Digital Health Support: Current Status and Future Development for Enhancing Dialysis Patient Care and Empowering Patients.

Chronic kidney disease poses a growing global health concern, as an increasing number of patients progress to end-stage kidney disease requiring kidney replacement therapy, presenting various challenges including shortage of care givers and cost-related issues. In this narrative essay, we explore innovative strategies based on in-depth literature analysis that may help healthcare systems face these challenges, with a focus on digital health technologies (DHTs), to enhance removal and ensure better control of broader spectrum of uremic toxins, to optimize resources, improve care and outcomes, and empower patients. Therefore, alternative strategies, such as self-care dialysis, home-based dialysis with the support of teledialysis, need to be developed. Managing ESKD requires an improvement in patient management, emphasizing patient education, caregiver knowledge, and robust digital support systems. The solution involves leveraging DHTs to automate HD, implement automated algorithm-driven controlled HD, remotely monitor patients, provide health education, and enable caregivers with data-driven decision-making. These technologies, including artificial intelligence, aim to enhance care quality, reduce practice variations, and improve treatment outcomes whilst supporting personalized kidney replacement therapy. This narrative essay offers an update on currently available digital health technologies used in the management of HD patients and envisions future technologies that, through digital solutions, potentially empower patients and will more effectively support their HD treatments.

Fluid Overload and Tissue Sodium Accumulation as Main Drivers of Protein Energy Malnutrition in Dialysis Patients.

Protein energy malnutrition is recognized as a leading cause of morbidity and mortality in dialysis patients. Protein-energy-wasting process is observed in about 45% of the dialysis population using common biomarkers worldwide. Although several factors are implicated in protein energy wasting, inflammation and oxidative stress mechanisms play a central role in this pathogenic process. In this in-depth review, we analyzed the implication of sodium and water accumulation, as well as the role of fluid overload and fluid management, as major contributors to protein-energy-wasting process. Fluid overload and fluid depletion mimic a tide up and down phenomenon that contributes to inducing hypercatabolism and stimulates oxidation phosphorylation mechanisms at the cellular level in particular muscles. This endogenous metabolic water production may contribute to hyponatremia. In addition, salt tissue accumulation likely contributes to hypercatabolic state through locally inflammatory and immune-mediated mechanisms but also contributes to the perturbation of hormone receptors (i.e., insulin or growth hormone resistance). It is time to act more precisely on sodium and fluid imbalance to mitigate both nutritional and cardiovascular risks. Personalized management of sodium and fluid, using available tools including sodium management tool, has the potential to more adequately restore sodium and water homeostasis and to improve nutritional status and outcomes of dialysis patients.

Quantitative assessment of sodium mass removal using ionic dialysance and sodium gradient as a proxy tool: Comparison of high-flux hemodialysis versus online hemodiafiltration.

