Significance of the determination of biomarkers of bone resorption and formation In patients with end-stage renal disease

Vodiči za poboljšanje kvaliteta života i edukaciju pacijenata sa krajnjim stadijumom bolesti bubrega (Kidney Disease Outcomes Quality Initiatives, KDOQI), objavljeni od strane američke Nacionalne Fondacije za bubreg (NKF) ukazuju na značaj biomarkera metabolizma kostiju koje bi trebalo određivati kod pacijenata sa krajnjim stadijumom bolesti bubrega (KSBB). Prema NKF pacijenti sa KSBB (stadijum 5) su oni čija je GFR ispod 15 mL/min/1,73 m2. To su predijalizni pacijenti, pacijenti koji su na terapiji hemodijalizom (HD) ili kontinuiranom ambulatornom peritonealnom dijalizom (CAPD). Osnovni serumski biomarkeri koje bi trebalo određivati kod svih pacijenata sa petim stadijumom bolesti bubrega su joni kalcijuma (Ca), joni neorganskog fosfata (P), joni magnezijuma (Mg), ukupna alkalna fosfataza (ALP), intaktni paratiroidni hormon (iPTH) i 25-hidroksi vitamin D (25D). Međutim, metabolizam kostiju najpouzdanije mogu da prikažu jedino biomarkeri koje stvaraju ćelije kostiju, osteoblasti i osteoklasti. Aktivnost osteoblasta, ćelija koje su odgovorne za stvaranje kostiju, najbolje odražavaju nivoi koštanog izoenzima alkalne fosfataze (BALP), koji je visoko specifičan za koštano tkivo. Aktivnost osteoklasta, ćelija koje su odgovorne za resorpciju kostiju, specifično odražavaju nivoi tartarat rezistentne kisele fosfataze (TRAP). Dobar marker resorpcije kostiju jeste i beta-karboksi terminalni deo ukrštenih veza kolagena I, beta-CrossLaps (beta-CTx). Specifični serumski biomarkeri kostiju predstavljaju "biohemijsku biopsiju" značajnu za lakšu procenu i praćenje metabolizma kostiju. Cilj ovog rada bio je da se utvrdi značaj određivanja biomarkera resorpcije i stvaranja kostiju kod KSBB pacijenata. Ispitivanjem je obuhvaćeno 40 predijaliznih pacijenata (18 žena i 22 muškarca) starosne dobi 25−79, 114 pacijenata na CAPD (49 žena i 65 muškaraca) starosne dobi 30−84 i 112 pacijenata na HD (53 žene i 59 muškaraca) starosne dobi 25−79. Prosek trajanja lečenja hemodijalizom bio je 76 meseci, dok su pacijenti na CAPD bili 35 meseci. Planirani biomarkeri formiranja i resorpcije kostiju su se određivali u serumu ispitivanih pacijenata na dan uzorkovanja i to kod predijaliznih i CAPD pacijenata kada su dolazili na rutinske kontrolne preglede, a kod pacijenata na HD neposredno pre terapije dijalizom. Radi određivanja referentnih intervala u serumu, analizirani biomarkeri su određivani i u grupi od 50 zdravih dobrovoljaca (25 žena i 25 muškaraca) starosne dobi od 20−70 godina. ALP, TRAP, Ca, P i Mg su određeni fotometrijski (Olympus AU2700 ISE). BALP je određen zonskom elektroforezom (Sebia Hydrasis), beta-CTx i iPTH su određeni ECLIA metodom (Rosche Elecsys), a 25D HPLC-om reverznih faza (ChromLineR Clinical HPLC software Version 4.20). Određivanje analiziranih biomarkera u serumu se smatralo pouzdanim na osnovu koeficijenata varijacije dobijenih testiranjem preciznosti u seriji (Kv: 0,6%−3,3%) i iz dana u dan (Kv: 1,0%−3,6%). Ustanovljena je normalna raspodela vrednosti za svaki od analiziranih biomarkera kod predijaliznih, HD i CAPD pacijenata. Kod sve tri ispitivane grupe pacijenata uočen je uticaj pola na vrednosti iPTH, kao i na vrednosti neorganskog fosfata kod HD pacijenata i na vrednosti CaxP kod CAPD pacijenata. Međutim, uticaj starosti je kod sve tri grupe pacijenata uočen jedino na vrednosti