Higher Body Mass Index is associated with increased arterial stiffness prior to target organ damage: a cross-sectional cohort study.

BACKGROUND: Obesity is associated with several neurohumoral changes that play an essential role in organ damage. Increased arterial stiffness causes functional vessel wall changes and can therefore lead to accelerated target organ damage as well. Whether obesity causes an independent increase in central arterial stiffness is, however, not yet fully known. METHODS: One hundred thirty-three patients (63.2% male) were included. Body Mass Index (BMI) was defined as body weight in kilograms, divided by the square of body height in meters. Chronic Kidney Disease Epidemiology Collaboration creatinine 2009 equation was used to estimate the glomerular filtration rate (eGFR). Non-invasive applanation tonometry was used for arterial stiffness measurements (Sphygmocor Atcor Medical, Sydney, Australia). All patients underwent coronarography. RESULTS: The mean age of our patients was 65.0 ± 9.2 years. Their mean BMI was 28.5 ± 4.4 kg/m2, eGFR 75.5 ± 17.2 ml/min/1.73 m2 and ankle-brachial index (ABI) 1.0 ± 0.1. Their arterial stiffness measurements showed mean carotid-femoral pulse wave velocity (cfPWV) 10.3 ± 2.7 m/s, subendocardial viability ratio (SEVR) 164.4 ± 35.0%, and pulse pressure (PP) 47.8 ± 14.5 mmHg. Spearman's correlation test revealed a statistically significant correlation between BMI and SEVR (r = -0.193; p = 0.026), BMI and cfPWV (r = 0.417; p < 0.001) and between BMI and PP (r = 0.227; p = 0.009). Multiple regression analysis confirmed an independent connection between BMI and cfPWV (B = 0.303; p < 0.001) and between BMI and SEVR (B = -0.186; p = 0.040). There was no association between BMI and kidney function, ABI, or coronary artery disease. CONCLUSION: Increased BMI is independently associated with augmented central arterial stiffness and reduced subendocardial perfusion but not with coronary artery disease, kidney function, or ABI.

Early Detection of Arteriovenous Fistula Stenosis in Hemodialysis Patients through Routine Measurements of Dialysis Dose (Kt/V).

BACKGROUND: Monitoring of arteriovenous (AV) fistula to detect hemodynamically important stenosis is crucial for the prevention of AV fistula thrombosis. The aim of our study was to analyze the importance of dialysis dose (Kt/V) during online postdilution hemodiafiltration (HDF) for early detection of AV fistula stenosis. METHODS: Hemodialysis patients with AV fistula were included in this study. We compared a group of 44 patients who have undergone fistulography and subsequently percutaneous transluminal angioplasty (PTA) of significant AV fistula stenosis (active group) with a group of 44 age- and sex-matched patients without PTA (control group). Observational time in both groups was the same. RESULTS: All patients had postdilution online HDF using a F5008 dialysis machine, which can measure online single-pool Kt/V. All data were analyzed during the performance of 2056 HDF procedures. In the active group, we found statistically significantly lower values of Kt/V, all 8 weeks before PTA. In the active group, there was a significant improvement in Kt/V in the first (p < 0.001) and second week (p = 0.049) after PTA. Three and 8 weeks after PTA, we did not find any statistically significant difference in Kt/V between both groups (p = 0.114; p = 0.058). Patients in the active group had statistically significantly lower substitution volumes and blood pump flow rates during HDF over the whole observation period before and after PTA. In contrast, there were no differences in venous pressure in the dialysis circuit between both groups throughout the observation period. CONCLUSION: In hemodialysis patients with AV fistula, treated with online HDF, routine measurements of Kt/V during each HDF are a beneficial, quick, and straightforward method for early detection of hemodynamically significant AV fistula stenosis.

Serum zinc values, ankle brachial index and mortality in hemodialysis patients.

