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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2017  |  Volume : 28  |  Issue : 4  |  Page : 758-763
Vitamin D levels and other biochemical parameters of mineral bone disorders and their association with diastolic dysfunction and left ventricular mass in young nondiabetic adult patients with chronic kidney disease


1 Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Department of Biochemistry, King George's Medical University, Lucknow, Uttar Pradesh, India
3 Department of Nephrology, King George's Medical University, Lucknow, Uttar Pradesh, India
4 Department of Cardiology, King George's Medical University, Lucknow, Uttar Pradesh, India
5 Division of Clinical and Experimental Medicine, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Date of Web Publication21-Jul-2017
 

   Abstract 


Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with end-stage renal disease. Chronic kidney disease (CKD)-associated cardiovascular mortality is more prevalent in those with diastolic heart failure and is an early predictor, while increased left ventricular mass (LVM) is a strong independent risk factor. Hypovitaminosis D is extensively being studied as a nontraditional risk factor for CVD. The aim of the present study is to look at the association of Vitamin D and other parameters of mineral bone disorder (MBD) with diastolic dysfunction and LVM in nondiabetic young adult patients with CKD. This was a hospital-based, cross-sectional observational study. Groups I and II comprised nondiabetic predialysis CKD patients (stage 4 and 5) and healthy controls, respectively. Groups IA and IB comprised cases with and without diastolic dysfunction, respectively. Vitamin D level was measured by enhanced chemiluminescence method and intact parathyroid hormone (iPTH) by electrochemiluminescence method. Parameters for diastolic function and LVM were assessed by Doppler echocardiography, tissue Doppler imaging, and M-mode echocardiography. Vitamin D level was significantly lower in Group I as compared to Group II. Diastolic dysfunction was present in 48.8% of the cases and was significantly associated with serum phosphorus and calcium-phosphorous product, but not with Vitamin D level. A statistically significant positive correlation between LVM and iPTH was found in our study. Hyperphosphatemia and high calcium-phosphorous product can be a better early predictor of diastolic dysfunction than Vitamin D while secondary hyperpara-thyroidism with increased LVM may be a bad prognostic marker.

How to cite this article:
Sonkar SK, Bhutani M, Sonkar GK, Pandey SK, Chandra S, Bhosale V. Vitamin D levels and other biochemical parameters of mineral bone disorders and their association with diastolic dysfunction and left ventricular mass in young nondiabetic adult patients with chronic kidney disease. Saudi J Kidney Dis Transpl 2017;28:758-63

How to cite this URL:
Sonkar SK, Bhutani M, Sonkar GK, Pandey SK, Chandra S, Bhosale V. Vitamin D levels and other biochemical parameters of mineral bone disorders and their association with diastolic dysfunction and left ventricular mass in young nondiabetic adult patients with chronic kidney disease. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2019 Dec 11];28:758-63. Available from: http://www.sjkdt.org/text.asp?2017/28/4/758/211337



   Introduction Top


Mortality associated with chronic kidney disease (CKD) is more commonly seen in diastolic heart failure.[1],[2],[3] Diastolic heart failure is a clinical syndrome characterized by the symptoms and signs of heart failure, a preserved ejection fraction (EF), and abnormal diastolic function. Diastolic dysfunction and increase in left ventricular mass (LVM) occur early in CKD.[4],[5] The increased prevalence of cardiovascular disease (CVD) in CKD patients derives from both traditional (classic) and non-traditional (CKD related) risk factors. Hypo-vitaminosis D is extensively being studied as a nontraditional risk factor for CVD owing to its increased prevalence in patients with CKD.[6] Vitamin D, apart from maintaining calcium, phosphorus, and parathyroid hormone homeostasis,[7],[8],[9] appears to play a major role as a cell differentiating and anti-proliferative factor with actions in a variety of tissues including the renal, cardiovascular, and immune systems.[9],[10],[11] Vitamin D deficiency is highly prevalent in the Indian subcontinent, with a prevalence of 70%–100% in the general population.[12] Hence, in this study, we assessed Vitamin D and other biochemical parameters of mineral bone disorder (MBD) and their association with diastolic dysfunction and LVM, which are early predictors of cardiovascular mortality, in nondiabetic young CKD patients.


