The Effect of Nutritional Interventions on Long-Term Patient Survival in Advanced Chronic Kidney Disease.

Patients with end-stage kidney disease (ESKD) are at high risk of malnutrition and subsequent related mortality when starting dialysis. However, there have been few clinical studies on the effect of nutritional interventions on long-term patient survival. A 2-year longitudinal study was conducted from January 2012 to December 2016. A total of 186 patients with non-dialysis ESKD started the nutritional education program (NEP), and 169 completed it. A total of 128 patients participated in a NEP over 6 months (personalized diet, education and oral supplementation, if needed). The control group (n = 45) underwent no specific nutritional intervention. The hospitalization rate was significantly lower for the patients with NEP (13.7%) compared with the control patients (26.7%) (p = 0.004). The mortality odds ratio for the patients who did not receive NEP was 2.883 (95% CI 0.993-8.3365, p = 0.051). The multivariate analysis showed an independent association between mortality and age (OR, 1.103; 95% CI 1.041-1.169; p = 0.001) and between mortality and the female sex (OR, 3.332; 95% CI 1.054-10.535; p = 0.040) but not between mortality and those with NEP (p = 0.051). Individualized nutrition education has long-term positive effects on nutritional status, reduces hospital admissions and increases survival among patients with advanced CKD who are starting dialysis programs.

COVID-19 incidence and outcomes in a home dialysis unit in Madrid (Spain) at the height of the pandemic.

INTRODUCTION: The 2019 coronavirus (COVID-19) is a viral infection caused by a new coronavirus that is affecting the entire world. There have been studies of patients on in-center hemodialysis (HD), but home dialysis population data are scarce. Our objective is to study the incidence and course of COVID-19 in a home dialysis unit (HDU) at the height of the pandemic. METHODS: an observational, retrospective study enrolling all patients diagnosed with COVID-19 from the HDU of Hospital Universitario La Paz [La Paz University Hospital] (Madrid, Spain) between March 10 and May 15, 2020. We collected clinical data from the HDU (57 patients on peritoneal dialysis [PD] and 22 patients on home hemodialysis [HHD]) and compared the clinical characteristics and course of patients with and without COVID-19 infection. RESULTS: twelve patients were diagnosed with COVID-19 (9 PD; 3 HHD). There were no statistically significant differences in terms of clinical characteristics between patients with COVID-19 and the rest of the unit. The mean age was 62 ± 18.5 years; most were men (75%). All patients but one required hospitalization. Ten patients (83%) were discharged following a mean of 16.4 ± 9.7 days of hospitalization. Two patients were diagnosed while hospitalised for other conditions, and these were the only patients who died. Those who died were older than those who survived. CONCLUSION: The incidence of COVID-19 in our HDU in Madrid at the height of the pandemic was high, especially in patients on PD. No potential benefit for preventing the infection in patients on home dialysis was observed. Advanced age and nosocomial transmission were the main factors linked to a worse prognosis.

[COVID-19 incidence and outcomes in a home dialysis unit in Madrid (Spain) at the height of the pandemic]. / Incidencia y resultados de la COVID-19 en una unidad de diálisis domiciliaria en Madrid (España) durante el pico de la pandemia.

INTRODUCTION: The 2019 coronavirus (COVID-19) is a viral infection caused by a new coronavirus that is affecting the entire world. There have been studies of patients on in-center hemodialysis, but home dialysis population data are scarce. Our objective is to study the incidence and course of COVID-19 in a home dialysis unit (HDU) at the height of the pandemic. METHODS: An observational, retrospective study enrolling all patients diagnosed with COVID-19 from the HDU of Hospital Universitario La Paz (La Paz University Hospital) (Madrid, Spain) between March 10 and May 15, 2020. We collected clinical data from the HDU (57 patients on peritoneal dialysis and 22 patients on home hemodialysis) and compared the clinical characteristics and course of patients with and without COVID-19 infection. RESULTS: Twelve patients were diagnosed with COVID-19 (9 peritoneal dialysis; 3 home hemodialysis). There were no statistically significant differences in terms of clinical characteristics between patients with COVID-19 and the rest of the unit. The mean age was 62±18.5 years; most were men (75%). All patients but one required hospitalization. Ten patients (83%) were discharged following a mean of 16.4±9.7 days of hospitalization. Two patients were diagnosed while hospitalized for other conditions, and these were the only patients who died. Those who died were older than those who survived. CONCLUSION: The incidence of COVID-19 in our HDU in Madrid at the height of the pandemic was high, especially in patients on peritoneal dialysis. No potential benefit for preventing the infection in patients on home dialysis was observed. Advanced age and nosocomial transmission were the main factors linked to a worse prognosis.

