Characterization of hypersensitivity reactions to polysulfone hemodialysis membranes.

BACKGROUND: In recent years, cases have been reported in which unexpected systemic hypersensitivity reactions occurred in patients dialyzed with polysulfone- or polyethersulfone-biocompatible membranes in the absence of other risk factors. The pathomechanisms involved in these reactions are largely unknown. OBJECTIVE: To characterize hypersensitivity reactions to polysulfone hemodialysis using clinical and laboratory data and to identify biomarkers suitable for endotype identification and diagnosis. METHODS: We prospectively collected data from 29 patients with suspected hypersensitivity reactions to polysulfone hemodialysis membranes. Clinical laboratory parameters such as tryptase, blood cell counts, and complement levels were recorded. Acute samples were obtained from 18 cases for the ex vivo assessment of basophil activation by flow cytometry analysis of CD63, CD203, and FcεRI cell membrane expression. Serum cytokines and anaphylatoxin concentrations were evaluated in 16 cases by Luminex and cytometric bead array analysis. RESULTS: Tryptase was elevated during the acute reaction in 4 cases. Evidence of basophil activation was obtained in 10 patients. Complement activation was found in only 2 cases. However, C5a serum levels tended to increase during the acute reaction in those patients with hypoxemia. Significantly higher serum levels of interleukin-6 were observed during the acute reactions to polysulfone hemodialysis (P = .0103). CONCLUSION: Based on biomarker analysis, various endotypes were identified, including type I-like (with the involvement of mast cells or basophils), complement, and cytokine (interleukin-6) release-related reactions, with some patients showing mixed reactions. Further research is needed to unravel the exact mechanisms involved in the activation of these cellular and molecular pathways.

CCN2 (Cellular Communication Network Factor 2) Deletion Alters Vascular Integrity and Function Predisposing to Aneurysm Formation.

BACKGROUND: CCN2 (cellular communication network factor 2) is a matricellular protein involved in cell communication and microenvironmental signaling responses. CCN2 is known to be overexpressed in several cardiovascular diseases, but its role is not completely understood. METHODS: Here, CCN2 involvement in aortic wall homeostasis and response to vascular injury was investigated in inducible <i>Ccn2</i>-deficient mice, with induction of vascular damage by infusion of Ang II (angiotensin II; 15 days), which is known to upregulate CCN2 expression in the aorta. RESULTS: Ang II infusion in CCN2-silenced mice lead to 60% mortality within 10 days due to rapid development and rupture of aortic aneurysms, as evidenced by magnetic resonance imaging, echography, and histological examination. <i>Ccn2</i> deletion decreased systolic blood pressure and caused aortic structural and functional changes, including elastin layer disruption, smooth muscle cell alterations, augmented distensibility, and increased metalloproteinase activity, which were aggravated by Ang II administration. Gene ontology analysis of RNA sequencing data identified aldosterone biosynthesis as one of the most enriched terms in CCN2-deficient aortas. Consistently, treatment with the mineralocorticoid receptor antagonist spironolactone before and during Ang II infusion reduced aneurysm formation and mortality, underscoring the importance of the aldosterone pathway in Ang II-induced aorta pathology. CONCLUSIONS: CCN2 is critically involved in the functional and structural homeostasis of the aorta and in maintenance of its integrity under Ang II-induced stress, at least, in part, by disruption of the aldosterone pathway. Thus, this study opens new avenues to future studies in disorders associated to vascular pathologies.

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.

Is peritoneal dialysis suitable technique CKD patients over 65 years? A prospective multicenter study.

