COVID-19: clinical course and outcomes of 36 hemodialysis patients in Spain.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is a lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), and even less is available in patients on maintenance hemodialysis therapy than in the general population. In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of all maintenance hemodialysis patients hospitalized with COVID-19 from March 12th to April 10th, 2020 as confirmed by real-time polymerase chain reaction. Baseline features, clinical course, laboratory data, and different therapies were compared between survivors and nonsurvivors to identify risk factors associated with mortality. Among the 36 patients, 11 (30.5%) died, and 7 were able to be discharged within the observation period. Clinical and radiological evolution during the first week of admission were predictive of mortality. Among the 36 patients, 18 had worsening of their clinical status, as defined by severe hypoxia with oxygen therapy requirements greater than 4 L/min and radiological worsening. Significantly, 11 of those 18 patients (61.1%) died. None of the classical cardiovascular risk factors in the general population were associated with higher mortality. Compared to survivors, nonsurvivors had significantly longer dialysis vintage, increased lactate dehydrogenase (490 U/l ± 120 U/l vs. 281 U/l ± 151 U/l, P = 0.008) and C-reactive protein levels (18.3 mg/dl ± 13.7 mg/dl vs. 8.1 mg/dl ± 8.1 mg/dl, P = 0.021), and a lower lymphocyte count (0.38 ×103/µl ± 0.14 ×103/µl vs. 0.76 ×103/µl ± 0.48 ×103/µl, P = 0.04) 1 week after clinical onset. Thus, the mortality among hospitalized hemodialysis patients diagnosed with COVID-19 is high. Certain laboratory tests can be used to predict a worsening clinical course.

Body composition affects the response to erythropoiesis-stimulating agents in patients with chronic kidney disease in dialysis.

BACKGROUND: The response to erythropoiesis-stimulating agents (ESA) in patients with chronic kidney disease (CKD) is variable. The body mass index (BMI) variations can modify the response to ESA. The objective was to assess the effect of body composition on the response to ESA in dialysis patients. METHODS: This is an observational cross-sectional study. Prevalent hemodialysis and peritoneal dialysis (PD) patients were selected. In the same day, a single blood test, a body composition analysis using bioimpedance spectroscopy and anthropometric measurements were performed. We collected ESA doses. We analyzed erythropoietin resistance index (ERI). The ERI was calculated dividing the weekly weight-adjusted (kg) dose of ESA (IU) by the hemoglobin level (g/dL). RESULTS: The study was comprised of 218 patients (58% men; age 65 (16) years old; 80% hemodialysis, 20% PD). There was an inverse correlation between ERI and BMI (p=0.01), fat tissue index (FTI) (p=0.01) and prealbumin (p=0.04). We found an independent association between higher ERI levels and lower FTI and prealbumin values. CONCLUSION: Response to ESA is influenced by body composition. Fat tissue favors the body's response to ESA.

Impact of Isometric Exercise in Adolescents With End Stage Kidney Disease and Unsuitable Vessels For An Autologous Arteriovenous Fistula.

INTRODUCTION: Despite the lack of calcification, to perform a native Arteriovenous Fistula (AVF) in young patients may pose a challenge due to small vessel diameter. We report a case series with no options of AVF in which vessel caliber improvement after isometric exercise allowed for radiocephalic fistula creation in all of them. METHODS: Since 2017 to 2019, four patients were referred to our unit to create an AVF. Following a first assessment with physical examination and doppler ultrasound, none of them were eligible for AVF performance due to small vessel caliber. Once they were considered unsuitable for it, they started an isometric exercise program. RESULTS: Age ranged from 13 to 19 years. There were three males and one female. Two were in predialysis and two in hemodialysis program. Initial diameters of the forearm cephalic vein and the radial artery respectively were: case A < 1.5/2.3 mm, case B 1.5/1.6 mm, case C < 1.5/1.6 mm and case D 2.1/1.3 mm. Median duration of exercise program was 13 weeks (range 5-23). Post-exercise vessel diameters were: case A 2.7/2.3 mm, case B 2.5/2 mm, case C 2.8/1.8 mm and case D 2.7/2 mm. Radiocephalic AVF were performed in the four cases. After a median follow up of 19 months (range 9-30 months), 75% of patients required further interventions but all of them had a functional AVF. CONCLUSIONS: In these four cases isometric preoperative exercise allowed the creation of AVF. Without the improvement in vessel diameter observed afterwards, all of them would have been rejected for AVF performance. Despite the high rate of adjunctive interventions needed, given the safety of the program and the potential risks of Central Venous Catheters, we consider it a valuable option.

