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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2011  |  Volume : 22  |  Issue : 6  |  Page : 1133-1141
Association of adequate dialysis parameters with left ventricular hypertrophy in hemodialysis patients


1 Department of Nephrology, Dialysis and Transplantation, Military Hospital Mohammed V, Rabat, Morocco
2 Department of Critical Care Unit, Idrissi Hospital, Kenitra, Morocco
3 Department of Cardiology, Military Hospital Mohammed V, Rabat, Morocco

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Date of Web Publication8-Nov-2011
 

How to cite this article:
Kadiri ME, Nechba RB, Zajjari YR, Kabbaj D, Bouzerda M, Oualim Z. Association of adequate dialysis parameters with left ventricular hypertrophy in hemodialysis patients. Saudi J Kidney Dis Transpl 2011;22:1133-41

How to cite this URL:
Kadiri ME, Nechba RB, Zajjari YR, Kabbaj D, Bouzerda M, Oualim Z. Association of adequate dialysis parameters with left ventricular hypertrophy in hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2019 Nov 13];22:1133-41. Available from: http://www.sjkdt.org/text.asp?2011/22/6/1133/87209

   Introduction Top


Cardiovascular complications are the leading cause of mortality and morbidity in hemodialysis (HD) patients accounting for 43% of all cause mortality, and the frequency of sudden cardiac death is almost 50% higher after long dialysis intervals. [1],[2],[3],[4],[5]

Left ventricular hypertrophy (LVH), a strong independent predictor of cardiovascular mortality, is potentially preventable and reversible. [6],[7],[8] Hypertension is the main cause for the development of LVH, [9],[10],[11],[12] but other potentially reversible factors such as anemia, volume overload, secondary hyperparathyroidism, uremia, dose of dialysis, and malnutrition may have an important role in its pathogenesis. [10]

Hypertension plays an important role in the development of cardiovascular disorders and mortality, [13],[14] and prevalence of hypertension in HD patients is approximately 75%. [15],[16],[17],[18] Reduced survival rate in HD patients when the predialysis mean arterial pressure was greater than 99 mmHg, [11] and blood pressure (BP) of less than 140/90 mmHg in them. [19],[20] However, some reports showed no linear relationship between elevated BP and poor prognosis in HD patients. [21]

Typically, anemia in chronic renal failure (CRF) patients on dialysis is accompanied by a hyper-dynamic state with an increase in cardiac output and LV volume overload, which are directly related with the development of LVH. [20],[21],[22],[23],[24],[25],[26],[27],[28]

Hyperparathyroidism (HPTH) is a common complication in CRF patients, and, it leads to cardiac fibrosis [29],[30],[31] throughout the cardiac receptors for PTH in cardiac fibroblasts and myocardiocytes. [32] The relationship between HPTH and cardiac dysfunction is controversial, [33],[34],[35] but HPTH produces an increase in cytosolic free calcium that may result in chronotropic and inotropic effects on myocardial cells. [36],[37] Together, with other factors, these changes may contribute to cardiac hyperthrophy. [38] In addition, calcium phosphate deposition on the coronary microcirculation and atherosclerosis induced possibly by HPTH can predispose the patient to ischemic cardiomyopathy. [39]

There is some direct evidence that the dialysis dose is inversely related with both gross and cardiovascular mortality in HD patients and directly related with improvement in cardiac structure abnormalities and dysfunction. [40],[41],[42],43]

Hypoalbuminemia, a marker of malnutrition, [44],[45],[46] has been independently related to both relative risk of death and LV dilation in dialysis patients. [10] It also predisposes patients to the development of both de novo congestive heart failure and de novo ischemic heart disease. [44] In addition, malnutrition is associated with inflammation, which is assessed with serum C-reactive protein (SCRP) and atherosclerotic cardiovascular disease (MIA syndrome). [46]

The present cross-sectional study aims to assess the prevalence of LVH in our HD population and evaluate the relationship between various parameters and analyze the influence of co-morbid factors on them.


   Patients and Methods Top


This study was performed within a HD unit of a medical center in Agadir, Morocco. Patients who had been on HD for at least three months were eligible for inclusion in the study. Of a total of 56 patients, 20 females (35%) and 36 (65%) males, median age of 51 years, ranging between 19 to 77 years, consented to participate, while 3 either refused. The median length of time on HD treatment was 8 ± 3 years.

[Table 1] shows the causes of chronic renal disease and the main characteristics of the study patients, including previous cardiovascular events, demographic characteristics, and biochemical and prevalence of LVH in the HD patients. At the time of the study, all the patients were dialyzed three times a week, using blood flow rates of 250-300 mL/min and dialysate flow rates of 500 mL/min. All the patients were dialyzed with a standard bicarbonate-containing dialysate bath (Na: 139 mmol/ L; K: 2 mmol/L; HCO3: 39 mmol/L; Ca: 1.75 mmol/L; Glucose: 5.55 mmol/L) and 1.1-1.7 m 2 dialyzers (100% polysulfone). The dialyzers were not reused. The patients were treated with oral sodium bicarbonate, calcium carbonate and/or sevelamer, as required to prevent acidosis and hyperphosphatemia. Eighteen patients were receiving anti-hypertensive drugs such as angiotensin-converting enzyme inhibitors, beta-blockers and calcium-blockers at the time of recruitment. Patients with residual renal function were treated with high doses of furosemide (250 to 500 mg/day) to increase urinary output and renal sodium excretion. Recombinant human erythropoietin was given to 30 patients. The Kt/V was assessed by ionic dialysance with the online monitoring clearance (OCM) of the HD machine, which provides a safe and accurate tool for continuous online monitoring of the total urea clearance. [47],[48]
Table 1: Baseline characteristics of the hemodialysis patients.

