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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.

Methods and potential biomarkers for the evaluation of endothelial dysfunction in chronic kidney disease: A critical approach

The impressive cardiovascular morbidity and mortality of chronic kidney disease (CKD) patients is attributable in a significant proportion to endothelial dysfunction (ED), arterial stiffness, and vascular calcifications. Abnormal vascular reactivity in these patients is more pronounced compared with other high-risk populations, but remains undiagnosed in the usual clinical setting. We briefly review the most important causes and risk factors of ED, oxidative stress, and inflammation related to arterial stiffness. We describe the main methods of ED investigation and the importance of using potential biomarkers together with classic techniques for a more comprehensive assessment of this condition. These methods include evaluation of: forearm blood flow by plethysmography, skin microcirculation by laser Doppler, and flow-mediated vasodilation by Doppler ultrasound imaging. Applanation tonometry is an easy-to-handle tool that allows a clinically reliable assessment of arterial stiffness and is also useful in quantifying endothelium-dependent and -independent vascular reactivity. We also discuss the diagnostic and therapeutic impact of new markers of ED in the CKD population. Improvement of endothelial function is an important challenge for clinical practice, and there are relatively few therapeutical strategies available. Therefore, a combined biomarker and bedside investigational approach could be a starting point for developing optimal therapeutic tools.

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.

A longitudinal study on illness perceptions in hemodialysis patients: changes over time.

Introduction Self-regulatory theory explains how patients’ illness representations influence self-management behavior. The aim of this study was to examine the changes that occur in disease perceptions after 6 years in hemodialysis patients. Material and methods A total of 81 clinically stable patients (53.6% males, meanage 54 ±12.54 years, mean hemoglobin level 11 ±1.52 g/dl, mean Kt/V 1.49 ±0.21) who were treated with hemodialysis three times weekly completed questionnaires on illness representations in 2005, and then at follow-up, in December 2011, 47 patients. IPQ-R (Illness Perceptions Questionnaire-Revised) was used to assess patients’ illness perceptions. Results After a long period of years (6 years), patients had a stronger perception of a chronic course of the disease (timeline; p < 0.001), considered hemodialysis more efficient in controlling end stage renal disease (ESRD) (treatment control; p < 0.05), considered that their disease had less serious consequences for their life (consequences; p < 0.05), and also registered a less intense emotional response to their illness (emotional representation; p < 0.05). Two of the seven components of illness representations (personal control, cyclical symptoms) remained unchanged. Treatment control perceptions were also predictive of mortality after controlling for covariates (age, gender, dialysis vintage, blood hemoglobin level and Kt/V) (HR = 0.13, 95% CI: 0.02–0.75, p = 0.022). Conclusions Our results show that patients’ illness perceptions vary over a significantly long follow-up period, in the sense of having more optimistic views towards their illness perceptions.

Changes in arterial stiffness following dialysis in relation to overhydration and to endothelial function.

IntroductionCardiovascular (CV) morbidity and mortality are greatly enhanced in patients with chronic kidney disease, partly due to increased arterial stiffness.Material and methodThe study included 63 stable HD patients. Stiffness parameters were evaluated by applanation tonometry before the mid-week HD sessions. Pre-HD bioimpedance parameters were measured. A phase angle <six degrees was previously reported as abnormal, reflecting extracellular overhydration. Fluid status was evaluated echocardiographic by measuring the inferior vena cava (IVC) diameter. Endothelium-dependent and endothelium-independent vascular reactivity were assessed by changes in Alx following sublingual nitroglycerin and inhaled salbutamol.ResultsPWV directly correlated with patients’ age and dialysis vintage. Patients with a phase angle <6°, were significantly overhydrated (larger IVC, increased ECW, and lower ICW), had stiffer arteries and greater left ventricle mass (LVM), compared with those with a phase angle >6°. Overhydration increases arterial stiffness, but has no influence on either EID or ED vascular reactivity.ConclusionIn hemodialysis, volume overload is an important contributor to increased arterial stiffness and modifies cardiovascular status especially by LV hypertrophy. Achieving normohydration may significantly ameliorate cardiac abnormalities and arterial stiffness and may impact major clinical events and CV mortality.

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.

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.