INTRODUCTION: The atherosclerotic state of haemodialysis (HD) patients may be influenced by heavy metals. The purpose of our study was to assess the relationship between serum zinc (Zn) ankle brachial index (ABI) as a non-invasive diagnostic tool for atherosclerosis, and mortality in chronic haemodialysis (HD) patients. METHODS: Sixty one HD patients were included (mean age 61.2 ± 13.8 years). The ABI was measured with an automated measuring device (ABPI MD, MESI®, Slovenia). Two groups of patients were formed based on the median value of Zn (14.1 mcmol/l). The average observation time was 2.8 years. Comorbidities (arterial hypertension (AH), diabetes mellitus (DM), dyslipidaemia), smoking and oral nutritional supplements (ONS) consumption were noted. Survival rates were analysed by Kaplan-Meier and Cox regression was used to determine the influence of Zn, ABI, AH, DM, dyslipidaemia, smoking and ONS. RESULTS: Zn values were between 9.2 and 23.5 mcmol/l (14.4 ± 2.34), ABI values ranged from 0.8 to 1.4 (1.14 ± 0.12). Patients with lower Zn values had lower ABI (p = 0.036). Mean survival time of patients with higher Zn values was 985 days ± 277 days and with lower Zn values 1055 ± 143 days. Six (19.4%) patients with lower Zn and five (16.7%) patients with higher Zn died. We found statistically insignificant lower survival in patients with higher Zn. We failed to find any predictor of all-cause mortality, except for ONS consumption (95% CI 1.6-33.3; p = 0.012). CONCLUSIONS: Lower Zn is associated with lower ABI in HD patients, but we found no impact of Zn on patient survival.

CHA2DS2-VASc Score as a Predictor of Cardiovascular and All-Cause Mortality in Chronic Kidney Disease Patients.

INTRODUCTION: Chronic kidney disease (CKD) is a risk factor for cardiovascular and all-cause mortality. Recognition of high-risk patients is important and could lead to a different approach and better treatment. The CHA2DS2-VASc score was originally used to predict cerebral infarction in patients with atrial fibrillation (AF), but it is also a useful predictor of outcome in other cardiovascular conditions, independent of AF. Therefore, the aim of our research was to assess the role of CHA2DS2-VASc score in predicting cardiovascular and all-cause mortality in CKD patients. METHODS: Stable nondialysis CKD patients were included. At the time of inclusion, medical history data and standard blood results were collected and CHA2DS2-VASc score was calculated. Patients were followed till the same end date, until kidney transplantation or until their death. RESULTS: Eighty-seven CKD patients were included (60.3 ± 12.8 years, 66% male). Mean follow-up time was 1,696.5 ± 564.6 days. During the follow-up, 21 patients died and 11 because of cardiovascular reasons. Univariate Cox regression analysis showed that CHA2DS2-VASc score is a significant predictor of cardiovascular and all-cause mortality. In multivariate Cox regression analysis, in which CHA2DS2-VASc score, serum creatinine, urinary albumin/creatinine, hemoglobin, high-sensitivity C-reactive protein, and intact parathyroid hormone were included, CHA2DS2-VASc score was an independent predictor of cardiovascular (HR: 2.04, CI: 1.20-3.45, p = 0.008) and all-cause mortality (HR: 2.06, CI: 1.43-2.97, p = 0.001). The same was true after adding total cholesterol, triglycerides, and smoking status to both the analyses. CONCLUSION: The CHA2DS2-VASc score is a simple, practical, and quick way to identify the risk for cardiovascular and all-cause mortality in CKD patients.

The association between pulse wave analysis, carotid-femoral pulse wave velocity and peripheral arterial disease in patients with ischemic heart disease.

INTRODUCTION: Functional changes in peripheral arterial disease (PAD) could play a role in higher cardiovascular risk in these patients. METHODS: 123 patients who underwent elective coronary angiography were included. Ankle-brachial index (ABI) was measured and arterial stiffness parameters were derived with applanation tonometry. RESULTS: 6 patients (4.9%) had a previously known PAD (Rutherford grade I). Mean ABI was 1.04 ± 0.12, mean subendocardial viability ratio (SEVR) 166.6 ± 32.7% and mean carotid-femoral pulse wave velocity (cfPWV) 10.3 ± 2.4 m/s. Most of the patients (n = 81, 65.9%) had coronary artery disease (CAD). There was no difference in ABI among different degrees of CAD. Patients with zero- and three-vessel CAD had significantly lower values of SEVR, compared to patients with one- and two-vessel CAD (159.5 ± 32.9%/158.1 ± 31.5% vs 181.0 ± 35.2%/166.8 ± 27.8%; p = 0.048). No significant difference was observed in cfPWV values. Spearman's correlation test showed an important correlation between ABI and SEVR (r = 0.196; p = 0.037) and between ABI and cfPWV (r = - 0.320; p ≤ 0.001). Multiple regression analysis confirmed an association between cfPWV and ABI (ß = - 0.210; p = 0.003), cfPWV and mean arterial pressure (ß = 0.064; p < 0.001), cfPWV and age (ß = 0.113; p < 0.001) and between cfPWV and body mass index (BMI (ß = - 0.195; p = 0.028), but not with arterial hypertension, dyslipidemia, diabetes mellitus or smoking status. SEVR was not statistically significantly associated with ABI using the same multiple regression model. CONCLUSION: Reduced ABI was associated with increased cfPWV, but not with advanced CAD or decreased SEVR.