   Patients and Methods Top


The present study was a hospital-based, cross-sectional observational study conducted in patients attending the nephrology unit for one year. Eighty-six nondiabetic predialysis CKD patients (stage 4 and 5), aged between 18 and 40 years (Group I), were enrolled after obtaining informed consent along with age- and sex-matched healthy volunteers (n = 40; Group II) for estimation of Vitamin D in our subset of population. The study was approved by the Ethical Committee of the university and the study conformed with the provision of Declaration of Helsinki (as revised in Tokyo in 2004). Group I was further divided as Group IA consisting of cases with diastolic dysfunction and Group IB comprising cases without diastolic dysfunction. Patients with severe anemia (Hb <6.0 g/dL), or taking erythropoiesis-stimulating agents, known malignancy, and/or heart failure (EF <40%) were excluded from the study. None of the study patients were smokers or on Vitamin D therapy. Patients with conditions that may influence collagen metabolism such as recent (<6 months) surgery or trauma, fibrotic diseases or active inflammatory conditions, patients on immunosuppressive medications, or presence of arteriovenous fistula for dialysis access were not enrolled in the study. None of the study patients had previous acute coronary events. The study population was evaluated for Vitamin D levels, intact parathyroid hormone (iPTH), and echocardiography. Cases were grouped on the basis of Vitamin D level. For the purposes of analysis, Vitamin D concentration was categorized based on the current Kidney Disease Outcomes Quality Initiative guidelines (K/ DOQI guidelines, 2003) as optimal level (>30 ng/mL), insufficient level (15–30 ng/mL), and deficient level (<15 ng/mL). We measured 25- hydroxyvitamin D3 (25-OH D3) levels as per the instruction provided with the kit of LIAISON® DiaSorin, Italy, by enhanced chemiluminescence method and iPTH by electrochemiluminescence method. Parameters for diastolic function and LVM mass were assessed by Doppler echocardiography, tissue Doppler imaging, and M-mode echocardiography. Diastolic dysfunction was observed in cases with CKD, according to the American Society of Echocardiography and the European Association of Echocardiography guidelines for assessment of diastolic function by echocardiography.

Statistical analysis of the data was performed on Statistical Package for the Social Sciences for Windows version 16.0 (SPSS Inc., Chicago, IL, USA). Appropriate parametric (Student’s t-test, independent samples t-test) and correlation tests were used to analyze data sets.


   Results Top


The mean age of nondiabetic CKD patients in Group I was 32.1 ± 7.5 years and all were found to be hypertensive (>140/90 mm Hg). Most of them had chronic glomerulonephritis. Mean Vitamin D level was significantly lower in Group I (14.6 ± 6.4 ng/mL) (P <0.001) and log iPTH was 2.3 ± 0.7 pg/mL. In Group II, healthy volunteers, Vitamin D level was 16.4 ± 4.7 ng/mL, serum protein was 7.1 ± 0.45 mg/dL, and albumin was 4.2 ± 0.61 mg/dL; all were significantly higher compared to cases. In Group I, 58.1% of cases had Vitamin D deficiency (<15 ng/mL), whereas in Group II, 50% had Vitamin D deficiency. It is to be noted that Vitamin D level was <30 ng/mL in all cases as well as controls.

In nearly half of the 86 cases, diastolic dysfunction was present (48.8% vs. 51.1%). None of the healthy controls had diastolic dysfunction irrespective of Vitamin D level. Vitamin D deficiency (< 15) was found in higher proportion in Group IA (66.7%) as compared to Group IB (50.0%). However, this difference was not found to be statistically significant (P = 0.26) [Table 1]. Comparison of different biochemical parameters among cases, i.e., Group I is shown in [Table 2].
Table 1: Association of Vitamin D levels in Group IA and Group IB cases.

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Table 2: Hematological and biochemical variables and cardiac indices in Group IA and Group IB patients (between-group differences).

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Serum phosphate level was found to be a significant risk factor for development of diastolic dysfunction (P <0.005) [Table 2], while with the calcium-phosphorus product (>55 mg2/dL2), it was P<0.05. Cases in Group I had a higher mean LVM index (LVMI) than controls (70.3 vs. 23.8, respectively) (P <0.001). The LVMI did not significantly correlate with Vitamin D level (R2 = 0.02) on a scatter plot. However, statistically significant positive correlation between LVMI and iPTH was found in our study (R2 = 0.3).