Impact of preoperative exercise in not initially candidates to native arteriovenous fistulas.

BACKGROUND: Native autologous arteriovenous fistula (AVFn) is the preferred vascular access for hemodialysis due to its long term patency and low complication rate. A challenging limitation is the anatomical inability to perform AVFn and failure of maturation. Preoperative isometric exercise (PIE) can increase vascular calibers and improve the rate of distal AVF. However, it is unknown whether PIE might enhance the performance of AVFn in patients who are not initially candidates. METHODS: A retrospective observational study was conducted over a population of 45 patients evaluated in vascular access clinic, 23 were not initially candidates for radiocephalic (NRC-AVF) and 22 were not candidates for autologous fistula at all (NA-AVF). They were assigned to perform PIE with handgrip device and revaluated. RESULTS: After 4-8 weeks of PIE, a AVFn was performed in 16 patients from NA-AVF group and a radiocephalic AVFn was performed in 21 patients from NRC-AVF group. Both groups experienced a significant and similar increase in venous caliber 0.91 ± 0.43 mm in NA-AVF versus 0.76 ± 0.47 mm in NRC-AVF (p = 0.336) and arterial caliber 0.18 ± 0.24 mm versus 0.18 ± 0.21 mm (p = 0.928), respectively. Nevertheless, primary failure rate was significantly higher in NA-AVF (n = 8, 50%) than in NRC-AVF group (n = 3, 14.3%) (p = 0.030). After 6 months, the fistula usability for dialysis was only 50% in NA-AVF, while 86.7% were dialyzed by fistula in NRC-AVF group (p = 0.038). CONCLUSIONS: PIE allowed the allocation of an AVFn in patients not initially candidates, but entailed a high rate of maturation failure. Patients not candidates to radiocephalic AVF benefited from PIE and preserved a long term usability of AVF for dialysis.

Expanded hemodialysis: Is anticoagulation of the dialysis circuit different from online hemodiafiltration and high-flux hemodialysis?

Expanded hemodialysis (HDx) has a high capacity for removing medium and medium-large molecules; however, there are no specific recommendations during HDx for anticoagulation of the dialysis circuit. We aimed to evaluate the differences in the efficacy of anticoagulation procedures using the venous port and 40 mg enoxaparin in HDx compared to high-flux hemodialysis (HF-HD) and postdilution online hemodiafiltration (HDF). We compared anticoagulant activity in 11 patients in HDx, HF-HD, and HDF under similar dialysis conditions. In the 33 dialysis sessions, 40 mg enoxaparin was administered through the venous port, and pre- and postdialysis antifactor Xa activity (aXa) and activated partial thromboplastin time (APTT), postdialysis clotting time of the vascular access, visual clotting score of the dialyzer, and any complications with the extracorporeal circuit or bleeding were registered. APTT postdialysis in HDx was not significantly different from that in HF-HD and HDF. Postdialysis aXa in HDx was not significantly different from that in HF-HD and HDF. We found no significant differences in visual clotting score of the dialyzer. Enoxaparin administered through the venous port was sufficient for anticoagulation within the extracorporeal circuit in HDx, HF-HD, and HDF. There were no differences in postdialysis aXa or APTT, most likely because when low molecular-weight heparin is applied through venous port, lesser enoxaparin concentration reaches the dialyzer. Thus, we conclude that the dose of enoxaparin administered through the venous port should not be adjusted according to dialysis technique.

Efficacy of enoxaparin in preventing coagulation during high-flux haemodialysis, expanded haemodialysis and haemodiafiltration.

BACKGROUND: Low-molecular-weight heparins (LMWHs) are easily dialysable with high-flow membranes; however, it is not clear whether the LMWH dose should be adjusted according to the membrane type and dialysis technique. This study aimed to evaluate the influence of the dialyser on anticoagulation of the extracorporeal dialysis circuit. METHODS: Thirteen patients received the same dose of LMWH through the arterial port via three dialysis techniques: high-flux haemodialysis (HF-HD), online haemodiafiltration (HDF) and expanded haemodialysis (HDx). All dialysis was performed under similar conditions: duration, 4 h; blood flow, 400 mL/min; and dialysate flow, 500 mL/min. Antifactor Xa (aXa) activity and activated partial thromboplastin time (APTT) were measured before and after the dialysis. Clotting time of the vascular access site after haemodialysis, visual clotting score of the dialyser and any complications with the extracorporeal circuit or bleeding were registered. RESULTS: Post-dialysis aXa activity in HF-HD (0.26 ± 0.02 U/mL) was significantly different from that in HDF (0.21 ± 0.02 U/mL, P = 0.024), and there was a trend in HDx (0.22 ± 0.01 U/mL, P = 0.05). APTT post-dialysis in HF-HD (30.5 ± 0.7 s) was significantly different from that in HDx (28.2 ± 0.64 s, P = 0.009) and HDF (28.8 ± 0.73 s, P = 0.009). CONCLUSIONS: AXa activity in HDF was significantly lower than that in HF-HD, possibly because of more losses of LMWH through the dialyser. Given the higher anticoagulant loss in HDF and probably in HDx than in HF-HD, the enoxaparin dose administered may be adjusted according to the dialysis technique.