Cystatin C and arterial stiffness in patients without chronic kidney disease.

BACKGROUND: Cystatin C (cysC) is freely filtered in the glomeruli, and its serum concentration is independent of muscle mass, diet, gender, or age. In patients with chronic kidney disease (CKD), cysC is associated with advanced atherosclerosis and increased arterial stiffness. The purpose of this study was to define possible associations between arterial stiffness parameters and cysC in patients without CKD. MATERIALS AND METHODS: The study included 111 non-CKD patients. Basic demographic and laboratory data were recorded. Arterial stiffness was measured by applanation tonometry (sphygmocor, Australia). RESULTS: Mean age of the patients was 64.3 ± 9.4 years, 65.8% were men. Most common co-morbidities were arterial hypertension (AH) (n = 86, 77.5%), hyperlipidemia (n = 64, 57.7%), and diabetes mellitus (DM) (n = 22; 19.8%). Mean creatinine was 77.7 ± 13.8 µmol/L (range 49 - 108), estimated GFR 81.3 ± 9.4 mL/min/1.73m2 (range 62 - 90), and cysC 0.94 ± 0.18 mg/L (range 0.67 - 1.63). Mean carotid-femoral pulse wave velocity (cfPWV) was 10.1 ± 2.4 m/s (range 6.2 - 16.8), subendocardial viability ratio (SEVR) 165.7 ± 36.1% (range 92 - 299), ejection duration (ED) 33.8 ± 4.4 ms (range 22 - 46), and pulse pressure (PP) 46.6 ± 14.8 mmHg (range 17 - 94). A statistically significant association was found between cysC and cfPWV (r = 0.472, p < 0.001), SEVR (r = -0.316, p < 0.001), ED (r = 0.217, p = 0.025), and pulse pressure (PP) (r = 0.241, p = 0.012). Multiple regression analysis between arterial stiffness parameters and cysC, age, male gender, AH, DM, hyperlipidemia, and eGFR confirmed a statistically significant and independent association between cysC and cfPWV (ß = 0.220, p = 0.038), between cysC and SEVR (ß = -0.278, p = 0.017), and between cysC and ED (ß = 0.241, p = 0.045). CONCLUSION: Elevated cysC is associated with increased cfPWV, increased ED, and decreased SEVR.

The impact of kidney function on survival in elderly patients diagnosed with acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is an aggressive hematological cancer that involves myeloid cells. Elderly patients with comorbidities and poor performance status (PS) receive treatment with hypomethylating agents or supportive care. Several models are available to predict treatment-related mortality and they all primarily focus on PS. Little is known about the impact of chronic kidney disease (CKD) on survival in elderly patients with AML. MATERIALS AND METHODS: We performed a retrospective analysis of 81 patients (51.9% male) aged over 65 years when the diagnosis of AML was established. The median observation period lasted 108 days (IQR 292, maximum 1,169). Patients' documentation was examined for previous illnesses, PS was calculated, basic laboratory blood tests and a bone marrow biopsy were done. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2. RESULTS: The median age of patients was 75 years (IQR 14, maximum 93). The mean eGFR was 59.5 ± 24.0 mL/min/1.73m2. CKD was present in almost half of patients (49.4%). Altogether, 69 (85.2%) patients died during the observation period. Kaplan-Meier survival analysis showed statistically lower survival for CKD patients (log-rank χ2 = 6.736; p = 0.009). Cox regression model, adjusted for age, comorbidities, and treatment, revealed the main predictors for patient survival to be PS, AML type, and blast percentage. CONCLUSION: Our results indicate that elderly patients with AML have worse survival when diagnosed with CKD, however CKD was not one of the main predictors of patient survival.

