The Key Role of Hepcidin-25 in Anemia in Multiple Myeloma Patients with Renal Impairment.

Background and objectives: Anemia is common in multiple myeloma (MM) and is caused by a complex pathomechanism, including impaired iron homeostasis. Our aim is to evaluate the biomarkers of iron turnover: serum soluble transferrin receptor (sTfR) and hepcidin-25 in patients at various stages of MM in relation with markers of anemia, iron status, inflammation, renal impairment and burden of the disease and as predictors of mortality. Materials and methods: Seventy-three MM patients (six with smoldering and 67 with symptomatic disease) were recruited and observed for up to 27 months. Control group included 21 healthy individuals. Serum sTfR and hepcidin were measured with immunoenzymatic assays. Results: MM patients with and without anemia had higher sTFR compared to controls, while only anemic patients had higher hepcidin-25. Both hepcidin-25 and sTfR were higher in anemic than non-anemic patients. Higher hepcidin-25 (but not sTfR) was associated with increasing MM advancement (from smoldering to International Staging System stage III disease) and with poor response to MM treatment, which was accompanied by lower blood hemoglobin and increased anisocytosis. Neither serum hepcidin-25 nor sTfR were correlated with markers of renal impairment. Hepcidin-25 predicted blood hemoglobin in MM patients independently of other predictors, including markers of renal impairment, inflammation and MM burden. Moreover, both blood hemoglobin and serum hepcidin-25 were independently associated with patients' 2-year survival. Conclusions: Our results suggest that hepcidin-25 is involved in anemia in MM and its concentrations are not affected by kidney impairment. Moreover, serum hepcidin-25 may be an early predictor of survival in this disease, independent of hemoglobin concentration. It should be further evaluated whether including hepcidin improves the early diagnosis of anemia in MM.

Transforming growth factor beta 1 as a risk factor for cardiovascular diseases in end-stage renal disease patients treated with peritoneal dialysis.

BACKGROUND: The aim of the study was to evaluate the relationship between the atherosclerotic changes in the carotid arteries expressed as common carotid artery intima-media thickness (CCA-IMT) with Body Mass Index (BMI), serum lipid levels, and selected inflammatory state markers in peritoneal dialysis (PD) patients. METHODS: The study included 67 patients (31 female and 36 male) on PD therapy for 30.4 +/- 24.2 months. Average age of the patients was 52.9 +/- 12.5 years (ranged from 19 to 75 years). The measurement of the CCA-IMT was performed by ultrasonography evaluation. BMI was calculated using the Quetelet formula. Serum lipid levels and hsCRP were performed using routine methods. IL-6, TGF-beta1, TNF-alpha, and hepatic growth factor (HGF) were tested with ELISA assays. RESULTS: In univariate analysis, the strongest factor influencing CCA-IMT was age (R = 0.54; p < 0.0001). CCA-IMT correlated positively with BMI (R = 0.39; p = 0.003). Of the inflammatory markers studied, significant correlations with CCA-IMT were shown for IL-6 (R = 0.35; p = 0.009), and TGF-beta (R = 0.31; p = 0.02). In multiple regression, only In TGF-beta1 (partial correlation coefficient = 0.29; p = 0.04) appeared to predict CCA-IMT independently of age and BMI, while IL-6 was not significant in the analysis. The regression model including age, BMI and TGF-beta1 as independent variables, explained 43% of CCA-IMT variance. Again, age was the strongest predictor of CCA-IMT (partial correlation coefficient = 0.50). CONCLUSIONS: Increased concentration of TGF-beta1 may be a biomarker of the development of cardiovascular diseases in patients treated with PD, as well as a prognostic factor in the evaluation of atherosclerosis progression in this group of patients.

[Cardiovascular calcification and five-years mortality in patients on maintenance hemodialysis]. / Zwapnienia w ukladzie sercowo-naczyniowym a 5-letnia smiertelnosc pacjentów leczonych powtarzanymi hemodializami.