The Impact of Age on Mortality in Chronic Haemodialysis Popu-Lation with COVID-19.

Age and chronic kidney disease have been described as mortality risk factors for coronavirus disease 2019 (COVID-19). Currently, an important percentage of patients in haemodialysis are elderly. Herein, we investigated the impact of age on mortality among haemodialysis patients with COVID-19. Data was obtained from the Spanish COVID-19 chronic kidney disease (CKD) Working Group Registry. From 18 March 2020 to 27 August 2020, 930 patients on haemodialysis affected by COVID-19 were included in the Registry. A total of 254 patients were under 65 years old and 676 were 65 years or older (elderly group). Mortality was 25.1% higher (95% CI: 22.2-28.0%) in the elderly as compared to the non-elderly group. Death from COVID-19 was increased 6.2-fold in haemodialysis patients as compared to the mortality in the general population in a similar time frame. In the multivariate Cox regression analysis, age (hazard ratio (HR) 1.59, 95% CI: 1.31-1.93), dyspnea at presentation (HR 1.51, 95% CI: 1.11-2.04), pneumonia (HR 1.74, 95% CI: 1.10-2.73) and admission to hospital (HR 4.00, 95% CI: 1.83-8.70) were identified as independent mortality risk factors in the elderly haemodialysis population. Treatment with glucocorticoids reduced the risk of death (HR 0.68, 95% CI: 0.48-0.96). In conclusion, mortality is dramatically increased in elderly haemodialysis patients with COVID-19. Our results suggest that this high risk population should be prioritized in terms of protection and vaccination.

The new marker YKL-40, a molecule related to inflammation, is associated with cardiovascular events in stable haemodialysis patients.

BACKGROUND: YKL-40 is a glycoprotein associated with inflammatory conditions, including atherosclerosis and endothelial dysfunction. The objective was to analyse serum YKL-40 levels in a haemodialysis population and explore their association with dialysis dosing measures, inflammation, body composition and development of cardiovascular (CV) events. METHODS: We performed a prospective study of 78 chronic haemodialysis patients enrolled in 2013 and followed up until 2018. At baseline, serum YKL-40, inflammatory and nutrition markers and body composition were assessed. During a median follow-up of 43 (interquartile range 24-66) months, CV events were recorded. RESULTS: The mean age of patients was 62 ± 16 years and 66% were men. The mean YKL-40 was 207 ± 106 ng/dL. Higher YKL-40 levels were associated with lower Kt/V urea, convective volume, serum albumin and prealbumin and with higher troponin T. During follow-up, 50% developed CV events. Cox analysis showed an association between CV events and YKL-40, diabetes, hypertension, C-reactive protein, lower prealbumin, ß2-microglobulin, glycosylated haemoglobin and troponin T values. The multivariate Cox analysis confirmed an independent association between CV events and YKL-40 {hazard ratio [HR] 1.067 [95% confidence interval (CI) 1.009-1.211]; P: 0.042}, troponin T [HR 1.037 (95% CI 1.009-1.683); P: 0.007], lower prealbumin [HR 0.827 (95% CI 0.224-0.988); P: 0.009] and diabetes [HR 2.103 (95% CI 1.554-3.172); P: 0.008]. Kaplan-Meier confirmed the association between CV events and YKL-40 (log rank 7.28; P = 0.007). CONCLUSIONS: YKL-40 is associated with CV events in haemodialysis patients. Higher dialysis dose and convective volume are associated with lower serum YKL-40 levels.

Exercise training during hemodialysis sessions: Physical and biochemical benefits.