The role of kidney function on patient survival after percutaneous coronary intervention for acute coronary syndrome in left main coronary artery disease.

BACKGROUND: The prevalence of chronic kidney disease (CKD) is increasing on a global scale. Patients with CKD have a reduced quality of life and are more likely to develop significant cardiovascular disease, most commonly coronary artery disease (CAD). Left main coronary artery disease (LMCAD) is one of the most severe forms of CAD, where revascularization is needed. The aim of the study was to determine the impact of CKD on the mortality of patients after undergoing percutaneous coronary intervention (PCI) for the acute coronary syndrome (ACS) due to LMCAD. MATERIALS AND METHODS: 210 Caucasian patients (142 male; 67.6%, mean age 69.2 ± 11.3 years) with ACS due to LMCAD who underwent primary PCI were included in this retrospective study. Basic demographic and laboratory data were recorded. Patients were divided into two groups by their estimated glomerular filtration rate (eGFR). Those in the CKD group had eGFR ≤ 60 mL/min/1.73m2 (n = 82), and those in the non-CKD group had eGFR > 60 mL/min/1.73m2 (n = 128). RESULTS: The mean survival time of patients in the CKD group was 1,550 ± 1,393 days, compared to the non-CKD group of 2,149 ± 1,235 days. Kaplan-Meier survival analysis showed a statistically significant (log-rank, p < 0.0005) difference in mortality for patients in the CKD group compared to those in the non-CKD group. Cox-regression analysis showed a correlation between CKD and mortality (B = 0.541, p = 0.036), independent of arterial hypertension, diabetes mellitus, total cholesterol, and triglycerides. CONCLUSION: CKD is an independent risk factor for increased mortality after PCI due to an ACS in LMCAD.

Assessment of volume status with bioimpendance prior to hemodialysis and its importance for predicting survival in hemodialysis patients.

BACKGROUND: Optimal fluid management is a physician's everyday challenge in patients on maintenance hemodialysis (HD). Bioimpedance spectroscopy (BIS) is a non-invasive method to estimate body composition, including estimates of fluid overload (FO). Our study aimed to analyze the association between FO and the mortality rate in HD patients. MATERIALS AND METHODS: We performed a retrospective single-center cohort study in 92 HD patients. The body composition was measured before HD using the portable whole-body BIS device Body Composition Monitor (BCM). We have analyzed the mortality rates of HD patients in two FO groups, a standard definition FO group (> 1.1 L), and a severe FO group (> 2.5 L) and compared them to mortality rates of patients without FO or without severe FO, respectively. RESULTS: The mean age of patients was 64.3 ± 13.0 years, mean dialysis vintage 64 months, 60.9% were men. 68 (73.9%) patients had FO of > 1.1 L and 30 (32.6%) had FO of > 2.5 L. During the follow-up period of 1,020 ± 417 days, 29 (31.5%) patients died. Kaplan-Meier survival analysis showed that patients with FO > 2.5 L had worse survival (p = 0.039). In a Cox regression model, which included FO > 2.5 L, age, dialysis vintage, hemoglobin, C-reactive protein, and albumin, only FO > 2.5 L and advanced age turned out to be predictors of death (p = 0.044 and p = 0.001, respectively). CONCLUSION: HD patients with FO > 2.5 L before HD have poorer survival than patients with normohydration or lower overhydration.

Lung ultrasound, hemoglobin, and NT-proBNP in peritoneal dialysis patients.

