Comparison of the removal of uraemic toxins with medium cut-off and high-flux dialysers: a randomized clinical trial

International audienceBACKGROUND:Accumulation of middle-weight uraemic toxins in haemodialysis (HD) patients results in increased morbidity and mortality. Whether medium cut-off HD (MCO-HD) improves removal of middle-weight uraemic toxins remains to be demonstrated.METHODS: This cross-over prospective study included 40 patients randomly assigned to receive either 3 months of MCO-HD followed by 3 months of high-flux HD (HF-HD), or vice versa. The primary endpoint was myoglobin reduction ratio (RR) after 3 months of MCO-HD. Secondary endpoints were the effect of MCO-HD on other middle-weight toxins and protein-bound toxins, and on parameters of nutrition, inflammation, anaemia and oxidative stress.RESULTS: Compared with HF-HD, MCO-HD provided higher mean RR of myoglobin (36 ± 8 versus 57 ± 13%, P < 0.0001), beta2-microglobulin (68 ± 6 versus 73 ± 15%, P = 0.04), prolactin (32 ± 13 versus 59 ± 11%, P < 0.0001), fibroblast growth factor 23 (20 ± 21 versus 41 ± 22%, P = 0.0002), homocysteine (43 ± 7 versus 46 ± 9%, P = 0.03) and higher median RR of kappa [54 (48-58) versus 70 (63-74)%, P < 0.0001] and lambda free light chain (FLC) [15 (9-22) versus 44 (38-49)%, P < 0.0001]. Mean ± SD pre-dialysis levels of beta2-microglobulin (28.4 ± 5.6 versus 26.9 ± 5.1 mg/L, P = 0.01) and oxidized low-density lipoprote (6.9 ± 4.4 versus 5.5 ± 2.5 pg/mL, P = 0.04), and median (interquartile range) kappa FLC [145 (104-203) versus 129 (109-190) mg/L, P < 0.03] and lambda FLC [106 (77-132) versus 89 (62-125) mg/L, P = 0.002] were significantly lower. Mean albumin levels decreased significantly (38.2 ± 4.1 versus 36.9 ± 4.3 g/L, P = 0.004), without an effect on nutritional status as suggested by unchanged normalized protein catabolic rate and transthyretin level.CONCLUSIONS: Compared with HF-HD, MCO-HD provides higher myoglobin and other middle molecules RR and is associated with moderate hypoalbuminemia. The potential benefits of this strategy on long-term clinical outcomes deserve further evaluation

Renal function decline and heart failure hospitalisation in patients with type 2 diabetes: Dynamic predictions from the prospective SURDIAGENE cohort

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The Added Value of Point-Light Display Observation in Total Knee Arthroplasty Rehabilitation Program: A Prospective Randomized Controlled Pilot Study

International audienceBackground and Objectives: The present study aimed to assess the potential benefit of the observation of rehabilitation-related point-light display in addition to a conventional 3-week rehabilitation program, the objective being to improve functional capacity in patients having undergone total knee arthroplasty.Materials and Methods: Patients randomized in the control group had conventional rehabilitation treatment with two sessions per day 5 days a week of physical therapy (90 min), whereas patients in the experimental group had a program of conventional rehabilitation combined with a point-light display observation two times per day (5 min) and 3 days a week.Results: The patients of both groups had improved their performances by the end of the program, and the pre- and post-test improvement were superior for the experimental group over the control group concerning the total WOMAC score (p = 0.04), the functional WOMAC score (p = 0.03), and correct recognition of point-light displays (p = 0.003).Conclusions: These findings provide new insight favoring systematic point-light display observation to improve functional recovery in patients with total knee arthroplast

Association of Circulating Biomarkers (Adrenomedullin, TNFR1, and NT-proBNP) With Renal Function Decline in Patients With Type 2 Diabetes: A French Prospective Cohort