BALP. Takođe, dužina trajanja HD imala je uticaj na vrednosti ALP BALP, a CAPD samo na vrednosti jona magnezijuma...Guidelines for improving the quality of life and education of patients with end-stage renal disease (Kidney Disease Outcomes Quality Initiatives, KDOQI), published by the U.S. National Kidney Foundation (NKF), indicate the importance of biomarkers of bone metabolism that should be determined in patients with end-stage renal disease (ESRD). According to the NKF, ESRD patients (stage 5) are those with a GFR below 15 ml/min/1.73 m2. These are predialysis patients, patients who are treated with hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). The basic serum biomarkers that could be determined in all patients with the fifth stage renal disease are: calcium ions (Ca), inorganic phosphate ions (P), magnesium ions (Mg), the total alkaline phosphatase (ALP), an intact parathyroid hormone (iPTH) and 25-hydroxy vitamin D (25D). However, the most reliable bone metabolism can be represented only by biomarker created by bone cells, osteoblasts and osteoclasts. The activity of osteoblasts, the cells responsible for bone formation, is well expressed by the levels of bone alkaline phosphatase isoenzymes (BALP), which is highly specific for bone tissue. The activity of osteoclasts, the cells responsible for bone resorption, specifically reflect levels of tartrate resistant acid phosphatase (TRAP). A good marker of bone resorption is the beta-carboxy terminal telopeptide of collagen type I, beta-CrossLaps (beta-CTx). Specific serum biomarkers of bone are "biochemical biopsy" important to facilitate the assessment and monitoring of bone metabolism. The aim of this study was to assess the usefulness of biomarkers of bone resorption and bone formation in ESRD patients. The study included 40 predialysis patients (18 women and 22 men) aged 25−79, 114 patients on CAPD (49 women and 65 men) aged 30−84 and 112 patients on HD (53 women and 59 men) aged 25−79. Average duration of the hemodialysis treatment was 76 months, while patients on CAPD treated 35 months. The analysed biomarkers of bone formation and resorption were determined in the serum of patients on the day of sampling and in predialysis patients and in patients on CAPD when they came to the routine check-ups, and in patients on HD immediately before dialysis therapy. To determine the reference intervals, analyzed biomarkers were measured in a group of 50 healthy volunteers (25 women and 25 men) aged 20−70 years. ALP, TRAP, Ca, P and Mg were determined photometrically (Olympus AU2700 ISE). BALP values were determined with zone electrophoresis (SEBIA Hydrasis), beta-CTx and iPTH values were determined with ECLIA (Elecsys Rosche) and 25D values were detrmined by HPLC with reversed phase detection (HPLC ChromLineR Clinical software Version 4:20). Determination of the analysed biomarkers is considered reliable based on the coefficients of variation obtained by precision testing in the series (Cv: 0.6%−3.3%) and from day to day (Cv: 1.0%−3.6%). We established the normal distribution of the values for each of the analysed biomarkers in predialysis and dialysed patients. There were different values of iPTH, P and CaxP levels in the all analysed groups according to gender. However, the effect of age was observed only on the values of BALP. Duration of the dialysis had impact only on the values of ALP and BALP in HD patients and on Mg levels in CAPD patients..

