Salt, Not Always a Cardiovascular Enemy? A Mini-Review and Modern Perspective.

Dietary salt intake is a long-debated issue. Increased sodium intake is associated with high blood pressure, leading to salt-sensitive hypertension. Excessive salt intake leads to arterial stiffness in susceptible individuals via impaired nitric oxide action and increased endothelin-1 expression, overactivity of the renal sympathetic nervous system and also via aldosterone-independent activation of the mineralocorticoid receptor. Salt restriction in such individuals reduces blood pressure (BP) values. The optimal level of salt restriction that leads to improved cardiovascular outcomes is still under debate. Current BP and dietary guidelines recommend low sodium intake for the general population. However, a specific category of patients does not develop arterial hypertension in response to sodium loading. In addition, recent research demonstrates the deleterious effects of aggressive sodium restriction, even in heart failure patients. This mini review discusses current literature data regarding the advantages and disadvantages of salt restriction and how it impacts the overall health status.

Reply to Campbell et al. Comment on "Hogas et al. Salt, Not Always a Cardiovascular Enemy? A Mini-Review and Modern Perspective. Medicina 2022, 58, 1175".

We thank Campbell et al. for their comment [...].

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.

Cisplatin and AKI: an ongoing battle with new perspectives-a narrative review.

Acute kidney injury (AKI) is a growing global health problem with increased mortality and morbidity. Cisplatin is achemotherapy drug first introduced in 1978, and since then, it became one of the most widely used and successful anti-cancer medication. However, there are risks associated with cisplatin administration, such as nephrotoxicity. Mechanisms of nephrotoxicity include proximal tubular injury, DNA damage, apoptosis, inflammation, oxidative stress, and vascular injury. Although various protocols are being used in clinical practice in nephrotoxicity prevention due to cisplatin, there are no clear guidelines regarding this approach. Most recommendations include hydration and avoiding additional nephrotoxic drugs. To prevent nephrotoxicity, future perspectives could rely on natural products, such as flavonoids or saponins or pharmacological products, such as aprepitant, but data are scarce in this direction. Repetitive administration of cisplatin could cause subclinical kidney injury, which over time, leads to chronic kidney disease (CKD). Therefore, more studies are needed to determine possible ways to prevent nephrotoxicity and avoid the burden of CKD worldwide.

Thyroid, Gonadal and Adrenal Dysfunction in Kidney Transplant Recipients: A Review for the Clinician.

While chronic kidney disease-associated mineral and bone disorders (CKD-MBD) prevail in the endocrinological assessment of CKD patients, other endocrine abnormalities are usually overlooked. CKD is associated with significant thyroid, adrenal and gonadal dysfunction, while persistent and de novo endocrinological abnormalities are frequent among kidney transplant recipients (KTR). Low T3 levels prior to transplantation may help identify those at risk for delayed graft function and are often found in KTR. Thyroid surveillance after kidney transplantation should be considered due to structural anomalies that may occur. Despite the rapid recovery of gonadal hormonal secretion after renal transplantation, fertility is not completely restored. Testosterone may improve anemia and general symptoms in KTR with persistent hypogonadism. Female KTR may still experience abnormal uterine bleeding, for which estroprogestative administration may be beneficial. Glucocorticoid administration suppresses the hypothalamic-pituitary-adrenal axis in KTR, leading to metabolic syndrome. Patients should be informed about signs and symptoms of hypoadrenalism that may occur after glucocorticoid withdrawal, prompting adrenal function assessment. Clinicians should be more aware of the endocrine abnormalities experienced by their KTR patients, as these may significantly impact the quality of life. In clinical practice, awareness of the specific endocrine dysfunctions experienced by KTR patients ensures the correct management of these complications in a multidisciplinary team, while avoiding unnecessary treatment.

The Role of the Prognostic Inflammatory and Nutritional Index (PINI) in the Evolution of Patients with Chronic Kidney Disease and Other Pathologies.

BACKGROUND: Protein-energy loss and inflammation are the main risk factors in the occurrence of complications in hemodialysis patients. The Prognostic Inflammatory and Nutritional Index (PINI) is a simple, inexpensive test to identify the early onset of inflammation and malnutrition in hemodialysis patients, critically ill subjects and those with malignancies. METHODS: A systemic review of English literature was conducted on the topic published between 1985 and 2022. A focused and sensitive search strategy was applied to the PUBMED database to identify relevant scientific articles in English. Once articles were identified, a detailed quality and bias assessment was performed. Two independent researchers analyzed the detailed data extraction. RESULTS: PINI proved to be a sensitive, powerful, low-cost and simple test. PINI has been useful in assessing evolution and prognostics in clinical care, with values above one being associated with a high risk of mortality and morbidity. It is useful in cases with surgical and postoperative complications, long hospitalization, as well as increased associated expenses. CONCLUSIONS: This is the first review of the literature on the above-mentioned topic (PINI) and is a valuable candidate for validating prognosis in patients with different pathologies.

Gut Microbiota in Chronic Kidney Disease: From Composition to Modulation towards Better Outcomes-A Systematic Review.