The very high cardiovascular mortality and morbidity in hemodialyzed patients (HD) is strongly associated with cardiovascular calcification. The aim of the study was to find the predictors of mortality in HD patients during 5-years observation period. The study group was composed of 64 patients (35 F, 29 M) aged 25-75 years (mean 48.9) hemodialyzed three times a week for 12-275 months (mean 77.8). The levels of hemoglobin, total protein, albumin, Ca, P, Ca x P, iPTH, cholesterol, triglycerides, fibrinogen, insulin, homocysteine, leptin, procalcitonin, CRP, IL-6, TGF-beta, PDGF were assessed and all patients underwent Calcium Score (CS) of coronary arteries (CACS) calculation using MSCT and B-mode ultrasound of carotid arteries for intima-media thickness (CCA-IMT), as well as echocardiographic assessment with LVMI calculation and heart valves evaluation at the start of observation. The self-elaborated Cumulative Calcification Index (CCl) was calculated as a sum of CACS Index according to Rumberger et al. (CS<10-0, 10400 - 3 points); number of calcified plaques in carotid arteries (0-0, 1 - 1, 2 - 2, 3 and more - 3 points) and the number of calcified heart valves. At the start of the study the median value of CCl was 4 and interquartile range 4. Only 2 (3%) patients were free of any type of cardiovascular calcification (CCl =0), 15 (23%) patients had minimal calcification (CCl 1 to 2 points), 33 (52%) average (2 - 6 points) and 14 (22%) patients had severe calcification (CCl>6). 21 (32,8%) patients died during observation period. Patients who died were older (56.9 vs. 45.3 yrs.) and had higher CS at the start (1275 vs. 356), higher CCA-IMT (0.948 vs. 0.687 mm) and CCl (6.15 vs. 3.63) values. Those patients had also higher CRP (0.645 vs. 0.245 mg/dl) and IL-6 (10.16 vs. 4.15 pg/ml) levels (p<0.05). LVMI and mean: hemoglobin, total protein, albumin, Ca, P, Ca x P, iPTH, cholesterol, triglycerides, fibrinogen, insulin, homocysteine, leptin, procalcitonin, TGF-beta as well as PDGF levels did not differ between the groups. In logistic regression model (p<0.00002), among tested parameters only CCl was an independent and statistically significant factor of mortality with OR=1.82 per every point of CCl (p<0.0003). Cardiovascular calcification expressed as CCl confirmed to be a strong predictor of mortality in HD patients.

[Pure red cell aplasia (PRCA) induced by anti-EPO antibodies: epidemiology, diagnosis and treatment]. / Wybiórcza aplazja ukladu czerwonokrwinkowego (PRCA), indukowana przeciwcialami anty-EPO: epidemiologia, diagnostyka i leczenie.

Pure red-cell aplasia (PRCA) is a serious, life threatening rare condition of multifactorial causes manifested as severe anemia with absence of erythroid precursors in the bone marrow. PRCA may be a consequence of antibody production against applied recombinant human erythropoietin (EPO). The first description of PRCA in the course of EPO therapy was performed in a patient receiving subcutaneously Eprex and in the next years after therapy with other erythropoiesis stimulating agents like erythropoietin beta, omega or darbepoetin. In the paper we describe epidemiology and diagnostic criteria of PRCA. The current treatment possibilities of this complication were described with special attention dedicated to different immunosuppressive agents and effectiveness of kidney transplantation with subsequent immunosuppression.

[Evaluation of polyneuropathy severity in chronic renal failure patients on continuous ambulatory peritoneal dialysis or on maintenance hemodialysis]. / Ocena stopnia nasilenia polineuropatii u chorych ze schylkowa niewydolnoscia nerek leczonych ciagla ambulatoryjna dializa otrzewnowa lub powtarzanymi hemodializami.

