Rafał Ficek

Calcification of coronary arteries and abdominal aorta in relation to traditional and novel risk factors of atherosclerosis in hemodialysis patients

BackgroundProcess of accelerated atherosclerosis specific for uremia increases cardiovascular risk in patients with chronic kidney disease (CKD) and may be influenced by the different structure of arteries. The study assesses the influence of traditional and novel risk factors on calcification of coronary arteries (CAC) and abdominal aorta (AAC) in hemodialysis patients (HD).MethodsCAC and AAC were assessed by CT in 104 prevalent adult HD and 14 apparently healthy subjects with normal kidney function (control group). Mineral metabolism parameters, plasma levels of FGF-23, MGP, osteoprotegerin, osteopontin, fetuin-A, CRP, IL-6 and TNF-α were measured.ResultsCAC and AAC (calcification score ≥ 1) were found in 76 (73.1%) and 83 (79.8%) HD respectively, more frequent than in the control group. In 7 HD with AAC no CAC were detected. The frequency and severity of calcifications increased with age. Both CAC and AAC were more frequently detected in diabetics (OR = 17.37 and 13.00, respectively). CAC score was significantly greater in males. CAC and AAC scores were correlated significantly with pack-years of smoking and plasma osteoprotegrin levels. However the independent contribution of plasma osteoprotegerin levels was not confirmed in multiple regression analysis. Age (OR = 1.13) and hemodialysis vintage (OR = 1.14) were the independent risk factor favoring the occurrence of CAC; while age (OR = 1.20) was the only predictor of AAC occurrence in HD.Conclusions1. AAC precedes the occurrence of CAC in HD patients. 2. The exposition to uremic milieu and systemic chronic microinflammation has more deteriorative effect on the CAC than the AAC.

Plasma Concentrations of Tumor Necrosis Factor Alpha May Predict the Outcome of Patients with Acute Renal Failure

Background/Aims: Elevated plasma tumor necrosis factor-α (TNFα) concentration is frequently found in patients with chronic renal failure on hemodialysis (HD) and correlates with their mortality. The present study aimed to analyze the relationship between plasma TNFα concentrations and survival of patients with nonseptic acute renal failure (ARF). Methods: Twenty-seven patients with ARF and 27 HD patients were examined. In ARF the patients’ plasma TNFα concentrations were assessed 3 times: before the first HD session (phase I), 5 days later at the anuric/oliguric phase (phase II), and at the polyuric phase at discharge of the patients from the hospital (phase III). In 17 ARF patients kidney function recovered and 10 patients died in phase I. Results: In ARF patients plasma TNFα concentration was markedly higher [70 pg/ml (37–275)] than reference values (<5 pg/ml) but significantly lower than in HD patients [216 pg/ml (18–350)]. Moreover, also plasma TNFα levels at the polyuric phase remained elevated. An initial plasma TNFα concentration in ARF patients lower than 70 pg/ml predicted the beneficial outcome with a sensitivity of 64.7% and a specificity of 70.0%. Conclusions: (1) Plasma TNFα concentration may predict the outcome in patients with ARF. (2) Plasma TNFα concentration remained elevated at the polyuric phase in ARF despite a marked improvement of excretory kidney function.

The Effect of Sodium Restricted Diet on Plasma Visfatin Levels in Hypertensive Patients with Visceral Obesity

Aim/Background: Experimental and clinical studies revealed contradictory data concerning the influence of renin-angiotensin-aldosterone (RAA) system activation on visfatin release. The aim of the present study was the assessment of the effect of dietary sodium restriction with RAA system activation on visfatin level in hypertensive and normotensive patients with visceral obesity. Methods: The study included 24 hypertensive patients with visceral obesity (12 women) and 22 normotensive subjects with visceral obesity (11 women) constituting the control group. Plasma renin activity, plasma insulin, aldosterone and visfatin levels were determined twice, on normal-salt diet after 6-8 h in recumbent position and the second time after 3 days of dietary sodium restriction and upright position for 2 h. Dietary compliance was controlled by 24 h natriuresis measurement. Results: Hypertensive patients had significantly higher plasma visfatin level than the control group [11.0 (8.5-13.5) vs. 6.8 (6.0-7.6) ng/ml, p=0.003]. Dietary sodium restriction and upright position caused significant increase in PRA and plasma aldosterone level in both groups. While, plasma visfatin level remained unaffected. In the combined group plasma visfatin levels correlated with BMI (r=0.398), waist circumference (r=0.391), glucose (r=0.328), insulin (r=0.663), HOMA-IR (r=0.698), triglycerides (r=0.500) and CRP (r=0.546) but not with percentage of fat mass, percentage of trunk fat, and blood pressure values. Conclusions: 1) Increased plasma visfatin concentration may play a significant role in the pathogenesis of hypertension in patients with visceral obesity. 2) RAA system activation by dietary sodium restriction and upright position has no effect on plasma visfatin levels in subjects with visceral obesity.