BACKGROUND: A bidirectional kidney-gut axis was described in patients with chronic kidney disease (CKD). On the one hand, gut dysbiosis could promote CKD progression, but on the other hand, studies reported specific gut microbiota alterations linked to CKD. Therefore, we aimed to systematically review the literature on gut microbiota composition in CKD patients, including those with advanced CKD stages and end-stage kidney disease (ESKD), possibilities to shift gut microbiota, and its impact on clinical outcomes. MATERIALS AND METHODS: We performed a literature search in MEDLINE, Embase, Scopus, and Cochrane databases to find eligible studies using pre-specified keywords. Additionally, key inclusion and exclusion criteria were pre-defined to guide the eligibility assessment. RESULTS: We retrieved 69 eligible studies which met all inclusion criteria and were analyzed in the present systematic review. Microbiota diversity was decreased in CKD patients as compared to healthy individuals. Ruminococcus and Roseburia had good power to discriminate between CKD patients and healthy controls (AUC = 0.771 and AUC = 0.803, respectively). Roseburia abundance was consistently decreased in CKD patients, especially in those with ESKD (p < 0.001). A model based on 25 microbiota dissimilarities had an excellent predictive power for diabetic nephropathy (AUC = 0.972). Several microbiota patterns were observed in deceased ESKD patients as compared to the survivor group (increased Lactobacillus, Yersinia, and decreased Bacteroides and Phascolarctobacterium levels). Additionally, gut dysbiosis was associated with peritonitis and enhanced inflammatory activity. In addition, some studies documented a beneficial effect on gut flora composition attributed to synbiotic and probiotic therapies. Large randomized clinical trials are required to investigate the impact of different microbiota modulation strategies on gut microflora composition and subsequent clinical outcomes. CONCLUSIONS: Patients with CKD had an altered gut microbiome profile, even at early disease stages. Different abundance at genera and species levels could be used in clinical models to discriminate between healthy individuals and patients with CKD. ESKD patients with an increased mortality risk could be identified through gut microbiota analysis. Modulation therapy studies are warranted.

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.

Epidemiology of biopsy-proven glomerulonephritis in the past 25 years in the North-Eastern area of Romania.

PURPOSE: The aim of this retrospective study was: to analyze the epidemiological patterns of the kidney disease based on clinical and histological features in a single-center in the N-E region of Romania, between 2011 and 2019 and to compare the biopsy results with the others periods, as well as the results from other countries. METHODS: We studied 442 renal biopsies. The indications for renal biopsy were represented by the clinical features: nephrotic syndrome, nephritic syndrome, asymptomatic urinary abnormalities, acute kidney injury, and chronic kidney disease of unknown etiology. RESULTS: During the past 8 years, the annual incidence of renal biopsies was constant, albeit this incidence remained lower than in other countries. Nephrotic syndrome was the most common indication for renal biopsy (47.6%). Primary glomerulonephritis (GN) was the most common diagnosis in each of the three periods, followed by secondary GN. Vascular nephropathy and TIN were constant as a proportion from the overall biopsies in each of the three periods. The membranoproliferative GN (24.4%) and membranous nephropathy (MN) (21.9%) were the most prevalent primary GN, while lupus nephritis (LN) was the most common secondary glomerular disease in young female patients (7.5%). Compared to 1994-2004 period, we observed a significant decrease of incidence of focal segmental glomerulosclerosis (FSGS) and mesangial proliferative GN, and a significant increases in the frequency of MN. CONCLUSION: The results of this study show that the GN distribution model was constant in N-E Romania and became similar to that observed in many countries with high socio-economic status.

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.

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.

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.

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.

Bioimpedance analysis versus lung ultrasonography for optimal risk prediction in hemodialysis patients.

Fluid overload is associated with adverse outcomes in hemodialysis (HD) patients. Two bedside methods are increasingly utilized to evaluate objectively fluid status-bioimpedance and lung ultrasonography, but there is no available direct, head-to-head comparison of their prognostic significance. Importantly, their predictive abilities have never been tested in a HD population, alongside those of a classic model that also incorporates established echocardiographic parameters of increased mortality risk. Between 26 May 2011 and 26 October 2012, we included in the study 173 patients undergoing chronic HD treatment for at least 3 months in a single dialysis unit. Relative fluid overload (RFO) and B-lines score (BLS) were used as candidate predictors. From Cox survival analysis we evaluated the increase in the predictive abilities for all-cause mortality of adding continuous RFO or BLS to a model including conventional predictors . 31 patients (17.9 %) died during a median follow-up of 21.3 (interquartile range 19.9-30.3) months. All Cox models showed good calibration. The C statistic for the all-cause mortality prediction increased significantly when the RFO was included into the baseline model (ΔC statistics 0.058 95 %CI = 0.003-0.114), but not when the BLS was included into the baseline model. Only the model that incorporated RFO showed significantly better risk reclassification abilities than the baseline model (IDI = 3.6 % and continuous NRI = 24.8 %). Fluid overload, as assessed by bioimpedance, and not by lung ultrasonography, improves risk prediction for death, beyond classical and echocardiographic-based risk prediction scores/parameters.

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.

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.

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.

Electrocardiogram abnormalities and heart rate variability in predicting mortality and cardiovascular events among hemodialyzed patients.

PURPOSE: The aim of the study was to evaluate the correlation between electrocardiographic parameters and heart rate variability with cardiovascular events and mortality among chronic hemodialysis patients. METHODS: In this prospective study, we enrolled 116 asymptomatic patients in whom we performed ambulatory 24-h electrocardiographic Holter monitoring and before and after hemodialysis electrocardiographs. We measured the interval (PR, QRS, QTc, QTc dispersion) differences on the surface electrocardiographs and obtained frequency-domain measures from Holter monitoring (VLF, LF, HF and the LF/HF ratio). RESULTS: During the follow-up period, 13 participants died (11.2 %) and 16 (13.8 %) patients experienced a cardiovascular event. The pre-post-dialysis difference in QTc interval was the best predictor for cardiovascular events (95 % CI 0.453-0.786), while pre-dialysis QRS interval was the predictor for all-cause mortality (95 % CI 1.134-3.136). Also, both outcomes were predicted by pre-post-dialysis difference in PR interval and VLF. CONCLUSIONS: Interval changes during hemodialysis are predictive for cardiovascular events and mortality. Autonomic dysfunction and changes in PR should be monitored routinely, particularly in patients with suspected coronary artery disease.