Association between chronic kidney disease and plasma homocysteine level - A hospital based study

 

 

Abstract              Background: Chronic kidney disease (CKD) is known to cause hyperhomocysteinemia which contributes to increased cardiovascular morbidity and mortalities. Hence the study aimed to find the homocysteine level in patients with chronic kidney disease. Material and methods: 50 patients with CKD were recruited in the study, and their fasting plasma homocysteine level was measured. Normal plasma homocysteine level was considered to be below 15 µmol/litre. Observations and Results: Of 50 patients (Males: 37, females: 13 Age range: 41-60), 36 patients had stage 5 CKD. Hyperhomocysteinemia was observed in 78% of CKD patients. 94.87% had mild hyperhomocysteinemia. End-stage renal disease patients had increased prevalence of hyperhomocysteinemia. No significant difference was found in hyperhomocysteinemia state between patients undergoing dialysis and without dialysis. Conclusion: Hyperhomocysteinemia is a highly prevalent condition seen in CKD patients.

Key Word: hyperhomocysteinemia, Chronic kidney disease, homocysteine

 

INTRODUCTION

Chronic kidney disease (CKD) is a serious clinical and public health challenge globally.¹ In India, it has been recently estimated that the age-adjusted incidence rate of end-stage renal disease (ESRD) to be 229 per million population, and >100,000 new patients enter renal replacement programs annually.²CKD is associated with age-related renal function decline accelerated in hypertension, diabetes, obesity and primary renal disorders.³ Cardiovascular disease (CVD) is the primary cause of morbidity and mortality where CKD is regarded as an accelerator of CVD risk and an independent risk factor for CVD events.⁴Homocysteine has been implicated as a potential risk factor for cardiovascular disease, which is the major cause of morbidity and mortality in patients with CKD.⁵ A moderate increase of plasma total homocysteine occurs in the early stages of CKD and increases as renal function decreases, indicating the important role of the kidney on homocysteine metabolism.^6,7 Hyperhomocysteinaemia, defined as a plasma total homocysteine level of 12 µmol/l, occurs already at a GFR of about 60 ml/min and when ESRD has been reached, the prevalence of hyperhomocysteinaemia is 85–100%.^8,10 Many studies are ongoing to find out whether decreasing homocysteine in CKD patients will decrease cardiovascular morbidity and mortality.¹¹ Even though many studies have shown significant association and a negative correlation between the decrease in Glomerular filtration rate and increase in homocysteine level.^12,14 There is a limited number of studies in the Indian context. Hence the current study was carried out with an aim to find the homocysteine level in patients with chronic kidney disease and to find its association and correlation with decreased renal function.

 

MATERIALS AND METHODS

The current study was a single centred observational study conducted in Thanjavur medical college and hospital recruited from January 2014 to August 2014 for a period of 8 months. Ethics approval for patient recruitment and data analysis was obtained from the Institutional Review Board. Inclusion criteria were patients with elevated blood urea and serum creatinine and showing feature of CKD in ultrasound abdomen. Patients with acute kidney injury, liver diseases, diabetics and current smokers or alcohol consumers were excluded. A total of 50 patients with chronic kidney disease in the hospital were recruited after obtaining the consent. Information about medical history, family history, current medication, and history of dialysis of participants was collected via self-report questionnaire. Investigations included assessment of blood urea, serum creatinine, electrocardiograph, plasma homocysteine, glomerular filtration rate (calculated), were measured by fluorescein polarisation, immunoassay. Statistical analyses were performed using the SPSS statistical software package for Microsoft Windows (version 14.0, SPSS Inc. Chicago, IL, USA). The data are presented as means and standard deviation or percentage unless indicated otherwise. Student's t-test and chi-square test were used to compare mean values and percentages respectively.