Restoration and maintenance of sodium are still a matter of concern and remains of critical importance to improve the outcomes in homeostasis of stage 5 chronic kidney disease patients on dialysis. Sodium mass balance and fluid volume control rely on the "dry weight" probing approach consisting mainly of adjusting the ultrafiltration volume and diet restrictions to patient needs. An additional component of sodium and fluid management relies on adjusting the dialysate-plasma sodium concentration gradient. Hypotonicity of ultrafiltrate in online hemodiafiltration (ol-HDF) might represent an additional risk factor in regard to sodium mass balance. A continuous blood-side approach for quantifying sodium mass balance in hemodialysis and ol-HDF using an online ionic dialysance sensor device ("Flux" method) embedded on hemodialysis machine was explored and compared to conventional cross-sectional "Inventory" methods using anthropometric measurement (Watson), multifrequency bioimpedance analysis (MF-BIA), or online clearance monitoring (OCM) to assess the total body water. An additional dialysate-side approach, consisting of the estimation of inlet/outlet sodium mass balance in the dialysate circuit was also performed. Ten stable hemodialysis patients were included in an "ABAB"-designed study comparing high-flux hemodialysis (hf-HD) and ol-HDF. Results are expressed using a patient-centered sign convention as follows: accumulation into the patient leads to a positive balance while recovery in the external environment (dialysate, machine) leads to a negative balance. In the blood-side approach, a slight difference in sodium mass transfer was observed between models with hf-HD (-222.6 [-585.1-61.3], -256.4 [-607.8-43.7], -258.9 [-609.8-41.3], and -258.5 [-607.8-43.5] mmol/session with Flux and Inventory models using VWatson , VMF-BIA , and VOCM values for the volumes of total body water, respectively; global P value < .0001) and ol-HDF modalities (-235.3 [-707.4-128.3], -264.9 [-595.5-50.8], -267.4 [-598.1-44.1], and -266.0 [-595.6-55.6] mmol/session with Flux and Inventory models using VWatson , VMF-BIA , and VOCM values for the volumes of total body water, respectively; global P value < .0001). Cumulative net ionic mass balance on a weekly basis remained virtually similar in hf-HD and ol-HDF using Flux method (P = n.s.). Finally, the comparative quantification of sodium mass balance using blood-side (Ionic Flux) and dialysate-side approaches reported clinically acceptable (a) agreement (with limits of agreement with 95% confidence intervals (CI): -166.2 to 207.2) and (b) correlation (Spearman's rho = 0.806; P < .0001). We validated a new method to quantify sodium mass balance based on ionic mass balance in dialysis patients using embedded ionic dialysance sensor combined with dialysate/plasma sodium concentrations. This method is accurate enough to support caregivers in managing sodium mass balance in dialysis patients. It offers a bridging solution to automated sodium proprietary balancing module of hemodialysis machine in the future.

An open-label randomized controlled trial of low-dose corticosteroid plus enteric-coated mycophenolate sodium versus standard corticosteroid treatment for minimal change nephrotic syndrome in adults (MSN Study).

First-line therapy of minimal change nephrotic syndrome (MCNS) in adults is extrapolated largely from pediatric studies and consists of high-dose oral corticosteroids. We assessed whether a low corticosteroid dose combined with mycophenolate sodium was superior to a standard oral corticosteroid regimen. We enrolled 116 adults with MCNS in an open-label randomized controlled trial involving 32 French centers. Participants randomly assigned to the test group (n=58) received low-dose prednisone (0.5 mg/kg/day, maximum 40 mg/day) plus enteric-coated mycophenolate sodium 720 mg twice daily for 24 weeks; those who did not achieve complete remission after week 8 were eligible for a second-line regimen (increase in the prednisone dose to 1 mg/kg/day with or without Cyclosporine). Participants randomly assigned to the control group (n=58) received conventional high-dose prednisone (1 mg/kg/day, maximum 80 mg/day) for 24 weeks. The primary endpoint of complete remission after four weeks of treatment was ascertained in 109 participants, with no significant difference between the test and control groups. Secondary outcomes, including remission after 8 and 24 weeks of treatment, did not differ between the two groups. During 52 weeks of follow-up, MCNS relapsed in 15 participants (23.1%) who had achieved the primary outcome. Median time to relapse was similar in the test and control groups (7.1 and 5.1 months, respectively), as was the incidence of serious adverse events. Five participants died from hemorrhage (n=2) or septic shock (n=3), including 2 participants in the test group and 3 in the control group. Thus, in adult patients, treatment with low-dose prednisone plus enteric-coated mycophenolate sodium was not superior to a standard high-dose prednisone regimen to induce complete remission of MCNS.

sST2 as a New Biomarker of Chronic Kidney Disease-Induced Cardiac Remodeling: Impact on Risk Prediction.