BACKGROUND: Chronic kidney disease (CKD) is increasing in patients older than 65 years and is related to morbidity, frailty, and dependence. Peritoneal dialysis (PD) has classically been associated with young patients with an active life. HYPOTHESIS: PD should be offered to patients over 65 years. We search for any unfavorable results that may advice not to recommend PD therapy for this group. OBJECTIVE: To describe PD treatment and outcomes in patients > 65 years, to compare their results with patients < 65 years and to identify areas with room for improvement in a real-life study. STUDY: Prospective, observational, and multicenter study performed in incident PD patients, from January 2003 until January 2018. RESULTS: We included 2,435 PD patients, 31.9% were older than 65 years; there was a difference of 25 years between both groups. Median follow up was 2.1 years. Older than 65 years group had more comorbidity: Diabetes (29.5% vs 17.2%; p < 0.001), previous CV events 34.5% vs 14.0%; p < 0.001), Charlson index (3.8 vs 3.0; p < 0.001). We did not find differences in efficacy and PD adequacy objectives fulfillment, anaemia management or blood pressure during follow-up. Peritonitis rate was higher in older 65 years group (0.65 vs 0.45 episodes/patient/year; p < 0.001), but there was not differences in germs, admission rate and follow up. Mortality was higher in older 65 years group (28.4% vs 9.4%) as expected. PD permanence probability was similar (2.1 years). The main cause of PD withdrawal was transplant in group < 65 years (48.3%) and transfer to HD in group > 65 years. The main reason was caregiver or patient fatigue (20.2%), and not technique failure (7.3%). Multivariate Cox regression analysis showed a relation (HR [95%CI]) between mortality and age > 65 years 2.4 [1.9-3.0]; DM 1.6 [1.3-2.1]; CV events 2.1 [1.7-2.7]. Multivariate Cox regression analysis identify a relation between technique failure and age > 65 years 1.5 [1.3-1.9]; DM 1.6 [1.3-1.9] and previous transplant 1.5 [1.2-2.0]. CONCLUSION: Patients older than 65 years fulfilled PD adequacy criteria during the follow up. We believe PD is a valid option for patients older 65 years. It is necessary to try to prevent infections and patient/caregiver fatigue, to avoid HD transfer for reasons not related to technique failure.

Interacciones farmacológicas de los captores del fósforo / Pharmacological interactions of phosphate binders

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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.

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.

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.

Reacciones de hipersensibilidad a membranas sintéticas de hemodiálisis / Hypersensitivity reactions to synthetic haemodialysis membranes

La realización de una sesión de hemodiálisis (HD) supone un cierto riesgo de aparición de reacciones adversas de hipersensibilidad, al estar en contacto abundantes cantidades de sangre con diferentes materiales de origen sintético. En HD han sido descritas reacciones de hipersensibilidad al óxido de etileno y a membranas no biocompatibles como el cuproamonio. También se han comunicado casos de hipersensibilidad con membranas biocompatibles como la polisulfona, e incluso con polisulfona asociada a polivinilpirrolidona. En este artículo queremos describir seis casos acontecidos en nuestro servicio de reacciones de hipersensibilidad mayoritariamente temprana a la sesión de HD, caracterizados por mal estado general, desaturación, broncoespasmo e hipotensión arterial, con buena respuesta a la suspensión temporal de la sesión y con reaparición en sesiones posteriores siempre que se utilizase un dializador sintético. Todas tienen en común no haberse dado de nuevo en sucesivas observaciones cuando las sesiones fueron realizadas con una membrana de celulosa (AU)

Undergoing a haemodialysis (HD) session poses a certain risk of hypersensitivity adverse reactions as large quantities of blood are in contact with various synthetic materials. Hypersensitivity reactions to ethylene oxide and non-biocompatible membranes, such as cuprophane, have been described in HD. Cases of hypersensitivity with biocompatible membranes, such as polysulfone, and even polysulfone-polyvinylpyrrolidone, have also been reported. In this article we describe six cases of mostly early-stage hypersensitivity reactions to HD occurring in our department, characterised by malaise, desaturation, bronchospasm and arterial hypotension, with good response to the session's temporary suspension and with reappearance in subsequent sessions that used a synthetic dialyser. No hypersensitivity reactions reappeared in successive observations when the sessions were carried out using a cellulose membrane (AU)

Hypersensitivity reactions to synthetic haemodialysis membranes.