Increased miR-7641 Levels in Peritoneal Hyalinizing Vasculopathy in Long-Term Peritoneal Dialysis Patients.

Peritoneal hyalinizing vasculopathy (PHV) represents the cornerstone of long-term peritoneal dialysis (PD), and especially characterizes patients associated with encapsulating peritoneal sclerosis. However, the mechanisms of PHV development remain unknown. A cross sectional study was performed in 100 non-selected peritoneal biopsies of PD patients. Clinical data were collected and lesions were evaluated by immunohistochemistry. In selected biopsies a microRNA (miRNA)-sequencing analysis was performed. Only fifteen patients (15%) showed PHV at different degrees. PHV prevalence was significantly lower among patients using PD fluids containing low glucose degradation products (GDP) (5.9% vs. 24.5%), angiotensin converting enzyme inhibitors (ACEIs) (7.5% vs. 23.4%), statins (6.5% vs. 22.6%) or presenting residual renal function, suggesting the existence of several PHV protective factors. Peritoneal biopsies from PHV samples showed loss of endothelial markers and induction of mesenchymal proteins, associated with collagen IV accumulation and wide reduplication of the basement membrane. Moreover, co-expression of endothelial and mesenchymal markers, as well as TGF-ß1/Smad3 signaling activation were found in PHV biopsies. These findings suggest that an endothelial-to-mesenchymal transition (EndMT) process was taking place. Additionally, significantly higher levels of miR-7641 were observed in severe PHV compared to non-PHV peritoneal biopsies. Peritoneal damage by GDPs induce miRNA deregulation and an EndMT process in submesothelial vessels, which could contribute to collagen IV accumulation and PHV.

The ideal position of the peritoneal dialysis catheter is not always ideal.

PURPOSE: Peritoneal catheter dysfunction is a frequent complication of peritoneal dialysis (PD). Traditionally, dysfunction has been attributed to catheter malposition, but whether the location of the catheter tip in the small pelvis really determines proper function is unclear. METHODS: We reviewed 900 abdominal X-ray images of PD patients from a 7-year period in two PD units that use different catheter types (straight and Swan Neck Curled). RESULTS: In 52% of the images, the dialysis catheter tip was located in the ideal position in the small pelvis and in 48% in other sites. Peritoneal catheter function was normal at the time of imaging in 87% of those with ideal catheter tip position, and in 74% of those with other than ideal position. The tip was located in small pelvis in 35% of images performed during catheter dysfunction and in 56% of those performed during normal catheter function. There were no differences between two catheter types. The positive predictive value of abdominal X-ray images to predict catheter function was 26%, and the negative predictive value 87%. We also found a significant positive correlation between polycystic kidney disease and normal catheter function. In contrast, obese patients were more likely to have catheter malfunction. Previous abdominal surgery was not associated with catheter dysfunction. CONCLUSION: Our data showed a higher probability of normal function of peritoneal catheters whose tips were located in the small pelvis. However, also malpositioned catheters generally functioned well, and malpositioning of the PD catheter did not in itself explain its malfunction.

Abnormalities in Glucose Metabolism, Appetite-Related Peptide Release, and Pro-inflammatory Cytokines Play a Central Role in Appetite Disorders in Peritoneal Dialysis.