Heart failure is the most frequent cardiac complication of chronic kidney disease (CKD). Biomarkers help identify high-risk patients. Natriuretic peptides (BNP and NT-proBNP) are largely used for monitoring patients with cardiac failure but are highly dependent on glomerular filtration rate (GFR). Soluble suppression of tumorigenicity 2 (sST2) biomarker is well identified in risk stratification of cardiovascular (CV) events in heart failure. Furthermore, sST2 is included in a bioclinical score to stratify mortality risk. The aims of this study were to evaluate (i) the interest of circulating sST2 level in heart dysfunction and (ii) the bioclinical score (Barcelona Bio-Heart Failure risk calculator) to predict the risk of composite outcome (major adverse coronary events) and mortality in the CKD population. A retrospective study was carried out on 218 CKD patients enrolled from 2004 to 2015 at Montpellier University Hospital. sST2 was measured by ELISA (Presage ST2® kit). GFR was estimated by the CKD-EPI equation (eGFR). Indices of cardiac parameters were performed by cardiac echography. No patient had reduced ejection fraction. 112 patients had left ventricular hypertrophy, and 184 presented cardiac dysfunction, with structural, functional abnormalities or both. sST2 was independent of age and eGFR (ρ = 0.05, p = 0.44, and ρ = -0.07, p = 0.3, respectively). Regarding echocardiogram data, sST2 was correlated with left ventricular mass index (ρ = 0.16, p = 0.02), left atrial diameter (ρ = 0.14, p = 0.04), and volume index (ρ = 0.13, p = 0.05). sST2 alone did not change risk prediction of death and/or CV events compared to natriuretic peptides. Included in the Barcelona Bio-Heart Failure (BCN Bio-HF) score, sST2 added value and better stratified the risk of CV events and/or death in CKD patients (p < 0.0001). To conclude, sST2 was associated with cardiac remodeling independently of eGFR, unlike other cardiac biomarkers. Added to the BCN Bio-HF score, the risk stratification of death and/or CV events in nondialyzed CKD patients was highly improved.

Physical inactivity and protein energy wasting play independent roles in muscle weakness in maintenance haemodialysis patients.

BACKGROUND: Muscle weakness is associated with increased mortality risk in chronic haemodialysis (CHD) patients. Protein energy wasting (PEW) and low physical activity could impair muscle quality and contribute to muscle weakness beyond muscle wasting in these patients. Aim of this study was to assess clinical and biological parameters involved in the reduction of muscle strength of CHD patients. METHODS: One hundred and twenty-three CHD patients (80 males, 43 females; 68,8 [57.9-78.8] y.o.) were included in this study. Maximal voluntary force (MVF) of quadriceps was assessed using a belt-stabilized hand-held dynamometer. Muscle quality was evaluated by muscle specific torque, defined as the strength per unit of muscle mass. Muscle mass was estimated using lean tissue index (LTI), skeletal muscle mass (SMM) assessed by bioelectrical impedance analysis and creatinine index (CI). Voorrips questionnaire was used to estimate physical activity. Criteria for the diagnosis of PEW were serum albumin, body mass index < 23 kg/m2, creatinine index < 18.82 mg/kg/d and low dietary protein intake estimated by nPCR < 0.80g/kg/d. RESULTS: MVF was 76.1 [58.2-111.7] N.m. and was associated with CI (ß = 5.3 [2.2-8.4], p = 0.001), LTI (ß = 2.8 [0.6-5.1], p = 0.013), Voorrips score (ß = 17.4 [2.9-31.9], p = 0.02) and serum albumin (ß = 1.9 [0.5-3.2], p = 0.006). Only serum albumin (ß = 0.09 [0.03-0.15], p = 0.003), Voorrips score (ß = 0.8 [0.2-1.5], p = 0.005) and CI (ß = 0.2 [0.1-0.3], p<0.001) remained associated with muscle specific torque. Thirty patients have dynapenia defined as impaired MVF with maintained SMM and were younger with high hs-CRP (p = 0.001), PEW criteria (p<0.001) and low Voorrips score (p = 0.001), and reduced dialysis vintage (p<0.046). CONCLUSIONS: Beyond atrophy, physical inactivity and PEW conspire to impair muscle strength and specific torque in CHD patients and could be related to muscle quality. TRIAL REGISTRATION: ClinicalTrials.gov NCT02806089.

[Online hemodiafiltration: Practical aspects, safety and efficacy]. / Hémodiafiltration en ligne : modalités pratiques, sécurité et efficacité de la méthode.

