Novel Biomarkers in Evaluating Cardiac Function in Patients on Hemodialysis-A Pilot Prospective Observational Cohort Study.

Chronic kidney disease patients treated by hemodialysis present a high cardiovascular morbidity and mortality. There is an imperative need for novel biomarkers for identifying these patients and to offer possible therapeutically interventions. We performed a prospective observational cohort study on 77 patients in the period of October 2021-October 2023. We measured serum plasma levels of interleukin 1-beta, galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion site. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. The mean age was 61.02 (±11.81) years, with 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54%), and more than two-thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-beta was correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle telesystolic diameter. Galectin 3 values were negatively correlated with aortic valve fibrosis and mitral valve calcifications, and human suppression tumorigenicity factor 2 was negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better assess cardiovascular disease in patients on maintenance hemodialysis.

Acute Kidney Disease following Acute Kidney Injury in Children-A Retrospective Observational Cohort Study on Risk Factors and Outcomes.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding AKD in children are scarce. The purpose of our study was to explore the risk factors for developing AKD based on exposures and susceptibilities in children with AKI doubled by the biological parameters from the first day of identified AKI. In addition, we followed the trajectory of AKD following an acute kidney injury (AKI) episode in children during hospital admission and after discharge with special considerations towards mortality and progression to new-onset CKD. Methods: We retrospectively evaluated 736 children, ages between 2 and 18 years old, with identified AKI during hospital admission in a tertiary care hospital from west Romania over a 9-year period. Results: AKD incidence following an AKI episode was 17%. Patients who developed AKD were older, with higher baseline serum creatinine, urea, C reactive protein and lower proteins, haemoglobin and sodium levels. In the adjusted model, no biological parameters influenced AKD development. Regarding certain exposures and personal susceptibilities in children with AKI, only anaemia independently increased the risk of AKD development by 2.47 times. However, out of the AKI causes, only the intrinsic causes of AKI independently increased the risk of progressing to AKD (glomerulonephritis by 4.94 and acute tubule-interstitial nephritis by 2.76 times). AKD increased the overall mortality by 2.6 times. The factors that independently increased the risk of CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: Only anaemia, glomerulonephritis and acute tubule-interstitial nephritis increased the risk of AKD development in children with AKI. AKD was an independent risk factor for mortality and new-onset CKD in children.

Benefits of exercise training during hemodialysis sessions: a prospective cohort study.

BACKGROUND: End-stage renal disease patients can be considered as 'cardiovascular time bombs' due to their tremendous cardiovascular risk. Our study has determined the impact of 3 months of exercise training during dialysis on some of the cardiovascular risk factors (arterial stiffness, body composition and physical performance) in a chronic hemodialyzed population. METHODS: The study group (n = 19) and control group (n = 16) of chronic hemodialysis patients from Timisoara, Romania, were enrolled in a prospective cohort study. The intervention--40 min of exercise training (with non-fistula hand and both lower limbs) during each hemodialysis session for 3 months--was applied only to the study group. The measurements made before and after intervention were aortic pulse wave velocity (PWV), aortic augmentation index, return time and both central and peripheral blood pressure for arterial stiffness evaluation, using the Arteriograph Tensiomed system, body composition by multifrequency bioimpedance and physical performance (Myotest PRO system and hand dynamometer). RESULTS: We found a significant 1-m/s reduction in PWV, a 12-second increase in return time and a 10-mm Hg reduction in both central and systolic blood pressure driven only by the exercise training. Exercise training significantly increased the skeletal muscle mass and the soft lean mass of the study group patients. Physical performance significantly improved in the study group jumping height by 1 cm, lower limbs explosive power by 3 W/kg and non-fistula hand strength prehension by 0.06 bar. CONCLUSIONS: Exercise training during dialysis has a positive effect on arterial stiffness, body composition and physical performance of chronic hemodialyzed patients.

Trends in mortality and comorbidities in hemodialysis patients between 2012 and 2017 in an East-European Country: a retrospective study.