   Discussion Top


Vitamin D is associated with diabetic CKD in adults, but our study shows this association in young nondiabetic patients. Patients with CKD have an exceptionally high rate of severe Vitamin D deficiency; this is largely due to the reduced ability of the kidney to convert 25- (OH) Vitamin D into the active form 1,25 dihydroxy Vitamin D. Emerging evidence suggests that the progression of CKD and many of the cardiovascular complications may be linked to hypovitaminosis D.[13],[14] Moreover, CKD patients with further decrease in glomerular filtration rate also have secondary hyperparathyroidism with hypocalcemia and hyperphosphatemia. Levin et al. in their study on 175 patients with progressive renal disease found that age was significantly different between the groups with and without left ventricular hypertrophy (55.4 ± 15.9 vs. 49.2 ± 14.5 years, respectively).[14] Young adults were included in our study group to remove the confounding factor of older age as a risk for cardiovascular changes. Modification of the biochemical or echocardiographic parameters by age-related morbidities such as diabetes mellitus and hypertension is thought to be less in study involving young population. In our study, the Vitamin D level was significantly lower in cases as compared to controls. This is similar to that reported by Kari et al.[15]

In the current study, there was no statistically significant association between Vitamin D deficiency and diastolic dysfunction in CKD patients (P = 0.26), which was in accordance to the report of Pandit et al.[16] Another study also reported that lower Vitamin D levels were not associated with any of the biochemical, conduction, or echocardiographic outcomes in individuals who were free of CVD at baseline.[17] These results are contrary to that observed in a study on 34 children with CKD, which showed that LVMI correlated with Vitamin D (r = -0.54; P <0.05) and serum iPTH levels correlated with diastolic dysfunction (E/E’ ratio [r = 0.63; P <0.05] and E’ [r = -0.61; P <0.05]).[18] Hence, variable results regarding this association have been observed in different studies. Further, large-scale studies are needed to find whether there is any true association between Vitamin D levels and diastolic dysfunction.

In the current study, the mean LVMI was significantly higher in cases (70.31 ± 29.80 g/m2) than in controls (23.8 ± 9.05 g/m2). This was consistent with other studies,[19],[20],[21] which showed increased prevalence of left ventricular hypertrophy in CKD patients. Patange et al[18] in a study on 34 children with CKD showed that LVMI inversely correlated with Vitamin D and it was also statistically significant (r = -0.54; P <0.05), whereas in our study, we did not find any significant correlation (r = -0.1 P >0.05). Another study showed no clinically significant improvement on administration of Vitamin D in patients with CKD.[22] We observed a mean level of serum phosphate of 7.3 ± 2.4 mg/dL and 5.5 ± 1.4 mg/dL in cases with and without diastolic dysfunction, respectively. It was found to be a significant risk factor for development of diastolic dysfunction in cases with CKD (P <0.005). A recent report by Mahdi et al.[23] states that phosphate burden that promotes loss of mineral from bone can also promote calcification in the vascular wall. Another study by Galetta et al showed a positive correlation between hyperphosphatemia and increased cardio-vascular morbidity in uremic patients on maintenance hemodialysis.[24] Similar results were observed by Block et al,[25] Tentori et al,[26] and Gutiérrez et al[27] in their respective studies. Elevated serum phosphorus is a predictable accompaniment of end-stage renal disease (ESRD) in the absence of dietary phosphate restriction or supplemental phosphate binders. The consequences of hyperphosphatemia include the development and progression of secondary hyperparathyroidism and a predisposition to metastatic calcification when the product of serum calcium and phosphorus is elevated. Both these conditions may contribute to the substantial morbidity and mortality seen in patients with ESRD.[28] A significant association between calcium-phosphorus product (>55 mg2/dL2) and diastolic dysfunction was found (P = 0.03) in our study which is similar to a study reported by Regmi et al.[29] Hyperphosphatemia leading to deranged mineral bone metabolism has adverse effects on left ventricular function. Mahdi et al[23] have also emphasized on maintaining calcium-phosphorous balance for healthy life as its imbalance can lead to irreversible damage to our body system.

