Zinc and Abdominal Aortic Calcification in Patients under Regular Hemodialysis

DISCUSSION

This research was done at Al-Hussein university hospital hemodialysis unit over a period of six month; from November 2021 to July 2022, and conducted on 40 Hemodialysis Patients. Demographic data and Clinical information were recorded. Laboratory data including CBC, calcium, phosphate, albumin, parathyroid hormone (PTH), total cholesterol, triglyceride, high-density lipoprotein (HDL), low density lipoprotein (LDL) Iron profiles (serum iron, TIBC, ferritin, T.SAT) and serum Zinc were evaluated and plain x ray abdomen lateral view was done in the standing position utilizing the standard radiographic equipment’s.

  In terms of demographic information, the average age of all patients under study was 44.6 ± 9.2 years, with a minimum age of 24 and a maximum age of 57. There were 11 females and 29 men (72.5%). (27.5 percent). Some patients also had other comorbid conditions; 5 of them (12.5%) had diabetes, and 24 had hypertension (60 percent). According to the study's findings, the average AAC score of all patients was 6.5 ±5.8, with the lowest AAC score being 0 and the highest being 18, and the average zinc score was 53.3 ±19.3, with the lowest zinc value being 28 and the highest value being 124.

In the current study, AAC score and age showed a very statistically substantial (p-value< 0.001) positive connection (r = 0.56).

In support of these results Hashim Al-Saedi et al., ⁹ found in his several investigations that Depending on the patient's age, aortic vascular calcification affects between 18.5 and 95 percent of individuals.

Craver L et al., ¹⁰ observed that Common risk factors such as hypertensive, diabetes mellitus, dyslipidemia, age, smoking, and CVD, as well as particular genetic diseases in CKD patients, all contribute to the acceleration of arterial calcification.

Also In support of these results Honkanen et al., ¹¹ observed that In the hemodialysis group, age, the existence of diabetes mellitus, and serum phosphorus were shown to be predictive factors of AAC. In the CORD trial, it was also shown that age, the length of dialysis, and a history of cardiovascular disease were unique predictors for AAC.

Furthermore, Kestenbaum B et al., ¹² observed that the main factor influencing vascular calcification is age. Age and AAC have repeatedly been shown to be directly correlated in CKD patients, dialysis patients, and the general population.

In addition, Rapa et al., ¹³ observed that Age-related increases in abdominal aorta calcifications are linked to conventional cardiovascular risk factors. Age, initial AAC, and hypertension are all independently linked to AAC advancement.

In agreement Honkanen H et al., ¹¹ in his study, found significant association between AACS and age, where calcification score increased rapidly with age.This comes in accordance with Honkanen H et al ¹¹.

Balla J et al., ¹⁴ observed that There is an inverse relationship between AAC and demographic factors such age, the frequency of dialysis, and hypertension.

Atkinson J et al.,¹⁵ observed that Vascular calcification worsens with age, and the thoracic aorta at 90 years old has 30 times more calcium buildup than it did at 20 years old in the elastin-rich layer of the media. High blood pressure is linked to age-related medial elastocalcinosis in arteries. In the general public, age-related vascular calcification only affects arteries and doesn't impact additional soft tissues.

Also In support of these results Moe SM et al., ¹⁶ observed that His research found a substantial age-related rise in AAC, which has also been seen in HD patients.

Allison MA et al., ¹⁷ observed that Age-related increases in abdominal aortic calcifications are linked to conventional CVD risk.

AAC has been shown to increase with time as a consequence of age or dialysis vintage in several investigations.¹⁸

In this research, the amounts of calcium and phosphorus in the corrected serum did not correspond to the severity of ACC. A number of factors contribute to the pathogenic process of vascular calcification in CKD patients, including abnormalities in the calcium and phosphate metabolic pathways, extracellular matrix metabolism variations, oxidative stress, and inflammation-related disruption of the equilibrium between calcification promoters and inhibitors.¹⁹

However, our research found no evidence of a connection between serum calcium and AAC rating. Our findings are in accordance with Volkovet al., ²⁰

In the current study, AAC score and PTH have a statistically substantial (p-value = 0.036) and favorable (r = 0.33) association.

In support of these results Yamada et al., ²¹ showed a positive connection between vascular calcification parathormone levels of hemodialysis patients.

Nitta K et al., ²² shown that High iPTH levels are VC risk factors. IPTH may boost intracellular Ca levels and cartilage matrix expression, which will aid in the development of VC.

In the current study, AAC score and blood albumin had a very statistically substantial (p-value 0.001) negative connection (r = -0.55).

In support of these results Herselman et al., ²³ It was observed in 2010 that lower serum albumin predicted increased all-cause vascular calcification in hemodialysis patients, and that the dynamics of serum albumin level is an effective predictor of all-cause death and cardiac death.

In the current study, there was a statistically substantial (p-value = 0.005) negative connection (r = - 0.43) between AAC score and serum zinc.

In support of the current study Nagy A et al.,⁴ observed that Zinc reduced the osteochondrogenic phenotypic transition of vasculature smooth muscle cells (VSMCs) generated by phosphate, which led to the synthesis of vascular calcification.

Also, in accordance with Vervloet M et al., ²⁴ who observed in his numerous investigations that In patients on dialysis, serum Zinc (Zn) concentrations are negatively correlated with VC.

Also, in accordance with Shimizu S et al., ²⁵ who observed that Patients on hemodialysis often have low serum Zn levels because they are frequently malnourished as a result of ongoing inflammation, uremia, and dietary restrictions.

Pasch A et al., ²⁶ observed that decreased zinc concentrations in CKD patients, particularly in dialysis patients.

Also, in support of these results Pasch A et al., ²⁶ observed that An increased arterial calcification was substantially correlated with decreased serum zinc levels.  

Also, in support of these results Moe SM et al., ¹⁶ observed that Recruiting leukocytes to induce pathological alterations in the vascular endothelium and promoting cardiovascular calcification, low plasma zinc levels in HD patients (mainly as a result of impaired renal function, decreased intestinal zinc absorption, and exogenous elements including food and medicines) stimulate the secretion of many inflammatory mediators and promote cardiovascular disease.

Also, in support of these results de Seigneux S et al., ²⁷ observed that in individuals with CKD, hypozincemia may be linked to an elevated risk of calcification.

Also, in support of these results Chen Z et al., ²⁸ observed that Zinc is crucial for preventing vascular smooth muscle from calcifying.

Also, in support of these results de Carvalho et al., ²⁹ observed that Low dietary zinc intake has been associated with calcification in the general population, and zinc has emerged as a prospective protective factor in cardiovascular calcification. Lack of zinc is linked to the advancement of CVD in those with chronic renal disease.

Also, in support of these results Voelkl et al., ³⁰ observed that zinc sulfate administration 1) reduced the expression of mRNA, which is a bone formation signal and contains the expression of zinc-finger protein TNF-induced protein, and 2) repressed phosphate-induced calcification 3 and 3) prevented NF-kB activation and bone/cartilage reprogramming, which in turn suppressed VSMC phosphate-induced calcification.³⁰

The zinc deficit in hemodialysis (HD) patients has been observed to be substantial, ranging from 40% to 78%.³¹

According to reports, consuming more zinc via diet may prevent aorta calcification by 8%.²⁸

In the current investigation, serum albumin levels had no effect on the association between serum zinc deficiency and abdominal aortic calcification. The information was comparable to the study indicating zinc deficiency was linked to HD patients' 2-year mortality.³²

CONCLUSION

AAC risk is increased by low serum zinc levels. Our research points to the advantages of dietary zinc on vascular calcification. Additional research is required to validate this connection.