Chronic inflammation, protein-energy wasting, and poor physical functioning are highly prevalent among patients with chronic kidney disease (CKD). These factors are associated with disability and increase of cardiovascular risk. The aim of this study is to evaluate the effects of exercise training during hemodialysis (HD) sessions on physical functioning, body composition, and nutritional and inflammatory status. We performed a prospective intervention study including patients on prevalent HD therapy. Patients were evaluated at baseline visit by Rehabilitation and Physiotherapy specialists and the exercise program was adapted to each patient's physical capacity. In addition to demographic, clinical, body composition and functional ability data, serum markers regarding nutritional and inflammatory status were collected at baseline and after 3 months of exercise training. We observed a significant improvement after 3-month follow-up in functional ability (6 minute walk test [6MWT] [403.15 ± 105.4 vs 431.81 ± 115.5 m, P < .001], sit-to-stand repetitions in 30 seconds [12.2 ± 4.2 vs 14.1 ± 5.0 repetitions, P = .003] and dynamometry [24.5 ± 11.9 vs 29.5 ± 12.5 kg, P < 0.001]), body composition with increase of body mass index (BMI) (23.7 ± 4.4 vs 24.1 ± 4.7 kg/m2 , P = 0.01) at the expense of lean tissue index (LTI) (14.9 ± 3.7 vs 16.2 ± 2.9 kg/m2 , P = 0.038) and lipid parameters with LDL-cholesterol decrease (70.2 ± 17.9 vs 64.9 ± 21.3 mg/dL, P = .03) and lower serum triglyceride levels (125.8 ± 54.0 vs 108.2 ± 44.6 mg/dL, P = .006). In addition, we found a decrease in iron (155.6 ± 148.2 vs 116.7 ± 110.8 mg, P = .029) and erythropoietin (117.5 ± 84.2 vs 99.2 ± 74.5 µg, P = .023) requirements. The implementation of exercise training programs during HD can improve physical functioning, body composition and lipid and anemia profile. Supervised exercise programs could be included as part of HD patient care to improve physical capacity in these patients.

Middle molecule elimination in expanded haemodialysis: only convective transport?

BACKGROUND: New high-retention onset dialysers have shown improved efficacy in the elimination of uraemic toxins, and their depurative capacity has been compared with high convective volumes of online haemodiafiltration. Haemodialysis (HD) using high-flux membranes leads to convective transport by internal filtration [direct filtration (DF)/backfiltration (BF)] and allows the removal of middle molecules (MMs). The aim of this study was to assess solute transport mechanisms in expanded HD (HDx). METHODS: In 14 4-h HDx sessions with Theranova-500 dialysers under similar dialysis conditions (blood flow 400 mL/min, dialysate flow 700 mL/min, dialysate temperature 35.5°C), pressures at the inlet and outlet of both dialyser compartments (P bi, P bo, P di and P do) were collected hourly to estimate DF/BF volumes by semi-empirical methods. Uraemic toxins with various molecular weights were measured pre-dialysis, at 1 h (pre-filter and post-filter) and post-dialysis to calculate molecules' reduction over time and dialyser in vivo clearances. RESULTS: Ultrafiltration was 1.47 ± 0.9 L and Kt/V 1.74 ± 0.3. Hydrodynamic data (P bi: 259 ± 39, P bo: 155 ± 27, P di: 271 ± 30, P do: 145 ± 29 mmHg and oncotic pressure 22.0 ± 3.5 mmHg) allowed the estimation of DF/BF rates. DF flow ranged from 29.5 ± 4.2 to 31.3 ± 3.9 mL/min and BF flow ranged from 25.1 ± 2.3 to 23.4 ± 2.6 mL/min. The highest calculated DF volume was 7506.8 ± 935.3 mL/session. Diffusive clearances (K d) of all solutes were higher than their convective transport (all P < 0.001) except for prolactin (23 kDa) clearances, which showed no differences. Total clearances of all solutes were correlated with their K d (ρ = 0.899-0.987, all P < 0.001) and Kt/V correlated with all reduction rates (ρ = 0.661-0.941, P = 0.010 to <0.001). DF flow was only associated with urea (ρ = -0.793, P = 0.001), creatinine (ρ = -0.675, P = 0.008) and myoglobin clearance (ρ = 0.653, P = 0.011). CONCLUSION: Results suggest that diffusive transport is a main mechanism of MM elimination in HDx. HDx offers an efficient depuration of MM without the need for high convective volumes.

High convective volumes are associated with improvement in metabolic profile in diabetic patients on online haemodiafiltration. / Los altos volúmenes convectivos se asocian a la mejoría del perfil metabólico en los pacientes diabéticos en hemodiafiltración online.