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The study protocol was approved by the local Ethics Committee and informed consent was obtained from each patient. The biochemical investigations were performed in all subjects after an overnight fast on a mid-week dialysis-free day.

The Kidney Disease Outcomes Quality Initiative recommends a pre-dialysis blood pressure goal of below 140/90 mmHg. [49],[50] Therefore, patients with pre-dialytic systolic blood pressures (SBP) >140 mmHg or diastolic blood pressures (DBP) >90 mmHg, or both, were considered to be hypertensive, as were those receiving any antihypertensive medication. Blood pressure measurements were made manually using a sphygmomanometer after a five min rest.

All echocardiographic examinations were performed by the same experienced sonographer, the day after HD, between May and June of 2008. The Vingmed System Five Norway echocardiographic system equipped with 2.5 MHz transducers was used. M-Mode and 2D measurements were done in accordance with methods recommended by the American Society of Echocardiography. Criteria for LVH were LVMI >134 g/m 2 for males and >110 g/m 2 for females. Cardiac mass was calculated using the formula derived by Reichek and Devereux. [51]

Blood sampling was performed during a midweek non-dialysis day after 20 to 30 minutes of quiet resting in semi-recumbent position. Serum albumin was determined by the reference method using immunonephelometry. [52],[53] SCRP was also measured by using an immunonephelometric method. The upper limit for normal values was set by the laboratory at 8 mg/L and levels below this limit were reported as normal but not quantified. Serum lipids, calcium, phosphate, and hemoglobin measurements were performed using standard methods in the routine clinical laboratory. [54],[55] The plasma concentrations of calcium, phosphorus, and intact PTH (iPTH) were classified into categories below, at or above the targets recommended in the Kidney Disease Outcomes Quality Initiative guideline, [56] which recommends serum concentrations of corrected calcium between 8.4 and 9.5 mg/dL (2.10 and 2.37 mmol/L), serum phosphorus concentrations between 3.5 and 5.5 mg/dL (1.13 and 1.78 mmol/L), and iPTH concentrations between 150 to 300 pg/ mL (15.8 to 31.6 pmol/L). Measurement of iPTH was performed with the electro-chemiluminescence immunoassay "ECLIA", which is intended for use on Elecsys immunoassay analyzer. [57]


   Statistical Analyses Top


Data are presented as mean values ± SD, and P<0.05 was considered as statistically significant. Comparisons for continuous variables were made by the Student's t-test or with the Mann-Whitney test for variables, which were not normally distributed. Spearman's rank correlation was used to determine the correlation between two variables. In the stepwise linear regression analysis for predicting LVMI, the following parameters were included in the model as independent variables: systolic blood pressure, diastolic blood pressure, hemoglobin levels, and iPTH serum levels.


   Results Top


The mean systolic BP was 122 ± 18 and diastolic BP 70 ± 12 mmHg. Eighteen patients (32%) were treated by blood pressure lowering drugs. Of the 17 diabetic patients, nine (16%) had cardiovascular diseases (CVD) and nine (16%) patients were active smokers. The prevalence of the LVH in our HD patients was 46%.

The mean of LVMI was 126 ± 33.4 g/m 2 [Table 1]. The patients were divided into two groups based on the LVMI [Table 2]. Twenty six (46%) patients had LVH according to the value of the LVMI, which was more in group I (>134 g/m 2 for males and >110 g/m 2 for females) than in group II [Table 2].
Table 2: Comparisons between hemodialysis patients with and without LVH.

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There was no significant difference between the two groups in age, length of time on HD, smoking, residual renal function, diabetic patients, blood pressure, level of serum albumin, hemoglobin, SCRP, calcium, phosphorus, iPTH, total cholesterol, LDL cholesterol, triglycerides, and erythropoietin use. The proportion of female patients was significantly higher in group I (10 of 26 patients, 38%) than in group II (10 of 30 patients, 33%) (P = 0.047). The mean serum levels of HDL was significantly lower in group I (0.39 ± 0.1 g/L) than in group II (0.42 ± 0.1 g/L) (P = 0.02). The mean Kt/V urea was significantly lower in group I (1.08 ± 0.1) than in group II (1.10 ± 0.2) (P = 0.001) [Table 2].