PURPOSE: The aim of this study was to evidence trends and changes in mortality, comorbid conditions, prognosis, and causes of death after 5 years of continuous evolution of hemodialysis (HD) patients in Romania. METHODS: We included two cohorts of stable HD patients (901 from 2012 and 1396 from 2017). Both cohorts were followed up for 1 year. The 5-year survivors of the 2012 cohort were identified in 2017 and their data changes were assessed. RESULTS: The 2017 patients were older, with longer time on dialysis, higher serum creatinine and urea levels, and required higher ultrafiltration volume per dialysis. They also had lower hemoglobin, lower C-reactive protein, higher albumin, higher calcium bicarbonate, and higher parathyroidectomy prevalence. The 2017 cohort presented with lower average dialysis flow, less administration of iron sucrose, had more catheters, lower hepatitis C prevalence, higher diabetes mellitus prevalence, higher heart valve calcifications, higher heart rate disorders, higher prevalence of left ventricular hypertrophy, and lower ejection fraction. Cardiovascular disease was the main cause of death in both years (50% in 2012 and 45.6% in 2017), followed by sepsis and cancer. The mortality was higher in 2017 compared to 2012 (14.1 vs 6.6%). The 5-year mortality was 37.2% with an average of 7.44%/year. The risk of death increased with age, higher C-reactive protein, higher phosphate, lower hemoglobin, and lower albumin. CONCLUSION: Cardiovascular disease remains the main causes of death in HD-treated patients but with decreasing trend. Developing regional therapeutic strategies for quality care with early intervention will most likely improve mortality.

Hepatitis C and hepatitis B virus infection in hemodialysis patients after nationwide direct antiviral agents therapy-experience of 10 Romanian HD centers.

PURPOSE: End-stage kidney disease patients (ESKD) receiving hemodialysis (HD) are at a greater risk of hepatitis virus (HV) infections due to the invasive nature of the procedures, frequent hospital stays and surgeries, as well as the immune deficiency status of ESKD. THE AIM: This study was to reassess the hepatitis virus infections prevalence in the HD population in Romania after 5 years of oral DAAs therapy and assess the impact on HD patients' outcomes in two cohorts (2015 and 2019). METHODS: We compared ESKD patients treated with HD in 10 HD centers from the historical regions of Romania in 2015 (n = 1401, Mean age 59.7 ± 12.92 years) with patients treated in the same centers in 2019 (n = 1698, mean age 61 ± 12.93 years). All patients went through HD therapy for more than 90 days. RESULTS: The patients from the 2019 cohort were significantly older (p = 0.005), had a longer duration of HD therapy (p < 0.0001), and had more vascular calcifications (p = 0.015); the crude one-year mortality rate did not differ from the 2015 cohort (9.9 vs. 10.7%, p = 0.46). The prevalence of HBV infection did not differ between the cohorts (4.7% vs. 4.8, p = 0.604) but the prevalence of HCV significantly decreased from 2015 to 2019 (16.9 vs. 10.5%, p < 0.0001). CONCLUSION: After 15 years of a nationwide infection prevention program for HV infections and 5 years of DAAs treatment in Romania, the prevalence of HBV did not change but HCV infections decreased significantly, however, it still remained high.

The Impact of Chronic Kidney Disease on the Mortality Rates of Patients with Urological Cancers-An Analysis of a Uro-Oncology Database from Eastern Europe.