Background: Appetite disorders are frequent and scantly studied in peritoneal dialysis (PD) patients and are associated with malnutrition and cardiovascular complications. Objective: We investigated the relationship between uremic insulin resistance, pro-inflammatory cytokines, and appetite-related peptides release (ARPr) with eating-behavior disorders in PD patients. Methods: We included 42 PD patients (12 suffering anorexia, 12 obese with high food-intake, and 18 asymptomatic) and 10 controls. We measured blood levels of ARPr including orexigens [neuropeptide-Y (NPY), ghrelin, and nitric-oxide], anorexigens [cholecystokinin, insulin, corticotropin-releasing factor, leptin, and adiponectin (Ad)], and cytokines (TNF-α, sTNFα-R2, and IL-6) both at baseline and after administering a standard-food stimulus (SFS). We also measured the expression of TNF-α, leptin and Ad-encoding mRNAs in abdominal adipose tissue. We compared these markers with eating motivation measured by a Visual Analog Scale (VAS). Results: Anorexics showed both little appetite, measured by a VAS, and low levels of orexigens that remained constant after SFS, coupled with high levels of anorexigens at baseline and after SFS. Obeses showed higher appetite, increased baseline levels of orexigens, lower baseline levels of anorexigens and cytokines and two peaks of NPY after SFS. The different patterns of ARPr and cytokines pointed to a close relationship with uremic insulin resistance. In fact, the euglycemic-hyperglycemic clamp reproduced these disorders. In anorexics, TNF-α fat expression was increased. In obese patients, leptin expression in fat tissue was down-regulated and showed correlation with the appetite. Conclusion: In PD, appetite is governed by substances that are altered at baseline and abnormally released. Such modulators are controlled by insulin metabolism and cytokines and, while anorexics display inflammatory predominance, obese patients predominantly display insulin resistance.

Multicenter Validation of the Emotional State Instrument for Dialysis Patients.

BACKGROUND: The Emotional State Instrument for Dialysis Patients (ES-D) is a brief semistructured questionnaire to assess emotional distress in patients undergoing dialysis. It was designed to be administered by a healthcare provider. A previous study showed preliminary indicators of its content and face validity. OBJECTIVE: The aim of the current multicenter study was to explore the ES-D's psychometric properties. METHODS: A total of 605 patients with kidney disease undergoing dialysis (524 hemodialysis and 81 peritoneal dialysis) in 19 Spanish dialysis centers completed the ES-D, along with anxiety, depression (Hospital Anxiety and Depression Scale), and resilience (Brief Resilience Scale) questionnaires. The 75 healthcare providers who performed the assessments completed a satisfaction survey. RESULTS: The ES-D showed adequate internal consistency (α = .73). Correlations between the ES-D scores and the scores for anxiety, depression, and resilience showed evidence of its convergent and concurrent validity. The receiver operating characteristic curve analyses showed that a cutoff of nine detected patients with moderate-to-severe emotional distress. According to these criteria, 35.4% of patients showed emotional distress. No significant differences were found between patients undergoing hemodialysis and peritoneal dialysis. The healthcare providers perceived the ES-D as useful for knowing the patients' emotional state, understanding patients' concerns, and establishing therapeutic relationships. CONCLUSIONS: The ES-D is a useful tool for healthcare providers to explore the emotional dimension of their patients. Thus, its development represents a step forward in the improvement of comprehensive assistance and the quality of life of patients with kidney disease undergoing dialysis.

Prominent Levels of the Profibrotic Chemokine CCL18 during Peritonitis: In Vitro Downregulation by Vitamin D Receptor Agonists.

Peritoneal dialysis (PD) is used as a renal replacement therapy, which can be limited by peritoneal membrane ultrafiltration failure (UFF) secondary to fibrotic processes. Peritonitis, a frequent complication of PD, is a major risk factor for peritoneal membrane fibrosis and UFF. Low peritoneal levels of the chemokine CCL18 are associated with preservation of peritoneal membrane function in PD. Given that CCL18 is involved in fibrotic processes and recurrent peritonitis, it is a risk factor for peritoneal membrane failure; thus, we evaluated CCL18 concentrations in peritoneal effluents from patients undergoing peritonitis episodes. Pharmacological interventions aimed at diminishing the production of CCL18 were also explored. Fivefold higher CCL18 peritoneal concentrations were found during acute bacterial peritonitis, in parallel with the increased infiltration of macrophages. Unexpectedly, CCL18 was also highly (50-fold) increased during sterile eosinophilic peritonitis, and peritoneal eosinophils were found to express CCL18. In vitro treatment of peritoneal macrophages with the vitamin D receptor agonist paricalcitol was able to reduce the secretion and the expression of CCL18 in isolated peritoneal macrophages. In conclusion, our study suggests that the chemokine CCL18 can be a mediator of peritoneal membrane failure associated with peritonitis episodes as well as providing a new potential therapeutic target.

