Long-term cardio-vascular risk assessment in chronic kidney disease and kidney transplanted patients following SARS-COV-2 disease: protocol for multi-center observational match controlled trial.

BACKGROUND: The coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced a pandemic since March 2020 by affecting more than 243 million people with more than 5 million deaths globally. SARS-CoV-2 infection is produced by binding to angiotensin-converting enzyme, which among other sites is highly expressed in the endothelial cells of the blood vessels, pericytes and the heart, as well as in renal podocytes and proximal tubular epithelial cells. SARS-CoV-2 and cardiovascular disease (CVD) are interconnected by risk factors association with an increased incidence of the disease and by determining de novo cardiac complications. At the same time, COVID-19 disease can lead to acute kidney injury directly, or due to sepsis, multi-organ failure and shock. Therefore, the pre-existence of both CVD and chronic kidney disease (CKD) is linked with a higher risk of severe disease and worse prognosis. METHODS: The main aim of this study is to assess the CV risk in a CKD (stage 3 to 5), dialysis and kidney transplanted population, following SARS-CoV-2 infection, with focus on the endothelial dysfunction as compared to a control group of matched patients. By using clinical evaluation, flow-mediated dilatation, carotid-femoral pulse wave velocity, intima-media thickness, echocardiographic parameters, lung ultrasound, bioimpedance spectroscopy and a series of novel biomarkers, the investigators will determine the long-term impact of this disease on CV and renal outcomes. DISCUSSION: This study will address the challenges and implications in long-term CV sequeale of COVID-19 and focus on a better understanding of the underlying mechanisms and possible therapeutic options. TRIAL REGISTRATION: Patient enrolment in the trial started in January 2021 and is expected to finish at the end of 2022. The study can be found on ClinicalTrials.gov database with NCT05125913 identifier. Registered on 18 November 2021 - Retrospectively registered.

Revisiting risk prediction tools for death and end-stage renal disease in older patients with advanced chronic kidney disease: a prospective study.

BACKGROUND: Risk assessment tools for predicting mortality and end-stage renal disease (ESRD) in the elderly with CKD have received growing attention. However, integrating risk equations into a multidimensional approach of elderly with CKD stage 3b-4 is lacking. METHODS: In this prospective observational study, we enrolled CKD stage 3b-4 patients aged ≥ 65 years. Bansal score for predicting mortality risk and Kidney Failure Risk Equation (KFRE) for estimating progression to ESRD were applied. Predicted outcome was compared with actual clinical end-points. All patients underwent comprehensive geriatric assessment (CGA), which is an interdisciplinary multidimensional process for geriatric evaluation and management. RESULTS: Participants (N = 184) were divided into two groups, according to Bansal score: Group 1 (low-risk of death, Bansal score < 7, N = 69) and Group 2 (high-risk of death, Bansal score ≥ 7, N = 115). Group 2 displayed a substantially higher cardiovascular disease burden than Group 1 and was significantly more likely to be depressed and at risk of malnutrition, according to CGA. Thirty-seven patients died, and 16 started dialysis. Group 2 displayed significantly higher all-cause mortality. In the univariable Cox regression, Group 2 had a fourfold increase in the risk of all-cause mortality, as compared with Group 1 (HR = 4.29, 95% CI 1.88-10.26, P < 0.001). Multivariable stepwise Cox analysis showed that Bansal score above 7 remained significantly associated with all-cause mortality (HR = 3.96, 95% CI 1.68-9.29, P < 0.001). Group 2 also displayed higher event rates for dialysis initiation. In Group 1, only four patients started dialysis, and three out of them had a high-risk of progression at baseline, according to KFRE. CONCLUSIONS: Using risk stratification tools and CGA in a population of elderly with advanced CKD, we found that two-thirds of the patients were at high risk of death, malnutrition and depression, with multimorbidity and four times worse probability of survival than those at lower risk of death.

Lung Ultrasound-Guided Fluid Management versus Standard Care in Surgical ICU Patients: A Randomised Controlled Trial.