(1) Background: The relationship between chronic kidney disease (CKD) and urological cancers is complex, as most of these cancers are diagnosed in patients with advanced ages, when the kidney function may be already impaired. On the other hand, urological cancers could represent a risk factor for CKD, significantly reducing the life expectancy of the patients. The main objective of our study was to analyze the impact of CKD on the overall mortality of patients diagnosed with the most frequent types of urological cancers. (2) Material and Methods: We conducted an observational retrospective cohort study on a group of 5831 consecutive newly diagnosed cancer patients, followed over a 2-year period (2019-2020), from a large Oncology Hospital in Romania. From this group, we selected only the patients diagnosed with urological malignancies, focusing on prostate cancer, bladder cancer and renal cancer; finally, 249 patients were included in our analysis. (3) Results: In the group of patients with prostate cancer (n = 146), the 2-year overall mortality was 62.5% for patients with CKD, compared with 39.3% for those with no initial CKD (p < 0.05). In the group of patients with bladder cancer (n = 62), the 2-year overall mortality was 80% for patients with initial CKD, compared with 45.2% for the patients with no initial CKD (p < 0.05). Finally, in the group of patients with renal cell carcinoma (n = 41), the 2-year overall mortality was 60% for patients with initial CKD, compared with 50% for the patient group with no initial CKD (p < 0.05). Various correlations between specific oncologic and nephrological parameters were also analyzed. (4) Conclusions: The presence of CKD at the moment of the urological cancer diagnosis is associated with significantly higher 2-year mortality rates.

Chronic kidney disease in cancer patients, the analysis of a large oncology database from Eastern Europe.

INTRODUCTION: Kidney dysfunction is prevalent in oncology patients and has an impact on their treatment and quality of life. The aim of our study was to analyze the prevalence of CKD in a large cohort of several types of cancer patients in an East European Region. MATERIAL AND METHODS: We conducted an observational retrospective cohort study on 5831 consecutive, biopsy-diagnosed cancer patients between January 2019 -December 2020 in the largest oncology hospital and outpatient clinic in Western Romania. 4342 subjects were included in the statistical analysis. RESULTS AND DISCUSSION: From the 24 cancer types, the most prevalent cancers were represented by: breast (22.02%), lung (10.18%) and colonic cancer (9.51%). The prevalence of CKD (G3 -G5) was 12.27% after the first year of follow-up and 13.42 after the second year. The prevalence of CKD was higher in patients with renal (50%), urinary tract (33.6%) and pancreatic cancers (19.6%) and lower in patients with colonic cancers (5.3%) and brain tumors (2.5%). At the end of our 2-year survey period, 0,7% of the CKD cases had an eGFR around 6 ml/min/1.73m2 -an indication for renal replacement therapy. CONCLUSION: Oncology patients have a significantly higher prevalence of CKD compared to the general population, dependent of the age of the patients and the type of cancer. The prevalence of advanced CKD was surprisingly high (stages G4-G5 Pre-Dialysis 22.15%) one third of the CKD- G5 patients having indication for initiation of renal replacement therapy. An onco- nephrology team should be needed for the best medical care of these patients.

Nutritional status improvement in elderly CKD patients: a systematic review.

PURPOSE: Almost all CKD patients have a poor nutritional status, while elderly CKD patients are specifically frail and malnourished. Our aim is to conduct a systematic review of the up to date primary studies that look at methods of improving nutritional status in CKD patients in the elderly demographic. METHODS: A focussed and sensitive search strategy was applied to the PUBMED database to identify relevant English language articles. Once articles were identified a detailed quality and bias assessment was performed. Two independent researchers (MZ and SM) then subsequently carried out detailed data extraction and analysis and this was subsequently verified by a third researcher (IN). RESULTS: A total of 19 studies were included in our systematic review which included 7 non-randomised control trials and 15 randomised controlled trials. The outcomes that we considered to be most relevant for our subject title were: mortality data, SGA, albumin, total protein, isoleucine, leucine, prealbumin, transferrin, leptin, valine, TAG, HDL, LDL and total amino acids. Detailed bias analysis of the different studies was also conducted. CONCLUSION: This is the first systematic review of the literature, so far, on the subject, involving elderly CKD patients. The quality of trials is low, very heterogenic in patients, methods and outcomes. However, we found a positive effect of dietary interventions on the nutritional status of most patients studied, highlighted by improvement in serum albumin and SGA, the most measured outcomes.

Clostridioides difficile Infection in Patients with Chronic Kidney Disease: A Systematic Review.