Bias in medical biochemistry- what laboratory professionals need to know?

In medical laboratories, bias presents quantitative expression of trueness, as analytical performance characteristic that describes systematic errors. Despite bias evaluation is an integral part of basic lessons of laboratory quality management, it is still difficult to achieve adequate bias estimation in routine laboratory practice. There are several principles that could be used to estimate bias, but fundamental for evaluating bias in routine medical laboratories is the availability of a suitable reference materials. Besides, it is important that the measuring method and measuring analytical system are in a stable state, and that they have completed an appropriate validation or verification process. This could be checked routinely by the results of internal and/or external quality control. In addition, information about the uncertainty of the certified reference material is a prerequisite for testing the bias. Significant efforts were made to minimized bias in routine laboratory practice, using reference measurement methods and commutable reference materials. Still, there are some challenges that remain for the laboratory professionals as the end users, due to remaining bias between measurement methods and systems from different and/or the same manufacturers

How Supplementation with SOD-Rich Plant Extract, Combined with Gliadin, Can Affect Oxidative Stress Markers and Zonulin Levels in Exercise-Induced Oxidative Stress

A randomized, double-blind, placebo-controlled study was conducted to investigate the influence of supplementation with a superoxide dismutase (SOD)-rich plant extract on markers of oxidative stress, zonulin levels and the performance of elite athletes. Participants were 30 international-level rowers, divided into an experimental group (n = 15) and a control group (n = 15). The rowers performed a maximal effort incremental test on a rowing ergometer at the beginning and at the end of the study. Markers of oxidative stress (total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), superoxide dismutase (SOD), glutathione peroxidase (GPx), advanced oxidation protein products (AOPPs), malondialdehyde (MDA), sulfhydryl (SH) groups, bilirubin, uric acid, albumin and zonulin) were determined in serum. A lower TOS (p = 0.010) and OSI (p = 0.004), a lower MDA (p = 0.001) and a higher level of SH groups (p = 0.031) were observed in the experimental group after supplementation. Physical performance was evaluated through metabolic efficiency, taking lactate levels and power output on the ergometer into account. After 6 weeks of supplementation, the relative increase in metabolic efficiency at a 4 mmol/L lactate concentration and maximal effort was significantly higher in the experimental group (p = 0.004 and p = 0.015, respectively). These results suggest that supplementation with a SOD-rich extract promotes lower oxidative stress, better antioxidant protection and, consequently, the better work performance of athletes

Effects of 6-Week Supplementation with GliSODin on Parameters of Muscle Damages, Metabolic, and Work Performance at International Level Rowers after Specific Maximal Effort

This study aimed to investigate the effect of supplementation with plant origin superoxide dismutase (SOD), GliSODin, on parameters of muscle damage, metabolic, and work performance at international level rowers. Twenty-eight rowers were included in a randomized, double-blind study. The study was conducted during a 6-week preparation period. At the beginning of the study and after 6 weeks of the supplementation period, all rowers were tested on a rowing ergometer. Blood samples were taken from the antecubital vein before and after every ergometer testing. Muscle damage markers creatine kinase (CK) and lactate dehydrogenase (LDH), total antioxidant capacity (TAC), inflammation parameters interleukin-6 (IL-6), and C-reactive protein (CRP) were measured. Rowing performance was assessed by lactate level in capillary blood and power output on the rowing ergometer. After supplementation, experimental group had significantly lower CK (p = 0.049) and IL-6 (p = 0.035) before and IL-6 (p = 0.050) after exhausting exercise on ergometer. Relative change of power output at 4 mmol/L concentration of lactate in blood, considering the initial and final test, was significantly higher (p = 0.020) in the supplemented group. It was concluded that GliSODin could be considered a good supplement in preventing some deleterious effects of intensive physical activity, including inflammation and muscle damage, and consequently, to enable a better rowing performance of elite rowers

Suplementacija magnezijuma i status gvožđa kod studentkinja - studija intervencije