The value of lung ultrasound (LU) in assessing extravascular lung water (EVLW) was demonstrated by comparing LU with gold-standard methods for EVLW assessment. However, few studies have analysed the value of B-Line score (BLS) in guiding fluid management during critical illness. The purpose of this trial was to evaluate if a BLS-guided fluid management strategy could improve fluid balance and short-term mortality in surgical intensive care unit (ICU) patients. We conducted a randomised, controlled trial within the ICUs of two university hospitals. Critically ill patients were randomised upon ICU admission in a 1:1 ratio to BLS-guided fluid management (active group) or standard care (control group). In the active group, BLS was monitored daily until ICU discharge or day 28 (whichever came first). On the basis of BLS, different targets for daily fluid balance were set with the aim of avoiding or correcting moderate/severe EVLW increase. The primary outcome was 28-day mortality. Over 24 months, 166 ICU patients were enrolled in the trial and included in the final analysis. Trial results showed that daily BLS monitoring did not lead to a different cumulative fluid balance in surgical ICU patients as compared to standard care. Consecutively, no difference in 28-day mortality between groups was found (10.5% vs. 15.6%, p = 0.34). However, at least 400 patients would have been necessary for conclusive results.

Evaluation of low-dose glucocorticoid regimen in association with cyclophosphamide in patients with glomerulonephritis.

BACKGROUND: The treatment of most glomerulonephritides is still based on a combination of an oral corticosteroid and an alkylating agent, with favorable outcomes, but with serious side effects. The objective of this study was to reduce the cumulative corticosteroid dose in patients with high risk of corticosteroid-related adverse events by replacing daily oral corticosteroids with intravenous (iv) methylprednisolone pulses, associated with monthly pulse i.v. cyclophosphamide (according to KDIGO guidelines) in patients with glomerulonephritis. METHODS: This was a retrospective cohort study conducted at a single nephrology centre. In the course of a 6-month run-in phase, all the patients received non-immunosuppressive pathogenic treatment. High-risk patients, who still had urinary protein excretion of at least 3.5 g per day at the end of these 6 months, received a combination of corticosteroids and cyclophosphamide. Patients were divided in two groups: group 1 (23 patients)-included patients with high risk of corticosteroid-related adverse events received monthly methylprednisolone 1 g/day, 3 days and i.v. cyclophosphamide for 6 months, and group 2 (84 patients)-received oral corticosteroids (as per KDIGO recommended dose) and i.v. cyclophosphamide. The primary outcome-time to a combined end-point of doubling of serum creatinine, ESRD, need for chronic renal replacement therapy or death; secondary outcomes: complete remission [proteinuria < 0.3 g per 24 h (urinary protein-creatinine rate < 300 mg/g [< 30 mg/mmol]]; partial remission (proteinuria > 0.3 but < 3.5 g per 24 h or a decrease in proteinuria by at least 50% from the initial value) and adverse events. RESULTS: At 6 months, there was no difference in the primary composite end-point: 8.7% patients from the group 1 and 20.2% patients from the group 2 (P = 0.199) reached this end-point. Similar data were also recorded at 12 months. Secondary end-points were also similar between treatment groups. More patients receiving oral corticosteroids experienced infections, but without statistical significance. CONCLUSION: Our data indicate that low i.v. dose corticosteroids and cyclophosphamide administered monthly in patients with high risk of corticosteroid-related adverse events and primary glomerulonephritis are equally effective, with fewer metabolic disorders and infections.

Lung Ultrasound Guided Fluid Management Protocol for the Critically Ill Patient: study protocol for a multi-centre randomized controlled trial.

BACKGROUND: In routine intensive care unit (ICU) practice, fluids are often administered without a safety limit, which may lead to fluid overload and decreased survival. Recently, B-lines score (BLS) has been validated as a lung ultrasound (LUS) quantification of pulmonary congestion. This suggests that LUS may provide a safety threshold to conduct fluid therapy and to avoid overhydration. However, there is no randomized study to test the utility of LUS in guiding fluid management in ICU patients by using a pre-specified BLS cut-off value as a threshold for fluid removal. METHODS: LUS Guided Fluid Management Protocol for the Critically Ill Patient is a prospective, multi-centre, randomized controlled trial. Five hundred ICU patients will be randomly assigned in a 1:1 ratio, to protocolized LUS-based fluid management or usual care. The trial intervention will start on ICU admission and will consist in daily assessment of BLS and triggered evacuation of excessive fluids with loop diuretics (Furosemide) when BLS ≥ 15. If rebalancing volume status with diuretics fails, forced evacuation by ultrafiltration will be used. The main endpoint is death from all causes at 28 days from randomization. The secondary outcomes are presence and time-course evolution of organ dysfunctions, ICU- and hospital length of stay, all-cause mortality at 90 days, and health economics data. DISCUSSION: If study results will show that LUS guided fluid management protocol improves outcome in ICU patients, it will be the base for other studies to refine this protocol or track those categories of critically ill patients to whom it may bring maximum benefits. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03393065 . Registered on 8 January 2018.