 

RESULTS

Table 1: Baseline characteristics of study participants(n=50)

Among the study population, the majority of the participants were in the age group of 51-60 (42%) years, and males 37(74%) with the mean age of 53.10±11.151 years. The mean weight of the study population was 57.82±11.5 kg. The mean serum urea and creatinine values were 113.66±32.1 mg/dl, 7.43±7.43 mg/dl respectively. The serum homocysteine level was 19.6±7.83 µmol/lt (Table 1)

 

Table 2: Stage CKD and ECG with normal and increased homocysteine level

If we compare plasma homocysteine level with corresponding glomerular filtration rate and stage of CKD it shows that as patient deteriorates to next lower level of chronic kidney disease incidence of hyperhomocysteinemia increases. Here in this study, we observed that in stage 4 and stage 5 of chronic kidney disease incidence of hyperhomocysteinemia were 72% and 96.67 % respectively. We observed that the majority of patients were having abnormal electrocardiograph indicating the majority of patients with Chronic kidney disease had some cardiac diseases. Of the 50 patients selected for the study 47 patients had abnormal electrocardiograph constituting 94% In those with hyper homo cysteinemia only three were found to have normal ECG All others were having abnormal ECG (Table 2)

 

Table 3: Distribution of study participants based on CKD stage and hyperhomocysteinemia

Table 3 shows the staging of CKD according to creatinine clearance and glomerular filtration rate as calculated by cockcroft Gault formula. Of the total population majority of patients, 36(72) were in CKD stage 5. In our study in those having hyperhomocysteinemia majority are falling in the group of mild hyperhomocysteinemia. Of the 39 patients with hyperhomocysteinemia, 37 patients were in the group of mild hyperhomocysteinemia. Only two were found to have moderate hyperhomocysteinemia. (table 3)

DISCUSSION

Recently, disulfuramino acid homocysteine has gained much importance because of its role in vascular thrombosis and genesis of atherosclerosis. Studies have shown an increased prevalence of hyperhomocysteinemia in CKD patients and its association with cardiovascular morbidity and mortality. In the current study, we found that 78% of CKD patients had hyperhomocysteinemia correlating with other studies conducted elsewhere in the world and hyperhomocysteinemia was more prevalent as stages of CKD increases. Menon V et al¹⁵reported that hyperhomocysteinemia was prevalent in 56% 0f CKD patients and hyperhomocysteinemia was partly amenable to treatment with vitamins in stages 3 and 4. Even though our study sample size was smaller, we found that hyperhomocysteinemia was more prevalent in the later stages of CKD. It was in accordance with the concept that as renal function deteriorates the homocysteine excretion decreases and its level increases in plasma. We even noted in the study that even if the patient was on dialysis, it was not affecting the homocysteine level elevation. However, Nair AP et al¹⁶ reported homocysteine level transiently decreased after a dialysis session but fell to normal range within two to three days to predialysis value. We observed that the majority of patients with CKD had some ECG abnormality correlating well with the statement that cardiovascular morbidities are the most important cause of mortality in patients with CKD.¹¹ Our main concern to evaluate for the presence or absence of hyperhomocysteinemia in CKD patients was to decrease the cardiovascular morbidity and mortality. So, its worthy to take measures to decrease homocysteine levels in patients with CKD. These findings should be considered understudies limitations. First, we could not exclude other genetic variations which might have influenced homocysteine level. Second, the exact correlation between decreased renal function and level of hyperhomocysteinemia could not be assessed due to the non-uniform distribution of sample size among CKD patients. Systematic reviews had reported the effect of B12 supplementation on decreasing homocysteine levels in patients with ESRDs when combined with folate supplementation.¹⁷ But the levels of Vit B12 and folic acid, pyridoxine level could not be measured in the current study due to financial restriction.

 

CONCLUSION

Level of homocysteine increased according to the stages of CKD. Hyperhomocysteinemia appears to be associated with increased cardiovascular disease risk among patients with CKD. Considering the study findings further large-scale longitudinal studies are recommended to explore further this association. Efforts must be taken by clinicians in identifying CKD patients with elevated homocysteine level owing to its increased susceptibility to cardiovascular risk.

