Jasna Trbojevic-Stankovic

Cardiovascular Mortality in Hemodialysis Patients: Clinical and Epidemiological Analysis

Cardiovascular Mortality in Hemodialysis Patients: Clinical and Epidemiological Analysis Cardiovascular diseases are the leading cause of death in hemodialysis (HD) patients. The annual cardiovascular mortality rate in these patients is 9%, with left ventricular (LV) hypertrophy, ischemic heart disease and heart failure being the most prevalent causes of death. The aim of this study was to determine the cardiovascular mortality rate and estimate the influence of risk factors on cardiovascular mortality in HD patients. A total of 115 patients undergoing HD for at least 6 months were investigated. Initially a cross-sectional study was performed, followed by a two-year follow-up study. Beside the standard biochemical parameters, C-reactive protein (CRP), homocysteine, cardiac troponins (cTn) and the echocardiographic parameters of LV morphology and function (LV mass index, LV fractional shortening, LV ejection fraction) were determined. Results were analyzed using Cox regression analysis, Kaplan-Meier and Log-Rank tests. The average one-year cardiovascular mortality rate was 8.51%. Multivariate Cox regression analysis identified increased CRP, cTn T and I, and LV mass index as independent risk factors for cardiovascular mortality. Patients with cTnT > 0.10 ng/mL and CRP > 10 mg/L had significantly higher cardiovascular mortality risk (p < 0.01) than patients with cTnT > 0.10 ng/mL and CRP ≤ 10 mg/L and those with cTnT ≤ 0.10 ng/mL and CRP ≤ 10 mg/L (p < 0.01). HD patients with high cTnT and CRP have a higher cardiovascular mortality risk. Kardiovaskularni Mortalitet kod Bolesnika na Hemodijalizi: Klinička i Epidemiološka Analiza Kardiovaskularne bolesti su vodeći uzrok smrti bolesnika koji se leče hemodijalizom. Jednogodišnja stopa kardiovaskularnog mortaliteta iznosi 9%, a od kardiovaskularnih bolesti najveću prevalenciju imaju hipertrofija leve komore, ishemijska bolest srca i srčana slabost. Cilj rada je bio da se utvrdi stopa kardiovaskularnog mortaliteta i da se ispita uticaj faktora rizika na razvoj kardiovaskularnog mortaliteta kod bolesnika na hemodijalizi. Ispitano je 115 bolesnika koji se leče hemodijalizom duže od šest meseci. Prvo je obavljena studija preseka, a zatim praćenje bolesnika u dvogodišnjem vremenskom periodu. Parametri ispitivanja obuhvatili su koncentraciju C-reaktivnog proteina, homocisteina, srčanog troponina T i I, kao i ehokardiografske parametre morfologije i funkcije leve komore. Za statističku analizu dobijenih podataka korišćeni su Coxova regresiona analiza, Kaplan-Meierov test i Log-Rankov test. Utvrđeno je da prosečna jednogodišnja stopa kardiovaskularnog mortaliteta iznosi 8,51%. Multivarijantna Coxova regresiona analiza je pokazala da su povećana koncentracija C-reaktivnog proteina, srčanog troponina T i I, i povećan indeks mase leve komore nezavisni faktori rizika za nastanak kardiovaskularnog mortaliteta. Bolesnici kod kojih je koncentracija srčanog troponina T - cTnT > 0,10 ng/mL i koncentracija CRP > 10 mg/L imaju statistički veoma značajno (p < 0,01) veći rizik od kardiovaskularnog mortaliteta u odnosu na bolesnike kod kojih je cTnT > 0,10 ng/mL i CRP ≤ 10 mg/L i statistički veoma značajno (p < 0,01) veći rizik od kardiovaskularnog mortaliteta u odnosuna bolesnike koji imaju cTnT ≤ 0,10 ng/mL i CRP ≤ 10 mg/L. Bolesnici koji se leče hemodijalizom kod kojih je povišena koncentracija srčanog troponina T i C-reaktivnog proteina imaju povećan rizik od kardiovaskularnog mortaliteta.