The predictive value of malnutrition for functional and cognitive status in elderly hemodialysis patients.

OBJECTIVE: The study aims to objectively and precisely describe, in elderly dialysis patients from a single center, the prevalence of malnutrition and severe cognitive/functional impairment and to establish the prognostic role of malnutrition assessment for patient's severe cognitive/functional status. DESIGN: Cross-sectional study. SETTING: A single dialysis center from north-eastern Romania. SUBJECTS: Eighty-one elderly ambulatory hemodialysis patients. INTERVENTION: The aim of the study was to establish in hemodialysis elderly patients a correlation between two malnutrition scores [Mini Nutritional Assessment (MNA) and Subjective Global Assessment (SGA)] and geriatric tests (Geriatric Depression Scale-GDS), daily activities (Activities of Daily Living-ADL, Instrumental Activities of Daily Living-IADL), and cognitive impairment scores (Mini Mental State Examination-MMSE). A correlation between objective malnutrition parameters (bioimpedance lean tissue index (LTI) and fat tissue index (FTI) by bioimpedance) was also assessed. MAIN OUTCOME MEASURE: Using area under the curve analysis, two malnutrition scores and bioimpedance assessed nutritional status were explored as possible predictors for the most severe category of functional and cognitive status. RESULTS: All patients had mild/moderate malnutrition by SGA, while the MNA test reported malnutrition in 14.5%, and 58% of cases. There was no correlation between subjective scores and objective biomarkers of malnutrition (albumin levels, bioimpedance-derived LTI, FTI). ROC curve analysis showed that MNA and SGA predict the most severe category of depression and functional impairment with relatively good accuracy (specificity, sensibility). CONCLUSION: The study confirms the important correlation between malnutrition and cognitive/functional impairment and confirms that malnutrition scores could be useful in predicting depression and physical dependance in elderly dialysis patients.

Prospective Validation of a Screening Biomarker Approach Combining Amino-Terminal Pro-Brain Natriuretic Peptide With Galectin-3 Predicts Death and Cardiovascular Events in Asymptomatic Hemodialysis Patients.

Cardiovascular (CV) disease is a major cause of death in hemodialysis patients. Biomarkers used to identify high-risk asymptomatic patients would allow early evaluation of cardiac dysfunction and appropriate therapeutic intervention. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) and galectin-3 (Gal-3) may serve this purpose. Plasma levels of NT-proBNP and Gal-3 were measured in 173 patients. Patients were prospectively followed for occurrences of major CV events or death. The association of NT-proBNP and Gal-3 with outcome was analyzed. The prognostic abilities for the combined outcome of Gal-3 and/or NT-proBNP were evaluated. During a median follow-up of 36 months, there were 47 incident outcomes (death and CV events). In the univariable Cox analysis, age, hypertension, albumin, phosphorus levels, and combined elevation of NT-proBNP with Gal-3 above the median (hazard ratio [HR] = 3.65, 95% confidence interval [CI] = 1.45-9.21) were associated with outcomes. In multivariable Cox analysis, both NT-proBNP and Gal-3 values above the median remained associated with outcomes (HR = 3.34, 95% CI = 1.30-8.56). In clinically asymptomatic dialysis patients, combined use of NT-proBNP and Gal-3 may improve risk stratification for death and CV events.

Dry weight assessment by combined ultrasound and bioimpedance monitoring in low cardiovascular risk hemodialysis patients: a randomized controlled trial.