Paricalcitol and Peritoneal Protein Loss in Peritoneal Dialysis: A Double-Center Study.

BACKGROUND/AIMS: Peritoneal protein loss (PPL) is associated with cardiovascular disease and mortality in peritoneal dialysis (PD). Controversial results have been published about the effect of paricalcitol in PPL among PD patients. This study intends to analyze the relationship between paricalcitol and PPL in PD. METHODS: In a retrospective study, prevalent PD patients were divided into 2 groups: "with paricalcitol" and "without paricalcitol". X2-test, Student's t test, Pearson correlation coefficient and Logistic Regression analysis were applied. RESULTS: Eighty-two patients were included. PPL was lower among patients medicated with paricalcitol (5.17 ± 1.71 vs. 6.79 ± 2.10 g/24 h, p = 0.0001). In multivariate analysis, paricalcitol and dialysate/plasma ratio of creatinine (D/P creatinine) were independently related to PPL (OR 4.270 [1.437-12.684], p = 0.009 and OR 0.205 [0.064-0.659], p = 0.008, respectively), adjusted for diabetes. CONCLUSION: Paricalcitol and D/P creatinine were independently related to PPL. Paricalcitol may have an effect on PPL in PD patients.

Relationship between bioimpedance-determined body composition and peritoneal transport in peritoneal dialysis.

PURPOSE: In peritoneal dialysis (PD) patients, body fluid homeostasis is dependent on peritoneal elimination of water and solutes. Patients with less favorable peritoneal transport parameters should be more overhydrated. Despite this, the association between faster transport and overhydration (OH) is weak, and the factors that influence hydration status are still poorly characterized. Modified peritoneal equilibration tests (PET) offer us new parameters that might correlate better with hydration status, like free water transport (FWT). The aim of this study was thus to establish the relationships between new peritoneal transport parameters and body composition parameters estimated by bioimpedance spectroscopy (BIS). METHODS: Prospective observational study on incident PD patients with a baseline and 1-year follow-up evaluation. RESULTS: 61 patients were included in the baseline evaluation, 19 of whom had a 1-year follow-up evaluation; 67.2% were fluid overloaded. There was a negative correlation between D/P creatinine and FWT (r = -0.598, p = 0.000). The fraction of FWT was negatively correlated with OH (r = -0.302, p = 0.018). Peritoneal protein losses (PPL) were also correlated with OH (r = 0.287, p = 0.028). There were no significant differences in OH according to small-solute transport status or fluid output parameters. After 1 year, we observed a significant worsening of renal function and an improvement in 24-hour ultrafiltration (UF) and hydration status, but we detected no differences in peritoneal transport of water or solutes that could explain these changes. CONCLUSIONS: There is a poor relationship between kidney/peritoneal function parameters and body composition parameters. The fraction of FWT and PPL may be underestimated markers of peritoneal health and of its contribution to the hydration status.

Improvement in Nutritional Status in Patients With Chronic Kidney Disease-4 by a Nutrition Education Program With No Impact on Renal Function and Determined by Male Sex.