Dialysis headache in patients undergoing peritoneal dialysis and hemodialysis

Abstract Objectives: Headache is among most frequently encountered neurological symptom during hemodialysis (HD), but still under investigated in peritoneal dialysis (PD) patients. The aim of this study was to assess the incidence and clinical characteristics of dialysis headache (DH) in HD and PD patients. Material and methods: A total of 409 patients (91 on PD and 318 on HD) were interviewed using a structured questionnaire, designed according to the diagnostic criteria of the International Headache Classification of Headache Disorders from 2004. Patients with DH underwent a thorough neurological examination. Results: DH was reported by 21 (6.6%) HD patients and 0 PD patients. PD patients had significantly lower serum sodium, potassium, calcium, phosphate, urea and creatinine, calcium–phosphate product, and diastolic blood pressure than HD patients. HD patients had significantly lower hemoglobin compared to PD patients. Primary renal disease was mostly parenchymal in HD patients, and vascular in PD patients. DH appeared more frequently in men, mostly during the third hour of HD. It lasted less than four hours, was bilateral, non-pulsating and without associated symptoms. Conclusion: Biochemical alterations may be implicated in the pathophysiology of DH. Specific features of DH might contribute to better understanding of this secondary headache disorder.

Malnutrition–Inflammation Complex Syndrome and Hepatitis C in Maintenance Hemodialysis Patients

Protein‐energy malnutrition and inflammation are among the leading causes of poor outcome in hemodialysis patients. Hepatitis C virus (HCV) infection is accompanied by elevated proinflammatory mediators, also found in dialysis patients with malnutrition–inflammation complex syndrome. We aimed to study the rate and characteristics of malnutrition–inflammation complex syndrome (MICS) in hemodialysis patients, especially those with hepatitis C. The study included 147 patients (mean age 55.1 ± 12.9 years), 24.5% of whom were HCV‐positive, undergoing adequate hemodialysis three times a week for the last 52.7 ± 52.5 months. Parameters of nutrition and inflammation were investigated to evaluate MICS. HCV‐positive vs. HCV‐negative patients had significantly higher hematocrit (29.6 ± 4.5 g/dL vs. 28.1 ± 4.3, P < 0.05), uric acid (345.8 ± 96.5 vs. 321.3 ± 118.8 µmol/mL, P < 0.05), aspartate aminotransferase (AST, also known as serum glutamic oxaloacetic transaminase [SGOT]) (23.3 ± 14.9 vs. 17.8 ± 9 U/L, P < 0.008), alanine aminotransferase (ALT, also known as serum glutamic pyruvic transaminase [SGPT]) (41.2 ± 28.7 vs. 26.6 ± 17.1 U/L, P < 0.0003), serum creatinine (980.4 ± 219.1 vs. 888.4 ± 202.9 µmol/mL, P < 0.022), intact parathyroid hormone (329.7 ± 630.5 vs. 110.2 ± 145.3 pg/mL, P < 0.002), malnutrition–inflammation score (7.4 ± 5.2 vs. 5.6 ± 4.1, P < 0.038), and Charlson comorbidity index (4.5 ± 1.5 vs. 4 ± 1.4, P < 0.05). MICS had a prevalence of 20–40% in our study. HCV‐positive patients had a significantly higher prevalence of MICS than HCV‐negative patients (30–40% vs. 20–30%).

Hyperphosphatemia - The Risk Factor for Adverse Outcome in Maintenance Hemodialysis Patients

Hyperphosphatemia - The Risk Factor for Adverse Outcome in Maintenance Hemodialysis Patients Hyperphosphatemia is a potent stimulator of vascular and valvular calcifications in hemodialysis patients. To determine the prevalence of hyperphosphatemia and assess its effect on the outcome of hemodialysis patients, a total of 115 chronic hemodialysis patients were studied. Laboratory parameters were determined at baseline, and after 12 and 24 months of follow-up. Valvular calcification was assessed with echocardiography. Laboratory parameters were statistically analyzed with ANOVA. Survival analysis was performed with the Kaplan-Meier test and Log-Rank test. Hyperphosphatemia was present in 31.30% of the patients, high calcium-phosphate (Ca × P) product in 36.52% and valvular calcifications in 48.70%. Patients with serum phosphate >2.10 mmol/L and Ca × P product >5.65 mmol2/L2 at baseline were at high risk for all-cause and cardiovascular mortality. Hyperphosphatemia is a risk factor for adverse outcome in patients on regular hemodialysis. Hiperfosfatemija - Faktor Rizika za Razvoj Nepovoljnog Ishoda Kod Bolesnika Koji se Leče Redovnim Hemodijalizama Hiperfosfatemija ima značajnu ulogu u kalcifikaciji srčanih valvula i koronarnih arterija bolesnika na hemodijalizi. Radi utvrđivanja prevalencije hiperfosfatemije i ispitivanja njenog uticaja na ishod bolesnika koji se leče redovnim hemodijalizama, ispitano je 115 bolesnika koji se leče redovnim hemodijalizama duže od 6 meseci. Laboratorijsko ispitivanje je sprovedeno na početku, posle 12 i 24 meseci praćenja bolesnika. Kalcifikacija srčanih valvula je procenjivana ehokardiografskom metodom. Za statističku analizu podataka korišćeni su jednofaktorska parametarska analiza varijanse - ANOVA i analiza preživljavanja (Kaplan-Meier test, Log-Rank test). Hiperfosfatemiju ima 31,30% bolesnika, povećan proizvod solubiliteta 36,52% bolesnika, a kalcifikaciju srčanih valvula 48,70% bolesnika. Bolesnici kod kojih je na početku ispitivanja koncentracija fosfata u serumu >2,10 mmol/L i proizvod solubiliteta >5,65 mmol2/L2 imaju visok rizik za razvoj opšteg i kardiovaskularnog mortaliteta. Hiperfosfatemija je faktor rizika za razvoj nepovoljnog ishoda kod bolesnika koji se leče redovnim hemodijalizama.