PURPOSE: Fluid overload is associated with adverse outcomes in hemodialysis (HD) patients. The precise assessment of hydration status in HD patients remains a major challenge for nephrologists. Our study aimed to explore whether combining two bedside methods, lung ultrasonography (LUS) and bioimpedance, may provide complementary information to guide treatment in specific HD patients. METHODS: In total, 250 HD patients from two dialysis units were included in this randomized clinical trial. Patients were randomized 1:1 to have a dry weight assessment based on clinical (control) or LUS with bioimpedance in case of clinical hypovolemia (active)-guided protocol. The primary outcome was to assess the difference between the two groups on a composite of all-cause mortality and first cardiovascular event (CVE)-including death, stroke, and myocardial infarction. RESULTS: During a mean follow-up period was 21.3 ± 5.6 months, there were 54 (21.6%) composite events in the entire population. There was a nonsignificant 9% increase in the risk of this outcome in the active arm (HR = 1.09, 95% CI 0.64-1.86, p = 0.75). Similarly, there were no differences between the two groups when analyzing separately the all-cause mortality and CVE outcomes. However, patients in the active arm had a 19% lower relative risk of pre-dialytic dyspnea (rate ratio-0.81, 95% CI 0.68-0.96), but a 26% higher relative risk of intradialytic cramps (rate ratio-1.26, 95% CI 1.16-1.37). CONCLUSIONS: This study shows that a LUS-bioimpedance-guided dry weight adjustment protocol, as compared to clinical evaluation, does not reduce all-cause mortality and/or CVE in HD patients. A fluid management protocol based on bioimpedance with LUS on indication might be a better strategy.

Efficacy of a remote web-based lung ultrasound training for nephrologists and cardiologists: a LUST trial sub-project.

Within the framework of the LUST trial (LUng water by Ultra-Sound guided Treatment to prevent death and cardiovascular events in high-risk end-stage renal disease patients), the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis Transplant Association established a central core lab aimed at training and certifying nephrologists and cardiologists participating in this trial. All participants were trained by an expert trainer with an entirely web-based programme. Thirty nephrologists and 14 cardiologists successfully completed the training. At the end of training, a set of 47 lung ultrasound (US) videos was provided to trainees who were asked to estimate the number of B-lines in each video. The intraclass correlation coefficient (ICC) for the whole series of 47 videos between each trainee and the expert trainer was high (average 0.81 ± 0.21) and >0.70 in all but five cases. After further training, the five underperforming trainees achieved satisfactory agreement with the expert trainer (average post-retraining ICC 0.74 ± 0.14). The Bland-Altman plot showed virtually no bias (difference between the mean 0.03) and strict 95% limits of agreement lines (-1.52 and 1.45 US B-lines). Only four cases overlapped but did not exceed the same limits. Likewise, the Spearman correlation coefficient applied to the same data series was very high (r = 0.979, P < 0.0001). Nephrologists and cardiologists can be effectively trained to measure lung congestion by an entirely web-based programme. This web-based training programme ensures high-quality standardization of US B-line measurements and represents a simple, costless and effective preparatory step for clinical trials targeting lung congestion.

Predictive Value for Galectin 3 and Cardiotrophin 1 in Hemodialysis Patients.

Patients with end-stage renal disease (ESRD) have an increased risk of all-cause mortality. The prognostic value of the new cardiac biomarkers, cardiotrophin 1 (CT-1) and galectin 3 (GAL-3), has not yet been defined in hemodialysis (HD) patients. The aim of this study was to determine the use of these novel biomarkers for predicting mortality in HD patients. Plasma GAL-3 and CT-1 concentrations were determined (at baseline) in 88 HD patients followed for 22.2 ± 4.7 months. During the follow-up period, 21 (23.9%) deaths were recorded. According to Cox analysis, the cutoff point for GAL-3 as a predictor of mortality was 23.73 ng/mL, while the cutoff point for CT-1 as a predictor of mortality was 36 pg/mL. In univariate analysis, only GAL-3 >23.73 ng/mL was an independent predictor of mortality (hazard ratio 2.60; 95% confidence interval, 1.09-6.18). In a multivariable Cox proportional hazards model, GAL-3 levels above the cutoff value remained an independent predictor of all-cause mortality. Our data suggest that similar to the general population, GAL-3 is an independent predictor of mortality in HD patients.

Overhydration, Cardiac Function and Survival in Hemodialysis Patients.

