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ORIGINAL ARTICLE
Year : 2019  |  Volume : 32  |  Issue : 3  |  Page : 922-927

Influence of secondary hyperparathyroidism on left ventricular function in maintenance hemodialysis patients


1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Internal Medicine, National Institute of Urology and Nephrology, Cairo, Egypt

Date of Submission23-Oct-2017
Date of Acceptance05-Nov-2017
Date of Web Publication17-Oct-2019

Correspondence Address:
Ahmad T. H. Abouseriwa
Nasr City, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_744_17

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  Abstract 


Objective
The aim of this work was to assess the influence of secondary hyperparathyroidism (SHPT) on left ventricular function in end-stage kidney disease in Egyptian patients under maintenance hemodialysis.
Background
SHPT is a common disorder in patients with chronic kidney disease. Parathyroid hormone (PTH) is a major uremic toxin and may be responsible for long-term consequences that include renal osteodystrophy, severe vascular calcifications, alterations in cardiovascular structure and function, immune dysfunction, and anemia. PTH has been identified as an important cardiotoxin in end-stage kidney disease and may cause deleterious effects in myocardium metabolism and function.
Materials and methods
A total of 86 end-stage kidney disease patients on maintenance hemodialysis were recruited from the Hemodialysis Unit in the National Institute of Urology and Nephrology in Cairo, Egypt. Patients were divided into two groups: group I – comprised 39 patients with controlled SHPT (PTH: 150–300 pg/ml) and group II comprised 47 patients with uncontrolled SHPT (PTH: ≥350 pg/ml).
Results
There was no statistically significant difference between the two groups as regards the systolic function and diastolic dysfunction or with respect to the development of left ventricular hypertrophy. On the other hand, there was a statistically significant correlation between uncontrolled SHPT and the development of valvular calcifications of mitral and aortic valves.
Conclusion
Uncontrolled SHPT in hemodialysis patients is not associated with the development of left ventricular hypertrophy in our studied patients.

Keywords: hemodialysis, left ventricular hypertrophy, secondary hyperparathyroidism


How to cite this article:
Ahmed HA, Yassein YS, Elzorkany KM, Abouseriwa AT. Influence of secondary hyperparathyroidism on left ventricular function in maintenance hemodialysis patients. Menoufia Med J 2019;32:922-7

How to cite this URL:
Ahmed HA, Yassein YS, Elzorkany KM, Abouseriwa AT. Influence of secondary hyperparathyroidism on left ventricular function in maintenance hemodialysis patients. Menoufia Med J [serial online] 2019 [cited 2019 Nov 16];32:922-7. Available from: http://www.mmj.eg.net/text.asp?2019/32/3/922/268842




  Introduction Top


Secondary hyperparathyroidism (SHPT) is a common disorder in patients with chronic kidney disease (CKD) and is characterized by excessive serum parathyroid hormone (PTH) levels, parathyroid hyperplasia, and an imbalance in calcium and phosphorus metabolism. SHPT develops early in the course of CKD and becomes more prominent as the kidney function declines. It is a major uremic toxin and may be responsible for long-term consequences that include renal osteodystrophy, severe vascular calcifications, alterations in cardiovascular structure and function, immune dysfunction, and anemia. These adverse effects may contribute to an increased risk of cardiovascular morbidity and mortality among end-stage renal failure patients [1].

Cardiovascular diseases such as coronary artery disease, congestive heart failure, arrhythmias, and sudden cardiac death represent the main causes of morbidity and mortality in patients with CKD. According to a well-established classification of cardiorenal syndrome, cardiovascular involvement in CKD is also defined as cardiorenal syndrome type 4 (chronic renocardiac) [2].

The pathogenesis of CKD–mineral and bone disorder has always been ascribed to a decline in 1,25-dihydroxy vitamin D levels leading to increases in serum PTH and subsequent alterations in calcium and phosphorus metabolism. Vitamin D deficiency, together with SHPT and hyperphosphatemia, was reported as a main factor contributing to high cardiovascular risks in CKD patients [3].