Purification of high molecular uremic toxins by conventional hemodialysis is limited. It remains associated with a high morbidity and excessively high mortality. Online hemodiafiltration using a high permeability hemodiafilter, an ultrapure dialysate, and which tends to maximize substitution volumes, provides a high efficiency and low bio-incompatibility renal supplementation. Regular use of online hemodiafiltration is associated with reduced morbidity (reduction of intradialytic hypotension episodes, improved blood pressure control, reduced inflammatory profile, better anemia correction and prevention of ß2-microglobulin-associated amyloidosis). Recently, several cohort studies have shown that hemodiafiltration with high substitution volume was associated with a significant reduction in mortality. Randomized studies have been conducted in Europe to confirm these facts. The high safety of online hemodiafiltration has been confirmed in clinical practice by prospective studies. Online hemodiafiltration has reached its full maturity phase and is expected to represent the new standard of renal replacement therapy.

Plasma PCSK9 concentrations during the course of nondiabetic chronic kidney disease: Relationship with glomerular filtration rate and lipid metabolism.

BACKGROUND: The association between proprotein convertase subtilisin/kexin type 9 (PCSK9), a critical regulator of low-density lipoprotein (LDL) metabolism, and kidney function is a matter of debate. OBJECTIVE: We aimed to assess the association of circulating PCSK9 concentrations with both glomerular filtration rate (eGFR) and serum lipid parameters in nondiabetic patients with chronic kidney disease (CKD). METHODS: Fasting plasma PCSK9 concentrations were measured by ELISA in 94 nondiabetic nondialysis CKD (ND-CKD) patients not receiving statins, at different stages of CKD. RESULTS: Plasma PCSK9 levels were associated neither to eGFR (P = .770) nor to proteinuria (P = .888) at several stages of CKD. In addition, plasma PCSK9 levels did not vary significantly between the different CKD stages. Plasma PCSK9 concentrations were positively correlated with apolipoprotein B (r = 0.221; P = .03) and triglycerides (r = 0.211; P = .04) but not with total cholesterol, calculated LDL-cholesterol, HDL cholesterol, lipoprotein(a), or CRP. CONCLUSION: In a homogeneous population of nondiabetic subjects without lipid-lowering therapy, plasma PCSK9 concentrations are not associated to eGFR at several stages of CKD. These data suggest that kidney function per se does not impact significantly PCSK9 metabolism.

Treatment tolerance and patient-reported outcomes favor online hemodiafiltration compared to high-flux hemodialysis in the elderly.

Large cohort studies suggest that high convective volumes associated with online hemodiafiltration may reduce the risk of mortality/morbidity compared to optimal high-flux hemodialysis. By contrast, intradialytic tolerance is not well studied. The aim of the FRENCHIE (French Convective versus Hemodialysis in Elderly) study was to compare high-flux hemodialysis and online hemodiafiltration in terms of intradialytic tolerance. In this prospective, open-label randomized controlled trial, 381 elderly chronic hemodialysis patients (over age 65) were randomly assigned in a one-to-one ratio to either high-flux hemodialysis or online hemodiafiltration. The primary outcome was intradialytic tolerance (day 30-day 120). Secondary outcomes included health-related quality of life, cardiovascular risk biomarkers, morbidity, and mortality. During the observational period for intradialytic tolerance, 85% and 84% of patients in high-flux hemodialysis and online hemodiafiltration arms, respectively, experienced at least one adverse event without significant difference between groups. As exploratory analysis, intradialytic tolerance was also studied, considering the sessions as a statistical unit according to treatment actually received. Over a total of 11,981 sessions, 2,935 were complicated by the occurrence of at least one adverse event, with a significantly lower occurrence in online hemodiafiltration with fewer episodes of intradialytic symptomatic hypotension and muscle cramps. By contrast, health-related quality of life, morbidity, and mortality were not different in both groups. An improvement in the control of metabolic bone disease biomarkers and ß2-microglobulin level without change in serum albumin concentration was observed with online hemodiafiltration. Thus, overall outcomes favor online hemodiafiltration over high-flux hemodialysis in the elderly.