BACKGROUND AND OBJECTIVES: Chronic subclinical volume overload occurs very frequently and may be ubiquitous in hemodialysis (HD) patients receiving the standard thrice-weekly treatment. It is directly associated with hypertension, increased arterial stiffness, left ventricular hipertrophy, heart failure, and eventually, higher mortality and morbidity. We aimed to assess for the first time if the relationship between bioimpedance assessed overhydration and survival is maintained when adjustments for echocardiographic parameters are considered. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: A prospective cohort trial was conducted to investigate the impact of overhydration on all cause mortality and cardiovascular events (CVE), by using a previously reported cut-off value for overhydration and also investigating a new cut-off value derived from our analysis of this specific cohort. The body composition of 221 HD patients from a single center was assessed at baseline using bioimpedance. In 157 patients supplemental echocardiography was performed (echocardiography subgroup). Comparative survival analysis was performed using two cut-off points for relative fluid overload (RFO): 15% and 17.4% (a value determined by statistical analysis to have the best predictive value for mortality in our cohort). RESULTS: In the entire study population, patients considered overhydrated (using both cut-offs) had a significant increased risk for all-cause mortality in both univariate (HR = 2.12, 95%CI = 1.30-3.47 for RFO>15% and HR = 2.86, 95%CI = 1.72-4.78 for RFO>17.4%, respectively) and multivariate (HR = 1.87, 95%CI = 1.12-3.13 for RFO>15% and HR = 2.72, 95%CI = 1.60-4.63 for RFO>17.4%, respectively) Cox survival analysis. In the echocardiography subgroup, only the 17.4% cut-off remained associated with the outcome after adjustment for different echocardiographic parameters in the multivariate survival analysis. The number of CVE was significantly higher in overhydrated patients in both univariate (HR = 2.46, 95%CI = 1.56-3.87 for RFO >15% and HR = 3.67, 95%CI = 2.29-5.89 for RFO >17.4%) and multivariate (HR = 2.31, 95%CI = 1.42-3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48-7.02 for RFO >17.4%) Cox regression analysis. CONCLUSIONS: The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations.

Prognostic significance of 25-hydroxivitamin D entirely explained by a higher comorbidity burden: experience from a South-Eastern European Dialysis Cohort.

Vitamin D deficiency is still a common problem particularly in the elderly and in individuals with various degrees of renal impairment. The present study aimed to evaluate the association between plasma concentrations of 25(OH)D and death in a large cohort of prevalent patients on hemodialysis (HD) from south-east Romania, a typical Balkan region. This is an observational prospective study that included a total of 570 patients on maintenance HD. Study patients were classified into three groups by baseline 25(OH)D levels: (1) sufficient 25(OH)D--i.e., >30 ng/mL; (2) insufficient 25(OH)D--i.e., between 10 and 29 ng/mL; and (3) deficient 25(OH)D--i.e., <10 ng/mL. During the follow-up period of 14 months, 68 patients (11.9%) died, the Kaplan-Meier analysis showing significant differences in all-cause mortality for chronic kidney disease patients in different 25(OH)D groups (P = 0.002). Unadjusted Cox regression analysis also showed significant differences in survival. The multivariate Cox regression model showed no significant differences in survival according to vitamin D levels. Hazard ratio for death in the "<10 ng/mL" group was 1.619 (P = 0.190) and in the "10-30 ng/mL" group was 0.837 (P = 0.609). In our dialysis population with a high comorbidity burden, low 25(OH)D concentration was not associated with mortality in the adjusted Cox model, suggesting that vitamin D deficiency could represent only a non-specific marker for a poor health status, with less impact on mortality.

Tissue advanced glycation end products (AGEs), measured by skin autofluorescence, predict mortality in peritoneal dialysis.

PURPOSE: The relation between tissue AGEs and mortality in end-stage renal disease (ESRD) is documented, but only in hemodialysis (HD) patients. This study aimed to measure and compare tissue AGEs levels in patients receiving either HD or peritoneal dialysis (PD) and to study the effect of these products on all-cause, cardiovascular or sepsis-related mortality. METHODS: Tissue AGEs were noninvasively assessed in 304 dialysis patients (202 on chronic HD and 102 on continuous ambulatory PD) by measuring skin autofluorescence using a validated Autofluorescence Reader (AGE Reader, DiagnOptics b.v., Groningen, The Netherlands). RESULTS: There was no difference in regard to AGEs levels between the HD (3.6 ± 0.8 AU)- and PD (3.5 ± 0.7 AU, p = 0.2)-treated patients. Diabetic patients had higher AGEs values in the HD group (3.97 ± 0.81 vs. 3.52 ± 0.77, p = 0.002), but not in the PD group (3.68 ± 0.6 vs. 3.45 ± 0.70, p = 0.26). In PD patients, increasing AGEs levels were associated with an elevated risk of all-cause mortality (a 2.09-fold increase for each increment of 1 AU in AGEs values) and sepsis (a 3.44-fold increase for each increment of 1 AU in AGEs values)-related mortality. Performing a similar analysis in diabetic patients, AGEs was associated only with sepsis-related mortality (a 3.08-fold increase for each increment of 1 AU in AGEs values). CONCLUSIONS: This is the first study that demonstrates a relationship between tissue AGEs levels and sepsis-related mortality in PD-treated or diabetic ESRD patients. Future studies are necessary to evaluate the non-cardiovascular effects of tissue AGEs in ESRD patients.