PTH acts on cardiomyocytes by binding to the PTH/PTHrP receptor, which induces a rise in the intracellular levels of calcium. Increased calcium levels activate protein kinase C and mediate hypertrophic as well as metabolic effects [4].

The correction of abnormalities in divalent ion metabolism in CKD and end-stage renal disease (ESRD) (including vitamin D deficiency, hyperphosphatemia, and hyperparathyroidism) might have beneficial effects on left ventricular hypertrophy (LVH), but there are no clinical trials at our disposal. Patients receiving vitamin D therapy show a lower frequency of cardiovascular events and improved survival in observational studies. Furthermore, several trials have detected that higher PTH levels (intact PTH levels >500 pg/ml) are associated with failure of LVH regression [5].

The management of SHPT should be started at the beginning of CKD stage III (estimated glomerular filtration rate: 60 ml/min). It is a complex process that requires good communication between the nephrologist, the dietitian, and the patient. It is important to recognize the treatment goals, which vary according to the stages of CKD. Serum levels of calcium, phosphorus, and intact PTH should be measured in all patients with CKD and estimated glomerular filtration rate of 60 ml/min. The National Kidney Foundation K/DOQI guidelines provide frequency of measurements and goals for serum phosphorus and PTH according to the CKD stage [6].

Finally, the treatment of LVH is mainly based on anemia and blood pressure control, together with the management of SHPT and optimization of renal replacement therapy maximization [2].

The aim of this work was to assess the influence of SHPT on left ventricular function in end-stage kidney disease in Egyptian patients under maintenance hemodialysis.


  Materials and Methods Top


Study population

This study was carried out on 86 end-stage kidney disease patients at the Hemodialysis Unit in the National Institute of Urology and Nephrology, Cairo, Egypt, between April 2014 and February 2016. Each patient was informed on the context of the study in detail. If he/she agrees with the conditions, an informed consent was obtained. The study was approved by the Ethics Committee and the Local Authority of the Institute.

The included patients (n = 86) were stable and on regular hemodialysis for at least 6 months, 3 sessions per week and 4 h/session. Their dry body weight was already judged by clinical methods. Patients were on Fresenius medical care 4008B (Melbourne, Australia) machine that uses a dialyzer with 1.3 m 2 surface area and bicarbonate-based dialysate.

Inclusion criteria

The study included adult patients aged more than or equal to 18 years of both sexes with ESRD on maintenance hemodialysis for more than or equal to 6 months with no history of cardiovascular diseases before starting hemodialysis.

Exclusion criteria

Patients who had ischemic heart disease or valvular heart diseases before dialysis, patients with congenital heart disease, patients with PTH levels of less than 150 pg/ml, patients with decompensated liver disease with ascites, patients with chronic obstructive airway diseases, and patients not compliant to their hemodialysis sessions were excluded.

All patients were subjected to full and detailed history including demographic data, recent symptoms, treatment history, family history, and past medical and surgical history. Complete physical examination with assessment of BMI was performed for the studied patients. Blood pressure measurements were taken by a sphygmomanometer as a mean of three times at different occasions in sitting position, mean arterial pressure=diastolic pressure+1/3 (systolic pressure–diastolic pressure) (normally 80–120 mmHg).

Laboratory investigations

Blood samples were obtained from all patients by clean venipuncture before a midweek hemodialysis session and immediately centrifuged, separated into aliquots for the following further assays, and stored at –20°C until measurement. Complete blood count was by automated cell counter CD 1800 (Nexcelom Bioscience, Lawrence city, Massachusetts, USA). Blood urea and serum creatinine were measured using autoanalyzer synchron CX5 Beckman (Diamond Diagnostics, Holliston, Middlesex Massachusetts, USA). Serum phosphate, calcium, albumin and liver function tests, serum sodium, potassium, fasting blood sugar, 2 h postprandial blood sugar, serum total cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, virology markers (hepatitis C virus antibody, hepatitis B virus surface antigen, HIVAb), and glycated hemoglobin, and urea reduction ratio, Kt/v (K: dialyzer clearance of urea, t: dialysis time, V: volume of distribution of urea) were measured using standard commercial assays. Special investigations included serum intact parathormone and transthoracic echocardiography.