Hemodiafiltration improves free light chain removal and normalizes κ/λ ratio in hemodialysis patients.

BACKGROUND/AIMS: Serum free light chain (FLC) levels are correlated with chronic kidney disease (CKD) stages and are highest in patients on hemodialysis (HD). Aim of this study was to assess the FLC removal efficiency of Elisio™-210H dialyzer using either high-flux HD or on line high efficiency hemodiafiltration (HDF) modalities in CKD-5D patients. METHODS: In this prospective and comparative study, 20 CKD-5D patients free from multiple myeloma were randomized in two groups: HD versus on line HDF. All patients were dialyzed with Elisio™-210H dialyzer. Serum samples were collected before and after the midweek dialysis session, before randomization and at the end of the study to measure κ and λ FLC concentrations. Reduction ratios were corrected for net ultrafiltration. RESULTS: For both HD and HDF mode, κ and λ FLC concentrations were significantly lower after dialysis than before but median reductions in κ and λ FLC levels were significantly higher in HDF versus HD groups (κ 73.5 vs. 65.5 %, p = 0.04 and λ 51.0 vs. 36.6 %, p = 0.07). After dialysis, all κ/λ ratio values were between 0.26 and 1.65 which is the reference range described in subjects with normal kidney function, for both HD and HDF groups (median κ/λ ratios were 0.80 [0.47-1.22] and 0.67 [0.50-0.79] respectively). CONCLUSION: This study shows the superiority of on line HDF compared with HD to remove both κ and λ FLC. Moreover, all post-dialysis κ/λ ratios reached normal reference range.

Cardiovascular risk stratification in hemodialysis patients in the era of highly sensitive troponins: should we choose between hs-troponin I and hs-troponin T?

BACKGROUND: New highly sensitive (hs) assays have challenged the interpretation of cardiac troponins (cTn). The present study was designed to evaluate simultaneously conventional cTnT and cTnI together with their corresponding highly sensitive determinations in stable hemodialysis (HD) patients. Ability of cTn to stratify HD patient risk was assessed. METHODS: A total of 224 stable HD patients was included in this observational study. cTnT and hs-cTnT were measured using Roche cTnT/hs-cTnT assays based on a Cobas e601® analyzer. cTnI and hs-cTnI were measured using Beckman AccuTnI/hs-TnI IUO assays on Access II system. Patients were followed up prospectively during 9 years. Relationship between cTn level and mortality was assessed through Cox survival analysis. RESULTS: The median cTnT and cTnI concentrations were 38.5 ng/L (IQR, 18.8-76) and 10 ng/L (IQR, 10-20), respectively. The median hs-cTnT and hs-cTnI concentrations were 62.5 ng/L (IQR, 38.8-96.3) and 13.9 ng/L (IQR, 8.4-23.6), respectively. The prevalence of values above the 99th percentile was significantly more marked with cTnT (85.3 and 97.8% for conventional and hs cTnT, respectively) than with cTnI (7.6 and 67.4% for conventional and hs cTnI, respectively). During the follow-up, 167 patients died, mainly from cardiac cause (n=77). The optimized cut-off values, determined by bootstrap method, predicting mortality were 38, 69, 20 and 11 ng/L for cTnT, hs-cTnT, cTnI and hs-cTnI, respectively. After full adjustment, elevated plasma concentrations of all troponin were significant predictors of mortality. CONCLUSIONS: A large proportion of patients free of acute coronary syndrome (ACS) has hs-cTn I or T higher than the 99th percentile which could be seen as a limiting factor for ACS screening. However, all generation and type of troponin assays could be reliable indicators of prognosis risk in HD patients.

Osteoprotegerin and sclerostin in chronic kidney disease prior to dialysis: potential partners in vascular calcifications.