Abstract Background: Literature data indicate the benefit of magnesium (Mg) supplementation. The aim of this study was to examine the effect of short-term Mg supplementation on iron status in healthy female participants. Methods: One hundred healthy female students of the University of Belgrade - Faculty of Pharmacy participated the study during eleven intervention days. Students ingested Mg preparations with the same dose of the active substance. The analysis included the measurement of serum iron, unsaturated iron binding capacity (UIBC), total iron binding capacity (TIBC), total Mg (tMg), ionized Mg (iMg), complete blood count, met-, carboxy- and oxy-haemoglobin (metHgb, COHgb, O2Hgb). Transferrin concentrations and percentage of transferrin saturation (SAT) were calculated manually. The association among the analyzed biochemical parameters was examined using polynomial regression. A principal component analysis (PCA) was used for the evaluation of interdependence between the analyzed parameters. Results: A statistically significant trend for change in O2Hgb (%) by tertiles of iMg concentrations was found (P = 0.029). Serum tMg reached significant positive correlation with the SAT at concentration levels greater than 0.9 mmol/L, after 11 days of intervention (R2=0.116). Ionized Mg in a concentration higher than 0.6 mmol/L is positively correlated with SAT and serum Fe (R2=0.214; 0.199, respectively). PCA revealed variability of 64.7% for two axes after 11 days. Conclusions: Mg supplementation leads to an improvement in the certain iron status parameters even in individuals with optimal levels of these indices. However, caution should be exercised when supplementing Mg, and laboratory monitoring of the interaction is required.Uvod: Literaturni podaci ukazuju na benefit suplementacije magnezijumom (Mg). Cilj ove studije bio je da se ispita uticaj kratkotrajne suplementacije Mg na status gvožđa kod zdravih žena. Metode: Sto zdravih studentkinja Univerzitet u Beogradu - Farmaceutskog fakulteta je učestvovalo u istraživanju tokom jedanaest dana intervencije. Studenti su uzimali preparate Mg sa istom dozom aktivne supstance. U serumu je određivano gvožđe, nezasićen kapacitet vezivanja gvožđa (UIBC), ukupan kapacitet vezivanja gvožđa (TIBC), ukupan Mg (tMg), jonizovni Mg (iMg), kompletna krvna slika, met-, karboksiioksihemoglobin (metHgb, COHgb, O2Hgb). Transferin i saturacija transferina (SAT) su izračunati ručno. Povezanost analiziranih biohemijskih parametara je ispitana pomoću polinomalne regresije. Za procenu međuzavisnosti između analiziranih parametara korišćena je analiza glavnih komponenti (PCA). Rezultati: Utvrđen je statistički značajan trend promene O2Hgb (%) po tertilima koncentracija iMg (P = 0,029). Ukupan Mg je dostigao značajnu pozitivnu korelaciju sa SAT pri koncentracijama većim od 0,9 mmol/L, nakon 11 dana intervencije (R2 = 0,116). Jonizovani Mg u koncentraciji većoj od 0,6 mmol/L pozitivno korelira sa SAT i gvožđem (R2 = 0,214; 0,199, redom). PCA analizom je pokazana varijabilnost od 64,7% za dve ose nakon 11 dana. Zaključak: Suplementacija Mg dovodi do poboljšanja određenih parametara statusa gvožđa čak i kod pojedinaca sa optimalnim nivoima ovih parametara. Međutim treba biti oprezan pri suplementaciji Mg, a dodatno je neophodno i laboratorijsko praćenje ovih interakcija

Uncertainty of Measurement in Laboratory Medicine

An adequate assessment of the measurement uncertainty in a laboratory medicine is one of the most important factors for a reliable interpretation of the results. A large number of standards and guidelines indicate the need for a proper assessment of the uncertainty of measurement results in routine laboratory practice. The available documents gene rally recommend participation in the proficiency schemes/external quality control, as well as the internal quality control, in order to primarily verify the quality performance of the method. Although all documents meet the requirements of the International Standard, ISO 15189, the standard itself does not clearly define the method by which the measurement results need to be assessed and there is no harmonization in practice regarding to this. Also, the uncertainty of measurement results is the data relating to the measured result itself, but all factors that influence the interpretation of the measured value, which is ultimately used for diagnosis and monitoring of the patient's treatment, should be taken into account. So in laboratory medicine, an appropriate assessment of the uncertainty of the measurement results should have the ultimate goal of reducing diagnostic uncertainty. However, good professional laboratory practice and understanding analytical aspects of the test for each individual laboratory is necessary to adequately define the uncertainty of measurement results for specific laboratory tests, which helps to implement good clinical practice. Also, setting diagnoses in medicine is a decision with a certain degree of uncertainty, rather than statistically and mathematically calculated conclusion