Complete blood count by automated cell counter CD 1800.

Lipid profile: total cholesterol, triglycerides were measured using the open system auto-analyzer synchron CX5 (Beckman) [7].

Kidney function tests: blood urea, serum creatinine were measured using the open system auto-analyzer synchron CX5 (Beckman).

Serum electrolytes: Na +, K +, Ca +2, PO −2, fetal bovine serum, 2 h postprandial blood sugar, and glycated hemoglobin were analyzed using the open system auto-analyzer synchron CX5 (Beckman) [8].

Intact parathyroid hormone (i-PTH): i-PTH concentration was measured with the Elecsys PTH assays. The electrochemiluminescence immunoassay (ECLIA) is intended for use on Elecsys and Cobas e-immune assay analyzers (F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124 Basel, Switzerland) [9].

Transthoracic echocardiography using Xario (frequency of 1–5 MHz; Toshiba, Toshiba Medical Systems, Tokyo, Japan) [10], assessing the systolic function, the LVH, left ventricular diastolic dysfunction, calcifications, and hypokinesia. The analysis of systolic function by echocardiogram is usually performed by the methods evaluating the ejection phase, in particular the fractional shortening and the ejection fraction [11]. The diastolic function examination focuses on pulsed Doppler recordings of left-sided mitral inflow E and A waves and pulmonary vein systolic, diastolic, and atrial reversal waves and the corresponding right-sided tricuspid inflow and hepatic vein flow waves [12]. Left ventricular mass is proportional to the body size. Different cutoff values were used in several prospective studies in order to define the presence of LVH. For instance, Silberber et al. have used a reference value of 125 g/m 2, whereas Parfrey et al. [13] used the values employed in the Framingham study (132 g/m 2 for men and 100 g/m 2 for women).

The patients were divided into two groups according to the level of serum PTH as follows. In group I there were 39 (45.3%) patients, with controlled SHPT (PTH: 150–300 pg/ml). In group II there were 47 (54.6%) patients, with uncontrolled SHPT (PTH: ≥350 pg/ml).

Statistical analysis

The data collected were tabulated and analyzed by statistical package for the social sciences, version 18.0 on IBM compatible computer (SPSS; SPSS Inc., Chicago, Illinois, USA). Two types of statistics were done descriptive statistics: for example, percentage, mean and SD, and analytic statistics: for example, χ2-test, Student's t-test. Pearson's correlation coefficient (r) test was used for correlating data. A P value of less than 0.05 was considered statistically significant.


  Results Top


The patients were divided into two groups according to the level of PTH as follows. Group I had 39 (45.3%) patients, with controlled SHPT (PTH: 150–300 pg/ml). Group II had 47 (54.6%) patients, with uncontrolled SHPT (PTH: ≥350 pg/ml). There was no statistically significant difference between the two studied groups as regards age, sex, BMI, dry body weight, and interdialytic weight gain except for the dry body weight showing a statistically significant difference being higher in group II (P < 0.001) [Table 1].
Table 1: Comparing demographic data between the two studied groups

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In our study, as regards comparing the echocardiographic parameters in both studied groups, there was no statistically significant difference regarding the systolic function, diastolic dysfunction, and the development of LVH. On the other hand, there was a statistically significant difference between the studied groups as regards the presence of valvular calcifications affecting both the mitral and aortic valves, being much more common in group II with uncontrolled SHPT (P = 0.038) [Table 2].
Table 2: Relations between the level of parathyroid hormone and other echo parameters in all patients and in either group

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In the present study, the receiver operating characteristic curve showed the accuracy of the PTH level as a marker for LVH in all the studied patients and in either group is of nonsignificant relationship with respect to sensitivity, specificity, positive predictive value, and negative predictive value [Table 3] and [Figure 1].
Table 3: Accuracy of the level of parathyroid hormone as a marker of left ventricular hypertrophy in the studied patients and in subgroups

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Figure 1: ROC curve showing low sensitivity and specificity of PTH as a marker of development of left ventricular hypertrophy in end-stage kidney disease patients on maintenance hemodialysis on comparing group I with controlled SHPT, group II with uncontrolled SHPT and all patients. PTH, parathyroid hormone; ROC, receiver operating characteristic; SHPT, secondary hyperparathyroidism.

