Influence of hemodialysis duration per week on parameters of dialysis adequacy and cardiovascular morbidity/Uticaj nedeljnog trajanja hemodijalize na parametre njene adekvatnostii kardiovaskularni morbiditet.
During the 1960s, chronic hemodialysis (HD) usually included three sessions per week in duration of 8 to 12 hours [1, 2]. Advanced dialysis membranes and techniques lead to reduction in the length of dialysis to 4 hours three times a week since the clinical outcome of such prescription was considered acceptable .
Generally speaking, the adequacy of dialysis implies not only the clearance of uremic toxins and partial control of the condition of patients having terminal renal failure but optimal rehabilitation as well . The following depend directly on the level of adequacy of dialysis: mortality rate, anemia severity, damage to immune competence, renal osteodystrophy, hypertension, cardiomyopathy, nutrition disorders and general quality of life .
In the first randomized clinical study which involved patients treated with HD, "National Cooperative Dialysis Study" (NCDS), no statistical correlation between the duration of HD treatment and treatment outcomes was found . Data from the NCDS gave the ground to introduce the concept of 'dialysis dose' in the form of the Kt/V urea formula, based on urea as a marker of uremia, and for more than two decades, the clearance of low-molecular weight uremic toxins remained the measure of dialysis adequacy . Several guidelines recommend minimum target values of Kt/V formula aimed at delivering an adequate dialysis dose to all patients [7,8]. As a result of the NCDS, dialysis time was not been considered the only key factor in the dialysis prescription. The randomized Hemodialysis study (HEMO) did not find advantages in survival of patients treated with higher dialysis dose (expressed by Kt/V) or using high-flux dialysis membrane . However, the HeMO did not take into account the duration of HD treatment because this parameter is not believed to be the key determinant of treatment outcomes, regardless of its contribution to Kt/V urea value. In the last few years, several studies have shown that increased dialysis length can lead to better correction of anemia parameters, along with the reduction in the frequency of administration and dose of erythropoietin stimulating agents (ESA) preparations. At the same time, the increased dialysis length was associated with better control of hyperphosphatemia and prevention of secondary hyperparathyreoidism, along with reduced frequency of administration of phosphate binders and metabolite of vitamin D [10-13]. Furthermore, there are several reports about the positive effects of increased HD session duration on nutritional parameters of patients [10, 14, 15] and higher survival rate [6, 16-20].
The aim of this one-year observational study was to compare parameters of dialysis adequacy and duration of HD treatment per week.
Material and Methods
This retrospective study included a total of 206 patients (128 man and 78 women/, their mean age being 61.0 [+ or -] 11.7 years) treated with chronic HD for more than 6 months at the Department of Renal Diseases ''Prof. Dr Vasilije Jovanovic'', Zvezdara University Medical Center, Belgrade. The patients were divided into 3 groups according to the total duration of dialysis treatment per week: group I 12 hours, group II - 15 hours, and group III - 17.5 or more hours per week. The patients from group I and II were treated by hospital HD, while the patients from group III were treated by home HD.
Data on patients, which had been taken from their medical records, included age, sex, duration of dialysis (expressed in months), presence of diabetes and hypertension, cardiovascular diseases until the beginning of the study; intake of vitamin D metabolites and phosphate binders, cumulative dose of calcium carbonate and vitamin D metabolites during the previous year, the use of statins and weekly dose of ESA. Body mass index (BMI) was calculated according to the patients' weight and height . Erythropoietin resistance index (ERI) was expressed as the quotient of average weekly ESA dose and body mass of patient divided by average hemoglobin value. Adequacy of dialysis is expressed using Kt/V for urea in accordance with Daugirdas formula .
Samples for laboratory analyses were taken at the beginning of dialysis procedure after a weekend pause once in three months and the following laboratory parameters were analyzed: total proteins, serum albumins, serum bicarbonates, C-reactive protein (CRP), hemoglobin (Hb), ferritin, calcium (Ca), phosphorus (P), total cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides, which were measured by standard laboratory techniques. The average of analysis was calculated for the period of one year except the values of parathormon, which was controlled at least twice a year using chemiluminescent assay (DPC, Diagnostic Product Corporation, USA).
Cardiovascular morbidity score was calculated for each patient and on the basis of previous medical dialysis data file, one point was given for each of the following diagnoses: cardiomyopathy, ischemic heart disease, peripheral vascular disease and stroke.