OBJECTIVE: Protein-energy wasting (PEW) is associated with increased morbidity and mortality and a rapid deterioration of kidney function in patients with chronic kidney disease (CKD). However, there is little information regarding the effect of nutrition intervention. The aims of this study were to evaluate the efficacy and safety of a nutrition education program (NEP) in patients with nondialysis dependent CKD (NDD-CKD), based on the diagnostic criteria for PEW proposed by the International Society of Renal Nutrition and Metabolism. The design of the study was a 6-month longitudinal, prospective, and interventional study. The study was conducted from March 2008 to September 2011 in the Nephrology Department of La Paz University Hospital in Madrid, Spain. SUBJECTS: A total of 160 patients with NDD-CKD started the NEP, and 128 finished it. INTERVENTION: The 6-month NEP consisted of designing an individualized diet plan based on the patient's initial nutritional status, and 4 nutrition education sessions. MAIN OUTCOME MEASURES: Changes in nutritional status (PEW) and biochemical, anthropometric and body composition parameters. RESULTS: After 6 months of intervention, potassium and inflammation levels decreased, and an improved lipid profile was found. Body mass index lowered, with increased muscle mass and a stable fat mass. Men showed increased levels of albumin and prealbumin, and women showed decreased proteinuria levels. The prevalence of PEW decreased globally (27.3%-10.9%; P = .000), but differently in men (29.5%-6.5%; P = .000) and in women (25.4%-14.9%; P = .070), 3 of the women having worsened. Kidney function was preserved, despite increased protein intake. CONCLUSION: The NEP in NDD-CKD generally improved nutritional status as measured by PEW parameters, but individual poorer results indicated the need to pay special attention to female sex and low body mass index at the start of the program.

Sustained low peritoneal effluent CCL18 levels are associated with preservation of peritoneal membrane function in peritoneal dialysis.

Peritoneal membrane failure (PMF) and, ultimately, encapsulating peritoneal sclerosis (EPS) are the most serious peritoneal dialysis (PD) complications. Combining clinical and peritoneal transport data with the measurement of molecular biomarkers, such as the chemokine CCL18, would improve the complex diagnosis and management of PMF. We measured CCL18 levels in 43 patients' effluent and serum at baseline and after 1, 2, and 3 years of PD treatment by retrospective longitudinal study, and evaluated their association with PMF/EPS development and peritoneal risk factors. To confirm the trends observed in the longitudinal study, a cross-sectional study was performed on 61 isolated samples from long-term (more than 3 years) patients treated with PD. We observed that the patients with no membrane dysfunction showed sustained low CCL18 levels in peritoneal effluent over time. An increase in CCL18 levels at any time was predictive of PMF development (final CCL18 increase over baseline, p = .014; and maximum CCL18 increase, p = .039). At year 3 of PD, CCL18 values in effluent under 3.15 ng/ml showed an 89.5% negative predictive value, and higher levels were associated with later PMF (odds ratio 4.3; 95% CI 0.90-20.89; p = .067). Moreover, CCL18 levels in effluent at year 3 of PD were independently associated with a risk of PMF development, adjusted for the classical (water and creatinine) peritoneal transport parameters. These trends were confirmed in a cross-sectional study of 61 long-term patients treated with PD. In conclusion, our study shows the diagnostic capacity of chemokine CCL18 levels in peritoneal effluent to predict PMF and suggests CCL18 as a new marker and mediator of this serious condition as well as a new potential therapeutic target.

Body composition analysis and adipocytokine concentrations in haemodialysis patients: abdominal fat gain as an additional cardiovascular risk factor. / Composición corporal y concentraciones de adipocitoquinas en hemodiálisis: la ganancia de grasa abdominal como factor de riesgo cardiovascular añadido.

INTRODUCTION: Abdominal fat and its increment over time in particular has become a cardiovascular risk factor in uraemic patients. OBJECTIVES: To analyse changes in abdominal fat in haemodialysis patients over one year and study their possible correlation with the variation in adipocytokine serum levels. As a secondary objective, we tried to validate the data obtained by bioelectrical impedance analysis (BIA) with data obtained by dual X-ray absorptiometry (DXA). MATERIAL AND METHODS: A prospective one-year study was performed in 18 patients on haemodialysis (HD). In each patient, body composition by BIA and DXA was estimated at baseline and after one year. Several adipocytokine and biochemical parameters were determined. RESULTS: A significant increase in phase angle [4.8° (4.1-5.6) vs. 5.2° (4.4-5.8), P<.05], BIA intracellular water [48.3% (43.1-52.3) vs. 50.3% (45.7-53.4), P<.05] and the ratio between the percentage of android/gynecoid (A/G) distribution of fat measured by DXA [1.00 (0.80-1.26) vs. 1.02 (0.91-1.30), P<.05] was observed. A statistically significant relationship between leptin and adiponectin concentrations and the percentage of fat mass measured by BIA, as well as the abdominal fat percentage estimated by DXA, was found (P<.01). CONCLUSION: HD patients exhibit a gain in fat mass over time, especially in the abdomen, evidenced by an increased A/G ratio. These findings might explain the increased cardiovascular risk in these patients.

