients (830). PATIENTS: 906 PD patients from 19 public hospitals with a mean age of 54.8 years (64.9% male); main ESRD aetiology: glomerulonephritis (25.4%), diabetes (16.7%), vascular-ischaemic (10.7%), interstitial (13.6%) and polycystic (11.2%). Comorbidity conditions: Charlson Index 5.1 (SD 2.4); 21.6% diabetes mellitus (DM), 24.0% cardiovascular (CV) events. RESULTS: Mean follow-up period on PD: 1.85 years (95% CI [1.68-2.02 years]). KM estimation for switching to HD due to PD failure was 5.46 years [4.42-6.50 years]. At the end of follow-up, 88 patients had died, 154 had been transferred to HD and 306 had received a graft (annual rate for patients on waiting list: 0.49 TX per year on PD). The best Cox multivariate model for switching from PD to HD includes: post-TX (HR: 1.63 [1.01-2.63]), DM (HR: 1.69 [1.19-2.40]) and age (1.01 [1.00-1.02]) per year. Post-TX patients were younger (43.8 years vs 55.3 years) and with less comorbidity conditions than de novo-PD patients (DM 18.4% vs 21.9%; CV 15.8% vs 24.7%). However post-TX patients had worse clinical evolution with a rapid decline of renal function (∆-3.88 vs -1.8 ml/min per year); a higher admission rate (0.9 vs 0.62 per year) but similar peritonitis rate (0.45 vs 0.53 episodes per year). They also needed to be transferred to HD more frequently (28.9% vs 15.8%; P<.006) and needed more time to TX (4.8 years vs 1.7 years, Kaplan-Meier). Consequently, time spent on PD was higher in the post-TX group (2.8 vs 1.8 year). LIMITATIONS: Observational study with absence of a standard protocol to switch PD-HD. CONCLUSION: PD seems to be a good first choice technique due to low mortality and high TX ratio in our area. A previous graft failure is associated with a higher rate of PD-failure but time spent on PD is enough to consider this technique as a good option.

Impact of an interdisciplinary training course on counselling and decision making support for nephrology department professionals.

A 12-hour training program was delivered to the professionals of a nephrology department. Contents of the course were about difficult communication skills in health care interactions. Counselling was the relational methodology instructed. The objective was to assess changes in attitudes in relation with bioethics principles and knowledge. Variables were measured before and after the training program. Sample was composed by 76 professionals (57% nurses, 26% auxiliary nurses y 17% nephrologists) for knowledge and 27 professionals for variable attitudes. Considering the total sample, results show changes in implication with bioethics principles (p <0.05) and knowledge (p <0.001). There are differences related to the kind of profession. Nurses benefit more from the training program attending in the variable knowledge (p <0.001).

[Approach to quality objectives in incidents of patients in peritoneal dialysis]. / Cumplimiento de objetivos de calidad y evolución de los pacientes incidentes en diálisis peritoneal.

INTRODUCTION: In 2007 the Scientific Quality-technical and Improvement of Quality in Peritoneal Dialysis was edited. It includes several quality indicators. As far as we know, only some groups of work had evaluated these indicators, with inconclusive results. AIM: To study the evolution and impact of guidelines in Peritoneal Dialysis. METHODS: Prospective cohort study of each incident of patients in Peritoneal Dialysis, in a regional public health care system (2003-2006). We prospectively collected baseline clinical and analytical data, technical efficacy, cardiovascular risk, events and deaths, hospital admissions and also prescription data was collected every 6 months. RESULTS: Over a period of 3 years, 490 patients (53.58 years of age; 61.6% males.) Causes of ERC: glomerular 25.5%, diabetes 16%, vascular 12.4%, and interstitial 13.3%. 26.48% were on the list for transplant. Dialysis efficacy: Of the first available results, the residual renal function was 6.37 ml/min, achieving 67.6% of all the objectives K/DOQI. 38.6% remained within the range during the entire first year. Anaemia: 79.3% received erythropoietic stimulating agents and maintained an average Hb of 12.1 g/dl. The percentage of patients in the range (Hb: 11-13 g/dl) improved after a year (58.4% vs 56.3% keeping in the range during this time of 25.6%). Evolution: it has been estimated that per patient-year the risk of: 1) mortality is 0.06 IC 95% [0.04-0.08]; 2) admissions 0.65 [0.58-0.72]; 3) peritoneal infections 0.5 [0.44-0.56]. CONCLUSION: Diabetes Mellitus patients had a higher cardiovascular risk and prevalence of events. The degrees of control during the follow-up in many topics of peritoneal dialysis improve each year; however they are far from the recommended guidelines, especially if they are evaluated throughout the whole study.