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  Discussion Top


In our study, the dry body weight is significantly higher in group II and is not in agreement with Cicekcioglu et al. [4] and Randon et al. [14], who found that there was no significant difference, which may be attributed to a better nutritional state and increased appetite with subsequent increase of dry body weight.

In our study, there is no significant difference as regards systolic function and ejection fraction, and this was in agreement with Cicekcioglu et al. [4], Al-Hilali et al. [15], Fujii et al. [16], and Randon et al. [14].

In our study, there is no significant difference as regards the LVH in two study groups and that the finding is not in agreement with those of Cicekcioglu et al. [4], Al-Hilali et al. [15], and Randon et al. [14], who have found that there was a significant correlation between PTH and LVH. However, our study finding agrees with Fujii et al. [16].

In our study, there is no statistically difference as regards the diastolic dysfunction which is not in agreement with Cicekcioglu et al. [4], who did not find any significant relation between the PTH level and valvular calcification.

Valvular calcifications of the aortic and mitral valves were significantly higher in group II compared with group I, and this was not in agreement with Abelhad et al. [17], who were studying the prevalence and risk factors of valvular calcifications in hemodialysis patients, in which medical charts of 111 hemodialysis patients were reviewed retrospectively and valvular abnormalities were found in 17 (15.3%) patients and as regard PTH concentrations, there was no significant difference between patients with and without valvular calcifications.

However, there are some limitations in the present study including: first, we performed not a cohort study but a cross-sectional study. If we had observed these patients for a longer period of time, we may have found a more significant effect of PTH on heart.

Second, our study was on a small scale. It included only 86 patients and 47 of them had uncontrolled SHPT.

Many of the studied patients had other comorbidities that might affect the left ventricular function such as diabetes mellitus, uncontrolled hypertension, anemia, and atrial fibrillation.


  Conclusion Top


Our study has shown that there is no significant correlation between uncontrolled SHPT (PTH >350 pg/ml) and LVH nor affecting the systolic function. On the other hand, the study shows that there is a significant correlation between uncontrolled SHPT and valvular calcifications affecting both aortic and mitral valves.

Recommendations

  1. Extension of the study on a larger number of hemodialysis patients
  2. Doing a prospective study instead of a cross-sectional study
  3. Periodic echocardiographic evaluation of ESRD patients on maintenance hemodialysis
  4. Study of serum i-PTH in the different stages of CKD patients and correlate it with the presence or absence of echocardiographic changes in such patients
  5. Tight control of i-PTH according to KDIGO 2013 guidelines justified by the correlation of valvular calcification
  6. Extension of the exclusion criteria to include other comorbidities that might affect left ventricular function such as diabetes mellitus, uncontrolled hypertension, anemia, pericardial effusion, and atrial fibrillation.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Blind E. Measurement of intact PTH by an extracting two site immunometric assay. In: Schmidt-Gayk H, Armbuster FP, editors., Calcium regulating hormone, vitamin D metabolites, cyclic AMP. Heideberg: Springer; 1990. 151.  Back to cited text no. 9
    
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Randon RB, Rohde LE, Comerlato L, Ribeiro JP, Manfro RC. The role of secondary hyperparathyroidism in left ventricular hypertrophy of patients under chronic hemodialysis. Secondary hyperparathyroidism and left ventricular hypertrophy. Braz J Med Biol Res 2005; 38:1409–1416.  Back to cited text no. 14
    
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Abelhad M, Kasongo A, Sabri F, Arous S, Ait-Faqih S, Habbal R. Prevalence and risk factors of valvular calcification in hemodialysis patients. Arch Cardiovasc Dis Suppl 2015; 7:202.  Back to cited text no. 17
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3]



 

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