Statistical calculations were performed using the Statistical Package for the Social Sciences (SPSS) (version 16.0) program. Data were expressed as percentage for discrete factors, and mean values for continuous variables. Statistical analyses included exploratory analysis method (descriptive and analytic statistics). Analysis of variance (ANOVA) was used to compare variables with normal distribution in different groups while Bonferroni test was used for setting the difference between groups (post hoc analyzing). In case where variables did not have normal distribution, Kruskal Walis test was used for comparing groups, and the differences between groups were analysed by Mann-Withney test.
The results are shown in tables and graphics. In all comparisons, a p value <0.05 was considered statistically significant.
Table 1 shows the characteristics of patients in relation to the HD treatment duration per week. The patients from group I were significantly older compared to the patients from group III. HD vintage was significantly different between the groups because the patients from groups III and II were treated longer with HD compared to the patients from group I. Group I included significantly more patients with diabetes while the groups did not differ regarding the presence of hypertension and use of statin therapy. The patients from group I were treated with low-flux membranes while the patients from group III were treated by hemodiafiltration (HDF) more frequently than patients from the two other groups. The patients from group I had the worst acid-base status, which was significantly different from the patients from two other groups. Adequacy of dialysis expressed through Kt/V was not statistically different among groups even though the patients in group II (treated with high-flux membrane) had the highest value of Kt/V.
The parameters of anemic syndrome are presented in Table 2. The patients in group III had the highest values of hemoglobin which was statistically different from the patients in group I and it was near to the statistical significance compared to the patients from group II. The patients in group I had the highest values of ferritin while the lowest value was observed in the patients from group III and this difference reached the statistical significance. A significant difference was observed in ESAs dosing: ESAs agents were given more frequently in the patients from group I and less frequently in the patients from group III. There was no difference between average weekly doses of ASE among the groups including those patients who had it in therapy. There was a difference regarding ERI between groups I and III - the ERI was lower in group III.
The parameters of nutrition and inflammation are shown in Table 3. BMI did not differ significantly among the groups. The highest value of serum albumin was found in the patients from group III and the difference was statistically significant compared to other two groups. There was no difference among the groups regarding CRP value. The patients from group III had significantly higher value of total cholesterol than the patients from group I. There were no differences among the groups in serum levels of low-density lipoprotein (LDL) and HDL cholesterol.
Parameters of mineral metabolism are shown in Table 4. The lowest values of intact parathyroid hormone (iPTH) were observed in the patients from group III while the highest values were found in the patients from group I and the difference was statistically significant. The patients in group I had the lowest value of serum calcium and it was statistically different compared to other two groups. There was no difference among the groups in values of serum phosphorus but the patients from group III used phosphate binder less frequently than the patients from two other groups. At the same time, the patients from group III had the highest cumulative yearly dose of calcium-carbonate which was significantly higher compared to the patients from group I. The patients from group III used the metabolite of vitamin D least frequently, but there was no significant difference among the groups in total dose of vitamin D metabolite per year.
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Scores of cardiovascular morbidity are shown in Graph 1. The patients in groups I and II had higher cardiovascular morbidity score compared to the patients in group III. Compared to the average value of cardiovascular morbidity score there was a statistically significant difference. The patients in group III had the lowest value of cardiovascular morbidity score (0.58) compared to the patients in group II (1.05) and group I (1.26).
During the early years of HD treatment, a session lasted for as long as 20 hours and it was conducted once or twice per week in hospital setting depending on residual kidney function and patient's symptoms . This way of treatment depended on the equipment availability and the quality of dialysis material. Home HD, which was conducted three times per week, was introduced into clinical practice in 1964 and soon became far more efficient (excellent blood pressure control, rare intradialytic collapse, satisfactory nutrition, no neuropathy and almost full rehabilitation) [24, 25]. Simultaneously with the development of dialysis technology, the regime of hospital treatment changed and dialysis sessions became shorter. As the consequence of shorter dialysis session during the 1980s, patients and nephrologists faced numerous problems including frequent intradialytic symptoms, nausea after HD and lower quality of patient's life.