[Incorporation of a psychologist into a nephrology service: criteria and process]. / Incorporación de un psicólogo en un servicio de nefrología: criterios y proceso.

Chronic kidney disease is associated with a wide range of stressful situations causing important physical and psychological repercussions. It is not usual that psychology professionals are active members of the nephrology teams. In consequence, these alterations are not properly assisted. Our aim is to present the introduction process of a psychologist in a nephrology department and its preliminary results. We designed a clearly defined introduction process, starting with a therapeutic communication training program for all the staff. In the model we have priorized pre-emptive interventions in order to promote the adaptation process, far from simple psychological symptom control. It is assumed the binomial patient-family as the major objective for care, choosing an interdisciplinary approach. We worked more from a health psychology perspective than from a mental health perspective. Over the year 2008 the number of patients assisted by the psychologist were 571 (mean 48 patients/month). The total number of interventions was 1,022. Majority of cases (45.2%) were derived from the advanced chronic kidney disease program, mostly related to demands about emotional impact of renal replacement therapy commencement. Others were: suspect of depression episode, adherence, primary caregiver emotional overwhelming, bereavement, anxiety and support in decision making process. This experience is a stimulus for the integral approach of the renal patient.

Are low concentrations of serum triiodothyronine a good marker for long-term mortality in hemodialysis patients?

INTRODUCTION: Low serum free triiodothyronine (FT3) concentrations have been reported in a high percentage of chronic renal failure patients and have been considered as an independent predictor of mortality in dialysis patients. OBJECTIVE: Our aim has been to evaluate the prognostic value of FT3 levels for long-term mortality in stable hemodialysis patients surviving at least 12 months. PATIENTS AND MEASUREMENTS: We retrospectively analyzed 89 stable hemodialysis patients (50 males; mean age 67.9 +/- 11.8 years). All patients had a baseline clinical and analytical evaluation. We analyzed the relationship between baseline FT3 and mortality by means of survival analysis (Kaplan-Meier) and Cox regression analysis. RESULTS: Mean values of thyroid function test were: thyrotropin (TSH) 2.02 +/- 1.5 microU/ml, free thyroxine (FT4) 1.26 +/- 0.23 ng/dl, and FT3 2.7 +/- 0.4 pg/ml. During a median follow-up time of 33.6 +/- 14.9 (12 - 62) months, 41 patients died. FT3 was similar in patients who died or survived (2.6 +/- 0.5 vs. 2.7 +/- 0.4 pg/ml ns). Kaplan-Meier analysis did not show significant differences in mean survival according to tertiles of FT3. In multivariate Cox regression analysis, FT3 was not a predictor of mortality (RR 0,001; 95% CI; 0.000 to 1.73). CONCLUSIONS: These data suggest that low FT3 levels are not predictive for mortality in a subgroup of stable HD patients who could survive more than 12 months.

[Role played by peritoneal dialysis in treating refractory heart failure]. / Papel de la diálisis peritoneal en el tratamiento de la insuficiencia cardíaca refractaria.