BACKGROUND AND OBJECTIVE: Online haemodiafiltration (OL-HDF) with high convective transport volumes improves patient survival in haemodialysis. Limiting the amount of convective volume has been proposed in patients with diabetes mellitus due to glucose load that is administered with replacement fluid. The objective of the study was to analyse the influence of substitution volume on the evolution of the metabolic profile and body composition of incident diabetic patients on OL-HDF. MATERIAL AND METHODS: Prospective observational study in 29 incident diabetic patients on postdilution OL-HDF. Baseline data included clinical and demographic data, laboratory parameters (metabolic, nutritional and inflammatory profile) and body composition with bioimpedance spectroscopy (BIS). Laboratory parameters and mean substitution volume per session were collected every 4 months, and in 23 patients a further BIS was performed after a minimum of one year. Variations in glycosylated haemoglobin (HbA1c), triglycerides, total cholesterol, LDL-c, HDL-c, albumin, prealbumin and C reactive protein (CRP) were calculated at one year, 2 years, 3 years, and at the end of follow-up. Quarterly and annual variations were calculated as independent periods, and changes in body composition were analysed. RESULTS: Age at baseline was 69.7±13.6 years, 62.1% were male, 72.3±13.9kg, 1.78±0.16m2, with 48 (35.5-76) months on dialysis. Approximately 81.5% received insulin, 7.4% antidiabetic drugs and 51.9% statins. Mean substitution volume was 26.9±2.9L/session and follow-up period (time on OL-HDF) was 40.4±26 months. A significant correlation was observed between mean substitution volume and the increase in HDL-c (r=0.385, p=0.039) and prealbumin levels (r=0.404, p=0.003) throughout follow-up. Moreover, substitution volume was correlated with a reduction in CRP levels at one year (r=-0.531, p=0.005), 2 years (r=-0.463, p=0.046), and at the end of follow-up (r=-0.498, p=0.007). Patients with mean substitution volume >26.9L/session had a higher reduction in triglycerides and CRP, and an increase in HDL-c levels. These patients with >26.9L/session finished the study with higher HDL-c (48.1±9.4mg/dL vs. 41.2±11.6mg/dL, p=0.025) and lower CRP levels (0.21 [0.1-2.22] mg/dL vs. 1.01 [0.15-6.96] mg/dL, p=0.001), with no differences at baseline. Quarterly comparisons between substitution volume and laboratory changes [n=271] showed a significant correlation with a reduction in HbA1c (r=-0.146, p=0.021). Similar findings were obtained with annual comparisons [n=72] (r=-0.237, p=0.045). An annual mean substitution volume over 26.6L/session (29.3±1.7L/session vs. 23.9±1.9L/session) was associated with a reduction in HbA1c (-0.51±1.24% vs. 0.01±0.88%, p=0.043). No correlation was observed between substitution volume and changes in weight, body mass index or BIS parameters. CONCLUSION: There is not enough evidence to restrict convective transport in diabetic patients on OL-HDF due to the glucose content of the replacement fluid.

Serum fibrinogen levels are an independent predictor of mortality in patients with chronic kidney disease (CKD) stages 3 and 4.

Patients with chronic kidney disease have substantial risk for cardiovascular mortality, but the relative importance of traditional and novel risk factors is unknown. Several studies in hemodialysis patients have demonstrated that inflammatory markers are potent predictors of mortality, however there are scarce data about stable patients with moderate chronic kidney disease. 128 outpatients with estimated glomerular filtration of less than 60 ml/min per 1.73 m(2) were included in the study. Medical records about cardiovascular factors were recorded. Analytical parameters and inflammation markers were determined in baseline period. Participants were initially recruited from January 2002 to May 2002. The average length of follow-up in this longitudinal study was 5.5 years. Mortality and non-fatal cardiovascular events were the end points. Median follow-up was 67.8 months, all cause of mortality was 22.7%/(n=29) and non-fatal cardiovascular events were 39.1% (n=50). In multivariate analysis adjusting for demographic, cardiovascular and kidney disease factors, age hazard ratio (HR): 1.01, interval confidence (IC): 1.00-1.10), previous congestive heart failure (HR: 3.50, IC: 1.10-11.17) and both high CRP (HR: 3.48, IC: 1.53-7.59) and serum fibrinogen (HR: 1.45, IC: 1.04-1.50) were independent predictors of all-cause of mortality. Age (HR: 1.06, IC: 1.01-1.11), high CRP (HR: 2.80, IC: 1.60-4.90), cardiac troponin T (HR: 1.21, IC: 1.04-1.40) and previous coronary disease (HR: 2.67, IC: 1.28-5.54) but not serum fibrinogen were independent predictors of non-fatal cardiovascular events. Both high CRP and high serum fibrinogen levels and previous congestive heart failure measured in CKD stages 3 and 4, are independent risk factors for all-cause of mortality. High CRP but not high serum fibrinogen is a risk factor for non-fatal cardiovascular events. These results suggest that high CRP and high serum fibrinogen provide prognostic information in CKD patients.