In our study, we classified 206 patients treated with chronic HD into 3 groups depending on overall dialysis duration per week - group I (12 hours), group II (15 hours) and group III (> 17,5 hours). The patients in group III were the youngest but they were treated by HD for the longest period of time--207 months on average. Although the patients in group I were older, had diabetes mellitus more frequently and were dialyzed with low-flux membranes more often, their Kt/V was not significantly different compared to the patients in groups
II and III. These data differ from other studies data, which could be the consequence of unequal groups examined regarding the number and characteristics of patients (residual kidney function). However, the patients with longer duration of dialysis procedure per week had better corrected acidosis, which was observed in other studies as well [10, 23]. Well-corrected anemia is one of crucial indicators of dialysis adequacy. This paper shows favorable effect of longer duration of HD on anemia correction considering the fact that the values of hemoglobin were higher in the groups with longer duration of HD treatment despite significantly less frequent use of ESAs (only 27% of patients in group
III vs. 86% in group I) and lower values of ferritin. The patients with the longest duration of HD had significantly lower resistance to ESAs applied, which could be a possible explanation for their lowest average dose of ESAs. Ok et al. reported similar results. After a year of treatment, the patients who had 8 hours treatment three times per week experienced the increase of hemogloblin value and at the same time, there was a decrease in frequency of ESAs use - from 55% to 24.7% with simultaneous reduction of weekly ESAs dose . The reason of favorable effect of longer dialysis on anemia in the setting of similar Kt/V is probably multifactorial. It is possible that longer HD leads to an increase in the clearance of middle molecules including the inhibitors of erythropoiesis .
Numerous studies, including this one, have indicated the importance of nutritional status for survival of dialysis patients. BMI values were not significantly different among the groups. However, the patients with longer duration of HD procedure were found to have significantly higher values of serum albumin and total cholesterol. These findings suggest better nutritional status of these patients, which is in accordance with data reported by other authors [10, 14, 15, 17, 27, 28]. Since CRP levels did not differ among the groups, better correction of anemia and nutritional status could not be the result of apparent or silent inflammation in our groups of patients. Better correction of acidosis in patients with longer duration of HD treatment may have contributed to better appetite and at the same time to better nutrition parameters. This study did not monitor leptine values but there is a possibility that prolonging the time of dialysis increases the elimination of leptin and consequently increases the appetite and parameters of nutrition.
This study confirmed the relationship between the control of mineral metabolism and duration of dialysis treatment. Lower values of iPTH were recorded in the patients from group III compared to the patients from group I (iPTH: 336 vs. 447, p < 0.05) although the patients in group III used vitamin D metabolites least frequently (19 % of patients). The patients from group I had the lowest calcium value, which is in accordance with iPTH values. There was no significant difference among the groups in phosphorus values even though the patients from group III used phosphate binders least frequently (group I- 84,4% vs. group II-85% vs. group III-54%). There was no difference among the groups in cumulative yearly dose of vitamin D metabolites, but a yearly dose of calcium carbonate was significantly higher in group III compared to other two groups, which could be explained by better appetite of these patients and more liberal diet. Reduced frequency of phosphate binder prescription following the prolonged duration of dialysis procedure as well as an increase in serum calcium were observed by other authors . Lower frequency of secondary hyperparathyroidism was recorded in Tassin group of patients as compared to other parts of France and Europe with less frequent use of phosphate binders .
The patients with the shortest duration of HD procedure had the highest cardiovascular morbidity score on average, which was statistically different in comparison to other two groups. In other words, the patients with longer duration of HD treatment were less likely to have any of cardiovascular diseases. As the result of less frequent morbidity, the lower mortality may be expected in patients treated with longer HD procedure. Numerous studies suggest lower mortality of patients whose HD procedures are longer than traditional four-hour dialysis session [10, 17, 19, 20, 29, 30].
This study has its weak points. Although the aim was to examine the impact of HD duration per week on adequacy parameters, the groups of patients were not homogenous by the type of dialysis membrane and dialysis techniques. Yet, Kt/V values did not differ among groups, which indicates a similar level of small molecules clearance. Elimination of molecules with higher molecular mass requires longer dialysis time, which justifies our criteria for creating groups according to dialysis duration. Namely, experience indicates that the application of high-flux membranes is not the only precondition for more adequate dialysis and centers which enable longer and slower dialysis have the best experience.
Patients treated with hemodialysis in duration longer than 12 hours had better dialysis adequacy expressed by better correction of acidosis and anemia, less frequent use of erythropoietin stimulating agents and lower resistance. At the same time, these patients had better correction of nutrition and mineral metabolism parameters with less frequent use/lower dose of phosphate binders and vitamin D metabolites. All these may be a possible reason for less frequent cardiovascular morbidity recorded in this group of patients.
Abbreviations HD --hemodialysis ESA --erythropoietin stimulating agents BMI --body mass index ERI --erythropoietin resistance index CRP --C--reactive protein HDL --high-density lipoprotein LDL --low-density lipoprotein iPTH --intact parathyroid hormone KtV --index of dialysis adequacy NCDS --National Cooperative Dialysis Study HEMO --hemodialysis study
Rad je primljen 8. VI 2014.