Undergoing a haemodialysis (HD) session poses a certain risk of hypersensitivity adverse reactions as large quantities of blood are in contact with various synthetic materials. Hypersensitivity reactions to ethylene oxide and non-biocompatible membranes, such as cuprophane, have been described in HD. Cases of hypersensitivity with biocompatible membranes, such as polysulfone, and even polysulfone-polyvinylpyrrolidone, have also been reported. In this article we describe six cases of mostly early-stage hypersensitivity reactions to HD occurring in our department, characterised by malaise, desaturation, bronchospasm and arterial hypotension, with good response to the session’s temporary suspension and with reappearance in subsequent sessions that used a synthetic dialyser. No hypersensitivity reactions reappeared in successive observations when the sessions were carried out using a cellulose membrane.

Can EPS development be avoided with early interventions? The potential role of tamoxifen--a single-center study.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD). Identification of patients at high risk for EPS ("EPS-prone") and delivery of appropriate interventions might prevent its development. Our aim was to evaluate the clinical characteristics and outcomes of all EPS and EPS-prone patients diagnosed at our PD unit. METHODS: For a 30-year period representing our entire PD experience, we retrospectively identified all patients with EPS (diagnosed according to International Society for Peritoneal Dialysis criteria) and all patients defined as EPS-prone because they met at least 2 established criteria (severe peritonitis, PD vintage greater than 3 years, severe hemoperitoneum, overexposure to glucose, and acquired ultrafiltration failure). RESULTS: Of 679 PD patients, we identified 20 with EPS, for an overall prevalence of 2.9%. Mean age at diagnosis was 50.2 ± 16.4 years, with a median PD time of 77.96 months (range: 44.36 - 102.7 months) and a median follow-up of 30.91 months (range: 4.6 - 68.75 months). Of patients with EPS, 10 (50%) received tamoxifen, 10 (50%) received parenteral nutrition, and 2 (10%) underwent adhesiolysis, with 25% mortality related to EPS. Another 14 patients were identified as EPS-prone. Median follow-up was 54.05 months (range: 11.9 - 87.04 months). All received tamoxifen, and 5 (36%) received corticosteroids; none progressed to full EPS. We observed no differences in baseline data between the groups, but the group with EPS had been on PD longer (84 ± 53 months vs 39 ± 20 months, p = 0.002) and had a higher cumulative number of days of peritoneal inflammation from peritonitis (17.2 ± 11.1 days vs 9.8 ± 7.9 days, p = 0.015). Overall mortality was similar in the groups. The incidence of EPS declined during our three decades of experience (5.6%, 3.9%, and 0.3%). CONCLUSIONS: Being a serious, life-threatening complication of PD, EPS requires high suspicion to allow for prompt diagnosis and treatment. Early detection of EPS-prone states and delivery of appropriate intervention might prevent EPS development. Tamoxifen seems to be a key strategy in prevention, but caution should be used in interpreting our results. Additional randomized controlled studies are needed.

IL-17A is a novel player in dialysis-induced peritoneal damage.

The classical view of the immune system has changed by the discovery of novel T-helper (Th) subsets, including Th17 (IL-17A-producing cells). IL-17A participates in immune-mediated glomerulonephritis and more recently in inflammatory pathologies, including experimental renal injury. Peritoneal dialysis patients present chronic inflammation and Th1/Th2 imbalance, but the role of the Th17 response in peritoneal membrane damage has not been investigated. In peritoneal biopsies from dialyzed patients, IL-17A immunostaining was found mainly in inflammatory areas and was absent in the healthy peritoneum. IL-17A-expressing cells included lymphocytes (CD4+ and γδ), neutrophils, and mast cells. Elevated IL-17A effluent concentrations were found in long-term peritoneal dialysis patients. Studies in mice showed that repeated exposure to recombinant IL-17A caused peritoneal inflammation and fibrosis. Moreover, chronic exposure to dialysis fluids resulted in a peritoneal Th17 response, including elevated IL-17A gene and protein production, submesothelial cell infiltration of IL-17A-expressing cells, and upregulation of Th17 differentiation factors and cytokines. IL-17A neutralization diminished experimental peritoneal inflammation and fibrosis caused by chronic exposure to dialysis fluids in mice. Thus, IL-17A is a key player of peritoneum damage and it may be a good candidate for therapeutic intervention in peritoneal dialysis patients.