UNLABELLED: The aim of the study was to assess severity of injury of the peripheral nervous system of chronic renal failure patients on continuous ambulatory peritoneal dialysis (CAPD) or on maintenance hemodialysis (HD) diagnosed based on the electrophysiological testing as well as to establish the effect of adequate dialysis dose on peripheral nerve functioning. The study was performed in 53 patients (21 males, 32 females) on CAPD for mean 16.9 +/- 14.4 months and 68 patients (46 males, 22 females) on HD for mean 47.5 +/- 46.5 months. Both groups were age matched (48.9 +/- 12.4 vs. 50.6 +/- 11.9 yrs; p= NS). Patients with co-existing diseases that could lead to disturbances in nerve conduction were excluded from the study group. METHODS: Electrophysiological testing was performed using Medelec Shaphire 2ME equipment. Nerve conductivity testing was performed in motor and sensory fibres of right ulnar nerve, motor fibres of right fibular nerve and left tibial nerve as well as in sensory fibres of right calf nerve. In the sensory nerves there were assessed: amplitude of the evoked sensory response, latency of the response and conduction velocity. In the motor nerves there were analyzed amplitude of the compound muscle action potential, latency of the evoked response, F-wave minimal latency and conduction velocity. Polyneuropathy was diagnosed if abnormal results obtained in electrophysiological examination were found in at least two out of four tested nerves. To assess dialysis adequacy in the CAPD group weekly Kt/V (wKt/ V) and weekly creatinine clearance (WCrCI) were used and in the HD patients the following indices were measured: Kt/V, PRU, TAC and TAD. RESULTS: Polyneuropathy diagnosed based on the above described criteria, was found in 59 (86.8%) HD patients and in 41 (77.4%) CAPD patients (p= NS). The results of motor conductivity testing showed significantly longer distal latency in HD patients in comparison to the CAPD patients in fibular nerve (4.9 +/- 0.9 vs. 4.5 +/- 0.8 ms; p< 0.05) and F-wave latency in ulnar nerve (29.3 +/- 3.1 vs. 27.3 +/- 2.5 ms; p< 0.05), in fibular nerve (52.4 +/- 6.4 vs. 48.5 +/- 7.94 ms; p< 0.05), in tibial nerve (54.8 +/- 7.8 vs. 50.6 +/- 7.12 ms; p< 0.05) and also significantly lower conduction velocity in ulnar nerve (51.9 +/- 5.9 vs. 55.6 +/- 6.99 m/s; p< 0.05), in fibular nerve (41.2 +/- 5.9 vs. 44.5 +/- 5.5 m/s; p< 0.05), in tibial nerve (40.1 +/- 5.81 vs. 42.7 +/- 4.6 m/s; p< 0.05). Mean value of sensory response amplitude evoked in ulnar nerve was significantly higher in the CAPD treated patients than in HD patients (21.2 +/- 14.8 vs. 15.1 +/- 11.4 microV; p< 0.05) and distal latency in calf nerve was significantly shorter (2.1 +/- 1.0 vs. 2.4 +/- 0.6 ms; p< 0.05). Analysing the effect of dialysis on peripheral nerve functioning in the group of CAPD patients a statistically significant relationship between the severity of peripheral nerve injury and WCrCl was demonstrated. Mean value of WCrCl in patients without features of neuropathy was significantly higher (83.3 +/- 28.98 l/week/ 1.73m2) in comparison with those with diagnosed polyneuropathy (59.9 +/- 15.9 l/week/1.73m2) (p< 0.01). Analyzing effect of WCrCl on conduction velocity in the tested nerves there was demonstrated that in patients with WCrCl value at least 60 l/week/1.73m2, mean velocity values were higher, and the statistically significant difference was found for sensory (p< 0.05) and motor (p< 0.01) fibers of ulnar nerve. Mean value of residual renal clearance in the CAPD treated patients without features of sensory and motor nerve injury was significantly higher (2.9 +/- 1.8 ml/min) when compared to the patients with diagnosed polyneuropathy (1.4 +/- 1.3 ml/min) (p= 0.006). In the hemodialyzed group no statistically significant relationship was found between conduction velocity in the tested nerves and indices of dialysis efficiency (Kt/V, PRU) as well as degree of exposure to uremic toxemia described by TAC and TAD. CONCLUSIONS: Polyneuropathy is a common complication in patients with chronic renal failure independently of a kind of the therapy. Well preserved residual renal function in CAPD patients plays an important role in improving effectiveness of the dialytic treatment, in consequence influencing preservation of proper peripheral nerve function.

The influence of sodium profiling on blood volume and intradialytic hypotension in patients on maintenance hemodialysis.