Recenziran 6. VII 2014.
Prihvacen za stampu 13. VII 2014.
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Petar S. DURIC (1), Zivka DURIC (1), Aleksandar JANKOVIC (1), Jelena TOSIC (1), Jovan POPOVIC (1) and Nada DIMKOVIC (1,2)
Clinical Division of Nephrology and Metabolic Disorders with Dialysis "Prof Dr Vasilije Jovanovic"
Clinical Hospital Center "Zvezdara" (1) University of Belgrade, Faculty of Medicine (2)
Corresponding Author: Dr Petar Duric, Klinicko-bolnicki centar Zvezdara 11000 Beograd, Dimitrija Tucovica 161, E-mail: firstname.lastname@example.org
Table 1. Characteristics of patients regarding duration of hemodialysis treatment per week (mean [+ or -] S.D.) Tabela 1. Karakteristike bolesnika u odnosu na ukupnu nedeljnu duzinu lecenja hemodijalizom (srednja vrednost [+ or -] S.D.) Group I/Grupa I (12 h) N = 160 Gender male/Pol muski % 58,8 Age, years/Godine starosti 62,6 [+ or -] 11,7 Dialysis vintage, months/ 76,9 [+ or -] 59 Duzina HD, meseci DM/DM % 17,5 HTN/HTA% 89,4 Statin use/Upotreba statina % 15,0 Low-flux/Niskopropusna % 43,8 High-flux/Visokopropusna % 40,0 HDF/HDF % 16,2 HC[O.sub.3.sup.-]/ 17,6 [+ or -] 2,1 HC[O.sub.3.sup.-] (mmol/L) Kt/V/ Kt/V 1,32 [+ or -] 0,25 Group I/Grupa II (15 h) N = 20 Gender male/Pol muski % 65,0 Age, years/Godine starosti 57,1 [+ or -] 9,8 Dialysis vintage, months/ 152,8 [+ or -] 75 Duzina HD, meseci DM/DM % 5,0 HTN/HTA% 100,0 Statin use/Upotreba statina % 40,0 Low-flux/Niskopropusna % 5,0 High-flux/Visokopropusna % 95,0 HDF/HDF % 0,0 HC[O.sub.3.sup.-]/ 21,4 [+ or -] 2,2 HC[O.sub.3.sup.-] (mmol/L) Kt/V/ Kt/V 1,51 [+ or -] 0,39 Group III/Grupa III ([greater than or equal to] 17.5 h) N = 26 Gender male/Pol muski % 80,0 Age, years/Godine starosti 54,2 [+ or -] 9,7 Dialysis vintage, months/ 207,0 [+ or -] 105 Duzina HD, meseci DM/DM % 3,8 HTN/HTA% 88,5 Statin use/Upotreba statina % 7,7 Low-flux/Niskopropusna % 0,0 High-flux/Visokopropusna % 6,2 HDF/HDF % 53,8 HC[O.sub.3.sup.-]/ 22,7 [+ or -] 2,1 HC[O.sub.3.sup.-] (mmol/L) Kt/V/ Kt/V 1,42 [+ or -] 0,32 p Gender male/Pol muski % 0,096 Age, years/Godine starosti <0,001 * Dialysis vintage, months/ <0,001 ** Duzina HD, meseci DM/DM % 0,026 HTN/HTA% 0,511 Statin use/Upotreba statina % 0,478 Low-flux/Niskopropusna % High-flux/Visokopropusna % <0,001 HDF/HDF % HC[O.sub.3.sup.-]/ <0,001 ([dagger]) HC[O.sub.3.sup.-] (mmol/L) Kt/V/ Kt/V 0,176 DM//diabetes mellitus/djabetes melitus'; HTN/HTA--arterial hypertension/arterijska hipertenzija; HDF--haemodiafiltration/ hemodijafiltracija; Kt/V--index of dialysis adequacy/indeks adekvatnosti dijalize/; HC[O.sub.3.sup.