Clostridioides difficile infection (CDI) is a health issue of utmost significance in Europe and North America, due to its high prevalence, morbidity, and mortality rate. The clinical spectrum of CDI is broad, ranging from asymptomatic to deadly fulminant colitis. When associated with chronic kidney disease (CKD), CDI is more prevalent and more severe than in the general population, due to specific risk factors such as impaired immune system, intestinal dysmotility, high antibiotic use leading to disturbed microbiota, frequent hospitalization, and PPI use. We performed a systematic review on the issue of prevention and treatment of CDI in the CKD population, analysing the suitable randomized controlled cohort studies published between 2000 and 2021. The results show that the most important aspect of prevention is isolation and disinfection with chlorine-based solution and hydrogen peroxide vapour to stop the spread of bacteria. In terms of prevention, using Lactobacillus plantarum (LP299v) proved to be more efficient than disinfection measures in transplant patients, leading to higher cure rates and less recurrent episodes of CDI. Treatment with oral fidaxomycin is more effective than with oral vancomycin for the initial episode of CDI in CKD patients. Faecal microbiota transplantation (FMT) is more effective than vancomycin in recurrent CDI in CKD patients. More large-sample RCTs are necessary to conclude on the best treatment and prevention strategy of CDI in CKD patients.

Liver Steatosis: Better Predictor of CKD in MAFLD Than Liver Fibrosis as Determined by Transient Elastography With Controlled Attenuation Parameter.

Background: Changing the term/concept of the non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction associated fatty liver disease (MAFLD) may broaden the pathological definition that can include chronic renal involvement, and, possibly, changes chronic kidney disease's (CKD's) epidemiological association with liver disease, because CKD is associated with metabolic disorders and almost all patients with CKD present some form of an atherogenic dyslipidemia. Our study explores the relationship between MAFLD and CKD using Transient Elastography (TE) with a Controlled Attenuated Parameter (CAP). Methods: We evaluated 335 patients with diabetes with MAFLD and with high CKD risk using TE with CAP (FibroScan®). The CKD was defined according to Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines. Logistic regression and stepwise multiple logistic regression were used to evaluate the factors associated with CKD. In addition, a receiver operating characteristic curve (ROC) analysis was used to assess the performance of CAP and TE in predicting CKD and its optimal threshold. Results: The prevalence of CKD in our group was 60.8%. Patients with CKD had higher mean liver stiffness measurements (LSM) and CAP values than those without CKD. We found that hepatic steatosis was a better predictor of CKD than fibrosis. Univariate regression showed that CAP values >353 dB/m were predictive of CKD; while the multivariate regression analysis (after adjustment according to sex, body mass index (BMI), low-density lipoprotein cholesterol (LDLc), and high-density lipoprotein cholesterol (HDLc), and fasting glucose) showed that CAP values >353 dB/m were more strongly associated with the presence of CKD compared to the LSM (fibrosis) values. Conclusion: In patients with MAFLD, CAP-assessed steatosis appears to be a better predictor of CKD compared to LSM-assessed hepatic fibrosis.

Exploring the relation between mortality and left ventricular structure and function in stable hemodialysis treated patients, a longitudinal multicenter cohort study.

Left ventricular (LV) structure and function anomalies are frequent during the CKD continuum and are associated with increased risk of mortality. Cross section and longitudinal ultrasound data are available for advanced CKD and transition to ESKD. Less information is available about LV changes during stable, long-term hemodialysis (HD) treatment. All stable HD patients from 9 HD centers (1034 patients, 671 males, age 58.71 ± 12.94 years) have been enrolled in January 2015. The cohort was followed-up for 4 years, kidney transplantation or death. Yearly, two-dimensional and M-mode continuous and Pulse Doppler echocardiography were performed. During the follow-up, the prevalence of cardiovascular comorbidities significantly increased (p < 0.0001), coronary artery disease (CAD) from 73.5 to 88.8%, peripheral artery disease (PAD) from 29 to 40.9%, cerebral vascular disease (CVD) from 20.4 to 30.8%, heart valves calcification (VC) from 65.6 to 89.3% and left ventricular hypertrophy (LVH) from 67.6 to 76.5%. The mortality risk increased with the presence of CAD (1.59-fold), PAD (1.61-fold), CVD (1.59-fold), and VC (1.77-fold). Mortality risk was increased in those with LVEF < 50% (LVEF 40-49% 1.5-fold and LVEF < 40% 2.3 fold). Among the survivors of the first year, LVEF varied (> 5% decrease, > 5% increase and ± 5% variations). More than 5% increase of LVEF was associated with higher mortality risk (crude 1.5-fold, adjusted 1.43-fold) compared to stationary EF (p = 0.001). Cardiovascular disease progresses during stable long-term HD therapy and increases mortality risk. HF becomes highly prevalent but only HF with decreased LVEF < 50% is associated with increased risk of mortality.