BACKGROUND: Osteoprotegerin (OPG), sclerostin and DKK1 constitute opposite bone turnover inhibitors, OPG inhibiting osteoclastogenesis while sclerostin and DKK1 exerting their inhibitory effects on osteoblastogenesis. Both proteins have been recognized as strong risk factors of vascular calcifications in non-dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between these inhibitors and coronary artery calcifications (CAC) in this population. METHODS: A total of 241 ND-CKD patients [143 males; 69.0 (25.0-95.0) years; median estimated glomerular filtration rate using CKD-EPI 35.1 (6.7-120.1) mL/min/1.73 m(2)] were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. OPG, sclerostin, DKK1 and mineral metabolism markers including PTH and bone alkaline phosphatase were measured. Logistic regression analyses were used to study the relationships between CAC and these markers. RESULTS: Decline in renal function was associated with a significant increase in OPG and sclerostin while a slight but significant decrease in DKK1 was observed. The main crude associations with presence of CAC were a high level of OPG [OR = 2.55 95% confidence interval (95% CI) (1.35-4.82) for a level ranging from 6.26 to 9.15 pmol/L and OR = 5.74 95% CI (2.87-11.5) for a level ≥9.15 pmol/L; P < 0.0001] and a high level of sclerostin [OR = 2.64 95% CI (1.39-5.00) for a level ranging from 0.748 to 1.139 ng/mL and OR = 3.78 95% CI (1.96-7.31) for a level ≥1.139 ng/mL; P = 0.0002]. A logistic regression model clearly showed that the risk to present CAC was significantly increased when both OPG (≥6.26 pmol/L) and sclerostin (≥0.748 ng/mL) levels were high [crude model: OR = 11.47 95% CI (4.54-29.0); P < 0.0001; model adjusted for age, gender, diabetes, body mass index and smoking habits: OR = 5.69 95% CI (1.76-18.4); P = 0.02]. No association between DKK1 and presence of CAC was observed. CONCLUSIONS: Our results strongly suggest that bone turnover inhibitors, OPG and sclerostin, are independently associated with CAC with potential additive effects in ND-CKD patients.

Pharmacologic therapies for chronic and acute decompensated heart failure: specific insights on cardiorenal syndromes.

In the setting of cardiorenal syndrome(s) (CRS), the main pathophysiological triggers of renal disease progression include increases in renal venous pressure, maladaptive activation of the renin-angiotensin-aldosterone (RAAS) and the sympathetic nervous systems, and a chronic inflammatory state. In acute decompensated heart failure (HF)/type 1 CRS, diuretics remain the mainstay of first-line therapy in order to prevent congestion and renal venous hypertension. In chronic HF/type 2 CRS, RAAS multiple inhibition has been recommended in addition to diuretics. However, cotreatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and mineralocorticoid receptor antagonists is likely to lead to more frequent occurrences of hyperkalemia and worsening renal function. In this review, the main pharmacological therapies of acute and chronic CRS are discussed regarding their indication as well as intended and side effects. Future therapies are suggested, underlining that a multidisciplinary approach to a deeper understanding of the pathophysiology of CRS is still required to improve specific treatment and clinical outcome.

Creatinine index as a surrogate of lean body mass derived from urea Kt/V, pre-dialysis serum levels and anthropometric characteristics of haemodialysis patients.

BACKGROUND AND OBJECTIVES: Protein-energy wasting is common in long-term haemodialysis (HD) patients with chronic kidney disease and is associated with increased morbidity and mortality. The creatinine index (CI) is a simple and useful nutritional parameter reflecting the dietary skeletal muscle protein intake and skeletal muscle mass of the patient. Because of the complexity of creatinine kinetic modeling (CKM) to derive CI, we developed a more simplified formula to estimate CI in HD patients. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: A large database of 549 HD patients followed over more than 20 years including monthly CKM-derived CI values was used to develop a simple equation based on patient demographics, predialysis serum creatinine values and dialysis dose (spKt/V) using mixed regression models. RESULTS: The equation to estimate CI was developed based on age, gender, pre-dialysis serum creatinine concentrations and spKt/V urea. The equation-derived CI correlated strongly with the measured CI using CKM (correlation coefficient  = 0.79, p-value <0.001). The mean error of CI prediction using the equation was 13.47%. Preliminary examples of few typical HD patients have been used to illustrate the clinical relevance and potential usefulness of CI. CONCLUSIONS: The elementary equation used to derive CI using demographic parameters, pre-dialysis serum creatinine concentrations and dialysis dose is a simple and accurate surrogate measure for muscle mass estimation. However, the predictive value of the simplified CI assessment method on mortality deserves further evaluation in large cohorts of HD patients.