An accurate evaluation of water content in the body of hemodialyzed patients seems to be an important problem in chronic dialysotherapy. Acute intradialytic hypotension observed in 20-33% of hemodialysis patients is a very common complication of this kind of renal replacement therapy. The study was performed in 40 uremic patients, treated with hemodialysis at the Nephrology Clinic of the University Hospital in Cracow. In every patient, 3 model dialysis sessions were carried out. Total fluid removal was the same during every hemodialysis. The first model hemodialysis (HD1) was performed with constant dialysate sodium concentration (140 mmol/L), the second (HD2) with linear and the third (HD3) with expotential decrease of dialysate sodium concentration (from 144 to 136 mmol/L). Every hemodialysis was also monitored continuously with Crit-Line 2 R system (In-Line Diagnostics, Riverdale, UT). Before and after the first model hemodialysis (HD1), ultrasound examination of abdominal cavity was performed. The measurement of inferior vena cava diameter (mm), circumference (mm), area (mm2), at hepatic veins orifice-level, on expiration was performed. The fluid removal during the first model hemodialysis resulted in significant reduction of the vena cava inferior diameter, circumference and area, measured with ultrasound on expiration. The statistically significant lower fall of blood volume after the first and second hour of the second model hemodialysis session (HD2) was observed when compared to the first hemodialysis (HD1) - p<0.05 was observed. The statistically significant lower frequency of hypotension during the second hemo-dialysis session (HD2) as compared to HD1 (chi2=5.25 p<0.05). Differences among HD1 and HD3 and HD2 and HD3 did not reach statistical significance. The monitoring of hemodialysis with the Crit-Line instrument permits for optimalization of dry weight of dialyzed patients and allows reaching higher ultrafiltration rates during dialysis without hypotensive episodes. The changes in the blood volume, approximately 5% per one hour of dialysis session are an optimal value for these patients.

[Influence of microinflammation and oxidative stress on atherosclerosis progression and calcifications in cardiovascular system of hemodialyzed patients during two years follow-up]. / Wplyw mikrozapalenia i stresu oksydacyjnego na progresje miazdzycy i zwapnien w ukladzie krazenia u chorych hemodializowanych w okresie dwuletniej obserwacji.

Atherosclerosis and calcifications in the cardio-vascular system are the most frequent causes of increased morbidity and mortality in patients with end-stage renal disease treated with hemodialyses. The aim of this study was to estimate the atherosclerosis progression and presence of calcifications in the circulatory system in patients treated with hemodialyses using, non-invasive imaging diagnostic techniques and to search for the relationships between these changes and microinflammation and oxidative stress during two years. The study was performed in 73 patients (36 female and 37 male), aged 25 to 75 years (mean -49.5), treated with hemodialyses, 3 times/week for 12 to 275 months (mean -73.8). In each patient before starting hemodialysis levels of: ox-LDL, Lp (a), procalcitonin, IL-1beta, IL-6, CRP, TGFbeta, TNFalpha, PDGF, AOPP and MPO were determined. Presence of artery calcifications was detected by Multi-Row Spiral Computed Tomography (MSCT) and expressed as coronary artery calcification score (CACS). Ultrasonography was used to evaluate CCA-IMT. During the study CACS increased significantly after 12 and 24 months (p < 0.00001) as compare with baseline. After 12 months, CACS increase significantly correlated with procalcitonin level (r = 0.30 p = 0.01) and after 24 months with CRP (r = 0.46; p = 0.0002) and IL-6 (r = 0.36; p = 0.005). Independent factor of coronary artery calcification progression after 24 months of observation was only CRP (beta = 0.569). CCA-IMT increased during the study and this increase was statistically significant (p < 0.00001). CCA-IMT increase correlated with CACS growth after 12 (r = 0.36; p = 0.003) and 24 months (r = 0.39; p = 0.002). After 12 months significant relationship was noted with procalcitonin (r = 0.29; p = 0.022). After 24 months CCA-IMT correlated with AOPP (r = -0.30; p = 0.017). The independent factor of CCA-IMT progression after 24 months of observation was only CACS (delta CACS beta = 0.49). From the performed study, we can conclude that exacerbation of atherosclerosis and calcification in the circulatory system of patients treated with maintenance hemodialyses depends on microinflammation and oxidative stress. Reasonable tools for diagnostic algorithm estimation of atherosclerosis advancement in this group of patients are non-invasive, visual diagnostic techniques such as MSCT and ultrasonography.

