Introduction

Chronic kidney disease (CKD) is gradual loss of kidney function over a period of years associated with many other complications. CKD is defined as abnormalities of kidney structure and function present for more than 3 months with implications for health caused by Diabetes Mellitus (31.5%), hypertension (27.4%), glomerulonephritis (13.5%), obstructive uropathy (5.4%), polycystic kidney disease (3.4%) and idiopathic (18%).1 Complications CKD include electrolyte imbalances, abnormal bone mineral metabolism, cardiovascular abnormalities. Prevalence of CKD in India is 800 per million people. Each year 2 lakh patients develop CKD in India among which 1 lakh people are undergoing dialysis.2 CKD is classified into five stages based on GFR and persistent albuminuria in which stage 4 and stage 5 patients require haemodialysis or kidney transplant. Criteria for initiating dialysis include the presence of uremic symptoms - the presence of hyperkalaemia, persistent extracellular volume expansion, acidosis, bleeding diathesis despite conservative measures and estimated GFR below 10ml/min/1.73m².

Patients undergoing long term haemodialysis have altered trace elements level may be due to decreased dietary intake, decreased absorption, altered dialysate concentration, increased excretion, etc.3 Zinc, an important trace mineral plays a significant role in immune function, metabolism of proteins, carbohydrates, nucleic acids, regulation of more than 300 enzyme activity and has antioxidant property which helps to protect cardiovascular disease.4, 5, 6 Magnesium, an abundant intracellular cation, is responsible for various metabolic process like protein synthesis cellular energy production and storage, cell growth, DNA and RNA synthesis and catalyses about 300 enzyme systems in our body.7, 8, 9, 10 Magnesium homeostasis is maintained by bone, intestine and kidney.

Patients with CKD have a high burden of cardiomyopathy, atherosclerosis and arteriosclerosis.11, 12 There are various factors that increases the cardiovascular disease in haemodialysis patients such as hypertension, glucose intolerance, dyslipidaemia, high serum homocysteine levels, altered calcium-phosphorous metabolism and other contributing factors like altered zinc levels and altered magnesium levels increases cardiovascular risk.12 Cardiovascular disease accounts for 50% of death among patients undergoing haemodialysis.13

Both zinc and magnesium levels are reduced in CKD patients undergoing haemodialysis. Reduced zinc levels lead to activation of many atherogenic factors such as increased production of reactive oxygen species and reduced magnesium levels leads to hypokalaemia causing cardiac arrhythmia, atrial fibrillation, ventricular fibrillation, both leading to cardiovascular disease.14

Materials and Methods

This Prospective cross-sectional study was conducted in CKD patients undergoing hemodialysis. The patients between the age 19 and 81 were included in the study. Patients with altered zinc (Wilson’s disease, acrodermatitis, enteropathica) and magnesium (hypothyroidism, milk alkali syndrome, GI disease) levels were excluded from the study. The patient was enrolled in the study after obtaining written informed consent. The patients’ detailed clinical history and examination is recorded. The Framingham risk score was calculated and the patient’s serum zinc levels and magnesium levels were calculated using spectrophotometric method and calmagite method respectively. Statistical analysis was performed using student's t test and chi square test, p-values <0.05 were considered as statistically significant.

Results

Totally about 100 patients undergoing haemodialysis were included in this study. Of these, 87 were males, 13 were females. Average years of age include 24 years to 76 years of age with standard deviation 49.34 ±12.1. 5ml of venous blood is collected post dialysis from which zinc, magnesium and HDL cholesterol, creatinine, urea, glucose values were calculated. And using these values Framingham score was calculated.

Discussion

We included 100 patients undergoing haemodialysis in our study and their serum zinc and magnesium levels were measured and Framingham score was calculated to estimate the cardiovascular risk. Out of 100 patients,59 patients have low risk, 28 patients have intermediate risk and 13 patients have high risk of developing cardiac disease. In addition to this, patients with low zinc and magnesium levels have increased risk of developing cardiovascular disease.

The mean value of serum magnesium was 1.81±0.81. In 100 patients, 37 patients were hypomagnesemic, 43 patients with normal range and 20 were hypermagnesemic. This indicates that patients who are undergoing dialysis may be prone to develop hypomagnesemia. Delmar J Mahler et al6 established that differences in dialysis concentration and dietary intake leads to changes in magnesium concentration. Hypomagnesemia is correlated with Framingham risk score to calculate 10-year cardiovascular risk. Of these, 67% patients have low risk, 13% patients have intermediate risk and 24% patients have high risk of developing heart disease. Hypomagnesemia causes alteration in Na⁺-k⁺-ATPase pump, increase in serum levels of inflammatory cytokines, IL-1, IL-6, TNF, increases endothelial cell secretion of IL-8, PDGF-BB and MMP-2, MMP-9 and tissue inhibitor of metalloproteinases, and decreased production of SOD and catalase, which leads to increased production of ROS. All these changes lead to increased cardiovascular stress and leads to cardiovascular disease. In 2007 Eiji Ishimura et al15 described the role of magnesium in its protective effects against cardiovascular disease, neoplasia, inflammation and infectious diseases and stated its deficiency increases cardiovascular risk. Haigney et al14 described decreased magnesium levels is associated with increased cardiovascular risk. In our study, level of decrease of magnesium levels in dialysis patients corresponds to the duration of dialysis. The patients who were undergoing haemodialysis for long periods develops hypomagnesemia than patients who were undergoing haemodialysis for short period. Cardiovascular disease accounts for increased mortality in CKD patients rather than the kidney failure. Mark. J. Sarnak et al.,16 William. G. Goodman et al17 and many authors suggests that cardiovascular events lead to increased mortality in chronic kidney disease patients. The 1998 report of NSK task force on cardiovascular disease in chronic renal failure recommended that patients with CKD are considered to be in the highest risk of developing subsequent cardiac events. These conclusions were confirmed by 2003 statement from American council on kidney in cardiovascular disease, high BP research, clinical cardiology, epidemiology and prevention.

Other patients with normal and above normal range have risk of developing cardiac disease which is attributed by the parameters used to calculate Framingham score.

And in our study, the mean value of serum zinc was 128.62±12.23. In our study, serum zinc levels were not altered during dialysis treatment. There was no correlation found between serum zinc level and cardiovascular disease.

Conclusion

This study shows the increased prevalence of hypomagnesemia among patients who are undergoing long term haemodialysis. And also, that patients with low magnesium levels are at increased risk of developing heart disease than patients with normal magnesium levels. And in this study, zinc level was not altered during dialysis treatment. Therefore, we conclude that magnesium levels are altered during dialysis treatment. So, monitoring of magnesium levels and maintaining normal magnesium levels by oral supplementation and altering dialysate concentration prevent increased risk of developing cardiovascular disease.

Conflict of Interest

The authors declare no conflict of interest.

Acknowledgement

Indian Council of Medical Research – Short Term Studentship 2018.