Efficacy of L-methylfolate and Methylcobalamine in Treating Hypertension and Its Impact on Serum Homocysteine in Hemodialysis Patients With Resistant Hypertension

Efficacy of L-methylfolate and Methylcobalamine in Treating Hypertension and Its Impact on Serum Homocysteine in Hemodialysis Patients With Resistant Hypertension

Efficacy of L-methylfolate and Methylcobalamine in Treating Hypertension and Its Impact on Serum Homocysteine in Hemodialysis Patients With Resistant Hypertension

The aim of the study is to evaluate the efficacy of L-methylfolate in combination with methylcobalamine in reducing homocysteine blood levels in hypertensive end-stage renal disease patients on regular hemodialysis and its association with blood pressure control in treatment of resistant hypertension

Ethical committee approval has been obtained from Ethics committee of Faculty of Medicine, Alexandria University Agreement from all participants should be taken in this clinical study by assigning an informed consent Adult end stage renal disease patients maintained on hemodialysis three times a week for at least 3 months with resistant hypertension will be recruited from hemodialysis unit in Alexandria University Hospitals Patients will be screened for resistant hypertension as determined by the mean of mid-week pre-dialysis BP > 140/90 mm Hg, post-dialysis BP > 130/80 mm Hg over a period of one month. A blood sample will be collected for homocysteine measurement at baseline Patients will be randomized using simple randomization technique via computer based program to take one tablet daily containing L-methylfolate and methylcobalamine or no treatment. Patients will be followed over a period of 3 months after which blood pressure measurement and blood sampling would be repeated and compared to baseline values As a measurement of the prognosis of elevated homocysteine, we should follow the development of myocardial infarction, stroke and cardiovascular events for 3 months The appropriate statistical tests will be held according to the study design and parameters to evaluate the significance of the results Results, conclusion, discussion and recommendations will be given

Adult end stage renal disease patients maintained on hemodialysis three times a week for at least 3 months with resistant hypertension as determined by pre-dialysis BP > 140/90 mm Hg, post-dialysis BP > 130/80 mm Hg despite the use of three or more drugs. Patients will be assigned to take one tablet daily containing L-methylfolate and methylcobalamine. Patients will be followed over a period of 3 months after which blood pressure measurement and blood sampling would be repeated and compared to baseline values.

Adult end stage renal disease patients maintained on hemodialysis three times a week for at least 3 months with resistant hypertension as determined by pre-dialysis BP > 140/90 mm Hg, post-dialysis BP > 130/80 mm Hg despite the use of three or more drugs. Patients will be followed over a period of 3 months after which blood pressure measurement and blood sampling would be repeated and compared to baseline values.

Dietary supplement labeled to contain methylfolate 800 micrograms and methylcobalamine 1000 micrograms

average pre-dialysis blood pressure target of ≤ 140/90 mm Hg or an average post-dialysis blood pressure target of ≤ 130/80 mm Hg

To achieve an average pre-dialysis blood pressure target of ≤ 140/90 mm Hg or an average post-dialysis blood pressure target of ≤ 130/80 mm Hg. This should be parallel to lowering of serum homocysteine compared to baseline values

As a measurement of the prognosis patients will be followed up for the development of myocardial infarction, stroke and cardiovascular events for 3 months.

Inclusion Criteria: Adult end stage renal disease patients maintained on hemodialysis three times a week for at least 3 months with resistant hypertension as determined by pre-dialysis BP > 140/90 mm Hg, post-dialysis BP > 130/80 mm Hg despite the use of three or more drugs Exclusion Criteria: Age > 75 years Excessive use of alcohol or smoking Severe hepatic impairment Acute kidney injury on top of chronic kidney disease Pregnant females Allergy or intolerance to any component of the formulation Medication side effects (methotrexate, theophylline, phenytoin, and cyclosporine) or any drug proven to cause hyperhomocysteinemia

Li J, Jiang S, Zhang Y, Tang G, Wang Y, Mao G, Li Z, Xu X, Wang B, Huo Y. H-type hypertension and risk of stroke in chinese adults: A prospective, nested case-control study. J Transl Int Med. 2015 Oct-Dec;3(4):171-178. doi: 10.1515/jtim-2015-0027. Epub 2015 Dec 30.

Cianciolo G, La Manna G, Coli L, Donati G, D'Addio F, Persici E, Comai G, Wratten M, Dormi A, Mantovani V, Grossi G, Stefoni S. 5-methyltetrahydrofolate administration is associated with prolonged survival and reduced inflammation in ESRD patients. Am J Nephrol. 2008;28(6):941-8. doi: 10.1159/000142363. Epub 2008 Jun 30.

Friedman AN, Bostom AG, Selhub J, Levey AS, Rosenberg IH. The kidney and homocysteine metabolism. J Am Soc Nephrol. 2001 Oct;12(10):2181-2189. doi: 10.1681/ASN.V12102181.

Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004 Sep 23;351(13):1296-305. doi: 10.1056/NEJMoa041031. Erratum In: N Engl J Med. 2008;18(4):4.