The evaluation of the effectiveness of multiple dose intradermal hepatitis B re-vaccination in hemodialyzed patients not responding to standard method of immunization.

Hepatitis B is a serious epidemiological problem in uremic patients treated with renal replacement therapy. A high proportion of hemodialyzed patients do not respond to the standard method of intramuscular (i.m.) hepatitis B vaccination. Low-dose intradermal (i.d.) inoculations and supplementary i.m. injections have been reported to improve the responsiveness in formerly non responding uremic patients. We applied a inoculation schedule of 10 microg Engerix B i.d. in 49 pts and i.m. (control group) in 13 pts once a week during 12 consecutive weeks in order to compare the effectiveness of the various ways of immunization in maintenance dialyzed patients not responding to standard vaccination. Serum anti-HBs antibody level, as well as biochemical and immunological parameters were examined. Already one month after initiation of the cycle, 57.1% of patients in the i.d. group responded by achieving the minimum protective anti-HBs antibody level (>10 IU/I.); while 14.3% reached full adequate anti-HBs antibody level (>100 IU/I.). After the full therapy period, anti-HBs antibody level >100 IU/I. was achieved in 42.9% of the patients, while a total of 81.7% of patients reached the anti-HBs antibody level >10 IU/I. In 18.4% of patients no response was observed. Surprisingly similar results were achieved in the i.m. group. Twelve months after termination of the inoculation cycle we noted decrease of anti-HBs antibody level; the values >100 IU/ I. was observed only in 18.4% of the study group, while 87.8% reached a titre >10 IU/I. We found a relationship between the effectiveness of immunization and RBC count, total serum protein and albumin levels and GGTP activity. Mitogen stimulation indexes in both groups were 4-5 times lower in comparison to reference values in the general population. In the study group that did not respond to vaccination, mitogen stimulation indexes were 2 times lower as compared to the group characterized as having a good response. In conclusion, the route of injection seems to be less important than the frequency and number of doses of the vaccine. Anemia and malnutrition may be responsible for the worse response to vaccination against hepatitis B virus.

[Present opinions concerning the administration of low molecular weight heparins in hemodialysis patients]. / Wspólczesne poglady na temat zastosowania heparyn drobnoczasteczkowych u chorych hemodializowanych.

Intradialytic anticoagulation is an essential element of the dialysis procedure. Patients with end stage renal failure, due to the repetitive nature of dialysis sessions are exposed in a chronic manner to side effects of drugs applied during the procedure. Popular administration of unfractionated heparin, concerning its unstable pharmacokinetic profile may cause thrombocytopenia, enhance hyperkalemia, osteoporosis, and lipid disturbances. In the past years, a clinical alternative to unfractionated heparin have become, as well as in dialysis therapy, low molecular weight heparins. Beside the beneficial pharmacokinetic aspect, these heparins are characterized by decreasing number and less intensified side effects associated with their administration.

[Evaluation of atherosclerosis progression in patients treated repeatedly with hemodialysis]. / Ocena stopnia rozwoju miazdzycy u chorych leczonych powtarzanymi hemodializami.