Rapid decline of kidney function in diabetic kidney disease is associated with high soluble Klotho levels.

BACKGROUND: Klotho is found in two forms: a transmembrane form and a soluble form (s-Klotho). In order to be excreted, s-Klotho, that is too large to be filtered, will probably reach the proximal convoluted tubule by a transcytosis process. The aim of our study was to show the relationship between the levels of s-Klotho and tubular injury in patients with diabetic kidney disease (DKD), using as tubular injury marker the kidney injury molecule-1 (KIM-1). METHODS: Our study included 63 DKD patients (stages 1-5, mean eGFR 65.15±32.45ml/min) with a mean age 58.13±12 years. In all patients we determined serum levels of: KIM-1 and s-Klotho using ELISA, urinary albumin/creatinine ratio (UACR) and reduction in the estimated glomerular filtration rate (eGFR) per year. RESULTS: We found a strong statistically significant correlation of s-Klotho with the rate of reduction of eGFR/year (r=0.714, p=0.0004) and with the tubular injury marker KIM-1 (r=0.758, p=0.005) and strong correlations of UACR with the rate of reduction of eGFR/year (r=0.53, p<0.01), KIM-1 (r=0.49, p<0.05) and s-Klotho (r=0.52, p<0.01). CONCLUSION: Despite previous published data, that shows a decrease of s-Klotho in chronic kidney disease, in our study the rapid annual decline of kidney function but not the level of eGFR was associated with increased s-Klotho. A possible explanation could be a more severe proximal tubule injury that could lead to a reduction of tubular excretion of s-Klotho as suggested by the correlation of s-Klotho levels with the serum levels of KIM-1.

The impact of acute kidney injury on short-term survival in an Eastern European population with stroke.

BACKGROUND: Stroke is one of the leading causes of death and of serious disability with significant impact on patients' long-term survival. The short-term evolution following stroke can associate acute kidney injury (AKI) as a possible complication, frequently overlooked and underestimated in clinical trials. We aimed to describe in an East European cohort (i) the incidence of AKI and its risk factors; (ii) the 30-day mortality and its risk factors and (iii) the relationship between mortality, pre-existent renal function and subsequent AKI. METHODS: A total of 1090 consecutive cases hospitalized-during a 12-month period-with a CT-confirmed diagnosis of stroke, from a distinct administrative region were included. Demographic details, comorbidities, laboratory and outcome data were retrieved from the electronic hospital database. All patients included in the study were followed for 30 days or until death. RESULTS: The mean age of this population was 66.1 +/- 11.5 years, 49.3% were males, mean glomerular filtration rate (GFR) 68.9 +/- 22.6 ml/min/1.73 m(2). The 30-day mortality rate was 17.2%. One hundred and fifty-eight patients presented with haemorrhagic stroke and 932 patients had ischaemic stroke. Stroke mortality was-14% for ischaemic stroke and almost twice as high for haemorrhagic stroke-36.3%. One hundred fifty-eight (14.5%) patients were classified as developing AKI. The AKI patients were older, had a higher baseline serum creatinine, lower GFR, higher serum glucose, higher prevalence of chronic heart failure and ischaemic heart disease, were more likely to have suffered a haemorrhagic stroke, and had a significantly higher 30-day mortality rate (43.1 vs 12.8%) (P < 0.05 for all). Independent predictors for AKI development in the logistic regression analysis were age, GFR, presence of comorbidities (ischaemic heart disease and chronic heart failure) and type of stroke (Cox and Snell R(2) 0.244; Nagelkerke R(2) 0.431; P < 0.05). In our study, we demonstrated that the occurrence of AKI is not a rare finding in stroke patients. This is the first study to report the incidence of AKI in a distinct geographic population base, in patients with stroke. Baseline renal function emerged as both a significant independent marker for short-term survival after an acute stroke (even after adjustment for baseline comorbidities) and as a risk factor for subsequent AKI.