Serum cystatin C levels in normal pregnancy.

AIM The aim of this study was to determine the levels of cystatin C, creatinine and creatinine clearance in different trimesters of uncomplicated pregnancy in women with normal kidney function. SUBJECTS AND METHODS A total of 109 pregnant women were included: group 1 - 38 women (average age 29.63 ± 4.3 y) in the first trimester, Group 2 - 32 women (average age 33.56 ± 5.95 y) in the second trimester and Group 3 - 39 pregnant women (average age 30.1 ± 6.95 y) in the third trimester. Serum cystatin C was determined by the PENIA method (Particle-Enhanced Nephelometric Immuno-Assay), using Behring tests (Behring Diagnostics GmbH, Marburg, Germany). Results were statistically analyzed using the ANOVA. RESULTS A statistically significant increase in serum cystatin C level was found in the third trimester of pregnancy (0.69 ± 0.16 mg/l vs. 0.78 ± 0.26 mg/l vs. 1.21 ± 0.30 mg/l). CONCLUSION It appears that cystatin C is not a reliable marker of kidney function in pregnancy and that its increase is connected with a combination of several factors, including endotheliasis, hormonal influence and glomerular filtration rate (GFR) alterations.

Levels of transforming growth factor β1 during first six months of peritoneal dialysis

Abstract Transforming-growth factor β1 (TGF-β1) is a powerful cytokine involved in physiological processes of growth, differentiation, gene expression, embryogenesis, tissue remodelling, wound healing as well as tumorigenesis, immunosuppression and fibrosis, like peritoneal membrane fibrosis on long-term peritoneal dialysis (PD) treatment. The aims of this study were to determine TGF-β1 levels in serum (s) and drained dialysate (dd), to assess their relations to sex, age, diabetes, dialysis modality, peritonitis and use of erythropoiesis stimulating agents (ESAs), inhibitors of angiotensin-converting enzyme (ACEi) and/or statins in 20 patients, 11 men and 9 women, mean age 62.90 ± 12.69 years, free of peritonitis during the first 6 months of PD treatment. There was no statistically significant difference in TGF-β1 concentrations in serum and drained dialysate at the beginning and after first 6 months of chronic PD, in patients of different sex, age and diabetic patients versus non-diabetic. The significant positive correlations between sTGF-β1 levels and glycemia at the beginning and cholesterolemia after 6 months of PD treatment suggest higher TGF-β1 concentrations in patients with unfavorable metabolic profile. Expression of TGF-β1 in effluent dialysate was significantly lower in patients on chronic PD using ACEi therapy, suggesting ACEi to have a protective effect on peritoneal membrane. Patients on ESA had slightly lower sTGF-β1 concentrations after the first 6 months of PD treatment.