Evaluación de un programa de Programa de Intervención Nutricionalen pacientes con enfermedad renal crónica avanzada (ERCA) / Evaluation of a nutrition education and physical activity intervention in Chilean low socioeconomic women

Introducción y Objetivos: La Enfermedad Renal Crónica Avanzada (ERCA) se asocia a una elevada prevalencia de malnutrición. La práctica habitual en estos pacientes va dirigida a reducir la ingesta proteica, recomendación que podría favorecer esta situación. Por ello, el objetivo de este estudio fue evaluar el efecto de un programa de intervención nutricional (PIN) sobre la función renal y el estado nutricional en pacientes con ERCA. Pacientes y Métodos: Se diseñó un estudio longitudinal y prospectivo con 93 pacientes (53,7% hombres, 66 ± 17años) que participaron en un PIN durante 6 meses con visitas mensuales. Al inicio y al final de la intervención se evaluaron: estado nutricional en función de los criterios de Chang, datos antropométricos, dietéticos y bioquímicos (albúmina, prealbúmina, aclaramiento de creatinina, fósforo y potasio séricos, Colesterol-total, LDL, HDL, triglicéridos y PCR). Resultados: Tras el PIN la ingesta calórica disminuyó en los normonutridos (1833 ± 318 vs 1571 ± 219 kcal p < 0,001) y se mantuvo en los malnutridos. Se redujo significativamente la ingesta proteica (69,9 ± 16,6 vs 54,9 ± 11 g p < 0,001), potasio (2938 ± 949 vs 2377 ± 743 mg, p < 0,0001) y fósforo (1180 ± 304 vs 946,6 ± 211 mg, p < 0,0001). Un 16,5% requirió suplementación. El porcentaje de pacientes que presentaba malnutrición según criterios de Chan disminuyó tras el PIN (41,7 % (27,8% leve, 10,10% moderada y 3,8% grave) vs 16,8% (8% leve, 5% moderada y 3,8% grave)). Tras el PIN incrementó significativamente el aclaramiento de creatinina (17,8 ± 5,2 vs 19,4 ± 6,9 ml/min, p < 0,01), albúmina (3,3 ± 0,5 g/dL vs 3,5 ± 0,4 g/dL, p < 0,05) y disminuyó el potasio sérico (4,8 ± 0,6 vs 4,5 ± 0,5 mmol/L, p < 0,05), Colesterol Total (179,8 ± 44,3 vs 170,0 ± 15,1 mg/dL, p < 0,05), LDL colesterol (113,2 ± 37,0 vs 108,3 ± 27,3 mg/dL, p < 0.01) y trigli-céridos (141,9 ± 60,8 vs 129,9 ± 52,7 mg/dL, p < 0,05). Conclusiones: La mejoría del estado nutricional y de la función renal conseguidos ponen de manifiesto la utilidad de este PIN dentro de un marco interdisciplinar en las consultas de ERCA (AU)