Peritoneal Membrane Preservation.

Peritoneal dialysis (PD) is a successfully used method for renal replacement therapy. However, long-term PD may be associated with peritoneal fibrosis and ultrafiltration failure. The key factors linked to their appearance are repeated episodes of inflammation associated with peritonitis and long-term exposure to bioincompatible PD fluids. Different strategies have been proposed to preserve the peritoneal membrane. This article reviews the functional and structural alterations related to PD and strategies whereby we may prevent them to preserve the peritoneal membrane. The use of new, more biocompatible, PD solutions is promising, although further morphologic studies in patients using these solutions are needed. Blockade of the renin-angiotensin-aldosterone system appears to be efficacious and strongly should be considered. Other agents have been proven in experimental studies, but most of them have not yet been tested appropriately in human beings.

Markers of endothelial damage in patients with chronic kidney disease on hemodialysis.

Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD142+/CD16+, CD14+/CD162+) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14+/CD162+ and CD142+/CD16+), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM.

The Communication and Bioethical Training (CoBiT) Program for assisting dialysis decision-making in Spanish ACKD units.

Healthcare professionals currently working in Advanced Chronic Kidney Disease (ACKD) units must cope with difficult situations regarding assisting patients with the dialysis decision-making process, and they are often untrained for these conversations. Although we have evidence from the literature that these skills can be learned, few professionals feel confident in this area. A Communication and Bioethical Training (CoBiT) Program for ACKD staff (physicians, nurses and allied health professionals) was developed to improve their ability and self-confidence in conducting these conversations. A four-stage study was conducted: (1) development of the CoBiT program, beginning with the creation of an interdisciplinary focus group (N = 10); (2) design of a questionnaire to assess self-confidence based on the areas identified by the focus group. The face validity of the instrument was tested using an inter-judge methodology (N = 6); (3) design of the format and contents of the program; (4) piloting the program. Thirty-six health professionals took an 8-h workshop based on role-playing methodology. Participants assessed their self-confidence in their communication skills before and after the program using self-report measures. The results show that after the program, participants reported significantly higher levels of self-confidence measured with a five-point Likert scale (p < 0.001). Participants felt that communication with colleagues of other professions significantly increased after the workshop (p = 0.004). The CoBiT program improves ACKD Unit healthcare professionals' self-confidence in their ability to perform a specific communication task.

Preventing peritoneal membrane fibrosis in peritoneal dialysis patients.

Long-term peritoneal dialysis causes morphologic and functional changes in the peritoneal membrane. Although mesothelial-mesenchymal transition of peritoneal mesothelial cells is a key process leading to peritoneal fibrosis, and bioincompatible peritoneal dialysis solutions (glucose, glucose degradation products, and advanced glycation end products or a combination) are responsible for altering mesothelial cell function and proliferation, mechanisms underlying these processes remain largely unclear. Peritoneal fibrosis has 2 cooperative parts, the fibrosis process itself and the inflammation. The link between these 2 processes is frequently bidirectional, with each one inducing the other. This review outlines our current understanding about the definition and pathophysiology of peritoneal fibrosis, recent studies on key fibrogenic molecular machinery in peritoneal fibrosis, such as the role of transforming growth factor-ß/Smads, transforming growth factor-ß ß/Smad independent pathways, and noncoding RNAs. The diagnosis of peritoneal fibrosis, including effluent biomarkers and the histopathology of a peritoneal biopsy, which is the gold standard for demonstrating peritoneal fibrosis, is introduced in detail. Several interventions for peritoneal fibrosis based on biomarkers, cytology, histology, functional studies, and antagonists are presented in this review. Recent experimental trials in animal models, including pharmacology and gene therapy, which could offer novel insights into the treatment of peritoneal fibrosis in the near future, are also discussed in depth.