BACKGROUND: Lung ultrasound (LUS) is a non-invasive technique for estimating extravascular lung water in patients with end-stage renal disease and heart diseases. In this study, we examined an association between the severity of lung congestion as detected by LUS B-lines (LUS comets), anemia, and serum biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) in peritoneal dialysis (PD) patients. MATERIALS AND METHODS: 19 patients, who were treated with PD in our dialysis center were enrolled. On the day of their routine check-up, we performed a lung auscultation, LUS on 28 typical locations and determined blood levels of hemoglobin and NT-proBNP. RESULTS: The average age of patients was 54 (range 30 - 71) years, the average duration of PD treatment was 53 (range 10 - 194) months, 63% (12) of the patients were male. Nine (47.4%) patients had peripheral edema, and only 1 (5.3%) patient had inspiratory crackles. Using LUS, we found mean 17 (range 1 - 87) lung comets. Mean hemoglobin level was 108.6 g/L (SD ± 10.4), mean NT-proBNP level 1,151 pmol/L (SD ± 1,077). We found a statistically significant correlation between the number of lung comets and hemoglobin level (r = -0.655; p = 0.002) and NT-proBNP (r = 0.759; p < 0.0001). Multiple regression analysis with the number of lung comets as dependent variable and hemoglobin and NT-proBNP levels as independent variables confirmed a statistically significant association between the number of lung comets and NT-proBNP (ß = 0.572; p = 0.009). CONCLUSION: In PD patients, the number of LUS comets is associated with hemoglobin and NT-proBNP.

Renal proximal tubular epithelial cells: review of isolation, characterization, and culturing techniques.

The kidney is a complex organ, comprised primarily of glomerular, tubular, mesangial, and endothelial cells, and podocytes. The fact that renal cells are terminally differentiated at 34 weeks of gestation is the main obstacle in regeneration and treatment of acute kidney injury or chronic kidney disease. Furthermore, the number of chronic kidney disease patients is ever increasing and with it the medical community should aim to improve existing and develop new methods of renal replacement therapy. On the other hand, as polypharmacy is on the rise, thought should be given into developing new ways of testing drug safety. A possible way to tackle these issues is with isolation and culture of renal cells. Several protocols are currently described to isolate the desired cells, of which the most isolated are the proximal tubular epithelial cells. They play a major role in water homeostasis, acid-base control, reabsorption of compounds, and secretion of xenobiotics and endogenous metabolites. When exposed to ischemic, toxic, septic, or obstructive conditions their death results in what we clinically perceive as acute kidney injury. Additionally, due to renal cells' limited regenerative potential, the profibrotic environment inevitably leads to chronic kidney disease. In this review we will focus on human proximal tubular epithelial cells. We will cover human kidney culture models, cell sources, isolation, culture, immortalization, and characterization subdivided into morphological, phenotypical, and functional characterization.

Hyperuricemia, the heart, and the kidneys - to treat or not to treat?

BACKGROUND: Hyperuricemia is a state in which the serum levels of uric acid are elevated. As such it has a pronounced effect on vascular and renal function with their consequences, while also showing some antioxidant effects that show to be beneficial. SUMMARY: Hyperuricemia has shown to have a J-shaped relationship with mortality, is frequently associated with development and progression of heart and kidney disease, and is correlated with malnutrition-inflammation-atherosclerosis syndrome, although several Mendelian studies have failed to show an association with morbidity and mortality. Hyperuricemia is usually associated with gout flares and tophi development but can also present as asymptomatic hyperuricemia. It is still uncertain whether asymptomatic hyperuricemia is an independent risk factor for cardiovascular or renal disease and as such its treatment is questionable. KEY MESSAGES: Some possible tools for future decision making are the use of noninvasive techniques such as pulse wave analysis, urinary sediment analysis, and joint ultrasound, which could help identify individuals with asymptomatic hyperuricemia that could benefit from urate lowering therapy most.

Cystatin C as a predictor of mortality in elderly patients with chronic kidney disease.