The results of bivariate correlation for LVMI are shown in [Table 2]. The LVMI correlated negatively with iPTH (r= -0.312, P = 0.017). However, hemoglobin (r=0.150, P = 0.271), calcium (r=-0.053, P = 0.705), phosphorus (r=-0.135, P = 0.341), systolic BP (r=-0.021, P = 0.876) or diastolic BP (r=0.007, P = 0.958), and serum albumin (r =-0.119, P = 0.384) did not correlate with LVMI [Table 3].
Table 3: Correlations of LVMI with other studied parameters (Spearman's rho test).

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In a stepwise linear regression analysis, iPTH was found to be an independent predictor of LVMI, with this model [Figure 1]. However, hemoglobin, systolic and diastolic BP were not found to be independent variables in this model (model r=0.330, P <0.001) [Table 4].
Figure 1: Levels serum of iPTH was an independent predictor of LVMI, in stepwise linear regression analysis.

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Table 4: The results of stepwise linear regression analysis for predicting LVMI

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   Discussion Top


LVH is common in patients on chronic HD, and it has been implicated as an independent risk factor for cardiovascular mortality in this population. In our study, 46% of the patients had LVH, which is lower than in most studies previously reported. [10],[58],[59]

Previous studies suggest gender dimorphism in the prevalence of LVH; however, this issue has never been approached in dialysis patients. Cheng et al showed that the prevalence of LVH determined by echocardiography was significantly higher in female dialysis patients than in males. [28] When our HD patients were divided into LVH or non-LVH groups, a significant difference in sex distribution was observed between them [Table 2].

Hypertension is a main cause for development of LVH in HD patients. [9],[10],[12],[14] In a prospective study in HD patients, Degoulet et al demonstrated an association between systolic and diastolic BP and cardiovascular mortality. [60] In our study, both systolic and diastolic BP were similar in the subgroups [Table 2], which may reflect well controlled BP. [50] The prevalence and treatment of hypertension in HD patients exceeds 85% in the United States. [61] In the present study, 32% of HD patients were receiving anti-hypertensive drugs and the difference was not statistically significant antihypertensive therapy between the subgroups [Table 2].

In the revised 2006 National Kidney Foundation Dialysis Outcomes Quality Initiative anemia guidelines, [62] a minimum Hb target of 11 g/dL was recommended without specification of a maximum target level. Such a target can be achieved in only a minority of patients, discourages flexibility in managing individual patients, and may promote cycling of Hb results greater than and less than the target". [62] In 2007, another update of the anemia guidelines narrowed the recommended target Hb range to 11 to 12 g/dL, but continued to emphasize the issue of Hb variability. [63] In our study, the mean of the hemoglobin was 11 ± 1.40 g/dL, and there was no significant association between anemia and LVH in the subgroups [Table 2]. These data suggest that our patients with anemia were correctly treated with erythropoietin.

Low HDL cholesterol and low Kt/V were associated with cardiovascular events. [64] Ikee showed a significant correlation between low HDL cholesterol and LVH [29] in the patients undergoing peritoneal dialysis. In the present study, the difference between low levels of serum HDL cholesterol and low Kt/V and LVH was statistically significant in the subgroups (respectively: P = 0.02, P = 0.001).

HPTH may play a role in the genesis of LVH. [10] In our study, LVMI negatively correlated with iPTH in the bivariate analysis (P = 0.017), and linear regression analysis revealed that iPTH was an independent predictor of LVH (P = 0.016). London et al [65] presented the same results concerning the correlation between PTH levels and LVM index, describing a significant negative association. The reason for this result is not clear, but may be related in part to some methodological aspects. Measurement of iPTH was performed with the electrochemiluminescence immunoassay in our study, and the same technique was used by London et al. [65] This technique detects the terminal C-fragment and measures predominantly inactive PTH metabolites whose excretion is reduced in renal failure. These metabolites have biological effects on target tissues including the heart and differ from those of intact PTH. [66] On the other hand, these conflicting results may be due to the use of single measures of calcium, phosphate, and PTH. Importantly, there have been few data on prospective changes in bone mineral metabolic parameters; therefore, the use of a single value is yet to be validated in patients with different dialysis durations. [67]

Higher Kt/V is positively associated with a lower rate of cardiovascular events. In a recent analysis of 22,000 patients enrolled in the Dialysis Outcomes and Practice Patterns Study (DOPPS), higher Kt/V was independently associated with lower mortality. [68] In our study, Kt/V was significantly lower in the LVH group than in the non-LVH group, [Table 2], suggesting that dose of dialysis should be optimized in an effort to reduce mortality and morbidity in this high risk population.

In summary, the present study demonstrated that the effects of the well known risk factors such as blood pressure, anemia, and hypoalbuminia were not significantly associated with LVH. Our HD patients had well controlled blood pressure and managed anemia besides the correct nutritional status according to the levels of serum albumin, which may explain in part the lower prevalence of LVH in our study (46%). Among the lipids profiles HDL cholesterol was significantly associated with LVH. Finally, the negatively correlation between level serum of iPTH and LVMI remains to be evaluated.

 
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Correspondence Address:
Moncef El M'barki Kadiri
Department of Nephrology, Dialysis and Transplantation, Military Hospital Mohammed V, Rabat
Morocco
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