Dijagnostičke karakteristike serološkog access SARS-CoV-2 IgG imunohemijskog testa

Uvod i cilj. Pandemija bolesti izazvane teškim akutnim respiratornim sindromom korona- virus 2 (SARS-CoV-2) dovela je do ekspanzije seroloških testova za određivanje antitela i an- tigena virusa. Access SARS-CoV-2 IgG je serološki test namenjen je za detekciju IgG antitela virusa, i može se koristiti kao dodatno sredstvo prilikom detekcije patogena, praćenja stanja pacijenata, procene imuniteta nakon infekcije i vakcinacije. Cilj istraživanja je bio da se odre- de dijagnostičke karakteristike i klinički značaj Access SARS-CoV-2 IgG testa. Metode. Istraživanjem je obuhvaćeno 94 ispitanika sa potvrđenom prethodnom SARS- CoV-2 infekcijom (PCR metodom) i 104 kontrolna ispitanika. IgG antitela su određena u se- rumu ispitanika primenom Access Sars-CoV-2 IgG testa, proizvođača Beckman Coulter, na imunohemijskom Access 2 imunoanalizatoru iste firme. Rezultati. Titar IgG antitela je bio značajno veći kod ispitanika koji su preležali infekciju (3,95 (1,36 - 11,44 S/CO) u odnosu na kontrolne ispitanike (0,03 (0,02 – 0,16 S/CO) (p < 0,001). ROC analizom je utvrđena statistički značajna AUC (0,946, p < 0,001), a osetljivost i specifičnost za potvrdu infekcije su redom bile 81% i 95%, za graničnu vrednost 0,955. Pozitiv- na i negativna prediktivna vrednost su bile 94% i 85%, redom. Dodatno je utvrđeno da je titar IgG antitela bio najveći u grupi ispitanika sa teškim oblikom infekcije, u poređenju sa ispita- nicima koji su imali lakši oblik i ispitanicima koji su imali blagu ili asimptomatsku infekciju (p = 0,048). Zaključak. Naši rezultati ukazuju na to da analizirani Access SARS-CoV-2 IgG serološki test ima zadovoljavajuće dijagnostičke karakteristike i može biti klinički značajan za procenu stanja imuniteta nakon preležane infekcije