BACKGROUND: The prevalence of chronic kidney disease (CKD) in the elderly is high. Serum cystatin C is an accurate marker of kidney function and it also has prognostic utility in CKD patients. The aim of our study was to determine the prediction of serum cystatin C and other markers of kidney function on long-term survival in elderly CKD patients. METHODS: Fifty eight adult Caucasian patients, older than 65 years, without known malignancy, thyroid disease and/or not on steroid therapy were enrolled in the study. In each patient, 51CrEDTA clearance, serum creatinine, serum cystatin C, and estimated glomerular filtration rate using different equations were determined on the same day and patients were then followed for 11 years or until their death. RESULTS: The means are as follows: 51CrEDTA clearance 53.3 ± 17.4 ml/min/1.73 m2, serum creatinine 1.62 ± 0.5 mg/dl, serum cystatin C 1.79 ± 0.5 mg/l, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation 40.1 ± 14 ml/min/1.73 m2, Berlin Initiative Study 2 (BIS2) equation 38.9 ± 10.7 ml/min/1.73 m2, full age spectrum (FAS) creatinine equation 43.8 ± 13.8 ml/min/1.73 m2, FAS cystatin C equation 40.1 ± 11.7 ml/min/1.73 m2. In the follow up period, 47 (81%) patients died. Cox regression analysis showed different hazard ratios (HRs) for death: for 51CrEDTA clearance HR 1.022 (95% CI 1.004-1.042; p = .015), serum creatinine HR 1.013 (95% CI 1.006-1.019; p = .001), serum cystatin C HR 2.028 (95% CI 1.267-3.241; p = .003), CKD-EPI creatinine equation HR 1.048 (95% CI 1.019-1.076; p = .001), BIS2 equation HR 1.055 (95% CI 1.021-1.088; p = .001), FAS creatinine equation HR 1.046 (95% CI 1.017-1.074; p = .001), FAS cystatin C equation HR 1.039 (95% CI 1.010-1.071; p = .009). CONCLUSIONS: Our results showed the highest HR for serum cystatin C among kidney function markers for prediction of outcome in elderly CKD patients.

Students as partners: Our experience of setting up and working in a student engagement friendly framework.

BACKGROUND: Student engagement (SE) in the curriculum is a positive indicator in the development of students deeply involved in their learning. It also has several benefits for the schools' level of educational innovation and quality assurance. METHOD: In order to identify the most important pearls from the last decade of educational developments within the field of SE at the Faculty of Medicine University of Maribor, we searched through our school's archives, publications and research in the field of medical education. RESULTS: Three areas were identified as the most important SE complements: (i) peer teaching, (ii) school governance, and (iii) extracurricular activities. The paper highlights how many student-driven initiatives move from informal frameworks toward a formal structure, elective courses, and, in the end, compulsory components of the curriculum. DISCUSSION: As demonstrated by the three educational achievements at our school, fostering a high level of SE can lead to innovative curricular changes, benefit the whole school and enable students to deliver highly impactful extracurricular projects.

Impact of short-term nutritional supplementation on surrogate markers of undernutrition in hemodialysis patients - prospective real-life interventional study.

INTRODUCTION: Hemodialysis (HD) patients are at increased risk for undernutrition, especially protein wasting. We present the results of a prospective study in HD patients after 4 months of intervention with oral nutritional supplements (ONS). METHODS: After a 3-month wash-out period, 92 HD patients were enrolled in the study. Patients were tested for undernutrition with composite parameters, laboratory tests, bioelectrical impedance analysis (BIA), and hand-grip strength test (HGS). All patients fulfilling criteria for, or at high risk of, undernutrition were given ONS in addition to their regular diet. The impact of short-term ONS on surrogate markers of undernutrition was statistically analyzed. RESULTS: Data for 84 patients, 45 (53.6%) male, average age 63.3 years, were available for analysis after 4 months. Patients were divided into three groups: group A (n = 28), patients with normal nutritional status (NUS) at baseline not necessitating ONS; group B (n = 43), patients entitled to receive ONS; group C (n = 13), patients entitled to receive but refused to take ONS. In group B patients, received on average 4.1 bottles of ONS (902 mL; 1,623.6 kcal; 73.06 g protein) per week. Baseline results showed statistically-significant differences between groups in serum albumin levels and phase angle (PhA) but not in HGS. After 4 months of ONS, we noticed stagnation of observed markers in group B. Interestingly, in group A, significant deterioration of serum albumin and PhA was observed, but HGS improved. There was a trend towards worsening of serum albumin levels and HGS in group C not reaching statistical significance. CONCLUSIONS: In undernourished HD patients after ONS we did not find statistically-significant improvement of NUS evaluating surrogate markers. Nevertheless, in undernourished patients not receiving ONS, serum albumin and HGS showed a trend towards worsening, and even in well-nourished patients, nutritional markers (serum albumin and PhA) declined. We speculate that a certain positive effect of ONS on nutritional status in undernourished HD patients could be observed already after short-term supplementation.
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Hyperuricemia and long-term survival in patients with chronic kidney disease undergoing hemodialysis.

