|Year : 2017 | Volume
| 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
Satyendra Kumar Sonkar1, Mohit Bhutani1, Gyanendra Kumar Sonkar2, Sant Kumar Pandey3, Sharad Chandra4, Vivek Bhosale5
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
Click here for correspondence address and email
|Date of Web Publication||21-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 2021 Oct 18];28:758-63. Available from: https://www.sjkdt.org/text.asp?2017/28/4/758/211337
| Introduction|| |
Mortality associated with chronic kidney disease (CKD) is more commonly seen in diastolic heart failure.,, 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., 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. Vitamin D, apart from maintaining calcium, phosphorus, and parathyroid hormone homeostasis,,, 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.,, Vitamin D deficiency is highly prevalent in the Indian subcontinent, with a prevalence of 70%–100% in the general population. 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|| |
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|| |
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.|
Click here to view
|Table 2: Hematological and biochemical variables and cardiac indices in Group IA and Group IB patients (between-group differences).|
Click here to view
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|| |
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., 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). 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.
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. 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. 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]). 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,,, which showed increased prevalence of left ventricular hypertrophy in CKD patients. Patange et al 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. 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. 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. Similar results were observed by Block et al, Tentori et al, and Gutiérrez et al 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. 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. Hyperphosphatemia leading to deranged mineral bone metabolism has adverse effects on left ventricular function. Mahdi et al 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 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. 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 in their study.
| Conclusion|| |
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|| |
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.
| References|| |
Bargman JM, Skorecki K. Chronic kidney disease. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrisons Principles of Internal Medicine. 18th
ed. New York: McGraw Hill; 2012. p. 2151-60.
Ahmed A, Rich MW, Sanders PW, et al. Chronic kidney disease associated mortality in diastolic versus systolic heart failure: A propensity matched study. Am J Cardiol 2007; 99:393-8.
Farshid A, Pathak R, Shadbolt B, Arnolda L, Talaulikar G. Diastolic function is a strong predictor of mortality in patients with chronic kidney disease. BMC Nephrol 2013;14:280.
Störk T, Möckel M, Danne O, Völler H, Eichstädt H, Frei U. Left ventricular hypertrophy and diastolic dysfunction: Their relation to coronary heart disease. Cardiovasc Drugs Ther 1995;9 Suppl 3:533-7.
Möckel M, Störk T. Diastolic function in various forms of left ventricular hypertrophy: Contribution of active Doppler stress echo. Int J Sports Med 1996;17 Suppl 3:S184-90.
Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008;117:503-11.
Jones G. Expanding role for Vitamin D in chronic kidney disease: Importance of blood 25-OH-D levels and extra-renal 1alpha-hydroxylase in the classical and nonclassical actions of 1alpha,25-dihydroxyvitamin D(3). Semin Dial 2007;20:316-24.
Li YC. Renoprotective effects of Vitamin D analogs. Kidney Int 2010;78:134-9.
Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-81.
Bouillon R, Carmeliet G, Verlinden L, et al. Vitamin D and human health: Lessons from Vitamin D receptor null mice. Endocr Rev 2008;29:726-76.
Nagpal S, Na S, Rathnachalam R. Noncalcemic actions of Vitamin D receptor ligands. Endocr Rev 2005;26:662-87.
Ritu G, Gupta A. Vitamin D deficiency in India: Prevalence, causalities and interventions. Nutrients 2014;6:729-75.
Williams S, Malatesta K, Norris K. Vitamin D and chronic kidney disease. Ethn Dis 2009; 19(4 Suppl 5):S5-8-11.
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.
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.
Pandit A, Mookadam F, Boddu S, et al. Vitamin D levels and left ventricular diastolic function. Open Heart 2014;1:e000011.
van Ballegooijen AJ, Visser M, Kestenbaum B, et al. Relation of Vitamin D and parathyroid hormone to cardiac biomarkers and to left ventricular mass (from the Cardiovascular Health Study). Am J Cardiol 2013;111:418-24.
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.
Metivier F, Marchais SJ, Guerin AP, Pannier B, London GM. Pathophysiology of anaemia: Focus on the heart and blood vessels. Nephrol Dial Transplant 2000;15 Suppl 3:14-8.
Laddha M, Sachdeva V, Diggikar PM, Satpathy PK, Kakrani AL. Echocardiographic assessment of cardiac dysfunction in patients of end stage renal disease on haemodialysis. J Assoc Physicians India 2014;62:28-32.
Ulasi II, Arodiwe EB, Ijoma CK. Left ventricular hypertrophy in African Black patients with chronic renal failure at first evaluation. Ethn Dis 2006;16:859-64.
Thadhani R, Appelbaum E, Pritchett Y, et al. Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: The PRIMO randomized controlled trial. JAMA 2012;307:674-84.
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.
Galetta F, Cupisti A, Franzoni F, et al. Left ventricular function and calcium phosphate plasma levels in uraemic patients. J Intern Med 2005;258:378-84.
Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004;15:2208-18.
Tentori F, Blayney MJ, Albert JM, et al. Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: The Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 2008;52:519-30.
Gutiérrez OM, Mannstadt M, Isakova T, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008;359:584-92.
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.
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.
Ha SK, Park HS, Kim SJ, Park CH, Kim DS, Kim HS. Prevalence and patterns of left ventricular hypertrophy in patients with predialysis chronic renal failure. J Korean Med Sci 1998;13:488-94.
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.
] [Full text]
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.
Satyendra Kumar Sonkar
Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh
[Table 1], [Table 2]
| Article Access Statistics|
| Viewed||2510 |
| Printed||36 |
| Emailed||0 |
| PDF Downloaded||380 |
| Comments ||[Add] |