Rizik razvoja multiple skleroze povezan sa oksidativnim stresom

Background: Multiple sclerosis (MS) is characterized by inflammation, demyelination and axonal degeneration. Oxidative stress (OS) plays a significant role in the pathogenesis of the disease. The aim of the study was to examine the association between OS and smoking on the MS development. Methods: The study included 175 patients with relapsing- remitting multiple sclerosis (RRMS) (76 males, 99 females) and 254 healthy subjects (81 males and 173 females). Oxidative stress biomarkers in serum, Total Antioxidant Status (TAS) and Total Oxidative Status (TOS) were determined spectrophotometrically. Oxidative Stress Index (OSI) was calculated as the ratio of TOS and TAS. Urinary 8-oxo- 7,8-dihydro-2’-deoxyguanosine were determined by HPLC-MS/MS and expressed as 8-oxodG/creatinine. Results: In females with RRMS were higher TOS, OSI and 8-oxodG/creatinine than in females in control group. The group of males with RRMS had lower level of TAS than the males in control group. Higher levels of 8-oxodG/creatinine was obtained in active, passive and former smokers with RRMS than in control group with the same exposition to tobacco smoke. Independent predictors of MS are passive smoking, increased OSI and increased levels of urinary 8-oxodG/creatinine. Conclusions: Our results demonstrate that the OS parameters should be included in the assessment of the risk for MS development. Due to the more sensitivity to oxidative stress, females may be at higher risk of MS development. This data indicates the importance of introducing the antioxidant therapy as a complementary treatment in patients with RRMS.Uvod: Multipla skleroza (MS) se karakteriše upalom, demijelinizacijom i degeneracijom aksona. Oksidativni stres (OS) igra značajnu ulogu u patogenezi bolesti. Cilj studije je bio da se ispita povezanost OS i pušenja na razvoj MS. Metode: Studija je obuhvatila 175 pacijenata sa relapsnoremitentnom multiplom sklerozom (RRMS) (76 muškaraca, 99 žena) i 254 zdrava ispitanika (81 muškarac i 173 žene). Biomarkeri oksidativnog stresa u serumu, ukupni antioksidativni status (TAS) i ukupni oksidativni status (TOS) su određeni spektrofotometrijski. Indeks oksidativnog stresa (OSI) je izračunat kao odnos TOS i TAS. Urinarni 8-okso7,8-dihidro-2'-deoksiguanozin je određen HPLC-MS/MS i izražen kao 8-oksoG/kreatinin. Rezultati: Kod žena sa RRMS bili su viši TOS, OSI i 8okodG/kreatinin nego kod žena u kontrolnoj grupi. Grupa muškaraca sa RRMS imala je niži nivo TAS od muškaraca u kontrolnoj grupi. Veći nivoi 8-okodG/kreatinina su dobijeni kod aktivnih, pasivnih i bivših pušača sa RRMS nego u kontrolnoj grupi sa istom izloženošću duvanskom dimu. Nezavisni prediktori MS su pasivno pušenje, povećan OSI i povećani nivoi 8-okodG/kreatinina u urinu. Zaključak: Naši rezultati pokazuju da parametre OS treba uključiti u procenu rizika za razvoj MS. Zbog veće osetljivosti na oksidativni stres, žene mogu biti izložene većem riziku od razvoja MS. Ovi podaci ukazuju na značaj uvođenja antioksidativne terapije kao komplementarnog lečenja kod pacijenata sa RRMS

Biological aspects of salivary hormones in male half-marathon performance

Physical effort is known to alter the blood levels of many hormones, but there are only a few studies about the biological changes of salivary hormones. The aim of this work was to determine whether salivary testosterone and salivary cortisol levels, measured two weeks before a half-marathon race, relate to running performance in male recreational athletes. A group of eleven male recreational athletes preparing for a half-marathon was included in the study. Saliva for testosterone and cortisol determinations was collected before and immediately after a 15-km training run, two weeks before the half-marathon. Individual official half-marathon times, expressed in hours, were used as a measure of performance. Mean testosterone concentrations were 1.07 +/- 0.33 nmol/l before the run and 0.88 +/- 0.35 nmol/l after the run (p lt 0.05). Mean cortisol concentrations were 12.28 +/- 8.46 nmol/l before the run and 38.08 +/- 19.63 nmol/l after the run (p lt 0.05). The pre-run salivary testosterone levels marginally correlated with the corresponding half-marathon running times (p=0.068, 95% bootstrap CI for slope -0.40 to -0.06). However, post-run salivary testosterone levels significantly correlated with the corresponding half-marathon running times (p=0.011, 95% bootstrap CI for slope -0.41 to -0.16), even considering correlations with the runners' age. Salivary cortisol levels, either pre- or post-run, did not correlate with the corresponding half-marathon running times. The results of this study suggest that post-exercise salivary testosterone levels could have the potential to predict performance in endurance running, at least in recreational athletes

Povezanost koncentracije mokraćne kiseline sa tradicionalnim i ne-tradicionalnim faktorima rizika za kardiovaskularne bolesti kod bolesnika na hemodijalizi – retrospektivna analiza