Potential novel biomarkers of cardiovascular dysfunction and disease: cardiotrophin-1, adipokines and galectin-3

Cardiovascular disease is one of the main burdens of healthcare systems worldwide. Nevertheless, assessing cardiovascular risk in both apparently healthy individuals and low/high-risk patients remains a difficult issue. Already established biomarkers (e.g. brain natriuretic peptide, troponin) have significantly improved the assessment of major cardiovascular events and diseases but cannot be applied to all patients and in some cases do not provide sufficiently accurate information. In this context, new potential biomarkers that reflect various underlying pathophysiological cardiac and vascular modifications are needed. Also, a multiple biomarker evaluation that shows changes in the cardiovascular state is of interest. This review describes the role of selected markers of vascular inflammation, atherosclerosis, atherothrombosis, endothelial dysfunction and cardiovascular fibrosis in the pathogenesis and prognosis of cardiovascular disease: the potential use of cardiotrophin-1, leptin, adiponectin, resistin and galectin-3 as biomarkers for various cardiovascular conditions is discussed.

Atherosclerotic Renal Artery Stenosis Prevalence and Correlations in Acute Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Interventions: Data From Nonrandomized Single-Center Study (REN-ACS)—A Single Center, Prospective, Observational Study

Background We are the first to evaluate the prevalence of renal artery stenosis (RAS) in consecutive patients with acute myocardial infarction (AMI) referred for primary percutaneous coronary intervention from a single tertiary center. As a novelty, we assessed hydration and metabolic status and measured arterial stiffness. We elaborated a predicting model for RAS in AMI. Methods and Results One hundred and eighty‐one patients with AMI underwent concomitantly primary percutaneous coronary intervention and renal angiography. We obtained data on demographics, medical history, cardiovascular risk factors, echocardiography, Killip class, and blood tests. In the first 24 hours post–primary percutaneous coronary intervention, we assessed bioimpedance through Body Composition Monitoring® and arterial stiffness through pulsed‐wave velocity, SphygmoCor®. Significant RAS (>50% lumen narrowing, RAS+) was present in 16.6% patients. In the RAS+ group we recorded significantly higher stiffness, CRUSADE score and dehydration, and more women with higher prevalence of multivascular coronary artery disease and heart failure. In our multivariate models, variables independently associated with RAS+ were previous percutaneous coronary intervention, low estimated glomerular filtration rate, multivascular coronary artery disease, and total/extracellular body water. These models had good specificity and low sensitivity. Conclusions We observed that RAS+ AMI patients have a particular hydration, metabolic, and endothelial profile that could generate more future major adverse cardiac events. Hence, renal angiography in AMI should be considered in specific subsets of patients. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02388139.

Screening for latent BK virus infection in a renal transplant population for the first time in Romania: a single-center experience

IntroductionThe BK virus nephropathy (BKVN) is one of the most important infectious complications in renal transplant recipients. As BKVN lacks any effective antiviral treatment, early diagnosis is required in order to try to limit viral replication and subsequent damage to the renal allograft, by reducing the immunosuppressive therapy. Our study, the first of its kind in Romania, aimed to assess the prevalence of BKVN among renal transplant patients in our center.Materials and methodsIn this cross-sectional study, we included 143 renal transplant patients from our center who had received their renal allograft between 2005 and 2010. We searched for latent BK virus infection by detection of serum anti-BK virus antibodies, using an in-house developed enzyme-linked immunosorbent assay (ELISA) technique. Serology was considered positive if results were >0.33 optical density units. In patients with positive serology, we searched for BKVN with qualitative (polymerase chain reaction, PCR) and quantitative (TaqMan real-time PCR) molecular techniques. Additionally, we searched for other viral infections, including hepatitis B (with HBsAg test), hepatitis C (with anti-HCV Abs test), and cytomegalovirus (CMV, with pp65Ag test).ResultsAll patients screened with ELISA were found to have positive BK virus serology and two of these were diagnosed with BKVN. Both patients with BKVN presented with acute impairment of the renal graft function, and one of them also developed a ureteral graft stenosis. In both cases, BKVN resolved after reduction of immunosuppressive doses. We also diagnosed hepatitis B in 18.18%, hepatitis C in 7.0%, and CMV in 27.97% of patients.ConclusionsOur study demonstrates for the first time the existence of BK virus in Romania, and we believe it opens the prospective of diagnosing BKVN in high-risk patients in our country in the future. In renal transplant patients from our center, we found the prevalence of BK virus infection to be as high as 100%. The prevalence of hepatitis B and CMV was also remarkably high. In patients with BKVN, the reduction of immunosuppression enables the spontaneous resolution of the disease.