On-line hemodiafiltration at home.

Survival with online hemodiafiltration (OL-HDF) is higher than with hemodialysis; frequent hemodialysis has also improved survival and quality of life. Home hemodialysis facilitates frequent therapy. We report our experience with 2 patients with stage 5 CKD who started home hemodialysis with OL-HDF in November 2016. After a training period at the hospital, they started home hemodialysis with OL-HDF after learning how to manage dialysis monitors and how to administer water treatment. We used the "5008-home" (FMC© ) monitor, and the Acqua C© (Fresenius Medical Care) for water treatment. Water conductivity was always checked before and during dialysis sessions and was always 2.5 to 3 mS/cm. Water cultures always fulfilled the criteria for ultrapurity. As far as we know, this is the first report on patients receiving OL-HDF at home. The technique proved to be safe and valid for renal replacement therapy and transfers the benefits of hospital convective therapy to the home setting. Future data will enable us to determine whether survival has also improved.

Any grade of relative overhydration is associated with long-term mortality in patients with Stages 4 and 5 non-dialysis chronic kidney disease.

BACKGROUND: Overhydration (OH) is associated with mortality in chronic kidney disease (CKD). A relative overhydration adjusted for extracellular water (OH/ECW) measured by bioimpedance >15% has shown an increased mortality risk in haemodialysis but few studies have been developed in advanced CKD. Our objective was to evaluate the effect of OH on mortality in patients with Stage 4 or 5 non-dialysis CKD. METHODS: We performed a prospective study of 356 patients enrolled in 2011 and followed up until 2016. At baseline we collected general characteristics, serum inflammatory and nutrition markers, cardiovascular events (CVEs) and body composition using bioimpedance spectroscopy. During a median follow-up of 50 (24-66) months we collected mortality data. RESULTS: The mean creatinine was 3.5 ± 1.3 mg/dL, median proteinuria was 0.5 [interquartile range (IQR) 0.2-1.5] g/24 h, median OH was 0.6 (IQR -0.4-1.5) L and mean relative OH (OH/ECW) was 2.3 ± 0.8%. We found that 32% of patients died. The univariate Cox analysis showed an association between mortality and age, diabetes, previous CVEs, Charlson comorbidity index, low albumin and pre-albumin, high C-reactive protein (CRP), low lean tissue and high OH/ECW. Multivariate Cox analysis confirmed an association between mortality and age {exp(B) 1.1 [95% confidence interval (CI) 1.0-1.3]; P = 0.001}, Charlson comorbidity index [exp(B) 1.1 (95% CI 1.0-1.2); P = 0.01], CRP [exp(B) 1.1 (95% CI 1.0-1.2); P = 0.04], OH/ECW [exp(B) 3.18 (95% CI 2.09-4.97); P = 0.031] and low lean tissue [exp(B) 0.82 (95% CI 0.69-0.98); P = 0.002]. Kaplan-Meier analysis confirmed higher mortality in patients with OH/ECW >0% (log rank 11.1; P = 0.001). CONCLUSION: Any grade of relative OH measured by OH/ECW >0% is associated with long-term mortality in patients with Stage 4 or 5 non-dialysis CKD.

Evaluation of the efficacy of a medium cut-off dialyser and comparison with other high-flux dialysers in conventional haemodialysis and online haemodiafiltration.

BACKGROUND: Online haemodiafiltration (OL-HDF) has been shown to reduce all-cause mortality versus conventional haemodialysis (HD); however, it is not always available. In these situations, a novel class of membranes with a higher pore size, medium cut-off (MCO) dialysers, could be promising. The aim of this study is to evaluate the efficacy of an MCO dialyser in the removal of small and medium-size molecules and compare it with standard high-flux (HF) dialysers in HD and OL-HDF. METHODS: In this crossover study, 18 prevalent HD patients were studied in three single mid-week dialysis treatments during three consecutive weeks as follows: first week with OL-HDF with a standard HF dialyser, second week with conventional HD with a standard HF dialyser and third week with conventional HD with an MCO dialyser. Reduction ratios (RRs) of different-sized molecules and albumin losses were collected for the different dialysers. RESULTS: MCO HD provided a greater reduction of middle and larger middle molecules compared with standard HF HD [rate reduction (RR) ß2-microglobulin 74.7% versus 69.7%, P=0.01; RR myoglobin 62.5% versus 34.3%, P=0.001; RR prolactin 60% versus 32.8%, P=0.001; RR α1-glycoprotein 2.8% versus -0.1%, P=0.01]. We found no difference in the clearance of small and larger middle molecules comparing MCO HD with OL-HDF. Albumin losses were 0.03  g/session with MCO HD and 3.1  g/session with OL-HDF (P=0.001). CONCLUSION: MCO HD is superior to standard HF HD in the removal of middle and larger middle molecules and it is not inferior to OL-HDF in the clearance of small and larger middle molecules. Thus it could be an alternative in patients in which it is not possible to perform OL-HDF.