A combined index of cardiac biomarkers as a risk factor for early cardiovascular mortality in hemodialysis patients.

BACKGROUND: Cardiac biomarkers, including cardiac troponin-I (cTn-I) and N-terminal pro brain natriuretic peptide (NT-proBNP) have been associated with poor outcome in hemodialysis (HD) patients. The present study was designed to evaluate these biomarkers as biological risk factors for early and late mortality in HD patients. In addition, a multimarker approach including inflammatory index was performed in order to improve the cardiovascular risk assessment of these patients. METHODS: cTnI, NT-proBNP and C-reactive protein (CRP) were measured at baseline (October through November 2002) in 130 HD patients [median age 69.0 (23.4-87.7) years old, 76 females, 54 males]. Patients were followed during 8 years. Adjusted hazard ratios (HRs) of death and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. RESULTS: During the follow-up, 82 patients died, mainly from cardiac cause (63.4%). Elevated cTnI, NT-proBNP or CRP were all associated with increased early (death within 2 years of follow-up) but not late mortality. Moreover, the combination of all parameters (CRP ≥10.51 mg/L and cTnI ≥0.037 µg/L and NT-proBNP ≥10,204 pg/mL) dramatically increased the short-term mortality especially the cardiovascular mortality (HR 8.58, 95% CI 1.59-46.2; p=0.0007). CONCLUSIONS: A combined index of cardiovascular risk factors could provide supplementary risk stratification in HD patients for early cardiovascular mortality, strongly supporting the annual routine determination of these biomarkers.

Prevention and management of dialysis catheter complications in the intensive care unit.

Dialysis dependence at hospital discharge after acute kidney injury (AKI) requiring renal replacement therapy (RRT) in the intensive care unit (ICU) is found in 10-15% of survivors. In case of severe AKI in the ICU, it is necessary to reconcile two objectives: the creation of an adequate temporary angioaccess for RRT and the preservation of the patient's vascular network in case of evolution to end-stage renal disease. A central venous catheter (CVC) is the best option for RRT in the ICU setting. Most catheter-related hazards can be prevented by following best clinical practices for insertion and handling of the CVC, and by knowing the advantages and disadvantages of the different types of catheters, the sites and techniques of insertion, the types of RRT modality for choosing the best CVC option, and the prophylactic and therapeutic measures to prevent and to manage the complications. We review here some important aspects of the CVC for the treatment of AKI in the ICU.

Bone biomarkers help grading severity of coronary calcifications in non dialysis chronic kidney disease patients.

BACKGROUND: Osteoprotegerin (OPG) and fibroblast growth factor-23 (FGF23) are recognized as strong risk factors of vascular calcifications in non dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between FGF23, OPG, and coronary artery calcifications (CAC) in this population and to attempt identification of the most powerful biomarker of CAC: FGF23? OPG? METHODOLOGY/PRINCIPAL FINDINGS: 195 ND-CKD patients (112 males/83 females, 70.8 [27.4-94.6] years) were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. Vascular risk markers including FGF23 and OPG were measured. Logistic regression analyses were used to study the potential relationships between CAC and these markers. The fully adjusted-univariate analysis clearly showed high OPG (≥10.71 pmol/L) as the only variable significantly associated with moderate CAC ([100-400[) (OR = 2.73 [1.03;7.26]; p = 0.04). Such association failed to persist for CAC scoring higher than 400. Indeed, severe CAC was only associated with high phosphate fractional excretion (FEPO(4)) (≥38.71%) (OR = 5.47 [1.76;17.0]; p = 0.003) and high FGF23 (≥173.30 RU/mL) (OR = 5.40 [1.91;15.3]; p = 0.002). In addition, the risk to present severe CAC when FGF23 level was high was not significantly different when OPG was normal or high. Conversely, the risk to present moderate CAC when OPG level was high was not significantly different when FGF23 was normal or high. CONCLUSIONS: Our results strongly suggest that OPG is associated to moderate CAC while FGF23 rather represents a biomarker of severe CAC in ND-CKD patients.

