DIALYSIS. PROTEIN-ENERGY WASTING, INFLAMMATION AND OXIDATIVE STRESS

Abstract

Introduction and Aims: Among the 600 to 700 mg of inorganic phosphate (Pi) removed during a 4-hour hemodialysis session, a maximum of 10% could be extracted from the extracellular space (1). The origin of the other 90% of removed Pi is unknown and two hypothesis have been proposed being either the intracellular compartment or bone. Spalding et al (2) hypothesized that Pi exchanges between intra and extracellular compartments were diffusive, suggesting that the intracellular compartment could be the main source of Pi removed during hemodialysis. Therefore, we proposed to test this hypothesis during a hemodialysis session, by using Phosphorus (31P) Magnetic Resonance Spectroscopy (MRS), which is the only tool allowing in vivo and dynamic measurement of the intracellular Pi concentration as well as the other’s phosphate metabolites such as Phosphocreatine (PCr) and ATP.Methods: 3-hour hemodialysis sessions were performed in 6 pigs, after surgical bi-nephrectomy, with a Prismaflex® generator and a M100® dialyser (Hospal). The extra-corporal circulation blood flow was maintained between 100 and 150 mL/min. 31P MRS exams were performed with a 1.5T Siemens Sonata system using a surface coil (20 cm) placed over the gluteal muscle region. 31P MR spectra (TR=10s, TE=0.35ms) were acquired every 2’40” before, during and after dialysis. Blood samples were obtained during the whole examination to measure plasma Pi concentrations.Results: During the dialysis, the mean PCr/Pi ratio decreased significantly (-6.9%, p<0.00001), while the Pi/βATP ratio increased (+22.2%, p<0.00001). Plasma Pi concentration felt rapidly within 60 min from 2.30 ± 0.18 mmol/L to 1.65 ± 0.10 mmol/L (-28,08%, p=0.003) then plateaued.Conclusions: This study demonstrated that intracellular Pi concentration did not decrease in parallel with the extracellular Pi decrease as proposed (2). In contrast, the intracellular Pi increase may reflect a cellular stress induced by hemodialysis and/or a strong intracellular Pi production.1. Gallar P et al. Nefrologia, 27:46-52, 2007.2. Spalding, et al. Kidney Int, 61:655-67, 2002.Introduction and Aims: Lipid lowering agents have decreasing effect on all-cause mortality as renal function declines losing statistical significance among patients with End Stage Renal Disease (ESRD). Low density lipoproteins (LDL) are capable of absorbing and inactivating bacterial toxins (S Bhakdi) and human LDL can prevent endotoxin induced lethality in mice (Feingold). The second highest leading cause of death among ESRD patients after cardiovascular diseases is infectious. We conducted this analysis to explore the relationship between blood lipid composition and both cardiovascular and infectious outcomes.Methods: The MONitoring Dialysis Outcomes [MONDO] consortium consists of hemodialysis (HD) databases from Renal Research Institute [RRI] clinics in the US, Fresenius Medical Care [FMC] clinics in Europe, Asia Pacific, Latin America, KfH clinics in Germany, Imperial College in the UK, Hadassah Medical Center, Israel, Pontifical Catholic University of Parana, Brazil, and University of Maastricht, The Netherlands. Databases from RRI and FMC Europe [17 countries] were used to identify all patients with in-center treatments [1/2006-12/2012] who survived ≥12 months on HD. Only those with at least one record of HDL and LDL cholesterol, triglycerides, and neutrophils to lymphocyte ratio (NLR) in the first 12 months were selected (baseline period). The mean clinical and laboratory parameters were computed for the first 12 months and hospitalizations and clinical events (deaths and hospitalizations) were observed in months 13 to 24 (Followup period). Hospitalizations and mortality were classified as cardiovascular (CVD)-related or infectious-related and Poisson regression models were constructed to explore associations between baseline parameters and the number of CVD and infectious events in the follow up period.Results: We studied 22746 patients [FMC Europe 16911; RRI 5835]. Higher HDL was associated with fewer CVD deaths and hospitalizations (adjusted by NLR) while higher LDL was associated with less infectious deaths and hospitalizations but had no relationship to CVD outcomes. The association between HDL and CVD events was still significant when adjusted for NLR, a marker of inflammation (table 1). Results adjusted for CRP were similar although no CRP data was available for North America (results not shown).Adjusted for geographic region, age, gender, race, BMI, diabetic status, NLR and albuminPoisson regression resultsConclusions: Higher HDL is associated with fewer CVD events, while higher LDL is associated with fewer infectious deaths and hospitalizations. These data may contribute to the inverse association between LDL and mortality in the dialysis populationIntroduction and Aims: Soluble CD40L (sCD40L) is a well-known proinflammatory and proatherogenic agent. The RISCAVID study demonstrated