The main cause of increased morbidity and mortality in patients on maintenance hemodialysis are cardiovascular complications due to accelerated atherosclerosis. Lipid profile disturbances, increased levels of homocysteine (HC), fibrinogen, iPTH as and Ca-P abnormalities seem to be the important factors in atherosclerosis progression. The aim of the study was to evaluate the advancement of atherosclerosis in patients on maintenance hemodialysis and to assess levels of pro-atherosclerotic factors. The study included 50 patients (30 M, 20 F) aged 21-75 years (mean 48.6 y) hemodialyzed three times a week for 12 to 282 months (mean 114.5 m). The homocysteine, fibrinogen, iPTH, calcium, phosphate and indices of lipid metabolism such as total cholesterol, HDL, LDL, triglicerides, Lp (a) and Apo B were measured before hemodialysis. To evaluate the advancement of atherosclerosis, all patients underwent MSCT using Somatom plus 4 apparatus with calcium scoring (CS) calculation and B-mode ultrasound for IMT using Acuson 128 XP 10 apparatus. The above applied methods helped to evaluate changes in central and peripheral arteries. In CS testing, coronary artery calcifications were present in 36 patients (72%). The CS ranged from 0 to 4345, with the mean CS being 584 (SD = 1012). The CS correlated significantly with age (r = 0.39; p < 0.005), P (r = 0.33; p < 0.05), CaxP product (r = 0.39; p < 0.05), iPTH (r = 0.43; p < 0.001) and with IMT (r = 0.56; p < 0.0001). The IMT ranged from 0.5 to 1.5, with mean of 0.89 (SD = 0.28). The IMT correlated significantly with age (r = 0.54; p < 0.0001), time on dialysis (r = 0.40; p < 0.01), fibrinogen (r = 0.43; p < 0.02), LDL (r = 0.30; p < 0.05), P (r = 0.29; p < 0.05), and CaxP product (r = 0.3; p < 0.05). Based on our study, we conclude that age, time on dialysis, increased levels of homocysteine, LDL cholesterol, fibrinogen, P, and iPTH as well as Ca-P disturbances are strong predictors of atherosclerosis in HD patients.

Osteoprotegerin as a marker of cardiovascular risk in patients on peritoneal dialysis.

INTRODUCTION: Arterial thickening contributes to elevated cardiovascular risk in patients on maintenance renal replacement therapy. The common carotid artery intima-media thickness (CCA-IMT) is an early atherosclerotic marker and may be used to assess the stratification of atherosclerotic advancement and resultant arterial calcification. OBJECTIVES: The aim of the study was to evaluate the associations between atherosclerotic changes in the common carotid arteries expressed as the CCA-IMT and the body mass index (BMI), serum lipid levels, C­reactive protein (CRP), and selected bone metabolism parameters including phosphorus, calcium, intact parathormone (iPTH), alkaline phosphatase, osteopontin, osteoprotegerin, osteocalcin, fetuin A, and fibroblast growth factor­23 (FGF­23) in patients treated with peritoneal dialysis. PATIENTS AND METHODS: The study included 67 patients with chronic kidney disease (36 men and 31 women) aged 53 ±13 years (range, 19-75 years) treated with peritoneal dialysis for 30 ±24 months. The CCA­IMT was assessed by ultrasonography using Acuson 128/10 XP. The BMI was calculated using the Quetelet formula. Serum lipid levels, phosphorus, calcium, iPTH, alkaline phosphatase, and CRP were measured using standard laboratory methods, while fetuin A, osteocalcin, osteoprotegerin, osteopontin, and FGF­23 using commercial enzyme­linked immunosorbent assay kits. RESULTS: Positive correlations were observed between CCA-IMT and age (r = 0.54, P <0.0001), BMI (r = 0.39, P = 0.003), and osteoprotegerin (r = 0.38, P = 0.004). In a multiple regression analysis, age (r = 0.41, P = 0.01), osteocalcin (r = 0.34, P = 0.04), and log­transformed osteoprotegerin values (r = 0.38, P = 0.02) remained independently associated with the CCA-IMT. The highest CCA­IMT values (0.85 ±0.21) were observed in patients with osteoprotegerin concentrations in the upper tertile. Osteoprotegerin concentrations strongly and positively correlated with the duration of dialysis treatment (r = 0.55, P <0.0001). CONCLUSIONS: The CCA­IMT has been shown to be a reliable noninvasive measure of subclinical atherosclerosis and, therefore, of associated increased vascular risk. Elevated serum osteoprotegerin levels may be useful as a prognostic marker of cardiovascular risk in dialyzed patients.

Antibodies against N-homocysteinylated proteins and their determinants in patients on long-term hemodialysis.