International audienceOBJECTIVE We explored the prognostic value of three circulating candidate biomarkers—midregional-proadrenomedullin (MR-proADM), soluble tumor necrosis factor receptor 1 (sTNFR1), and N-terminal prohormone brain natriuretic peptide (NT-proBNP)—for change in renal function in patients with type 2 diabetes.RESEARCH DESIGN AND METHODS Outcomes were defined as renal function loss (RFL), ≥40% decline of estimated glomerular filtration rate (eGFR) from baseline, and rapid renal function decline (RRFD), absolute annual eGFR slope <–5 mL/min/year. We used a proportional hazard model for RFL and a logistic model for RRFD. Adjustments were performed for established risk factors (age, sex, diabetes duration, HbA1c, blood pressure, baseline eGFR, and urinary albumin-to-creatinine ratio [uACR]). C-statistics were used to assess the incremental predictive value of the biomarkers to these risk factors.RESULTS Among 1,135 participants (mean eGFR 76 mL/min, median uACR 2.6 mg/mmol, and median GFR slope −1.6 mL/min/year), RFL occurred in 397, RRFD developed in 233, and 292 died during follow-up. Each biomarker predicted RFL and RRFD. When combined, MR-proADM, sTNFR1, and NT-proBNP predicted RFL independently from the established risk factors (adjusted hazard ratio 1.59 [95% CI 1.34–1.89], P < 0.0001; 1.33 [1.14–1.55], P = 0.0003; and 1.22 [1.07–1.40], P = 0.004, respectively) and RRFD (adjusted odds ratio 1.56 [95% CI 1.7–2.09], P = 0.003; 1.72 [1.33–2.22], P < 0.0001; and 1.28 [1.03–1.59], P = 0.02, respectively). The combination of the three biomarkers yielded the highest discrimination (difference in C-statistic = 0.054, P < 0.0001; 0.067, P < 0.0001 for RFL; and 0.027, P < 0.0001 for RRFD).CONCLUSIONS In addition to established risk factors, MR-proADM, sTNFR1, and NT-proBNP improve risk prediction of loss of renal function in patients with type 2 diabetes

Acute Kidney Injury Predicts Major Adverse Outcomes in Diabetes: Synergic Impact With Low Glomerular Filtration Rate and Albuminuria

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Influence of micro- and macro-vascular disease and Tumor Necrosis Factor Receptor 1 on the level of lower-extremity amputation in patients with type 2 diabetes

Abstract Background Patients with type 2 diabetes (T2D) face a high amputation rate. We investigated the relationship between the level of amputation and the presence of micro or macro-vascular disease and related circulating biomarkers, Tumor Necrosis Factor Receptor 1 (TNFR1) and Angiopoietin like-2 protein (ANGPTL2). Methods We have analyzed data from 1468 T2D participants in a single center prospective cohort (the SURDIAGENE cohort). Our outcome was the occurrence of lower limb amputation categorized in minor (below-ankle) or major (above ankle) amputation. Microvascular disease was defined as a history of albuminuria [microalbuminuria: uACR (urinary albumine-to-creatinine ratio) 30–299 mg/g or macroalbuminuria: uACR ≥ 300 mg/g] and/or severe diabetic retinopathy or macular edema. Macrovascular disease at baseline was divided into peripheral arterial disease (PAD): peripheral artery revascularization and/or major amputation and in non-peripheral macrovascular disease: coronary artery revascularization, myocardial infarction, carotid artery revascularization, stroke. We used a proportional hazard model considering survival without minor or major amputation. Results During a median follow-up period of 7 (0.5) years, 79 patients (5.5%) underwent amputation including 29 minor and 50 major amputations. History of PAD (HR 4.37 95% CI [2.11–9.07]; p < 0.001), severe diabetic retinopathy (2.69 [1.31–5.57]; p = 0.0073), male gender (10.12 [2.41–42.56]; p = 0.0016) and serum ANGPTL2 concentrations (1.25 [1.08–1.45]; p = 0.0025) were associated with minor amputation outcome. History of PAD (6.91 [3.75–12.72]; p < 0.0001), systolic blood pressure (1.02 [1.00–1.03]; p = 0.004), male gender (3.81 [1.67–8.71]; p = 0.002), and serum TNFR1 concentrations (HR 13.68 [5.57–33.59]; p < 0.0001) were associated with major amputation outcome. Urinary albumin excretion was not significantly associated with the risk of minor and major amputation. Conclusions This study suggests that the risk factors associated with the minor vs. major amputation including biomarkers such as TNFR1 should be considered differently in patients with T2D