Daily intake and serum concentration of menaquinone-4 (MK-4) in haemodialysis patients with chronic kidney disease.

OBJECTIVES Decreased concentration of menaquinone-4 (MK-4) seems to be an important risk factor of vascular calcification in haemodialysis (HD) patients. Optimal dietary intake, as well as serum MK-4 reference range, in HD has not been determined, yet. The aim of the present study was to assess daily vitamin K1 and MK-4 intakes and their relation to serum MK-4 concentration in HD patients. DESIGN AND METHODS Daily vitamin K1 and MK-4, micro- and macronutrients and energy intakes were assessed using 3-day food diary completed by patients and serum MK-4 concentration was measured by HPLC [limit of quantification (LOQ): 0.055 ng/mL] in 85 HD patients (51 males) and 22 apparently healthy subjects. RESULTS Daily MK-4 intake was significantly lower (by 29%) among HD, while K1 consumption was similar in both groups. Daily MK-4 intake was associated with fat and protein consumption in HD (r=0.43, p<0.001 and r=0.33, p=0.004, respectively). In HD serum MK-4 concentration was more frequently below LOQ (in 41% HD and 5% controls, p<0.001) and in those HD with quantifiable values was lower than in the controls (by 42%). The correlations between MK-4 concentrations and both MK-4 and K1 daily intakes were weaker in HD (r=0.38 and r=0.30 respectively) than in the control group (r=0.47 and r=0.45, respectively). In multiple regression analysis the variability of serum MK-4 concentrations in HD patients was explained by its daily intake. CONCLUSIONS Decreased serum MK-4 concentration in HD patients is caused by lower dietary MK-4 intake, mainly due to diminished meat consumption, and in addition, probably reduced K1 conversion.

N-Terminal Prohormone of Brain Natriuretic Peptide but not C-Terminal Pre-Pro Vasopressin (Copeptin) Level is Associated with the Response to Antihypertensive Therapy in Haemodialysis Patients

Background/Aims: Volume overload, frequently clinically asymptomatic is considered as a causative factor limiting the effectiveness of antihypertensive therapy in haemodialysis (HD) patients. Therefore, the aim of this study was to assess plasma levels of N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) and a C-terminal portion of the precursor of vasopressin (CT-proAVP, copeptin), surrogate markers of volume overload in HD patients in relation to the number of antihypertensive drugs used in the hypertension treatment. Methods: One hundred and fifty adult HD patients (92 males) were enrolled into this study. Clinical data concerning blood pressure (BP) measurements prior haemodialysis session and pharmacotherapy were collected from all patients. In addition to routine laboratory parameters, plasma levels of NT-proBNP and CT-proAVP were measured, and daily sodium and water consumption were estimated with a portion-size food frequency questionnaire. Results: Among 145 (96.7%) hypertensive HD patients, 131 were receiving antihypertensive medication. Despite antihypertensive therapy, 31.0% had inadequate BP control. Plasma concentration of NT-proBNP was associated with systolic (R=0.19; p=0.02) but not diastolic BP values and with the number of received antihypertensive drugs (R=0.21; p=0.01). The highest NT-proBNP values were observed in patients receiving 3 or more antihypertensive drugs. In contrast, no significant correlation was found between plasma CT-proAVP concentrations and BP values as well as and the number of antihypertensive drugs. Receiver operator curve analysis showed that NT-proBNP values over 13,184 pg/mL predicted the use of at least 3 antihypertensive drugs in maximal doses in the therapy of hypertension, similar analyses performed for CT-proAVP showed much less specificity. Conclusions: 1. Increased levels of NT-proBNP seems to be a better biomarker of multidrug antihypertensive therapy requirement than CT-proAVP. 2. Whether estimation of NT-proBNP in these patients will be also better biomarker than copeptin in the prediction of cardiovascular complications related to hypertension needs further investigations.