Rationale and design of the PHYSICALFAV trial: a randomized controlled trial to evaluate the effect of preoperative isometric exercise on vascular calibre and maturation of autologous arteriovenous fistulas.

BACKGROUND: A good vascular access (VA) is vital for haemodialysis (HD) patients. HD with an autologous arteriovenous fistula (AVF) is associated with higher survival, lower health care costs and fewer complications. Although a distal forearm AVF is the best option, not all patients are good candidates for this approach and the primary failure rate ranges from 20% to 50%. The optimal AVF depends mainly on the anatomical and haemodynamic characteristics of the artery and the vein chosen for the anastomosis. These characteristics can be modified by performing physical exercise. VA guidelines suggest that isometric exercises should be performed both before and after the AVF is created. While the literature contains few data on the potential efficacy of preoperative exercise, small observational studies point to an improvement in venous and arterial calibre. Postoperative exercise also seems to improve maturation, although there is no consensus on the appropriate exercise protocol. METHODS: The PHYSICALFAV trial (NCT03213756) is an open-label, multicentre, prospective, controlled, randomized trial designed to evaluate the usefulness of preoperative isometric exercise (PIE) in pre-dialysis patients or in prevalent HD patients who are candidates for a new AVF. Patients are randomized 1:1 to the PIE group (isometric exercises for 8 weeks) or the control group (no exercise). The main endpoint is whether the rate of primary failure is lower in the PIE group than in the control group. RESULTS: The trial has already started, with 40 patients having been enrolled as of 21 March 2018; 26.5% of the estimated sample.

Comparison of urea recirculation and thermodilution for monitoring of vascular access in patients undergoing hemodialysis.

Introduction It is important to monitor vascular access in patients with stage 5 chronic kidney disease receiving hemodialysis. Access recirculation can help to detect a need for intervention. OBJECTIVES: To compare urea recirculation with recirculation by thermodilution using blood temperature monitoring to predict a need for intervention of vascular access over a 6-month period. METHODS: We analyzed urea recirculation and blood temperature monitoring simultaneously in 61 patients undergoing hemodialysis. During the 6-month follow-up, we recorded all cases of angioplasty or surgery (thrombectomy or reanastomosis). In line with previous studies, we considered a value to be positive when urea recirculation was >10% and blood temperature monitoring >15%. Receiver operating characteristic curves were constructed. RESULTS: Mean urea recirculation was 9.5% ± 6.6% and mean blood temperature monitoring 12.9% ± 4.3% (p = 0.001). Urea recirculation >10% had a sensitivity of 80% and specificity of 78%. Blood temperature monitoring >15% had a sensitivity of 33% and specificity of 85%. During follow-up, 25% of patients developed need for intervention of vascular access. We found an association between vascular access dysfunction and urea recirculation. The Kaplan-Meier analysis confirmed an association between urea recirculation and risk of vascular access dysfunction (log rank = 17.2; p = 0.001). We were unable to confirm this association with blood temperature monitoring (log rank = 0.879; p = 0.656). CONCLUSION: Urea recirculation is better predictor of vascular access dysfunction than thermodilution.

Low lean tissue mass is an independent risk factor for mortality in patients with stages 4 and 5 non-dialysis chronic kidney disease.

