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Journal of Parathyroid Disease 2016,4(1),31–33
Mini-Review

Pulmonary hypertension and deficiency of vitamin D

Sara Beigrezaei1, Hamid Nasri2*

Abstract
Pulmonary hypertension has been observed to be elevated among end-stage renal disease and patients who are on dialysis. Several
investigations, have demonstrated that, pulmonary hypertension in end-stage kidney failure patients is related to expressively
enhanced mortality and morbidity. Pulmonary hypertension represents a group of comparatively erratic illnesses that causes different
pulmonary vascular alterations including vasoconstriction, endothelial and smooth muscle cell proliferation, thrombosis and
inflammation cause sustained high pulmonary vascular resistance and pulmonary arterial pressure. Hyperparathyroidism secondary
to vitamin D deficiency may has a role in higher pulmonary arterial pressure and might be a relationship between pulmonary
hypertension and vitamin D deficiency.
Keywords: Vitamin D, Pulmonary hypertension, Parathyroid hormone, Hyperparathyroidism, 25-hydroxyvitamin D, Endothelial
dysfunction, Parathormone
Please cite this paper as: Beigrezaei S, Nasri H. Pulmonary hypertension and deficiency of vitamin D. J Parathyr Dis. 2016;4(1):31-
33.
Copyright © 2016 The Author(s); Published by Nickan Research Institute. This is an open-access article distributed under the terms
of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.

Introduction of vitamin D causes an increase in parathyroid hormone

The role of vitamin D is known in the regulation of mus- secretion that in the beginning, relax the vasculature and
culoskeletal health and homeostatic stability of the body will finally tighten it, thus leading to hypertension. It will
(1). Recently role of vitamin D has attracted the attention occur due to an increase of intracellular calcium lev­els and
of many researchers that found its role in pathogenesis casing endothelial and vascular growth dys­function (7).
of many chronic diseases, such as diabetes, hyperten-
sion, infections, and cancer (2). Vitamin D receptors are Materials and Methods
discovered to be expressed in a different tissues, such as For this mini-review, we used a diversity of sources by
cardiomyocytes, vascular smooth muscle cells and endo- search­ing through PubMed/Medline, Scopus, EMBASE,
thelial cells (2). Deficiency of vitamin D activates the re- EBSCO and directory of open access journals (DOAJ).
nin-angiotensin-aldosterone system and can provide sus- The search was conducted, using combination of the fol-
ceptibility to hypertension (3). Furthermore, parathyroid lowing key words and or their equivalents; vitamin D, Pul-
hormone and vitamin D have been associated with blood monary hypertension, parathyroid hormone, hyperpara-
pressure control (4). Vitamin D deficiency leads to an en- thyroidism, 25-hydroxyvitamin D, endothelial dysfunc-
hanced in parathyroid hormone secretion (3). Pulmonary tion and parathormone. Titles and abstracts of articles
hypertension (PH) represents a group of comparatively were investigated of review article, clinical trials, cohort
erratic illnesses that causes different pulmonary vascular studies, case-control studies, and report that relevance to
alterations including vasoconstriction, endothelial and the intended topic.
smooth muscle cell proliferation, thrombosis and inflam-
mation cause sustained high pulmonary vascular resis- Pulmonary hypertension, parathyroid hormone and
tance and pulmonary arterial pressure (5). vitamin D
One study proposes that hyperparathyroidism secondary Various studies have established that vitamin D may play
to vitamin D deficiency may has a role in higher pulmo- a role in several chronic lung diseases, including asthma,
nary arterial pressure and might be a relationship between chronic obstructive pulmonary disease (COPD), respi-
PH and vitamin D deficiency (6). Activation of renin-an- ratory infections and pulmo­nary arterial hypertension
giotensin-aldosterone system is associated with PH (2). (6,8,9).
The mechanism of parathyroid hormone that induced A recent study that conducted on bone mineral density
hypertension is thought to be through increasing intra- and secondary hyperparathyroidism in PH, remarkably,
cellular Ca++(4). This study also proposed, the effect of found a mainly noticeable increase of the mean parathor-
vitamin D on hypertension may also be through parathy- mone (PTH) serum levels in patients with PH (5). An en-
roid hormone and metabolism of cal­cium (7). Deficiency hanced PTH was observed in more than 50% of all PH

Received: 3 February 2016, Accepted: 2 March 2016, ePublished: 3 March 2016

1
School of Nutrition & Food Science, Isfahan University of Medical Sciences, Isfahan, Iran. 2Department of internal Medicine, Isfahan University of
Medical Sciences, Isfahan, Iran.
*Corresponding author: Professor Hamid Nasri, Email; hamidnasri@med.mui.ac.ir
Beigrezaei S et al