-]-bicarbonate/bikarbonat, * group I vs. group III/grupa I vs. grupa III/, p = 0,002; ** group I vs. group II/grupa I vs. grupa II, p < 0,001, group I vs. group III/ grupa I vs. grupa III/, p < 0,001; ([dagger]) group I vs. group II/ grupa I vs. grupa II/, p < 0,001, group I vs. group III/grupa I vs. grupa III, p < 0,001 Table 2. Parameters of anemia in relation to duration of hemodialysis treatment per week (mean [+ or -] S.D.) Tabela 2. Parametri anemije u odnosu na ukupnu nedeljnu duzinu leccenja hemodijalizom (srednja vrednost [+ or -] S.D.) Group I/Grupa I (12 h) N = 160 Hemoglobin/Hemoglobin, 10,5 [+ or -] 1,0 g/dL Ferritin/Feritin, 366,6 [+ or -] 179 umol/L ESA use/ASE upotreba, % 86,3 ESA, IU/week/ASE, 5636 [+ or -] 4348 (med 4000) IJ/nedeljno ERI/ERI 8,8 Group I/Grupa II (15 h) N = 20 Hemoglobin/Hemoglobin, 11,4 [+ or -] 1,1 g/dL Ferritin/Feritin, 356,0 [+ or -] 438 umol/L ESA use/ASE upotreba, % 65,0 ESA, IU/week/ASE, 6061 [+ or -] 4107 (med 5000) IJ/nedeljno ERI/ERI 7,8 Group III/Grupa III ([greater than or equal to] 17.5 h) N = 26 Hemoglobin/Hemoglobin, 12,2 [+ or -] 1,7 g/dL Ferritin/Feritin, 150,5 [+ or -] 234 umol/L ESA use/ASE upotreba, % 26,9 ESA, IU/week/ASE, 3785 [+ or -] 3314 (med 2000) IJ/nedeljno ERI/ERI 4,86 p Hemoglobin/Hemoglobin, <0,001 * g/dL Ferritin/Feritin, <0,001 ** umol/L ESA use/ASE upotreba, % <0,001 ([dagger]) ESA, IU/week/ASE, 0,321 IJ/nedeljno ERI/ERI 0,029 ([double dagger]) ESA//erythropoietin stimulating agents/ASE--Agensi stimulacije eritropoeze; ERI//erythropoietin resistance index/ERI--in- deks rezistencije na ASE; * group I vs. group II/grupa I vs. grupa II, p < 0,001, group I vs. group III/grupa I vs. grupa III/, p < 0,001, group II vs. group III/grupa II vs. grupa III, p = 0,056; ** group I vs. group II/grupa I vs. grupa II, p = 0,018, group I vs. group III/ grupa I vs. grupa III, p < 0,001, group II vs. group III/grupa II vs. grupa III/, p < 0,001; ([dagger]) Chi/square (Cohrane /Armitage test for trend)/Hi kvadrat test/: p < 0,001; ([double dagger]) group I vs. group III/grupa I vs. grupa III, p = 0,029 Table 3. Parameters of nutrition and inflammation in relation to weekduration of hemodialysis treatment per week (mean [+ or -] S.D.) Tabela 3. Parametri nutricije i inflamacije u odnosu na ukupnu nedeljnu duzinu lecenja hemodijalizom (srednja vrednost [+ or -] S.D.) Group I/Grupa I Group I/Grupa II (12 h) N=160 (15 h) N=20 BMI/BMI, kg/rtf 24,1 [+ or -] 4,3 24,7 [+ or -] 4,4 CRP/CRP, mg/L 9,6 [+ or -] 10,1 6,8 [+ or -] 8,0 Serum albumin/Serumski 38,2 [+ or -] 2,8 40,7 [+ or -] 2,3 albumin, g/L Total cholesterol/ 4,5 [+ or -] 1,0 4,7 [+ or -] 1,4 Ukupni holesterol, mmol/L LDL cholesterol/LDL 2,6 [+ or -] 0,7 2,5 [+ or -] 1,0 holesterol, mmol/L HDL cholesterol/HDL 1,1 [+ or -] 0,3 1,1 [+ or -] 0,3 holesterol, mmol/L Triglycerides/ 1,8 [+ or -] 0,8 2,1 [+ or -] 1,3 Trigliceridi, mmol/L Group III/Grupa III p ([greater than or equal to] 17.5 h) N=26 BMI/BMI, kg/rtf 25,7 [+ or -] 4,9 0,223 CRP/CRP, mg/L 8,0 [+ or -] 6,2 0,181 Serum albumin/Serumski 42,3 [+ or -] 2,5 <0,001* albumin, g/L Total cholesterol/ 5,1 [+ or -] 1,0 0,017** Ukupni holesterol, mmol/L LDL cholesterol/LDL 2,9 [+ or -] 0,9 0,163 holesterol, mmol/L HDL cholesterol/HDL 1,1 [+ or -] 0,4 0,599 holesterol, mmol/L Triglycerides/ 2,4 [+ or -] 1,6 0,110 Trigliceridi, mmol/L * group I vs. group II-grupa I vs. grupa II, p < 0,001, group I vs. group III-grupa