Associated renal and cardiac diseases have a high prevalence among the population in several clinical contexts: acute renal failure in the context of decompensated heart failure (HF), HF patients who develop chronic kidney disease (CKD) and patients with CKD who develop HF. In recent years, cardiorenal syndrome has been described as deteriorating kidney function in the context of HF. However, there are other clinical situations for which nephrologists can contribute their knowledge as a part of an integral treatment strategy, as is the case with refractory HF (RHF). All of these situations require an interdisciplinary cooperative effort between cardiologists and nephrologists with the aim of providing integral treatment. This article aims to review the role of the nephrologist in HF treatment, with an emphasis on the subgroup of patients with RHF and current evidence regarding the usefulness of peritoneal dialysis (PD) as a chronic coadjuvant treatment.

[Effect of using icodextrin as a starting therapy for peritoneal permeability]. / Efecto del uso de icodextrina de inicio sobre la permeabilidad peritoneal.

UNLABELLED: Peritoneal permeability differs between patients at the time of starting peritoneal dialysis (PD) and it can increase along with time on the technique. This fact is related to peritonitis, the biocompatibility of the dialysis fluids and the use of glucose as osmotic agent. The aim of the present study was to evaluate if the use of one exchange a day of icodextrine from the time of DP initiation affects the evolution of peritoneal permeability. PATIENTS AND METHODS: 56 patients starting PD (mean age: 48.3 +/- 14.0; 62.5% males; 17.9% diabetics) that used one exchange a day with icodextrine from the time of starting PD. We performed a peritoneal transport kinetic study at the time of starting PD and then every 6 months during two years. We calculated the peritoneal mass transfer area coefficient of creatinine (Cr-MTAC) and urea (U-MTAC) as well as the D/P creatinine relationship (D/P Cr). As a control group we used the results of Cr-MTC of 249 patients that had used glucose as the only osmotic agent from the time of starting PD. RESULTS: The peritoneal transport, calculated using Cr-MTC, U-MTC and D/P Cr, diminished at 12 months (11.7+/-5.7 vs. 8.1+/-3.1; 23.5+/-7.3 vs. 18.9+/-3.8; 0.72+/-0.09 vs. 0.67+/-0.08; respectively), staying stable afterwards.We found that high transporters (HA) patients (higher quatril Cr-MTC ) showed a higher diminution of Cr-MTAC along the first year of treatment. The diminution of Cr-MTAC after 12 months using icodextrine was significantly higher (p<0.001) that the one observed in the control group that only used glucose as osmotic agent (10.5+/-5.3 vs. 10.1+/-4.6). We found that high transporters (HA) patients (higher quatril Cr-MTC) showed a higher decrease of Cr-MTAC along the first year of treatment. CONCLUSION: the use of icodextrine at the time of starting PD might help to correct the high transport status observed in some patients during the first months of treatment. The peritoneal transport kinetic studies performed at 6 and 12 months after starting PD are more representative of the long term peritoneal transport characteristics of the patients than those performed at the time of starting PD.

[Anatomic-functional correlation of the peritoneal membrane]. / Correlación anátomo-funcional de la membrana peritoneal.

Ultrafiltration failure is the most frequent alteration of peritoneal transport in peritoneal dialysis (PD) patients, and is a frequent cause of technical withdrawal. At the beginning of the therapy, there is a great functional diversity, but alter the third or fourth years the 20% of patients develop progressive ultrafiltration failure and an increase of the small solute transport. In parallel to this functional alteration, the peritoneum of PD patients shows morphological alterations, such as loss or transformation of mesothelial cells, basal membrane reduplication, submesothelial fibrosis, hyalinazing vasculopathy and neoangiogenesis. There are scant comparative studies of morphofunctional correlation. Most of them have been reported on long-term PD patients and showed a progressive increase of fibrosis and vasculopathy with time on PD, specially in patients with ultrafiltration failure and in those with sclerosing peritonitis. The peritoneal vessel number do not always increase with time on PD, and it is associated with advanced ultrafiltration failure. Some short-term studies have demonstrated that the initial lesion related to the high small solute peritoneal transport is the epithelial to mesenchimal transition of the mesothelial cell (the transformation of mesothelial cell into fibroblastic cell). The higher secretion of extracellular matrix and vascular endothelial growth factor by the transformed mesothelial cells should participated on later development of fibrosis and high peritoneal permeability, not always in relation with higher 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.