ENDOTHELIAL DYSFUNCTION ASSESSED BY LASER DOPPLER POST-OCCLUSIVE HYPEREMIA IN CHRONIC KIDNEY DISEASE PATIENTS.

UNLABELLED: This study was intended to investigate the microcirculation endothelial dysfunction through a laser Doppler method (PORH post-occlusive reactive hyperemia) in patients with chronic kidney disease. MATERIALS AND METHODS: The study included 299 patients diagnosed with chronic kidney disease, which were divided into three groups: hemodialysis patients, peritoneal dialysis patients and patients with chronic kidney disease stages 3-4. Endotelial dysfunction was assesed with the Laser Doppler Perfusion Monitor type device (Periflux System Monitor 5001). RESULTS: The values of the parameters we evaluated with postocclusive reactive hyperemia were altered in all patients with chronic kidney disease. In the dialysis groups there was no statistically significant correlation between parameters we tested by measuring PORH and the method of renal replacement therapy or dialysis duration. The same was observed in patients with pre-dialysis chronic kidney disease. CONCLUSIONS: Post-occlusive reactive hyperemia, a novel method for assessing endothelial dysfunction on the microcirculatory system and early marker of cardiovascular damage requires more studies to validate in patients advanced renal disfunction.

Bioimpedance-guided fluid management in maintenance hemodialysis: a pilot randomized controlled trial.

BACKGROUND: Chronic subclinical volume overload happens very frequently in hemodialysis patients and is associated directly with hypertension, increased arterial stiffness, left ventricular hypertrophy, and ultimately higher mortality. STUDY DESIGN: Randomized controlled parallel-group trial. SETTING & PARTICIPANTS: 131 patients from one hemodialysis center, randomly assigned into 2 groups. INTERVENTION: Dry weight prescription using results derived from repeated 3-month bioimpedance measurements to guide ultrafiltration for strict volume control (bioimpedance group; n=62) compared with clinical judgment without bioimpedance measures (clinical-methods group; n=69) for 2.5 years. OUTCOMES: The primary outcome was all-cause mortality over 2.5 years (the duration of the intervention). Secondary outcomes were change in relative arterial stiffness, fluid overload, and blood pressure (BP) over 2.5 years. MEASUREMENTS: Bioimpedance measurements were performed using a Body Composition Monitor device. Pulse wave velocity analysis was performed at baseline, 2.5 years (end of intervention), and 3.5 years (end of study). Relative fluid overload and BP were assessed at 3-month intervals. RESULTS: The unadjusted HR for all-cause death in the bioimpedance group (vs the clinical-methods group) was 0.100 (95% CI, 0.013-0.805; P=0.03). After 2.5 years, we found a greater decline in arterial stiffness, relative fluid overload, and systolic BP in the bioimpedance group than the clinical-methods group. Between-group differences in change from baseline to the end of intervention were -2.78 (95% CI, -3.75 to 1.80)m/s for pulse wave velocity (P<0.001), -2.99% (95% CI, -5.00% to -0.89%) for relative fluid overload (P=0.05), and -2.43 (95% CI, -7.70 to 2.84)mmHg for systolic BP (P=0.4). LIMITATIONS: Echocardiography was not performed as cardiovascular assessment and the caregivers were not masked to the intervention. CONCLUSIONS: Our study showed improvement in both surrogate and hard end points after strict volume control using bioimpedance to guide dry weight adjustment. These findings need to be confirmed in a larger trial.

Superior predictive value for NTproBNP compared with high sensitivity cTnT in dialysis patients: a pilot prospective observational study.