Literature data indicate that increased uric acid (UA) levels are an important risk factor for cardiovascular disease. The aim of this study was to examine the association of UA with cardiovascular risk factors in patients with hemodialysis using retrospective analysis. In 110 patients, we studied the values of basic renal function parameters, bone metabolism and cardiovascular risk factors in the period from 2010 to 2017. The results indicate a significant increase in urea (P=0.004), creatinine (P=0.028) and inorganic phosphate (P=0.001), as well as significant differences in gender (P=0.013), in risk categories defined on the basis of the UA decision limit (cut off <350 μmol/L). After controlling the effects of most parameters, statistically significant correlation coefficients were obtained for UA and urea (r=0.361; P=0.0013), creatinine (r=0.388; P=0.0005) and inorganic phosphate (r=0.366; P=0.0011). Significant regression coefficients were obtained for UA and male gender (β=-0.227, P=0.004), age (β=-0.298, P˂0.001), urea (β=0.271, P=0.005) and inorganic phosphate (β=0.232, P=0.009). The predictive value of independent parameters in relation to UA was confirmed for male gender (OR=3.595; 95% CI: 1.421-9.094; P=0.007) and inorganic phosphate (OR=14.842; 2.518-87.472, P=0.003). By Cox regression analysis of proportional hazard ratio, we obtained the most significant combined effect of the body mass index, dialysis and diastolic pressure on UA concentration in relation to the duration of hemodialysis (P <0.0001). The results of this long-term study suggest that UA can not be considered an independent cardiovascular risk factor, but that HD patients need to strategically control the level of MK in order to reduce the resulting complications, morbidity and mortality.Literaturni podaci ukazuju da povećana koncentracija mokraćne kiseline (MK) predstavlja značajan faktor rizika za kardiovaskularne bolesti. Cilj ove studije bio je da se retrospektivnom analizom ispita povezanost MK sa faktorima rizika za kardiovaskularne bolesti kod bolesnika na hemodijalizi. Za 110 bolesnika analizirane su vrednosti osnovnih parametara funkcije bubrega, metabolizma kostiju i faktora rizika za kardiovaskularne bolesti u periodu od 2010. do 2017. godine. Rezultati ukazuju na značajno povećanje koncentracije uree (P=0,004), kreatinina (P=0,028) i neorganskog fosfata (P˂0,001), kao i značajne razlike u zavisnosti od pola (P=0,013) u kategorijama rizika definisanim na osnovu granične koncentracije MK (cut off <350 μmol/L). Nakon kontrolisanja efekta većine parametara, statistički značajne vrednosti koeficijenata korelacije dobijene su za MK i ureu (r=0,361; P=0,0013), kreatinin (r=0,388; P=0,0005) i neorganski fosfat (r=0,366; P=0,0011). Značajni regresioni koeficijenti su dobijeni za MK i muški pol (β=-0,227, P=0,004), godine starosti (β=-0,298, P˂0,001), ureu (β=0,271, P=0,005) i neorganski fosfat (β=0,232, P=0,009). Prediktivna vrednost nezavisnih parametara u odnosu na MK je potvrđena za muški pol (OR=3,595; 95% CI: 1,421-9,094; P=0,007) i neorganski fosfat (OR=14,842; 95% CI: 2,518-87,472, P=0,003). Cox-ovom regresijom proporcionalnih nepoželjnih ishoda dobijen je najznačajniji udruženi efekat indeksa telesne mase i adekvatnosti dijalize na koncentraciju MK u odnosu na dužinu trajanja hemodijalize (P<0,0001). Rezultati ove dugoročne studije ukazuju da se MK ne može smatrati nezavisnim faktorom rizika za kardiovaskularne bolesti, ali da je kod bolesnika na HD, potrebno strateški kontrolisati nivo MK u cilju smanjenja posledičnih komplikacija, morbiditeta i mortaliteta