an increased cardiovascular risk in patients with sCD40L serum levels exceeding 7.6 ng/ml. The aim of our study was to evaluate the effect of different hemodialysis membranes on sCD40L levels in hemodialytic patients (HD).Methods: Twenty-three stable HD patients were randomized as follow: Group 1. Nine patients were dialyzed for three months with Polyamide (PA) or polysulfone (PS) membranes and then shifted (time 0) in polymethylmethacrylate (PMMA) membrane for a further three months; Group 2. Six patients were dialyzed for three months with PMMA membrane and subsequently shifted to PA / PS for a further three months; Group 3 and 4, eight patients were maintained in PMMA or PA / PS membrane. We measured the sCD40L serum levels (ELISA) at times 0, 30, 60 and 90 days. Furthermore, to investigate inflammation and apoptosis induced by uremic serum in vitro, HUVEC cells were incubated with serum of patients of group 1 and 2.Results: In vivo study. The group 1 sCD40L serum levels were significantly reduced after three months from 10.4±1.6 ng/ml) at time 0 to 5.2±0.9 ng/ml at time 90, (p<0.001) below the threshold of 7.6 ng/ml. In group 2 sCD40L serum level increased from 6.5±1.3 ng/ml to 7.8±1.7 ng/ml, but the difference was not statistically significant. In groups 3 and 4 the levels of CD40L were stable. In vitro study. Less pro-inflammatory (monocyte adhesion and ICAM -1 and E- seletin expression) and proapoptotic (XTT and TUNEL) activity was detected in HUVEC cells incubated with serum of patients from group 1 compared to group 2. These effects were reduced on HUVEC treated with siRNA, confirming the role of sCD40L.Conclusions: These preliminary data demonstrated an effect of the PMMA in the reduction of circulating sCD40L, probably due to its adsorbitive properties. This effect could reduce the cardiovascular risk in HD patients.Introduction and Aims: In MHD, protein-energy malnutrition can be critical and is one of the main causes of mortality. In MHD patients, nutritional and inflammatory conditions could progress or regress during follow-up period, and may cause the adverse events and premature mortality in MHD. However, few studies had reported regarding the influence of changes in nutritional or inflammatory status on adverse events or survival in MHD. In this study, we evaluated the relationship between the changes in nutritional or inflammatory indexes and the adverse events or mortality.Methods: Study design: Prospective, observational multi center study. Observational period: 2 years. Subject and measurement: In 1086 MHD patients, blood levels of Hb, albumin, prealbumin, high sensitive CRP (hCRP), were measured every 3 month. And body mass index (BMI) is also evaluated.Results: In logistic regression analysis, Hb (p=0.008, Exp (β)=0.797) and pre-albumin (p=0.001, Exp (β) =0.968) were selected as the significant predictors of the change in BMI during the follow up period. Moreover, age (p=0.003, Exp (β) =1.039) was selected as a significant predictor of the change in serum albumin. In the time dependent cox hazard model, in patients who were under 62 years old, there were no significant changes in BMI and serum albumin levels during 2 years. On the other hand, in the patients over 62 years old, BMI (p=0.0025, from 21.4 ± 0.17 to 21.2 ± 0.17) and serum albumin (p=0.0001, from 3.72 ± 0.015 to 3.66 ± 0.017 g/dL) levels were significantly decreased during the follow-up period. Patients who showed the decline in BMI were associated with the elevated risks for cerebro-cardiovascular disease (CCVD) (p=0.012, HR: 2.19) and hospitalization (p=0.002, HR: 1.57). Moreover, patients who showed the decline in serum albumin also associated with higher risk for infectious disease (p=0.001, HR: 1.55) and hospitalization (p=0.049, HR: 1.35). In addition, patients who showed the increase in hCRP had a higher risk for CCVD (p=0.023, HR: 0.44) and death (p=0.023, HR: 0.32).Conclusions: This study revealed that the downward trend of nutritionnal status was prominent in elderly MHD. Furthermore, the progress in malnutrition and inflammation could be associated with the several adverse events in MHD patients.Introduction and Aims: Periodontal disease (PD) was reported as highly prevalent in haemodialysis (HD) patients and was associated with inflammation-malnutrition complex and higher mortality. We aimed to assess the extention of PD and its impact on HD patients’ survival.Methods: In this prospective single center observational study 263 stable HD patients (age: 57 [50-65] years; 60% males; HD vintage 6.9 [6.2-7.6] years; primary kidney disease: glomerulopathies in 34% cases, diabetic nephropathy in 11%) were enrolled and followed for a median period of 24.6 months. Periodontal status was examined according to WHO recommendations by a single examiner and quantified based on loss of clinical attachment level (CAL): no/mild periodontitis (CAL<3mm), moderate or severe periodontitis (CAL 3-4 mm or ≥5mm, respectively). Demografic data, smoking status, haematologic d