BACKGROUND/AIMS: The clinical utility of the new biomarker, high sensitivity cardiac T troponin (hs-cTnT) is still unclear in dialysis patients. Furthermore, the prognostic value of combining N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and hs-cTnT has not been explored so far. The objective of this pilot study was to determine the utility of hs-cTnT alone versus hs-cTnT in combination with NT-proBNP for predicting death in a stable hemodialysis cohort. METHODS: A prospective observational pilot study including 98 chronic asymptomatic hemodialysis patients with a follow up period of 24 months was designed. The cut-off values for NT-proBNP and hs-cTnT were calculated using receiver operating characteristic (ROC) analysis, using mortality as an end-point. Based on the cut-off values, the cohort was divided into four groups. Group 1--NT-proBNP < 14275 pg/ml and hs-cTnT < 69.48 ng/l; group 2--NT-proBNP < 14275 pg/ml and hs-cTnT > 69.48 ng/l; group 3--NT-proBNP > 14275 pg/ml and hs-cTnT < 69.48 ng/l; group 4--NT-proBNP > 14275 pg/ml and hs-cTnT > 69.48 ng/l. Survival for each group was determined using the Kaplan-Meier method and Cox regression analysis. RESULTS: During the follow-up period 16 patients died. According to the ROC curves analysis, the cut-off point for hs-cTnT and for NT-proBNP were 69.43 ng/l (AUC = 0.618; p = 0.04) and 14275 pg/ml (AUC = 0.722; p = 0.003), respectively. In univariate Cox analysis, both hs-cTnT (HR = 3.34; p = 0.016) and NT-proBNP (HR = 5.94; p = 0.01) were predictors of death. In the multivariable Cox proportional hazards model, only NT-pro-BNP levels above the cut-off value remained an independent predictor of all-cause mortality. The combined elevation of both biomarkers did not improve significantly the prognostic value compared with NT-proBNP alone (HR = 6.15 versus HR =4 .78; p = 0.338). CONCLUSION: NT-pro-BNP is a strong predictor of overall mortality in asymptomatic hemodialysis patients. The addition of hs-cTnT did not improve the prognostic accuracy compared with NT proBNP alone.

Predicting mortality in haemodialysis patients: a comparison between lung ultrasonography, bioimpedance data and echocardiography parameters.

BACKGROUND: The use of lung ultrasonography to evaluate extravascular lung water and its consequences has received growing attention in different clinical areas, including, in recent years, end-stage renal disease patients treated by haemodialysis (HD). Lung congestion is a direct consequence of either overall overhydration and/or cardiac dysfunction, but the exact contribution of each of these tests to mortality is unknown. METHODS: In this prospective observational study, we enrolled 96 patients from a single HD unit undergoing thrice weekly HD. We used three different methods of evaluation: lung ultrasonography (pre- and post-dialysis), bioimpedance spectroscopy (pre- and post-dialysis) and echocardiography (pre-dialysis). The objective of the study was to test for the first time the prognostic value of ultrasound lung comets (ULC) combined with bioimpedance-derived data [total body water (TBW), extravascular water, hydration status-ΔHS] and several echocardiographic parameters. Mortality was analysed after a median of 405.5-day follow-up. RESULTS: Pre-dialysis lung congestion was classified as moderate (ULC = 16-30) in 19.8% of the patients and severe in 12.5% of patients (ULC > 30), while only 19.8% appear to be hyperhydrated (ΔHS > 15%). The pre-dialysis ultrasound lung congestion score correlated significantly with all of the bioimpedance-derived parameters. In a multivariate Cox model that included ULC score, demographic, ecocardiographic and bioimpedance parameters, the factors that remained significantly associated with survival time were the pre-dialysis ULC score and left ventricular mass index. The pre-HD ULC score has a significant discriminating power for survival, while the bioimpedance-derived hydration status has no discriminatory abilities in terms of survival. CONCLUSIONS: To our knowledge, this study is the first one that compares three different strategies to predict mortality in haemodialysed patients. The lung comet score emerged as the best predictor for the relationship hydration status-mortality, independently of bioimpedance-derived parameters in this population.

Evaluation of advanced glycation end products accumulation, using skin autofluorescence, in CKD and dialysis patients.