Nutritional biomarkers and heart failure requiring hospitalization in patients with type 2 diabetes: the SURDIAGENE cohort

International audienceAbstract Background Heart failure (HF) is a growing complication and one of the leading causes of mortality in people living with type 2 diabetes (T2D). Among the possible causes, the excess of red meat and the insufficiency of vegetables consumption are suspected. Such an alimentation is associated with nutritional biomarkers, including trimethylamine N -oxide (TMAO) and its precursors. Here, we aimed to study these biomarkers as potential prognostic factors for HF in patients with T2D. Methods We used the SURDIAGENE (SURvival DIAbetes and GENEtics) study, a large, prospective, monocentric cohort study including 1468 patients with T2D between 2001 and 2012. TMAO and its precursors (trimethylamine [TMA], betaine, choline, and carnitine) as well as thio-amino-acids (cysteine, homocysteine and methionine) were measured by liquid chromatography-tandem mass spectrometry. The main outcome was HF requiring Hospitalization (HFrH) defined as the first occurrence of acute HF leading to hospitalization and/or death, established by an adjudication committee, based on hospital records until 31st December 2015. The secondary outcomes were the composite event HFrH and/or cardiovascular death and all-cause death. The association between the biomarkers and the outcomes was studied using cause-specific hazard-models, adjusted for age, sex, history of coronary artery disease, NT-proBNP, CKD-EPI-derived eGFR and the urine albumin/creatinine ratio. Hazard-ratios (HR) are expressed for one standard deviation. Results The data of interest were available for 1349/1468 of SURDIAGENE participants (91.9%), including 569 (42.2%) women, with a mean age of 64.3 ± 10.7 years and a median follow-up of 7.3 years [25th–75th percentile, 4.7–10.8]. HFrH was reported in 209 patients (15.5%), HFrH and/or cardiovascular death in 341 (25.3%) and all-cause death in 447 (33.1%). In unadjusted hazard-models, carnitine (HR = 1.20, 95% CI [1.05; 1.37]), betaine (HR = 1.34, [1.20; 1.50]), choline (HR = 1.35, [1.20; 1.52]), TMAO (HR = 1.32, [1.16; 1.50]), cysteine (HR = 1.38, [1.21; 1.58]) and homocysteine (HR = 1.28, [1.17; 1.39]) were associated with HFrH, but not TMA and methionine. In the fully adjusted models, none of these associations was significant, neither for HFrH nor for HFrH and/or CV death, when homocysteine only was positively associated with all-cause death (HR = 1.16, [1.06; 1.27]). Conclusions TMAO and its precursors do not appear to be substantial prognosis factors for HFrH, beyond usual cardiac- and kidney-related risk factors, whereas homocysteine is an independent risk factor for all-cause death in patients with T2D

Urinary Sodium Concentration Is an Independent Predictor of All-Cause and Cardiovascular Mortality in a Type 2 Diabetes Cohort Population

Objective. Sodium intake is associated with cardiovascular outcomes. However, no study has specifically reported an association between cardiovascular mortality and urinary sodium concentration (UNa). We examined the association of UNa with mortality in a cohort of type 2 diabetes (T2D) patients. Methods. Patients were followed for all-cause death and cardiovascular death. Baseline UNa was measured from second morning spot urinary sample. We used Cox proportional hazard models to identify independent predictors of mortality. Improvement in prediction of mortality by the addition of UNa to a model including known risk factors was assessed by the relative integrated discrimination improvement (rIDI) index. Results. Participants (n=1,439) were followed for a median of 5.7 years, during which 254 cardiovascular deaths and 429 all-cause deaths were recorded. UNa independently predicted all-cause and cardiovascular mortality. An increase of one standard deviation of UNa was associated with a decrease of 21% of all-cause mortality and 22% of cardiovascular mortality. UNa improved all-cause and cardiovascular mortality prediction beyond identified risk factors (rIDI = 2.8%, P=0.04 and rIDI = 4.6%, P=0.02, resp.). Conclusions. In T2D, UNa was an independent predictor of mortality (low concentration is associated with increased risk) and improved modestly its prediction in addition to traditional risk factors