INTRODUCTION: Uric acid (UA), a breakdown product of purines, has been associated with mortality in different populations. Less is known about associations between hyperuricemia and mortality in chronic kidney disease (CKD) patients, later undergoing hemodialysis (HD), during a long observation period. The aim of this study was to determine the impact of elevated UA levels on long-term (19.5 years) survival of CKD patients. METHODS: 120 CKD patients (49 female, 71 male) enrolled in our study were observed from their first visit at the patients' nephrology outpatient clinic (NOC). All patients later started HD and were followed until their death or January 1, 2016. UA was measured regularly from venous sampling during NOC visits and HD sessions. Patients with mean UA below 420 µmol/L were defined as normouricemic, patients with mean UA above 420 µmol/L as hyperuricemic. No patients were treated for hyperuricemia. Survival rates were analyzed using Kaplan-Meier survival curves. Cox regression model was used to assess the influence of UA, age, arterial hypertension, diabetes mellitus, total cholesterol, triglycerides, smoking, and body mass index on the survival of our patients. RESULTS: Mean UA was 383.6 ± 83, range 220 to 710 µmol/L. 86 (71.7%) patients were normouricemic, and 34 (28.3%) hyperuricemic. 43 (50.0%) normouricemic and 28 (82.4%) hyperuricemic patients died. Kaplan-Meier survival analysis showed the risk of death to be higher for hyperuricemic patients (log-rank test; p < 0.0001). With Cox multivariable regression model, the mean UA still remained a predictor of mortality in our patients (p < 0.0001). CONCLUSIONS: The results indicate an association between UA and long-term survival of CKD patients and show that hyperuricemia was directly associated with higher mortality among our patients.
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Measurement of breath ammonia for detection of patients with chronic kidney disease.

BACKGROUND: In a healthy individual, ammonia is converted to urea in the liver. Urea is then transported through the bloodstream and then excreted into the urine by the kidneys. In patients with chronic kidney disease (CKD), the accumulated urea is degraded by salivary urease into ammonia, which is then excreted by breathing. Breath ammonia can therefore be used for detecting the increased nitrogen-bearing wastes. In our pilot study, an electrochemical sensor was used to measure and analyze breath ammonia in healthy volunteers and patients with CKD. PATIENTS AND METHODS: In our study, 8 patients with CKD (stages 4 and 5) and 6 healthy volunteers were enrolled. All participants were nonsmokers and without pulmonary or liver disease. One controlled breath sample was collected from each participant. Immediately after the sample was collected, a gas analyzer was used for measuring breath ammonia in our participants. RESULTS: Mean creatinine value of CKD patients was 455.2 ± 294.1 µmol/L and 62.1 ± 7.5 µmol/L for healthy volunteers. Breath ammonia levels (3.32 ± 2.19 ppm vs. 0.49 ± 0.08 ppm; p = 0.003) and measured electric current (4.33 ± 0.25 mA vs. 4.01 ± 0.01 mA; p = 0.003) were significantly higher in the CKD group. CONCLUSIONS: The results of our pilot study show that breath monitoring of ammonia can be a simple, useful, fast, and noninvasive tool for detection of advanced kidney impairment.
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Relationship between subendocardial viability ratio and hemoglobin in patients with chronic kidney disease.