Relationship Between Leptin Level, Inflammation, and Volume Status in Maintenance Hemodialysis Patients: Leptin, Inflammation, and Volume Status in HD

Maintenance hemodialysis (HD) patients often experience fluctuations of volume status. Although hypervolemia possibly induces systemic inflammation, the relationship between volume status and leptin has not yet been well defined. The aims of this study were to determine the levels of leptin, C‐reactive protein (CRP), and ferritin in relation to volume status and to assess the relationship between leptin and volume and inflammatory status in chronic HD patients. This prospective study included 93 HD patients divided, based on evaluation using the body composition monitor, into normovolemic and hypervolemic groups (overhydration/extracellular water [OH/ECW] ≤ 15% and OH/ECW > 15%, respectively). The levels of leptin and inflammatory markers (CRP, ferritin) were determined during a mid‐week dialysis session in all patients. There were more hypervolemic patients after 12 months of follow up than at baseline (41% vs. 38%). Hypervolemic patients had significantly lower leptin levels (11.42 ± 19.24 ng/mL vs. 34.53 ± 40.32 ng/mL at baseline and 13.41 ± 22.04 ng/mL vs. 41.54 ± 21.78 ng/mL at 12 months), longer time on dialysis, and poorer nutritional status than normovolemic patients. Inflammation was present regardless of the volume status, but hypervolemic patients had significantly higher CRP and ferritin than normovolemic patients. A statistically significant reverse correlation was found between leptin level, hyperhydration index, and OH/ECW. No significant correlation was found between leptin and inflammatory markers CRP and ferritin.

The Evaluation of Angiotensin-Converting Enzyme Inhibitors in Renal Elimination with Selected Molecular Descriptors

Abstract Angiotensin-converting enzyme (ACE) inhibitors modulate the function of the renin-angiotensin-aldosterone system, and they are commonly prescribed antihypertensive drugs especially in patients with renal failure. In this study, the relationships between several molecular properties of eight ACE inhibitors (enalapril, quinapril, fosinopril, ramipril, benazepril, perindopril, moexipril, trandolapril) and their renal elimination data, from relevant literature, were investigated. The ’molecular descriptors of the ACE inhibitors, which included aqueous solubility data (logS); an electronic descriptor, polar surface area (PSA);, a constitutional parameter, molecular mass (Mr); and a geometric descriptor, volume value (Vol), as well as lipophilicity descriptors (logP values), were calculated using different software packages. Simple linear regression analysis showed the best correlation between renal elimination data and lipophilicity descriptor AClogP values (R2 = 0.5742). In the next stage of the study, multiple linear regression was applied to assess a higher correlation between the ACE inhibitors’ renal elimination data and lipophilicity, AClogP, with one additional descriptor as an independent variable. Good correlations were established between renal elimination data from the literature and the AClogP lipophilicity descriptor using the constitutional parameter (molecular mass (R2 = 0.7425)) or the geometric descriptor (volume value (R2 = 0.7224)) as an independent variable. The application of computed molecular descriptors in evaluating drug elimination is of great importance in drug research.

Quality of sleep in hemodialysis patients: The role of demographic and clinical characteristics

Introduction: Sleep disorders are common among patients treated with chronic dialysis. Still, these conditions are seldom diagnosed and often undertreated, because they are attributed to the renal disease itself and/or considered a reaction to dialysis treatment. Aim: The aim of this study was to assess the prevalence of poor sleep quality and its relations with demographic and clinical characteristics of patients undergoing chronic hemodialysis (HD). Material and Methods: A cross-sectional observational study was performed on 82 patients (49 men, mean age 64.77 ± 10.00 years, range 30-85) on HD maintenance in a University Hospital Center in Belgrade. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Other relevant data were collected by general questionnaire and from patients’ medical histories. Data were analyzed with Chi-square, Fisher and T test, using the SPSS (version 21.0). Results: The mean PSQI was 6.74 ± 3.99. Poor quality of sleep (PSQI>5) was present in 47 (57.3%) patients. Patients treated with hemodiafiltration statistically more often had significantly better quality of sleep (p=0.047), whereas patients receiving dialysis treatment in the afternoon shift more frequently had poor quality of sleep (p=0.017). Age, sex, employment status, comorbidities, dialysis vintage and adequacy were not related to the quality of sleep significantly. Conclusion: The type of dialysis treatment and dialysis shift are closely interrelated with the quality of sleep in patients on chronic HD treatment.

Chromatography methods in investigation of lipophilicity of the biological active substances

This paper presents the review of the methods used in research of the biological active substances hydrophobicity, a very important property. The biological activity of some substances depends on their pharmacokinetics and pharmacodynamics. These processes depend on the molecules capability to interact with two different media: aqueous (cells interior) and non-aqueous (cells membrane), or on the molecule lipophilicity. Today, great attention is given to investigation and systematic determination of drugs lipophilicity. In these researches chromatography methods have an important role.