Introduction and Objectives: Advanced Chronic Kidney Disease (ACKD) is associated with high prevalence of malnutrition. The habitual continuous dietary restrictions used in clinical practice. increased the malnutrition risk. The aim of this study was to evaluate the effects of a Nutritional intervention Program (NIP) on renal function and nutritional status in patients with ACKD. Patients and Methods: 93 patients, (53.7% men, 66 ± 17 years) were included in a prospective longitudinal study. The patients recived a NIP during 6 months with mensual visits. At baseline and six months the outcome assessed were: nutritional status by Chang criteria, anthropometric, dietetic and biochemical parameters (albumin, prealbumin, creatinine clearance, serum phosphorus, potassium, total-Cholesterol, LDL, HDL, triglycerides, and PCR). Results: After intervention, caloric intake decreased in nourished patients (1833 ± 318 vs 1571 ± 219 kcal p = .001). and it was constant in malnourished patients. The intake of protein (69,9 ± 16,6 vs 54,9 ± 11 g p < 0.001), potassium (2938 ± 949 vs 2377 ± 743 mg p < 0.001) and phosphorus (1180 ± 304 vs 946,6 ± 211 mg p < 0.001) significantly decreased. 16.5% patients required supplementation. A total of 41.7% of patients were malnourished at baseline (27.8% mild, 10.10% moderate and 3.8% severe), and 16.8% at the end (8% mild, 5% moderate and 3.8% severe) by Chang criteria. At the end of NIP, patients significantly increased creatinine clearance (17,8 ± 5,2 vs 19,4 ± 6,9 ml/min, p < 0,01), albumin (3,3 ± 0,5 vs. 3,5 ± 0,4 g/dL, p < 0,05), and decreased serum potassium (4,8 ± 0,6 vs 4,5 ± 0,5 mmol/L, p < 0,05), total cholesterol (179,8 ± 44,3 vs 170,0 ± 15,1 mg/dL, p < 0,05), LDL (113,2 ± 37,0 vs 108,3 ± 27,3 mg/dL, p < 0.01) and tryglicerides (141.9 ± 60.8 vs 129.9 ± 52.7 mg/dL, p < 0.05). Conclusions: The study reflected a NIP usefulness in the nutritional status and renal function improvements within an interdisciplinary framework during ACKD consultations (AU)

Repeated analysis of estimated insulin resistance using the HOMAIR index in nondiabetic patients on peritoneal dialysis and its relationship with cardiovascular disease and mortality.

Terminal chronic renal failure patients show early insulin resistance (IR), characterised by alterations in the hydrocarbon metabolism and hyperinsulinaemia generally associated with dyslipidaemia and a proinflammatory condition. Cardiovascular disease (CVD) is the main cause of mortality in patients on dialysis. There is a strong association between IR, hyperinsulinism and CV disease. The objective of this study was to evaluate the effect of peritoneal dialysis (PD) on IR and its effects on the subsequent CVD morbidity and mortality in nondiabetic uraemic patients. It involved 69 nondiabetic patients on PD, 35 incident patients (≤ 3 months on PD) and 34 prevalent patients (>3 months on PD), with 2 estimated insulin resistance measurements 12 months apart using the insulin resistance index (HOMAIR). The mean HOMAIR value in incident patients was 1.8 ± 1.3 and 2.2 ± 2.1 at baseline situation and at 12 months respectively (not significant [NS]). In prevalent patients these values were 2.3 ± 1.3 and 2.5 ± 2.2 (NS). In our study, the mean glucose, insulin and IR concentrations measured by the HOMAIR and QUICKI indexes (the latter being a quantitative control for insulin sensitivity control) were similar at baseline situation and the following year, in both incident and prevalent patients. We did not find any significant differences in relation to CVD comorbidity, ischaemic heart disease, heart failure or cerebrovascular or peripheral comorbidity neither in the HOMAIR index or insulin levels. To conclude, nondiabetic patients on PD do not display a significant increase in HOMAIR levels and this remains the case over time when on dialysis. This, in turn, suggests that PD is not an IR risk factor. The fact that the IR indexes are not associated with CVD morbidity or mortality seems to suggest that this is a less significant factor in the field of PD.

Análisis repetido de la resistencia insulínica estimada mediante índice HOMAIR en pacientes no diabéticos en diálisis peritoneal y su relación con la enfermedad cardiovascular y mortalidad / Repeated analysis of estimated insulin resistance using the HOMAIR index in nondiabetic patients on peritoneal dialysis and its relationship with cardiovascular disease and mortality