AIMS: Pulse wave analysis (PWA) uses the technique of applanation tonometry to obtain a peripheral pulse pressure waveform from which central hemodynamic information is derived. Using PWA, subendocardial viability ratio (SEVR) can be measured. SEVR represents a noninvasive measure of myocardial perfusion. It is related to the work of the heart, the oxygen consumption, and the energy supply of the heart. Anemia is a common complication of chronic kidney disease (CKD). A complex relationship exists between CKD, cardiovascular disease (CVD), and anemia. The aim of our study was to assess the relationship between SEVR and hemoglobin in non-dialysis CKD patients. MATERIAL AND METHODS: We examined the associations between PWA hemodynamic parameters, 24-hour ambulatory blood pressure (BP) measurements, and laboratory variables including hemoglobin, cardiac biomarkers troponin I, NT-proBNP, and hs-CRP in a cohort of 91 nondialysis CKD patients. PWA was assessed by radial applanation tonometry (SphygmoCor, Atcor, Sydney, Australia). The patients were divided into two groups according to the median value of hemoglobin. RESULTS: Mean age of included patients was 60.2 years, 67% were men, 44% were smokers, 25.3% had diabetes. A significant correlation between hemoglobin and SEVR was found (r = 0.26; p = 0.012). With multivariate regression analysis, SEVR as dependent variable turned out to be statistically significantly associated with hemoglobin (ß = 0.344, p = 0.013) and with troponin I (ß = -0.217, p = 0.037). Patients in the group with lower hemoglobin had statistically-significantly higher serum creatinine, cystatin C, NT-proBNP, and 24-hour ambulatory systolic BP and lower e-GFR, SEVR, and office diastolic BP. CONCLUSIONS: Results of our study show that SEVR is independently associated with hemoglobin in nondialysis CKD patients. CKD patients with lower hemoglobin have lower SEVR.
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Albuminuria is Associated With Subendocardial Viability Ratio in Chronic Kidney Disease Patients.

BACKGROUND/AIMS: Albuminuria is a well-established marker of subclinical organ damage. Pulse-wave analysis (PWA) employs the technique of applanation tonometry to obtain a peripheral pulse pressure waveform, from which central hemodynamic data are derived by application of the transfer function. Using PWA we can measure the subendocardial viability ratio (SEVR) and ejection duration (ED). SEVR or the Buckberg index is a non-invasive estimate of myocardial workload, oxygen supply and perfusion and a measure of the ability of the arterial system to meet the heart`s energy requirements. ED is the duration of ventricular ejection. The objective of this study was to evaluate the relationship between albuminuria and PWA parameters in chronic kidney disease (CKD) patients. METHODS: We studied 86 CKD patients aged 59.8±13.5 years, 56 (65.1%) were male. PWA analysis and 24-hour ambulatory blood pressure (24hABP) monitoring were performed. The following parameters were calculated: (1) aortic augmentation index with and without correction for a heart rate of 75 (Aix and AIx@ HR75), (2) SEVR, calculated as the ratio of the diastolic pressure time index and the systolic pressure time index, (3) ED, (4) estimated central aortic systolic and diastolic pressure and (5) central aortic pulse pressure calculated as the difference between estimated aortic systolic and diastolic BP. Blood samples and urine albumin-to-creatinine ratio (UACR) were analyzed; UACR values were natural log transformed (lnUACR). RESULTS: Using CKD-EPI creatinine-cystatin C formula the eGFR in patients was 7-130 ml/min/1.73 m² (mean 32.6; SD±24.6). We found statistically significant correlation between lnUACR and cystatin C (r=0.308; P=0.004), eGFR (r=-0.219; P=0.04), hemoglobin (r=-0.255; P=0.02), phosphorus (r=0.222; P=0.04), iPTH (r=0.268; P=0.01), SEVR (r=-0.254; P=0.02) and ED (r=0.315; P=0.003). No statistically significant correlations between lnUACR and cardiac biomarkers TnI, NT-proBNP, central aortic BP and 24h ABP values were found. Using multiple regression analysis statistically significant association was found between SEVR as dependent variable and lnUACR (ß=-0.223, P=0.039), sex (ß=-0.216, P=0.035), and diabetes (ß=0.332, P=0.001). Multiple regression analysis with ED as dependent variable has shown statistically significant association with lnUACR (ß=0.242, P=0.031) and diabetes (ß=-0.275, P=0.01). Patients were stratified into tertiles according to the lnUACR. Statistically significant differences in serum creatinine (P=0.001), cystatin C (P=0.012), hemoglobin (P=0.03), calcium (P=0.036), iPTH (P=0.008), SEVR (P=0.007) and ED (P=0.004) were found between tertiles. In post hoc analysis we found statistically significant differences between first and third tertile in SEVR (P=0.002; 95% CI:10.5-45) and in ED (P=0.001; 95% CI:-6.89-(-1.87)). CONCLUSIONS: Nondialysis CKD patients with higher levels of albuminuria have lower SEVR and higher ED and our results have shown the importance of central hemodynamic parameters like are SEVR and ED as a better or earlier noninvasive hemodynamic indexes in these patients.