Background: Mortality in patients with stages 4 and 5 chronic kidney disease (CKD) is higher than in the general population. Body composition predicts mortality. Our objective was to evaluate the effect of body composition on mortality in patients with stages 4 and 5 non-dialysis CKD. Methods: We performed a prospective study of 356 patients with stages 4 and 5 non-dialysis CKD. At baseline, we recorded general characteristics, history of cardiovascular events, body composition, serum inflammatory markers, nutrition and cardiac biomarkers. Body composition was analysed using bioimpedance spectroscopy. We recorded the lean tissue index (LTI), fat tissue index (FTI) and overhydration (OH). During a median (range) follow-up of 22 (3-49) months, we recorded mortality, cardiovascular events and progress to renal replacement therapy. Results: At baseline, mean (± standard deviation) age was 67 ± 13 years (men 64%; diabetes 36%). Mean body mass index was 28.2 ± 12.8 kg/m2, the FTI was 12.3 ± 5.6 kg/m2, the LTI was 15.7 ± 3.4 kg/m2 and median (interquartile range) OH was 0.6 (-0.4 to 1.5) L. Sixty-four (18%) patients died during follow-up. The univariate Cox analysis showed an association between mortality and age, low LTI, high Charlson comorbidity index, previous cardiovascular events, OH, low albumin and prealbumin levels, and high C-reactive protein levels. Kaplan-Meier analysis revealed higher survival in patients with a higher LTI (log-rank, 9.47; P = 0.002). The multivariate Cox analysis confirmed an association between mortality and low LTI (P = 0.031), previous cardiovascular events (P = 0.003) and high Charlson comorbidity index (P = 0.01). We did not find any association between body composition and cardiovascular events or renal replacement therapy. Conclusions: A low LTI is an independent factor for mortality in patients with stages 4 and 5 CKD.

Is High-Volume Online Hemodiafiltration Associated With Malnutrition?

Chronic malnutrition is a common problem in patients with end-stage renal disease on hemodialysis. Some studies have reported albumin loss into dialysis fluid during postdilution online hemodiafiltration (OL-HDF). The aim of the study was to assess the nutritional status of patients on high-volume OL-HDF and to demonstrate that higher convective clearances are not associated with malnutrition due to possible loss of nutrients with ultrafiltration. Demographic and clinical data, corporal composition with bioimpedance spectroscopy, dialysis features, albumin loss into dialysis fluid and laboratory parameters were collected in twenty-eight patients with ESRD undergoing postdilution OL-HDF with stable convective volumes over 28 L/session. Convective volume (CV) in the last six months was 32.51 ± 3.52 L per session. Cross-sectional analysis of dialysis features showed 32.7 ± 3.34 L of CV and high reduction rates of beta-2-microglobulin (84.2 ± 3.8%) and cystatin-C (81.6 ± 3.47%). Beta-2-microglobulin reduction showed a positive correlation with prealbumin levels (P = 0.048). CV was only correlated with cystatin-C reduction (P = 0.025). Estimated albumin loss into dialysis fluid (1.82 ± 1.05 g/session) was not related to laboratory or bioimpedance nutritional parameters, or to CV. Among patients with higher CV, serum albumin levels maintained more stability during the observational period. High volume OL-HDF results in better convective clearances and is not associated with malnutrition. Albumin and nutrients loss into dialysis fluid should not be a limiting factor of the substitution volume.

Adding access blood flow surveillance reduces thrombosis and improves arteriovenous fistula patency: a randomized controlled trial.

PURPOSE: Stenosis is the main cause of arteriovenous fistula (AVF) failure. It is still unclear whether surveillance based on vascular access blood flow (QA) enhances AVF function and longevity. METHODS: We conducted a three-year follow-up randomized, controlled, multicenter, open-label trial to compare QA-based surveillance and pre-emptive repair of subclinical stenosis with standard monitoring/surveillance techniques in prevalent mature AVFs. AVFs were randomized to either the control group (surveillance based on classic alarm criteria; n = 104) or to the QA group (QA measured quarterly using Doppler ultrasound [M-Turbo®] and ultrasound dilution [Transonic®] added to classic surveillance; n = 103).The criteria for intervention in the QA group were: 25% reduction in QA, QA<500 mL/min or significant stenosis with hemodynamic repercussion (peak systolic velocity [PSV] more than 400 cm/sc or PSV pre-stenosis/stenosis higher than 3). RESULTS: At the end of follow-up we observed a significant reduction in the thrombosis rate in the QA group (0.025 thrombosis/patient/year in the QA group vs. 0.086 thrombosis/patient/year in the control group [p = 0.007]). There was a significant improvement in the thrombosis-free patency rate (HR, 0.30; 95% CI, 0.11-0.82; p = 0.011) and in the secondary patency rate in the QA group (HR, 0.49; 95% CI, 0.26-0.93; p = 0.030), with no differences in the primary patency rate between the groups (HR, 0.98; 95% CI, 0.57-1.61; p = 0.935).There was greater need for a central venous catheter and more hospitalizations associated with vascular access in the control group (p = 0.034/p = 0.029).Total vascular access-related costs were higher in the control group (€227.194 vs. €133.807; p = 0.029). CONCLUSIONS: QA-based surveillance combining Doppler ultrasound and ultrasound dilution reduces the frequency of thrombosis, is cost effective, and improves thrombosis free and secondary patency in autologous AVF.