Los pacientes con enfermedad renal crónica terminal muestran precozmente resistencia insulínica (RI), caracterizada por alteraciones en el metabolismo hidrocarbonado e hiperinsulinemia generalmente asociada a dislipemia y a un patrón pro inflamatorio. La enfermedad cardiovascular (CV) constituye la principal causa de mortalidad en los pacientes en diálisis. Existe una fuerte asociación entre RI, hiperinsulinismo y enfermedad CV. El objetivo del presente estudio fue evaluar el efecto de la diálisis peritoneal (DP) sobre la RI y sus efectos sobre la morbimortalidad CV subsiguiente en pacientes urémicos no diabéticos. Se incluyeron 69 pacientes no diabéticos en DP, 35 incidentes (< 3 meses en DP) y 34 prevalentes (> 3 meses en DP), con 2 mediciones de resistencia insulínica estimada mediante el índice de resistencia a la insulina (HOMAIR), separadas entre sí por 12 meses. El valor medio de HOMAIR en pacientes incidentes fue 1,8 ± 1,3 y 2,2 ± 2,1 en situación basal y a los 12 meses, respectivamente (no significativa [ns]). En pacientes prevalentes estos valores fueron 2,3 ± 1,3 y 2,5 ± 2,2 (ns). En nuestro estudio, las concentraciones medias de glucosa, insulina y RI medida por el HOMAIR y QUICKI (índice cuantitativo de control de la sensibilidad a la insulina) fueron similares en situación basal y al año de seguimiento, tanto en incidentes como en prevalentes. No objetivamos diferencias significativas en relación con la comorbilidad CV, cardiopatía isquémica, insuficiencia cardíaca o comorbilidad vascular cerebral o periférica, ni en función del índice HOMAIR, ni en el de los niveles de insulina. En conclusión, los pacientes no diabéticos en DP no presentan elevación significativa de los niveles de HOMAIR, ni se modifica con paso del tiempo en diálisis, lo que sugiere que la DP no es un factor de riesgo de RI. El hecho de que los índices de RI no se asocien a morbilidad o mortalidad CV parece sugerir el menor peso de este factor en el ámbito de la DP (AU)

Terminal chronic renal failure patients show early insulin resistance (IR), characterised by alterations in the hydrocarbon metabolism and hyperinsulinaemia generally associated with dyslipidaemia and a proinflammatory condition. Cardiovascular disease (CVD) is the main cause of mortality in patients on dialysis. There is a strong association between IR, hyperinsulinism and CV disease. The objective of this study was to evaluate the effect of peritoneal dialysis (PD) on IR and its effects on the subsequent CVD morbidity and mortality in nondiabetic uraemic patients. It involved 69 nondiabetic patients on PD, 35 incident patients (<3 months on PD) and 34 prevalent patients (>3 months on PD), with 2 estimated insulin resistance measurements 12 months apart using the insulin resistance index (HOMAIR). The mean HOMAIR value in incident patients was 1.8±1.3 and 2.2±2.1 at baseline situation and at 12 months respectively (not significant [NS]). In prevalent patients these values were 2.3±1.3 and 2.5±2.2 (NS). In our study, the mean glucose, insulin and IR concentrations measured by the HOMAIR and QUICKI indexes (the latter being a quantitative control for insulin sensitivity control) were similar at baseline situation and the following year, in both incident and prevalent patients. We did not find any significant differences in relation to CVD comorbidity, ischaemic heart disease, heart failure or cerebrovascular or peripheral comorbidity neither in the HOMAIR index or insulin levels. To conclude, nondiabetic patients on PD do not display a significant increase in HOMAIR levels and this remains the case over time when on dialysis (AU)

[Evaluation of a Nutritional Intervention Program in advanced chronic kidney disease (ACKD) patients]. / Evaluación de un Programa de Intervención Nutricional en pacientes con enfermedad renal crónica avanzada (ERCA).

