Effect of increased convective clearance by on-line hemodiafiltration on all cause and cardiovascular mortality in chronic hemodialysis patients – the Dutch CONvective TRAnsport STudy (CONTRAST): rationale and design of a randomised controlled trial [ISRCTN38365125]

BACKGROUND: The high incidence of cardiovascular disease in patients with end stage renal disease (ESRD) is related to the accumulation of uremic toxins in the middle and large-middle molecular weight range. As online hemodiafiltration (HDF) removes these molecules more effectively than standard hemodialysis (HD), it has been suggested that online HDF improves survival and cardiovascular outcome. Thus far, no conclusive data of HDF on target organ damage and cardiovascular morbidity and mortality are available. Therefore, the CONvective TRAnsport STudy (CONTRAST) has been initiated. METHODS: CONTRAST is a Dutch multi-center randomised controlled trial. In this trial, approximately 800 chronic hemodialysis patients will be randomised between online HDF and low-flux HD, and followed for three years. The primary endpoint is all cause mortality. The main secondary outcome variables are fatal and non-fatal cardiovascular events. CONCLUSION: The study is designed to provide conclusive evidence whether online HDF leads to a lower mortality and less cardiovascular events as compared to standard HD

What is new in uremic toxicity?

Uremic syndrome results from a malfunctioning of various organ systems due to the retention of compounds which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. If these compounds are biologically active, they are called uremic toxins. One of the more important toxic effects of such compounds is cardio-vascular damage. A convenient classification based on the physico-chemical characteristics affecting the removal of such compounds by dialysis is: (1) small water-soluble compounds; (2) protein-bound compounds; (3) the larger “middle molecules”. Recent developments include the identification of several newly detected compounds linked to toxicity or the identification of as yet unidentified toxic effects of known compounds: the dinucleotide polyphosphates, structural variants of angiotensin II, interleukin-18, p-cresylsulfate and the guanidines. Toxic effects seem to be typically exerted by molecules which are “difficult to remove by dialysis”. Therefore, dialysis strategies have been adapted by applying membranes with larger pore size (high-flux membranes) and/or convection (on-line hemodiafiltration). The results of recent studies suggest that these strategies have better outcomes, thereby clinically corroborating the importance attributed in bench studies to these “difficult to remove” molecules

Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

Reference values for multifrequency bioimpedance analysis in dialysis patients

Reference values for multifrequency bioimpedance analysis in dialysis patients.van de Kerkhof J, Hermans M, Beerenhout C, Konings C, van der Sande FM, Kooman JP.St. Catharina Hospital, Eindhoven, The Netherlands.BACKGROUND: The role of multifrequency bioimpedance(MF-BIA) in the assessment of fluid status in dialysis patients is still not fully elucidated. Especially, the predictive value of reference values for extracellular water (ECW) has not yet been addressed. Aim of the present study was to validate cut-off values for MF-BIA in the diagnosis of hypervolemia in dialysis patients, using strict clinical criteria and echocardiography as reference techniques. METHODS: 90 patients [42 on hemodialysis; 48 on peritoneal dialysis] were divided into the following groups: clinically normovolemic (mean 24- or 48-hour systolic blood pressure below 133 mm Hg without use of antihypertensive agents; n = 12), 'hypervolemic' (mean systolic blood pressure above 133 mm Hg with 2 or more antihypertensive agents; n = 34) or undetermined (n = 44). The 80th percentile for normalized ECW in the clinically normovolemic patients was used as reference value. 20 healthy age-matched controls were included for comparison. RESULTS: The 80th percentiles for ECW:body weight (BW) and ECW:height in 'normovolemic' subjects were, respectively, 0.245 liters/kg and 10.96 liters/m in males, and 0.232 liters/kg and 9.13 liters/m in females. ECW:BW and ECW:height were above these values in, respectively, 26 (sensitivity 76%) and 29 (sensitivity 86%) of the 34 'hypervolemic' patients. In the undetermined group, left ventricular end-diastolic diameter was significantly different between patients with normalized ECW below and above these cut-off values (49.0 +/- 5.1 vs. 52.4 +/- 5.7 mm; p &lt; 0.05). Use of the ECW:TBW ratio resulted yielded low sensitivity (45%). ECW:height was lower in the 'normovolemic' dialysis patients compared to healthy controls (9.7 +/- 1.3 l/m versus 12.2 +/- 1.9 l/m). CONCLUSION: In our study population, ECW by MF-BIA, normalized for height was able to predict hypervolemia, based on strict clinical criteria, with a sensitivity of 86% and a specificity of 80%. The normalization procedure for ECW may influence the classification of hydration status. Strictly normotensive dialysis patients had lower normalized ECW than healthy control subjects.<br/