INTRODUCTION: The factors that determine the level of antibodies against N-homocysteinylated (N-Hcy) proteins have not been established so far. The clinical significance of these antibodies and their effect on cardiovascular (CV) risk in patients with end-stage renal disease (ESRD) are still unknown. OBJECTIVES: The aim of this study was to identify the factors that determine the level of antibodies against N-Hcyalbumin and N-Hcy hemoglobin in patients on long-term hemodialysis (HD). PATIENTS AND METHODS: The study involved 247 subjects on long-term HD (110 women, 137 men; age range, 23-89 years) and 60 controls matched for age, sex, and CV risk factors (serum creatinine level <140 micromol/l). Serum antibodies against N-Hcyalbumin and N-Hcyhemoglobin were determined using an in-house enzyme-linked immunosorbent assay. Total homocysteine (tHcy), folate, and 8-isoprostaglandin F2alpha (8-iso-PGF(2alpha)) were also measured. RESULTS: Patients on HD had higher serum levels of anti-N-Hcy-albumin (absorbancy at 490 nm: 0.56 [0.49-0.623] vs. 0.259 [0.198-0.338], P <0.0001) and anti-N-Hcy-hemoglobin antibodies (0.659 [0.597-0.723] vs. 0.379 [0.289-0.442], P <0.0001) as compared with controls. The level of both antibodies correlated with tHcy (r = 0.56, P <0.0001 and r = 0.67, P <0.0001, respectively), 8-iso-PGF(2alpha) (r = 0.48, P <0.0001 and r = 0.63, P <0.0001, respectively), and folate (r = -0.18, P = 0.0054 and r = -0.38, P <0.0001, respectively), but not with HD duration, the initial cause of ESRD, and CV comorbidity. CONCLUSIONS: In HD patients, tHcy is an independent predictor of antibodies against N-Hcy proteins. Folate and 8-iso-PGF(2alpha) concentrations were not independently associated with the levels of both antibodies.

Factors involved in vascular calcification and atherosclerosis in maintenance haemodialysis patients.

BACKGROUND: Atherosclerosis and vascular calcifications are common causes of morbidity and mortality in maintenance haemodialysis patients. In addition to the well-known traditional risk factors, uraemia-specific factors appear to enhance dramatically the progression of the pathological processes involved. The aim of the present study was to evaluate the degree of atherosclerosis and vascular calcifications in chronic haemodialysis patients using non-invasive imaging methods, and to identify potentially involved factors. METHODS: The study included 73 patients (36 females, 37 males), aged 25-75 years, who were on haemodialysis treatment for 12-275 months (mean dialysis vintage 73.8 months). We assessed the following circulating parameters: calcium (Ca), phosphorus, 'intact' parathyroid hormone (iPTH), 25OH vitamin D, lipids, oxidized LDL (ox-LDL), Lp(a), homocysteine, leptin, IL-1-beta, IL-6, CRP, TGF-beta, TNF-alpha, (PDGF), advanced oxidation protein products (AOPP) and myeloperoxidase activity (MPO). Coronary artery calcification score (CACS) was assessed using multi-row spiral CT (MSCT). Intima-media thickness index of the common carotid artery (CCA-IMT) and presence of cervical artery atherosclerotic plaques were evaluated by ultrasonography. RESULTS: Coronary artery calcifications were observed in 79.5% of the patients, with CACS ranging from 0 to 4987. In univariate analysis, a positive correlation was observed between CACS and age, BMI, iPTH, CRP, IL-6 and CCA-IMT, whereas an inverse correlation existed with 25OH vitamin D, TGF-beta and PDGF. CCA-IMT ranged from 0.4 to 1.1 mm. It was positively correlated, in univariate analysis, with age, CACS, CRP and Il-6, and negatively with 25OH vitamin D, TGF-beta and PDGF. Only CACS remained as independent predictive factor of CCA-IMT in multivariate analysis. Atherosclerotic plaques were found in the carotid arteries of 53 patients (72%). The number of plaques was positively correlated with age, CACS, phosphorus, MPO, CRP and IL-6, and inversely with 25OH vitamin D in univariate analysis. In multivariate regression analysis, only age and CACS remained as independent variables. CONCLUSION: In addition to classic risk factors, the degree of atherosclerosis and vascular calcification in our dialysis patient population were associated with several factors that are frequently abnormal in advanced chronic renal failure, but except age, all of them were interdependent. Notably, as in the general population, CACS was an independent predictor of the degree of atherosclerosis in haemodialysis patients.

Changes in common carotid artery intima-media thickness over 1 year in patients on peritoneal dialysis.