Two mutations in the thiazide-sensitive NaCl co-transporter gene in a Romanian Gitelman syndrome patient: case report.

BACKGROUND: Gitelman syndrome (GS) is considered as the most common renal tubular disorder, and we report the first Romanian patient with GS confirmed at molecular level and diagnosed according to genetic testing. PATIENT AND METHODS: This paper describes the case of a 27-year-old woman admitted with severe hypokalemia, slight hypomagnesemia, hypocalcemia, hypocalciuria, metabolic alkalosis, hyperreninemia, low blood pressure, limb muscle weakness, marked fatigue and palpitations. Family history revealed a consanguineous family with autosomal-recessive transmission of GS with two cases over five generations. RESULTS: Next-generation sequencing technology detected two different homozygous mutations c.1805_1806delAT and c.2660+1G>A in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl co-transporter, confirmed by the Sanger method. CONCLUSION: Clinicians should be aware of the existence of GS, manage the condition properly and consider the risk of disease recurrence to the next generations.

The impact of acute kidney injury on in-hospital mortality in acute ischemic stroke patients undergoing intravenous thrombolysis.

INTRODUCTION: Acute kidney injury (AKI) increases the risk of death in acute ischemic stroke (AIS) patients. Intravenous thrombolytic therapy (iv. rt-PA) seems to be the most effective treatment for AIS patients. The effects of AKI on iv. rt-PA treated AIS cases is less studied. Our paper addresses this issue. METHODS: 45 consecutive stroke patients treated with iv. rt-PA (median age = 64 years; 29 male) and 59 age and sex matched controls not eligible for iv. rt-PA have been enrolled in our study. Subjects were followed-up until hospital release or death (median follow up time = 12 days). RESULTS: The prevalence of AKI did not differ between iv. rt-PA treated patients and controls (35.5% vs. 33.89%). In both groups, AKI was associated with increased in-hospital mortality: 50.0% vs. 3.4% p<0.0001 (in the rt-PA treated), and 45% vs. 30.7% (in controls). AKI iv. rt-PA treated patients had a significantly higher risk of in hospital mortality as compared to the no-AKI iv. rt-PA treated (HR = 15.2 (95%CI [1.87 to 124.24]; P = 0.011). In a Cox-multivariate model, the presence of AKI after iv. rt-PA remained a significant factor (HR = 8.354; p = 0.041) influencing the in-hospital mortality even after correction for other confounding factors. The independent predictors for AKI were: decreased eGFR baseline and elevated serum levels of uric acid at admission, (the model explained 60.2% of the AKI development). CONCLUSIONS: The risk of AKI was increased in AIS patients. Thrombolysis itself did not increase the risk of AKI. In the iv. rt-PA patients, as compared to non-AKI, those which developed AKI had a higher rate of in-hospital mortality. The baseline eGFR and the serum uric acid at admission were independent predictors for AKI development in the iv. rt-PA treated AIS patients.

The Survival of Roma Minority Patients on Chronic Hemodialysis Therapy - A Romanian Multicenter Survey.