[Hemodialysis in patients with chronic renal insufficiency]. / Hémodialyse chez les patients atteints d'insuffisance rénale chronique.

Hemodialysis is the most advanced form of artificial renal support. It ensures the survival of almost 2 million patients wordwide. Considerable progress has been made in recent years thanks to a better understanding of uremia, optimization of treatment modalities and more personalized treatment schedules. Increase of uremic toxins removal, improvement of hemodynamic tolerance of the sessions, reduction of proinflammatory reactions due to the bioincompatibility system are major advances that may explain the reduction of morbidity and mortality in dialysis patients. New technologies (nanotechnology, biotechnology, microelectronics) are now expected to introduce further progresses by miniaturizing devices and providing them with an "artificial intelligence" capable of interacting with the patient. The main obstacle remains ageing of uremic patients, increasing prevalence of comorbidities and shortage of social resources that are not conducive to innovation. By promoting a more physiological, longer and more effective hemodialysis performed at home with help of teledialysis monitoring that would probably be an interesting option to evaluate on a medico-economical point of view.

Spontaneous renal artery dissection with renal infarction.

Spontaneous renal artery dissection (SRAD) is a rare entity, which often presents diagnostic difficulties because of its non-specific clinical presentation. We report six cases complicated with renal infarction, occurring in middle-aged male patients without risk factors, illustrating the difficulty and delay for diagnosing SRAD. Ultrasound and Doppler imaging were not sensitive enough to confirm the diagnosis, and contrast-enhanced abdominal computed tomography was used to correct the diagnosis and allow the clinicians to propose appropriate treatment. We conclude that considering the urgency in diagnosing and treating SRAD, contrast enhanced abdominal tomography and/or abdominal magnetic resonance imaging should be proposed as soon as a suspicion of SRAD is evoked by the clinical presentation.

Does hemodiafiltration improve the removal of homocysteine?

High prevalence of hyperhomocysteinemia is common in hemodialysis (HD) patients and could contribute to worsen the cardiovascular risk. Beyond vitamin B status, dialysis modality itself could influence homocysteine (Hcy) levels. The objective was compare the reduction rate (RR) of Hcy and cysteine in stable dialyzed patients treated by standard HD or hemodiafiltration (HDF). Seventy-five patients undergoing stable dialysis through standard high-flux HD (n = 35) or HDF (n = 40) were included. Biological parameters were determined before and after a midweek dialysis session. Urea percent reduction per session and Kt/V index (K, body urea clearance, T, time of dialysis, and V, urea distribution volume), defined as a marker of dialysis efficacy, were similar between HD and HDF groups. By contrast, higher RR of beta2 microglobulin (ß2m) was observed in HDF compared with HD (78.6 vs. 72.0%, respectively; P < 0.001). Likewise, higher RR of Hcy was obtained with HDF compared to HD (46.0 vs. 41.5%, respectively; P < 0.05), whereas the RR of cysteine was similar in both groups. Interestingly, a positive correlation between Hcy RR and urea Kt/V index was observed (r = 0.29, P < 0.05) and between Hcy RR and ß2m RR (r = 0.45, P < 0.001). Time-averaged concentration (TAC) of Hcy was lower with HDF compared with HD (17.8 vs. 19.1 µmol/L, respectively), although not significant. There was no difference in median Hcy according to dialysis modality for neither pre- nor postdialysis levels. Significant higher removal of Hcy was observed with HDF compared with standard HD, although urea Kt/V index was similar. Enhanced removal of middle molecules, such as ß2m, could be involved in Hcy RR improvement with HDF.