Nebivolol, a ß1-adrenergic blocker, protects from peritoneal membrane damage induced during peritoneal dialysis.

UNLABELLED: Peritoneal dialysis (PD) is a form of renal replacement treatment, which employs the peritoneal membrane (PM) to eliminate toxins that cannot be removed by the kidney. The procedure itself, however, contributes to the loss of the PM ultrafiltration capacity (UFC), leading consequently to the technique malfunction. ß-blockers have been considered deleterious for PM due to their association with loss of UFC and induction of fibrosis. Herein we analyzed the effects of Nebivolol, a new generation of ß1-blocker, on PM alterations induced by PD fluids (PDF).In vitro: We found that mesothelial cells (MCs) express ß1-adrenergic receptor. MCs were treated with TGF-ß to induce mesothelial-to-mesenchymal transition (MMT) and co-treated with Nebivolol. Nebivolol reversed the TGF-ß effects, decreasing extracellular matrix synthesis, and improved the fibrinolytic capacity, decreasing plasminogen activator inhibitor-1 (PAI-1) and increasing tissue-type plasminogen activator (tPA) supernatant levels. Moreover, Nebivolol partially inhibited MMT and decreased vascular endothelial growth factor (VEGF) and IL-6 levels in supernatants.In vivo: Twenty-one C57BL/6 mice were divided into 3 groups. Control group carried a catheter without PDF infusion. Study group received intraperitoneally PDF and oral Nebivolol during 30 days. PDF group received PDF alone. Nebivolol maintained the UFC and reduced PM thickness, MMT and angiogenesis promoted by PDF. It also improved the fibrinolytic capacity in PD effluents decreasing PAI-1 and IL-8 and increased tPA levels. CONCLUSION: Nebivolol protects PM from PDF-induced damage, promoting anti-fibrotic, anti-angiogenic, anti-inflammatory and pro-fibrinolytic effects.

Fibroblast Growth Factor 21 (FGF-21) in Peritoneal Dialysis Patients: Natural History and Metabolic Implications.

BACKGROUND: Human fibroblast growth factor 21 (FGF-21) is an endocrine liver hormone that stimulates adipocyte glucose uptake independently of insulin, suppresses hepatic glucose production and is involved in the regulation of body fat. Peritoneal dialysis (PD) patients suffer potential interference with FGF-21 status with as yet unknown repercussions. OBJECTIVES: The aim of this study was to define the natural history of FGF-21 in PD patients, to analyze its relationship with glucose homeostasis parameters and to study the influence of residual renal function and peritoneal functional parameters on FGF-21 levels and their variation over time. METHODS: We studied 48 patients with uremia undergoing PD. Plasma samples were routinely obtained from each patient at baseline and at 1, 2 and 3 years after starting PD therapy. RESULTS: Plasma FGF-21 levels substantially increased over the first year and were maintained at high levels during the remainder of the study period (253 pg/ml (59; 685) at baseline; 582 pg/ml (60.5-949) at first year and 647 pg/ml (120.5-1116.6) at third year) (p<0.01). We found a positive correlation between time on dialysis and FGF-21 levels (p<0.001), and also, those patients with residual renal function (RRF) had significantly lower levels of FGF-21 than those without RRF (ρ -0.484, p<0.05). Lastly, there was also a significant association between FGF-21 levels and peritoneal protein losses (PPL), independent of the time on dialysis (ρ 0.410, p<0.05). CONCLUSION: Our study shows that FGF-21 plasma levels in incident PD patients significantly increase during the first 3 years. This increment is dependent on or is associated with RRF and PPL (higher levels in patients with lower RRF and higher PPL). FGF-21 might be an important endocrine agent in PD patients and could act as hormonal signaling to maintain glucose homeostasis and prevent potential insulin resistance. These preliminary results suggest that FGF-21 might play a protective role as against the development of insulin resistance over time in patients undergoing a continuous glucose load.