OBJECTIVE: The Roma minority represents the largest ethnic group in Central and South-East European countries. Data regarding the mortality in Roma hemodialysis subjects are limited. We evaluated the 3 year mortality of ESRD Roma patients treated with hemodialysis (HD). STUDY DESIGN AND SETTING: Our prospective cohort study included 600 ESRD patients on HD therapy recruited from 7 HD centers, from the main geographical regions of Romania. The median age of the patients was 56 (19) years, 332 (55.3%) being males, 51 (8.5%) having Roma ethnicity. RESULTS: Roma ESRD patients initiate dialysis at a younger age, 47.8 years vs. 52.3 years (P = 0.017), present higher serum albumin (P = 0.013) and higher serum phosphate levels (P = 0.021). In the Roma group, the overall 3 year mortality was higher when compared to Caucasians (33.3% vs. 24.8%). The multivariate survival analysis revealed that being of Roma ethnicity is an independent risk factor for mortality (HR = 1.74; 95% CI = 1.04-2.91; P = 0.035). CONCLUSIONS: Roma patients with ESRD initiate HD therapy at a younger age as compared to Caucasians. They have a higher 3 year mortality rate and are dying at a younger age. Roma ethnicity represents an independent risk factor for mortality in our cohort.

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.

Vitamin D deficiency--prognostic marker or mortality risk factor in end stage renal disease patients with diabetes mellitus treated with hemodialysis--a prospective multicenter study.

BACKGROUND: End stage renal disease (ESRD) patients on renal replacement therapy (RRT) with diabetes mellitus (DM) have a higher mortality rate and an increase prevalence of vitamin D deficiency compared to those without DM. It is still debated if vitamin D deficiency is a risk factor or a prognostic marker for mortality in these patients. This study investigated the prevalence of vitamin D deficiency and its impact on all-cause mortality in HD patients with DM. METHODS: Our prospective non-interventional cohort study included 600 patients on hemodialysis therapy (HD) (median aged 56, interquartile range (19) years, 332 (55.3%) males) recruited from 7 HD centers, from all main geographical regions of Romania. The prevalence of DM was 15.3%. They were then followed regarding: dialysis duration, dialysis efficiency, renal anemia, CKD-MBD, inflammatory status and comorbidities: coronary artery disease (CAD), peripheral vascular disease (PVD) and stroke. The deficiency of 25-OH vitamin D was defined as a value lower than 12 ng/mL. RESULTS: Patients were followed for 3 years. The overall 3 year mortality was 25.5% (153 individuals), being higher in patients with DM as compared to those without DM (33.7% vs. 24.0%; P = 0.049). The time-related prognosis was also influenced by the presence of DM, at the survival analysis resulting in a HR of 1.52 [1.03 to 2.26] 95% CI, P = 0.037, for death in dialyzed patients with DM. In DM patients, 25-OH vitamin D deficiency was significantly higher (37.0% compared to 24.0%, P = 0.009). Furthermore, in patients with DM we observed a shorter dialysis duration (2 vs. 3 years, P<0.001) and a lower intact parathyroid hormone (iPTH) (258.0 pg/ml vs. 441.9 pg/ml, P = 0.002). Regarding the presence of comorbidities at the inclusion in the study, the presence of diabetes in dialyzed patients was associated with increased prevalence of CAD (87.0% vs. 58.1%, P<0.001), PVD (67.4% vs. 17.3%, P<0.001) and history of stroke (29.3% vs. 14.0%, P<0.001). In patients with DM the presence of 25-OH vitamin D deficiency increased the probability of death (50.0% vs. 24.1%; P = 0.011). In multiple Cox proportional hazards analysis, vitamin D deficiency remained an independent predictor for mortality in dialysis patients with DM (HR = 1.71, 95% CI 1.21 to 2.43, P = 0.003). In the same time, multiple Cox proportional hazards analysis showed that age (HR = 1.02 per one year increase, P = 0.004), CAD (HR = 1.55, P = 0.046) and PVD (HR = 1.50, P = 0.029) were independent predictors for mortality in dialysis patients with DM. CONCLUSIONS: ESRD patients with DM treated with HD have a higher overall mortality than non-DM patients. Vitamin D deficiency is significantly more prevalent in HD patients with DM. Low 25-OH vitamin D levels were associated with increased all-cause mortality in these patients. According to our data, in HD patients with DM, screening for vitamin D deficiency (and its correction) should be mandatory for an optimal risk reduction strategy.

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.