PURPOSE: Advanced glycation end products (AGE), biomarkers of metabolic stress, are frequently encountered in chronic kidney disease (CKD) patients with cardiovascular disease. Our aim was to evaluate tissue accumulation of AGEs in CKD patients and possible correlations with traditional and non-traditional cardiovascular risk factors. METHODS: Skin AF was measured using AGE Reader in 310 patients: 157 haemodialysis patients (HD) (mean age 60 years, dialysis vintage 29 months, 19.1% diabetic), 102 peritoneal dialysis patients (PD) (mean age 56.3 years, dialysis vintage 16 months, 17.6% diabetic), 32 CKD patients (mean age 68 years, CKD duration 30 months, 34.4% diabetic) and 19 type 2 diabetic patients, without renal failure (mean age 59 years and median duration of diabetes 36 months). RESULTS: HD patients have higher AGE levels compared to PD ones. Dialysis patients have the highest skin AF values compared to CKD patients (P < 0.05) and diabetic, without renal impairment, patients (P < 0.01). Skin AF levels in patients using ARBs and statins are comparable to those without treatment in dialysis group (HD + PD) but significantly different in PD sub-group and CKD patients. In dialysis patients, diabetes explains 17% of AGE values variance. In PD skin, AF correlates with CKD duration (P < 0.01) and dialysis vintage (P < 0.05). Skin AF values were significantly higher in anuric PD patients (P < 0.05). In our CKD group, we found no significant association with diabetes or GFR. CONCLUSIONS: CKD patients have higher AGE values depending on duration (disease, RRT) and GFR (dialysis adequacy and RRF). Other important determinants were diabetes and age.

The prevalence of chronic kidney disease in the general population in Romania: a study on 60,000 persons.

INTRODUCTION: Chronic kidney disease (CKD) is a major public health problem worldwide, due to its epidemic proportions and to its association with high cardiovascular risk. Therefore, screening for CKD is an increasingly important concept, aiming for early detection and prevention of progression and complications of this disease. MATERIALS AND METHODS: We studied the prevalence of CKD in the adult population of Iasi, the largest county in Romania, based on the results of a national general health screening program from 2007 to 2008. The patients were tested for CKD with serum creatinine and urinary dipstick. We used two different methods to estimate the glomerular filtration rate (eGFR): the simplified Modification of Diet in Renal Disease (MDRD) and the CKD Epidemiology Collaboration (CKD-EPI) equations. Based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria, we defined CKD as the presence of either eGFR < 60 ml/min/1.73 m(2) and/or dipstick proteinuria. The classification of CKD by stage was also done according to the KDIGO criteria. RESULTS: The study population included 60,969 people. The global prevalence of CKD was found to be 6.69% by the MDRD formula and 7.32% when using the CKD-EPI equation. The prevalence of CKD was much higher in women than in men: 9.09% versus 3.7%, by MDRD, and 9.32% versus 4.85%, by CKD-EPI. By age groups, the prevalence of CKD was 0.95% and 0.64% in persons aged 18-44 years old, 4.27% and 3.57% (45-64 years old), 13.36% and 15.34% (65-79 years old), and 23.59% and 34.56% (>80 years old), according to MDRD and CKD-EPI, respectively. By stages, the prevalence of CKD stage 3a (eGFR 59 to 45 ml/min/1.73 m(2)) was 5.72% by MDRD and 5.96% according to CKD-EPI, whereas the prevalence of stages 3b, 4, and 5 taken together (eGFR < 45 ml/min/1.73 m(2)) was 0.96% (MDRD) and 1.35% (CKD-EPI). Patients with CKD were significantly older (71.0 years versus 53.7 years) and had lower levels of serum Hb, total cholesterol, and glutamic pyruvic transaminase, and significantly higher serum creatinine and blood glucose, in comparison with the individuals without CKD. Impaired fasting glucose (106 mg/dl) was found in the CKD population, but not in non-CKD individuals. CONCLUSIONS: Our study is one of the largest ever reported on the prevalence of CKD worldwide, the first one in Romania, and one of the very few of its kind in Europe (particularly in Eastern Europe). The study showed that the prevalence of CKD in our country is around 7%, which is lower than in other countries; however, this could be underestimated due to population selection bias. The prevalence is similar with the MDRD and the CKD-EPI equations; it increases with age and is much higher in women than in men. Impaired fasting glucose was detected in CKD patients, a finding that should probably raise the awareness of the high cardiovascular risk associated with CKD.