BACKGROUND: Accelerated atherosclerosis and vascular calcifications increase cardiovascular morbidity and mortality in patients on dialysis. Common carotid artery (CCA) intima-media thickness (IMT) is considered useful for imaging atherosclerosis non-invasively. Since chronic inflammation may accelerate atherosclerosis in end-stage renal disease patients, the aim of this 1 year study was to assess changes in CCA-IMT in stable peritoneal dialysis (PD) patients, and to search for possible associations between these changes and selected cytokines, acute phase proteins and other risk factors of atherosclerosis. METHODS: Of the original cohort of 61 stable patients on PD-28 female, 33 male; mean age 50.4+/-13.6 years; dialyse for a median of 17.5 months at inclusion (range 1-96 months)-47 patients survived the 1 year period on PD. CCA-IMT was assessed at baseline and after 12 months. Pro-inflammatory cytokines (IL-6, TNFalpha), acute phase proteins (CRP, fibrinogen), calcium-phosphate balance and lipid profile were assessed at baseline and after 6 and 12 months. Anthropometric parameters (age, weight, BMI, waist-to-hip ratio) were measured at baseline. RESULTS: The mean CCA-IMT at baseline, 0.66+/- 0.19 mm, increased by a mean of 0.098+/-0.17 to 0.76+/-0.21 mm (P<0.001) in 1 year. In 14 patients (29.8%) at least one plaque was found in the CCAs examined. At the end of follow-up: 28 patients (59.6%) had increases in CCA-IMT (from 0.63+/-0.2 to 0.83+/- 0.21 mm; P = 0.03), and 19 (40.4%) remained stable or even showed slight, but non-significant, decreases of CCA-IMT (from 0.72+/-0.17 to 0.66+/-0.17 mm, P = NS). The 'progressors' had significantly higher initial BMI (P<0.05), and mean concentrations of calcium (P = 0.005), IL-6 (P = 0.05), TNFalpha (P = 0.05), CRP (P = 0.005) and lower HDL-cholesterol than 'non-progressors'. In univariate analysis, DeltaCCA-IMT correlated positively with age (R = 0.32, P = 0.03), BMI (R = 0.29, P = 0.05) and mean concentrations of CRP (R = 0.37, P = 0.01), TNFalpha (0.52, P = 0.0002), but inversely with HDL-cholesterol (R = -0.37, P = 0.01). In multiple regression analysis, however, only age appeared to be independently associated with increase in CCA-IMT (beta = 0.37, P<0.01; R(2) for the model 0.14). CONCLUSIONS: Our results suggest a possible role of non-specific inflammation in the progression of atherosclerosis in patients treated with PD, in addition to age.

Acute renal failure in patients with rhabdomyolysis.

BACKGROUND: Rhabdomyolysis is a relatively rare, not always diagnosed cause of acute renal failure (ARF). This fact motivated us to present the results of ARF treatment in the course of this polyetiological clinical syndrome. MATERIAL/METHODS: The analysis was performed on 84 patients (6 F, 78 M) ranging in age from 18 to 82 years (mean 46.5), in whom rhabdomyolysis was diagnosed based on clinical manifestation and laboratory test results (CPK, GTP, GOT, LDH). RESULTS: The most frequent cause of rhabdomyolysis was alcoholic intoxication (41 patients), often accompanied by hypothermia (15 patients) or trauma (30 patients). Isolated trauma was found in 30 patients, epileptic seizure in 5, and physical exercise in 1 case. In 17 patients, besides alcohol consumption, trauma or epileptic seizure, the use of tranquilizers, anticonvulsants, or narcotic drugs was additionally noted. 78 patients developed ARF requiring dialysis therapy; 49 patients recovered, 5 required maintenance dialysis, and 30 died. CONCLUSIONS: During the initial phase of ARF in the course of rhabdomyolysis dynamic increases in serum urea and creatinine were observed, as well as a tendency to hyperkalemia. The treatment results and mortality rate in our study group were primarily influenced by the patients' general condition at admission, as well as the extent of organ damage caused by the primary etiological factor. Favorable treatment results were obtained especially in those patients who were hospitalized in a nephrological center, while the worst outcomes were noted in those patients dialyzed in intensive care units, most with multiple trauma.