Implication for health policy/practice/research/ angiotensin–aldosterone system as a result of vitamin D

medical education deficiency (13). Endothelial dysfunction that is a current
High level of parathormone as a consequence of low outcome in renal failure patients as established by reduced
vitamin D levels was related to higher pulmonary nitric oxide and endothelin-1 levels, has been suggested
artery pressure, particularly in hemodialysis and pre- to impact on PHT development (15), though these results
dialysis patient. were found in a small study population that they propose
the role of end-stage renal disease in the pathogenesis of
PH. In fact, these findings clearly are helping to suggest
patients (5). renal transplantation for patients with higher pulmonary
Furthermore, in this study, patients with left heart failure artery pressure (15).
were evaluated as controls. Seventy percent of PH patients Likewise, a recent study described the prevalence, de-
were cured with loop diuretics. They noticed, no variation terminants and consequences of PH among patients on
in mean PTH serum levels between loop diuretic-treated hemodialysis (16). Some of the main results of this study
and not treated patients in the two study groups and addi- was the higher prevalence of PH among end-stage renal
tionally not related with impaired renal function. There- disease who were on hemodialysis. Study showed that, the
fore, it seems that neither enhanced creatinine nor diuret- independent factors of PH are increased left atrial diam-
ics responsible for elevated PTH levels, and factors except eter, low urea decrease ratio and no vitamin D receptor
renal failure or diuretics, probably deficiency of vitamin activator use (16). Vitamin D receptor activators improve
D, endothelial dysfunction or changed hemodynamics, diastolic function and are consequently possible to de-
seems to be responsible for secondary hyperparathyroid- crease afterload for the right ventricle (17). Importantly,
ism in PH. In pulmonary hypertensive patients, enhanced this study does not confirm, the relation of serum calci-
PTH associated negatively with serum 25-hydroxyvitamin um, phosphorus or parathyroid hormone with PH (16).
D levels too (5). Demir et al compared systolic pulmonary artery pressure
between patients with vitamin D deficiency and control
Pulmonary hypertension in patient with renal failure groups (6). They found significant association between
Pulmonary hypertension has been observed to be elevated pulmonary artery pressure and vitamin D (6). In patients,
among end-stage renal disease and patients who are on di- enhanced pulmonary artery pressure associated positively
alysis (10). Several investigations, have demonstrated that, with PTH and negatively with 25-hydroxyvitamin D lev-
PH in end-stage kidney failure patients is related to ex- els. In this study, systolic pulmonary artery pressure level
pressively enhanced mortality and morbidity (10,11). The of the patients was significantly elevated than the systolic
pathogenesis of PH in hemodialysis patients is not clearly pulmonary artery pressure levels of the control group. Ad-
recognized (11). ditionally, the PTH levels of patients groups were signifi-
A study, investigated a group of hemodialysis patients with cantly higher than the PTH levels of the control persons.
end-stage renal disease via arteriovenous fistula that was These observations demonstrated that deficiency vitamin
created on the hand, and with acetate basis dialysate and D may be associated with PHT. This result proposes that
polysulfone membranes (12). This study showed a signif- hyperparathyroidism secondary to vitamin D deficiency
icant association of pulmonary artery systolic pressure may have a role in elevated pulmonary artery pressure (6).
with serum PTH in hemodialysis patients, positively (12).
Other study showed 35.9% prevalence for PH in patients Hypertension in dialysis patients
with proteinuria stage 1–4 chronic kidney disease(13). Low 25-hydroxyvitamin D levels and high parathyroid
Additionally, PTH status were significantly elevated in hormone have been related to hypertension (18). Our
patients with PH compared with individuals with normal previous study assessed the influence of serum PTH on
pulmonary artery pressure. PTH levels were positively as- the severity of hypertension in end-stage renal disease pa-
sociated with pulmonary artery pressure (13). Moreover, tients on regular hemodialysis (19). In this study, the main
PH induced via enhanced PTH levels, is related to pul- outcome was a positive association between serum PTH
monary vascular calcification, a finding that also has been and level of hypertension. Positive association significant-
detected in an experimental dog model of chronic kidney ly was similarly observed between stages of hypertension
disease (14). (19). Secondary hyperparathyroidism and hypertension
Secondary hyperparathyroidism is proposed to be a risk are two components involved in enhanced atherosclerosis
factor for PH in patients with chronic kidney disease (13). in hemodialysis patients resulting in enhanced mortality
Chronic kidney disease is a disorder with reduced active (19). The pathogenesis of hypertension in patients under-
vitamin D levels as a result of diminished 1 alpha-hy- going maintenance hemodialysis treatment is multifac-
droxylation of vitamin D in the kidneys, which causes torial for example sodium and water loading as a conse-
enhanced PTH levels (13). Recently a study stated that quence of the impaired excretory capacity of the kidneys,
hyperparathyroidism as a consequence of low vitamin D extremely enhanced activity of the renin-angiotensin-al-
levels was related with higher pulmonary artery pressure dosterone system and sympathetic nervous system, and
(6). The investigator suggested that enhanced pulmonary also enhanced levels of the vasoconstrictor endothelin-1,
artery pressure may be caused by activation of the renin– accumulation of endogenous inhibitors of nitric oxide