In our study, using correlation analysis with LVMI as an outcome of interest, iPTH was found to be an important predictor showing linear relationship, which was statistically significant (r = 0.47, P <0.05). Similar results were obtained by Ha et al[30] in their study on 62 predialysis CKD patients. Furthermore, Al-Hilali et al found positive correlation between iPTH and LVMI in their study on 130 patients on hemodialysis.[31] This may be due to the potential role of iPTH on inter-myocardiocytic fibrosis, i.e., nonreparative interstitial fibrosis with collagen fiber deposition, commonly found in uremic patients and animals as observed by Amann et al[32] in their study.


   Conclusion Top


Vitamin D deficiency is highly prevalent in CKD patients as well as in healthy population. CKD patients have lower mean Vitamin D as compared to healthy age- and sex-matched controls. The healthy controls, despite being Vitamin D deficient, did not have diastolic dysfunction on echocardiography. Vitamin D deficiency was not statistically significantly associated with diastolic dysfunction or LVMI in nondiabetic CKD patients. However, hyperphosphatemia and calcium-phosphorous product came out to be a better predictor for diastolic dysfunction and hence, early predictor of cardiovascular mortality in predialysis CKD patients. Secondary hyperparathyroidism may be a bad prognostic marker of cardiovascular morbidity and mortality due to left ventricular hypertrophy in CKD.


   Acknowledgment Top


The authors are thankful to the laboratory technical staff of Cardiology, Nephrology, and Biochemistry Department of King George’s Medical University, Lucknow, India, for the help and cooperation in carrying out this work.

Conflict of interest: None declared.



 
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Levin A, Singer J, Thompson CR, Ross H, Lewis M. Prevalent left ventricular hypertrophy in the predialysis population: Identifying opportunities for intervention. Am J Kidney Dis 1996;27:347-54.  Back to cited text no. 14
    
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Kari JA, El Desoky SM, El-Morshedy SM, Habib HS. Vitamin D insufficiency and deficiency in children with chronic kidney disease. Ann Saudi Med 2012;32:473-8.  Back to cited text no. 15
    
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Pandit A, Mookadam F, Boddu S, et al. Vitamin D levels and left ventricular diastolic function. Open Heart 2014;1:e000011.  Back to cited text no. 16
    
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Patange AR, Valentini RP, Gothe MP, Du W, Pettersen MD. Vitamin D deficiency is associated with increased left ventricular mass and diastolic dysfunction in children with chronic kidney disease. Pediatr Cardiol 2013;34:536-42.  Back to cited text no. 18
    
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Mahdi AA, Brown RB, Razzaque MS. Osteoporosis in populations with calcium intake: Does phosphate toxicity explain the paradox? Indian J Clin Biochem 2015;30:365-7.  Back to cited text no. 23
    
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Strózecki P, Adamowicz A, Nartowicz E, Odrowaz-Sypniewska G, Wlodarczyk Z, Manitius J. Parathormon, calcium, phosphorus, and left ventricular structure and function in normotensive hemodialysis patients. Ren Fail 2001;23:115-26.  Back to cited text no. 28
    
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Regmi P, Malla B, Gyawali P, et al. Product of serum calcium and phosphorus (Ca × PO4) as predictor of cardiovascular disease risk in predialysis patients. Clin Biochem 2014;47:77- 81.  Back to cited text no. 29
    
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Al-Hilali N, Hussain N, Ataia AI, Al-Azmi M, Al-Helal B, Johny KV. Hypertension and hyperparathyroidism are associated with left ventricular hypertrophy in patients on hemodialysis. Indian J Nephrol 2009;19:153-7.  Back to cited text no. 31
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32.
Amann K, Ritz E, Wiest G, Klaus G, Mall G. A role of parathyroid hormone for the activation of cardiac fibroblasts in uremia. J Am Soc Nephrol 1994;4:1814-9.  Back to cited text no. 32
    

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Correspondence Address:
Satyendra Kumar Sonkar
Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh
India
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PMID: 28748877

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    Abstract
   Introduction
   Patients and Methods
   Results
   Discussion
   Conclusion
   Acknowledgment
    References
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