I vs. grupa III, p < 0,001; ** group I vs. group III-grupa I vs. grupa III, p = 0,013, LDL--lipoprotein male gustine, HDL--lipoprotein veike gustine Table 4. Parameters of mineral metabolism in relation to duration of hemodialysis treatment per week (mean [+ or -] S.D.) Tabela 4. Parametri metabolizma minerala u odnosu na ukupnu nedeljnu duzinu lecenja hemodijalizom (sred-nja vrednost [+ or -] S.D.) Group I/Grupa I (12 h) N = 160 iPTH/iPTH, pg/ml 446 [+ or -] 500 (med 280) Calcium/Kalcijum, mmol/L 2,28 [+ or -] 0,17 Phosphorus/Fos/or, mmol/L 1,60 [+ or -] 0,41 Phosphate binders/Vezivaci 84,4 fosfata, % Yearly cumulative CaC[O.sub.3] 1139,3 [+ or -] 545 dose Kumulativna godisnja doza CaC[O.sub.3] Vit D metabolites/Vit D 50,6 metaboliti, % Yearly cumulative dose of vit 367,0 [+ or -] 284 D metabolites Kumulativna godisnja doza metabolita vit D Group I/Grupa II (15 h) N = 20 iPTH/iPTH, pg/ml 363 [+ or -] 382 (med 245) Calcium/Kalcijum, mmol/L 2,42 [+ or -] 0,19 Phosphorus/Fos/or, mmol/L 1,45 [+ or -] 0,30 Phosphate binders/Vezivaci 85,0 fosfata, % Yearly cumulative CaC[O.sub.3] 1371,2 [+ or -] 678 dose Kumulativna godisnja doza CaC[O.sub.3] Vit D metabolites/Vit D 65,0 metaboliti, % Yearly cumulative dose of vit 480,4 [+ or -] 311 D metabolites Kumulativna godisnja doza metabolita vit D Group III/Grupa III ([greater than or equal to] 17.5 h) N=26 iPTH/iPTH, pg/ml 336 [+ or -] 481 (med 87) Calcium/Kalcijum, mmol/L 2,38 [+ or -] 0,18 Phosphorus/Fos/or, mmol/L 1,62 [+ or -] 0,49 Phosphate binders/Vezivaci 53,8 fosfata, % Yearly cumulative CaC[O.sub.3] 1546,4 [+ or -] 836 dose Kumulativna godisnja doza CaC[O.sub.3] Vit D metabolites/Vit D 19,2 metaboliti, % Yearly cumulative dose of vit 462,0 [+ or -] 404 D metabolites Kumulativna godisnja doza metabolita vit D p iPTH/iPTH, pg/ml 0,041 * Calcium/Kalcijum, mmol/L <0,001 ** Phosphorus/Fos/or, mmol/L 0,137 Phosphate binders/Vezivaci <0,001 ([dagger]) fosfata, % Yearly cumulative CaC[O.sub.3] 0,047 dose Kumulativna godisnja ([double dagger]) doza CaC[O.sub.3] Vit D metabolites/Vit D 0,020 ([section] metaboliti, % Yearly cumulative dose of vit 0,374 D metabolites Kumulativna godisnja doza metabolita vit D * group I vs. group III/grupa I vs. grupa III, p=0,011; **group I vs. group II/grupa I vs. grupa II, p = 0,003, group I vs. group III/ grupa I vs. grupa III, p = 0,012; ([dagger]) Chi/square (Cohrane/ Armitage test for trend)/Hi kvadrat test, p < 0,001; ([double dagger]) group I vs. group III/grupa I vs. grupa III, p = 0,036; ([section]) Chi/square (Cohrane/Armitage test for trend)/Hi kvadrat test, p = 0,02; CaC[O.sub.3]//calcium/carbonate/kalcijum-karbonat; iPTH//intact parathyroid hromone/intaktni paratiroidni hormon
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|Title Annotation:||Original study/Originalni naucni rad|
|Author:||Duric, Petar S.; Duric, Zivka; Jankovic, Aleksandar; Tosic, Jelena; Popovic, Jovan; Dimkovic, Nada|
|Date:||Nov 1, 2014|
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