INTRODUCTION AND OBJECTIVES: Advanced Chronic Kidney Disease (ACKD) is associated with high prevalence of malnutrition. The habitual continuous dietary restrictions used in clinical practice. increased the malnutrition risk. The aim of this study was to evaluate the effects of a Nutritional intervention Program (NIP) on renal function and nutritional status in patients with ACKD. PATIENTS AND METHODS: 93 patients, (53.7% men, 66±17 years) were included in a prospective longitudinal study. The patients recived a NIP during 6 months with mensual visits. At baseline and six months the outcome assessed were: nutritional status by Chang criteria, anthropometric, dietetic and biochemical parameters (albumin, prealbumin, creatinine clearance, serum phosphorus, potassium, total-Cholesterol, LDL, HDL, triglycerides, and PCR). RESULTS: After intervention, caloric intake decreased in nourished patients (1833 ±318 vs. 1571±219 kcal p=.001). and it was constant in malnourished patients. The intake of protein (69,9 ± 16,6 vs 54,9 ± 11 g p < 0.001), potassium (2938 ± 949 vs 2377 ± 743 mg p < 0.001) and phosphorus (1180 ± 304 vs 946,6 ± 211 mg p < 0.001) significantly decreased. 16.5% patients required supplementation. A total of 41.7% of patients were malnourished at baseline (27.8% mild, 10.10% moderate and 3.8% severe), and 16.8% at the end (8% mild, 5% moderate and 3.8% severe) by Chang criteria. At the end of NIP, patients significantly increased creatinine clearance (17,8 ± 5,2 vs 19,4 ± 6,9 ml/min, p < 0,01), albumin (3,3 ± 0,5 vs. 3,5 ± 0,4 g/dL, p < 0,05), and decreased serum potassium (4,8 ± 0,6 vs 4,5 ± 0,5 mmol/L, p < 0,05), total cholesterol (179,8 ± 44,3 vs 170,0 ± 15,1 mg/dL, p < 0,05), LDL (113,2 ± 37,0 vs 108,3 ± 27,3 mg/dL, p < 0.01) and tryglicerides (141.9 ± 60.8 vs 129.9 ± 52.7 mg/dL, p < 0.05).\ CONCLUSIONS: The study reflected a NIP usefulness in the nutritional status and renal function improvements within an interdisciplinary framework during ACKD consultations.

Introducción y Objetivos: La Enfermedad Renal Crónica Avanzada (ERCA) se asocia a una elevada prevalencia de malnutrición. La práctica habitual en estos pacientes va dirigida a reducir la ingesta proteica, recomendación que podría favorecer esta situación. Por ello, el objetivo de este estudio fue evaluar el efecto de un programa de intervención nutricional (PIN) sobre la función renal y el estado nutricional en pacientes con ERCA. Pacientes y Métodos: Se diseñó un estudio longitudinal y prospectivo con 93 pacientes (53,7% hombres, 66±17años) que participaron en un PIN durante 6 meses con visitas mensuales. Al inicio y al final de la intervención se evaluaron: estado nutricional en función de los criterios de Chang, datos antropométricos, dietéticos y bioquímicos (albúmina, prealbúmina, aclaramiento de creatinina, fósforo y potasio séricos, Colesterol-total, LDL, HDL, triglicéridos y PCR). Resultados: Tras el PIN la ingesta calórica disminuyó en los normonutridos (1833±318 vs 1571±219 kcal p.

The influence of initial peritoneal transport characteristics, inflammation, and high glucose exposure on prognosis for peritoneal membrane function.

BACKGROUND: Fast transport status, acquired with time on peritoneal dialysis (PD), is a pathology induced by peritoneal exposure to bioincompatible solutions. Fast transport has important clinical consequences and should be prevented. OBJECTIVE: We analyzed the repercussions of initial peritoneal transport characteristics on the prognosis for peritoneal membrane function, and also whether the influence of peritonitis and high exposure to glucose are different according to the initial peritoneal transport characteristics or the moment when such events occur. METHODS: The study included 275 peritoneal dialysis patients with at least 2 peritoneal function studies (at baseline and 1 year). Peritoneal kinetic studies were performed at baseline and annually. Those studies consist of a 4-hour dwell with glucose (1.5% during 1981 - 1990, and 2.27% during 1991 - 2002) to calculate the peritoneal mass transfer coefficients of urea and creatinine (milliliters per minute) using a previously described mathematical model. RESULTS: Membrane prognosis and technique survival were independent of baseline transport characteristics. Fast transport and ultrafiltration (UF) failure are reversible conditions, provided that peritonitis and high glucose exposure are avoided during the early dialysis period. The first year on PD is a main determining factor for the membrane's future, and the mass transfer coefficient of creatinine at year 1 is the best functional predictor of future PD history. After 5 years on dialysis, permeability frequently increases, and UF decreases. Icodextrin is associated with peritoneal protection. CONCLUSIONS: Peritoneal membrane prognosis is independent of baseline transport characteristics. Intrinsic fast transport and low UF are reversible conditions when peritonitis and high glucose exposure are avoided during the early dialysis period. Icodextrin helps in glucose avoidance and is associated with peritoneal protection.