32 Journal of Parathyroid Disease, Volume 4, Issue 1, March 2016

Pulmonary hypertension and vitamin D

synthesis and decreased formation of vasodepressor fac- 5. Ulrich S, Hersberger M, Fischler M, Huber LC, Senn
tors (20,21). O, Treder U, et al. Bone mineral density and secondary
Hypertension is one of the major risk factors for cardio- hyperparathyroidism in pulmonary hypertension. Open
Respir Med J. 2009;3:53-60.
vascular morbidity and mortality in the population that
6. Demir M, Uyan U, Keçeoçlu S, Demir C. The relationship
are more common in dialysis patients than the non-ure-
between vitamin D deficiency and pulmonary hypertension.
mic individuals (19). Cardiovascular diseases establish Prague Med Rep. 2013;114:154-61.
a main cause of mortality in hemodialysis patients (19). 7. Rostand SG. Vitamin D, blood pressure, and African
While hypertension and secondary hyperparathyroidism Americans: toward a unifying hypothesis. Clin J Am Soc
are common characters of the uremic syndrome, it has Nephrol. 2010;5:1697-703.
been proposed that may they have a role in the pathogen- 8. Finklea JD, Grossmann RE, Tangpricha V. Vitamin D and
esis of hypertension in patients with end-stage renal dis- chronic lung disease: a review of molecular mechanisms and
ease (22). clinical studies. Adv Nutr. 2011;2:244-53.
9. Herr C, Greulich T, Koczulla RA, Meyer S, Zakharkina T,
Functions of parathyroid hormone to keep calcium levels
Branscheidt M, et al. The role of vitamin D in pulmonary
in the blood and release of calcium is stimulated via de-
disease: COPD, asthma, infection, and cancer. Respir Res.
creased calcium levels in the blood (19). PTH causes vi- 2011;12:31.
tamin D activation, enhanced calcium absorption during 10. Nasri H, Shirani S, Baradaran A. Pulmonary artery pressure
intestine, enhanced bone resorption, enhanced calcium in maintenance hemodialysis patients. Pak J Biol Sci.
reabsorption in the kidney and enhanced phosphate ex- 2006;9:107-10.
cretion in the urine. The clear consequence of PTH activi- 11. Kawar B, Ellam T, Jackson C, Kiely D. Pulmonary hypertension
ty is an enhanced in blood calcium level without a raise in in renal disease: epidemiology, potential mechanisms and
the level of phosphate (19). Hypertension could be caused implications. Am J Nephrol. 2013;37:281-90.
12. Mousavi SS, Tamadon MR, Nasri H, Ardalan MR. Impact
via an enhanced in total peripheral resistance or an en-
of parathyroid hormone on pulmonary artery pressure in
hanced in blood volume. PTH can aggravate hypertension
hemodialysis patients. J Parathyr Dis. 2014;2:71-2.
by enhancing of these factors (19). 13. Genctoy G, Arikan S, Gedik O. Secondary hyperparathyroid-
Conclusion ism is associated with pulmonary hypertension in older pa-
Several causes have been suggested to have a role in the tients with chronic kidney disease and proteinuria. Int Urol
Nephrol. 2015;47:353-8.
pathogenesis of PH in patients with pre-dialysis chron-
14. Akmal M, Barndt RR, Ansari AN, Mohler JG, Massry
ic kidney disease and patients on hemodialysis, such as SG. Excess PTH in CRF induces pulmonary calcification,
some clinical, hemodynamic and metabolic abnormalities pulmonary hypertension and right ventricular hypertrophy.
(13,23). Kidney Int. 1995;47:158-63.
According to numerous studies high levels of PTH as a 15. Yigla M, Keidar Z, Safadi I, Tov N, Reisner SA, Nakhoul F.
consequence of low vitamin D levels were related to high- Pulmonary calcification in hemodialysis patients: correlation
er pulmonary artery pressure, particularly in hemodialy- with pulmonary artery pressure values. Kidney Int.
sis and pre-dialysis patients. More investigations are need- 2004;66:806-10.
ed to conduct the impact of PTH and vitamin D levels on 16. Agarwal R. Prevalence, determinants and prognosis of
pulmonary hypertension among hemodialysis patients.
hypertension and PH in patients with kidney disease.
Nephrol Dial Transplant. 2012;27:3908-14.
Authors’ contribution 17. Bodyak N, Ayus JC, Achinger S, Shivalingappa V, Ke Q, Chen
SB and HN wrote the manuscript equally. YS, et al. Activated vitamin D attenuates left ventricular
abnormalities induced by dietary sodium in Dahl salt-
Conflicts of interest sensitive animals. Proceedings of the National Academy of
The authors declared no competing interests. Sciences. 2007;104:16810-5.
Ethical considerations 18. Lavie CJ, Lee JH, Milani RV. Vitamin D and cardiovascular
Ethical issues (including plagiarism, data fabrication, double disease: will it live up to its hype? J Am Coll Cardiol.
2011;58:1547-56.
publication) have been completely observed by the authors.
19. Baradaran A, Nasri H. Correlation of serum parathormone
Funding/Support with hypertension in chronic renal failure patients treated
None. with hemodialysis.Saudi J Kidney Dis Transpl. 2005;16:288.
20. Sobotova D, Zharfbin A, Svojanovsky J, Nedbalkova M.
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Journal of Parathyroid Disease, Volume 4, Issue 1, March 2016 33