[New peritoneal dialysis solutions and their combinations]. / Nuevas soluciones de diálisis peritoneal y sus combinaciones.

Peritoneal dialysis (PD) treatment has been related to functional and structural changes in peritoneum. The biocompatibility of the PD fluids is one of the most important factors related to this complication. New solutions for PD have been developed in an effort to reduce the bioincompatibility of conventional glucose containing, lactate-buffered solutions, and thereby to improve the clinical outcomes of PD. The use of new manufacturing techniques, buffer presentation, and new osmotic alternatives to glucose (amino acids, icodextrin) have allowed potentially improved peritoneal survival (in terms of structure and function) and improved subjective patient experience. Additional benefits have also included enhanced management of salt and water removal, supported nutritional status and improvement in the systemic metabolic derangements associated with conventional PD treatment, based on glucose-containing lactate-buffered solutions. In vitro and in vivo studies have shown the biocompatibility of these new solutions to be superior to that of standard solutions. This review summarized the characteristics of the next generation of PD fluids currently available and analyzed the potential benefits related to the combination of the different elements.

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.

[Pasteurella multocida and Candida albicans peritonitis]. / Peritonitis por pasteurella multocida y Candida albicans.

Peritonitis is a well-known complication of peritoneal dialysis (PD) treatment. Repetitive episodes may induce an irreversible damage of the peritoneal membrane and are a frequent cause of PD drop-out. The great majority of the episodes are due to Staphylococci, Streptococci or gram- negative organisms. Unusual organisms have been reported, specially in immunosuppressed hosts. Few cases of Pasteurella Multocida (PM) have been described in PD patients. To our knowledge, we describe the first case preceding a Candida Albicans (CA) peritonitis. A review of the literature of PM peritonitis and the relation between these two microorganisms is discussed.

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.

Tissue models of peritoneal fibrosis.

OBJECTIVE: To evaluate the utility of peritoneal pathologic samples, unrelated to peritoneal dialysis (PD) treatment, for the study of peritoneal fibrosis and inflammation. METHODS: Comparative morphologic and immunohistochemical study of peritoneal pathologic samples unrelated to PD with peritoneal biopsies from PD patients with special emphasis on the expression of myofibroblastic and epithelial-to-mesenchymal transition markers. RESULTS: Regarding morphology, PD-related simple fibrosis was less cellular, with greater stromal hyalinization, determining a homogeneous, hypocellular aspect of the submesothelium. In contrast, non-PD fibrosis was more cellular with an extracellular matrix showing a dense and fibrillar quality with wide bundles of collagen. Hylinazing vasculopathy was only present in PD samples. Myofibroblastic differentiation and epithelial-to-mesenchymal transition were common findings in all situations of peritoneal fibrosis. Calponin and calretinin are useful cellular markers to study such fibrogenic mechanisms and correlate with other well-known markers such as a -SMA and cytokeratins. Their expression was much more intense in those samples showing acute inflammation (peritonitis). CONCLUSIONS: Non-PD models of peritoneal fibrosis seem very useful to evaluate important features of human peritoneal pathology such us fibrogenesis, and inflammation. Fibrogenic events such as myofibroblastic differentiation and epithelial-to-mesenchymal transition are evident in these tissue samples allowing us to use them as an accessible source for in vivo and ex vivo studies. Both events show their maximal expression in situations of acute inflammation supporting the important role that peritonitis episodes play in the progression of fibrosis.

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.