Two-in-one protocol: simultaneous small-pore and ultrasmall-pore peritoneal transport quantification.

BACKGROUND: Reduced free water transport (FWT) through ultrasmall pores contributes to net ultrafiltration failure (UFF) and should be seen as a sign of more severe functional deterioration of the peritoneal membrane. The modified peritoneal equilibration test (PET), measuring the dip in dialysate Na concentration, estimates only FWT. Our aim was to simultaneously quantify small-solute transport, FWT, and small-pore ultrafiltration (SPUF) during a single PET procedure. METHODS: We performed a 4-hour, 3.86% glucose PET, with additional measurement of ultrafiltration (UF) at 60 minutes, in 70 peritoneal dialysis patients (mean age: 50 ± 16 years; 61% women; PD vintage: 26 ± 23 months). We calculated the dialysate-to-plasma ratios (D/P) of creatinine and Na at 0 and 60 minutes, and the Na dip (Dip(D/PNa60')), the delta dialysate Na 0-60 (ΔDNa(0-60)), FWT, and SPUF. RESULTS: Sodium sieving (as measured by ΔDNa(0-60)) correlated strongly with the corrected Dip(D/PNa60') (r = 0.85, p < 0.0001) and the corrected FWT (r = 0.41, p = 0.005). Total UF showed better correlation with FWT than with indirect measurements of Na sieving (r = 0.46, p < 0.0001 for FWT; r = 0.360, p < 0.0001 for Dip(D/PNa60')). Corrected FWT fraction was 0.45 ± 0.16. A negative correlation was found between time on PD and both total UF and FWT (r = -0.253, p = 0.035 and r = -0.272, p = 0.023 respectively). The 11 patients (15.7%) diagnosed with UFF had lower FWT (89 mL vs 164 mL, p < 0.05) and higher D/P creatinine (0.75 vs 0.70, p < 0.05) than did the group with normal UF. The SPUF correlated positively with FWT in the normal UF group, but negatively in UFF patients (r = -0.709, p = 0.015). Among UFF patients on PD for a longer period, 44.4% had a FWT percentage below 45%. CONCLUSIONS: Measurement of FWT and SPUF is feasible by simultaneous quantification during a modified 3.86% glucose PET, and FWT is a decisive parameter for detecting causes of UFF in addition to increased effective capillary surface.

Effect of self-administered intraperitoneal bemiparin on peritoneal transport and ultrafiltration capacity in peritoneal dialysis patients with membrane dysfunction. A randomized, multi-centre open clinical trial.

BACKGROUND: Progressive peritoneal membrane injury and dysfunction are feared repercussions of peritoneal dialysis (PD), and may compromise the long-term feasibility of this therapy. Different strategies have been attempted to prevent or reverse this complication with limited success. METHODS: We performed a randomized, open multi-centre trial, aimed at scrutinizing the efficacy of self-administered intraperitoneal (i.p.) bemiparin (BM) to modulate peritoneal membrane dysfunction. The main outcome variables were peritoneal creatinine transport and the ultrafiltration (UF) capacity, estimated during consecutive peritoneal equilibration tests. The trial included a control group who did not undergo intervention. The treatment phase lasted 16 weeks with a post-study follow-up of 8 weeks. RESULTS: Intraperitoneal BM did not significantly improve creatinine transport or the UF capacity, when the whole group was considered. However, we observed a time-limited improvement in the UF capacity for the subgroup of patients with overt UF failure, which was not observed in the control group. Intraperitoneal injection of BM did not carry an increased risk of peritoneal infection or major haemorrhagic complications. CONCLUSIONS: Our data do not support the systematic use of BM for management of peritoneal membrane dysfunction in PD patients. Further studies on the usefulness of this approach in patients with overt UF failure are warranted. Intraperitoneal administration of BM is safe in PD patients, provided regulated procedures are respected.