 

REFERENCES

1. Long Y, Nie J. Homocysteine in Renal Injury. Kidney Dis (Basel). 2016;2(2):80-7.
2. Singh AK, Farag YM, Mittal BV, Subramanian KK, Reddy SR, Acharya VN, et al. Epidemiology and risk factors of chronic kidney disease in India - results from the SEEK (Screening and Early Evaluation of Kidney Disease) study. BMC Nephrol. 2013;14:114.
3. Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013;382(9889):339-52.
4. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalisation. N Engl J Med. 2004;351(13):1296-305.
5. Nerbass FB, Draibe SA, Feiten SF, Chiarello PG, Vannucchi H, Cuppari L. Homocysteine and its determinants in non dialysed chronic kidney disease patients. J Am Diet Assoc. 2006;106(2):267-70.
6. Busch M, Göbert A, Franke S, Ott U, Gerth J, Müller A, et al. Vitamin B₆ Metabolism in Chronic Kidney Disease – Relation to Transsulfuration, Advanced Glycation and Cardiovascular Disease. Nephron Clinical Practice. 2010;114(1):c38-c46.
7. Arnadottir M, Hultberg B, Nilsson-Ehle P, Thysell H. The effect of reduced glomerular filtration rate on plasma total homocysteine concentration. Scand J Clin Lab Invest. 1996;56(1):41-6.
8. van Guldener C. Why is homocysteine elevated in renal failure and what can be expected from homocysteine-lowering? Nephrology Dialysis Transplantation. 2006;21(5):1161-6.
9. Wollesen F, Brattström L, Refsum H, Ueland PERM, Berglund L, Berne C. Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus. Kidney International. 1999;55(3):1028-35.
10. Veldman BAJ, Vervoort G, Blom H, Smits P. Reduced plasma total homocysteine concentrations in Type 1 diabetes mellitus is determined by increased renal clearance. Diabetic Medicine. 2005;22(3):301-5.
11. Subbiah AK, Chhabra YK, Mahajan S. Cardiovascular disease in patients with chronic kidney disease: a neglected subgroup. Heart Asia. 2016;8(2):56-61.
12. Cheng Y, Kong FZ, Dong XF, Xu QR, Gui Q, Wang W, et al. Influence of renal function on the association between homocysteine level and risk of ischemic stroke. Am J Transl Res. 2017;9(10):4553-63.
13. Francis ME, Eggers PW, Hostetter TH, Briggs JP. Association between serum homocysteine and markers of impaired kidney function in adults in the United States. Kidney International. 2004;66(1):303-12.
14. Chao MC, Hu SL, Hsu HS, Davidson LE, Lin CH, Li CI, et al. Serum homocysteine level is positively associated with chronic kidney disease in a Taiwan Chinese population. J Nephrol. 2014;27(3):299-305.
15. Menon V, Wang X, Greene T, Beck GJ, Kusek JW, Selhub J, et al. Homocysteine in chronic kidney disease: Effect of low protein diet and repletion with B vitamins. Kidney Int. 2005;67(4):1539-46.
16. Nair AP, Nemirovsky D, Kim M, Geer EB, Farkouh ME, Winston J et al. Elevated homocysteine levels in patients with end-stage renal disease. Mt Sinai J Med. 2005;72(6):365-73.
17. Amini M, Khosravi M, Baradaran HR, Atlasi R. Vitamin B12 supplementation in end-stage renal diseases: a systematic review. Med J Islam Repub Iran. 2015;29:167.

 

 

 

 

 

Policy for Articles with Open Access
Authors who publish with MedPulse International Journal of Anesthesiology (Print ISSN:2579-0900) (Online ISSN: 2636-4654) agree to the following terms:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
Authors are permitted and encouraged to post links to their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.