Role of homocysteine level as risk factor in the occurrence of cardiovascular events in renal transplant recipients
Background: Traditional risk factors like elevated homocysteine levels may not completely explain the higher CVD seen in RTRs. Identification and optimisation of modifiable risk factors may help to reduce the occurrence of CVD in such population. To study the role of homocysteine level as risk factor in the occurrence of cardiovascular events in renal transplant patients. Another objective was to evaluate the other risk factors in the occurrence of CVD in such population.
Methods: Thirty renal transplant recipients and thirty healthy controls were studied. Inclusion criteria were transplant duration >6 months and patients with chronic stable renal function over the last 3 months. Samples for fasting plasma homocysteine were collected and plasma homocysteine was then estimated. All the patients were followed up every month for 6 months and evaluated for occurrence of any cardiovascular event.
Results: The mean hornocysteine levels were found to be 27.4±7.902 µmol/L in cases and 10.86±1.98 µmol/L in controls. There was no statistically significant relationship between homocysteine levels and transplant duration, mean IMT levels, proteinuria, and presence of left ventricular hypertrophy or choice of immunosuppressive regimen. Of the 30 patients, 6 patients (20%) had evidence of cardiovascular event. In the absence of other conventional factors, age of the patient, creatinine clearance (index of graft function) and mean intima-media thickness were more closely related with cardiovascular events.
Conclusions: Plasma homocysteine failed to show as an independent risk factor for cardiovascular events. New, emerging cardiovascular risk factors (e.g. Lipoprotein (a), high sensitivity C-reactive protein, fibrinogen, tissue plasminogen activator and plasminogen activator inhibitor-1) should be studied to design effective therapy to delay the progression of atherosclerosis and prolong the life of renal transplant recipients.
Neale J, Smith AC. Cardiovascular risk factors following renal transplant. World J Transplant. 2015;5(4):183-95.
Agarwal SK, Dash SC, Mehta SN, Gupta S, Bhowmik D, Tiwari SC, et al. Results of renal transplantation on conventional immunosuppression in second decade in India: a single centre experience. J Assoc Physicians India. 2002;50:532-6.
Faeh D, Chiolero A, Paccaud F. Homocysteine as a risk factor for cardiovascular disease: should we (still) worry about? Swiss Med Wkly. 2006;136(47-48):745-56.
Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutrition J. 2015;14:6.
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;351:1296-305.
Liefeldt L, Budde K. Risk factors for cardiovascular disease in renal transplant recipients and strategies to minimize risk. Transpl Int. 2010;23:1191-204.
Winkelmayer WC, Kramar R, Curhan GC, Chandraker A, Endler G, Födinger M, et al. Fasting plasma total homocysteine levels and mortality and allograft loss in kidney transplant recipients: a prospective study. J Am Soc Nephrol. 2005;16:255-60.
Ducloux D, Motte G, Challier B, Gibey R, Chalopin JM. Serum total homocysteine and cardiovascular disease occurrence in chronic, stable renal transplant recipients: a prospective study. J Am Soc Nephrol. 2000;11:134-7.
Bostom AG. Homocysteine: “Expensive creatinine” or important, modifiable risk factor for arteriosclerotic outcomes in renal transplant recipients? J Am Soc Nephrol. 2000;11:149–51.
Dimeny E, Hultberg B, Wahlberg J et al. Serum total homocysteine concentration does not predict outcome in renal transplant recipients. Clin Transplant. 1998;12:563–568.
Hagen W, Fodinger M, Heinz G, Buchmayer H, Hörl WH, Sunder-Plassmann G. Effect of MTHFR genotypes and hyperhomocysteinemia on patient and graft survival in kidney transplant recipients. Kidney Int. 2001;59(Suppl 78):S253–7.
Massy ZA, Chadefaux-Vekemans B, Chevalier A, Bader CA, Drüeke TB, Legendre C, et al. Hyperhomocysteinaemia: a significant risk factor for cardiovascular disease in renal transplant recipients. Nephrol Dial Transplant. 1994;9(8):1103-8.
Kumar RT, Ferraris JR, Ramirez JA, Galarza CR, Waisman G, Janson JJ, et al. Hyperhomocysteinemia in stable pediatric, adolescents, and young adult renal transplant recipients. Transplantation. 2001;71(12):1748-51.
Serafimowiez A, Kukula K, Cieciura T, Shaibani B, Baczkowska T, Soin J, et al. Homocysteine and lipid peroxidation products: important atherosclerosis risk factors in renal allograft recipients? Transplant Proc. 2000;32(6):1367-8.
Lentine KL, Brennan DC, Schnitzler MA. Incidence and predictors of myocardial infarction after kidney transplantation. J Am Soc Nephrol. 2005;16:496-506.
Salonen JT, Salonen R. Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb. 1991;11:1245-9.
Brzosko S, Hryszko T, Lebkowska U, Malyszko J, Malyszko JS, Mysliwiec M. Plasma tissue-type plasminogen activator, fibrinogen, and time on dialysis prior to transplantation are related to carotid intima media thickness in renal transplant recipients. Transplant Proc. 2003;35(8):2931-4.
Toz H, Duman S, Altunel E, Seziş M, Ozbek S, Ozkahya M, et al. Intima media thickness as a predictor of atherosclerosis in renal transplantation. Transplant Proc. 2004;36(l):156-8.
Pedrinelli R, Dell'Omo G, Penno G, Mariani M. Non-diabetic microalbuminuria, endothelial dysfunction and cardiovascular disease. Vase Med. 2001;6:257-64.
Peddi VR, Dean DE, Hariharan S, Cavallo T, Schroeder TJ, First MR. Proteinuria following renal transplantation: correlation with histopathology and outcome. Transplant Proc. 1997;29:101-3.
Roodnat JI, Mulder PG, Rischen-Vos J, van Riemsdijk IC, van Gelder T, Zietse R, et al. Proteinuria after renal transplantation affects not only graft survival but also patient survival. Transplantation. 2001;72:438-44
Fernández-Fresnedo G, Escallada R, Rodrigo E, De Francisco AL, Cotorruelo JG, Sanz De Castro S, et al. The risk of cardiovascular disease associated with proteinuria in renal transplant patients. Transplantation. 2002;73:1345-8.
Cherukuri A, Welberry-Smith MP, Tattersall JE, Ahmad N, Newstead CG, Lewington AJ, et al. The clinical significance of early proteinuria after renal transplantation. Transplantation. 2010;89:200-7.
Cherukuri A, Tattersall JE, Lewington AJ, Newstead CG, Baker RJ. Resolution of low-grade proteinuria is associated with improved outcomes after renal transplantation-a retrospective longitudinal study. Am J Transplant. 2015;15:741-53.
Deepa R, Velmurugan K, Saravanan G, Karkuzhali K, Dwarakanath V, Mohan V. Absence of association between serum homocysteine levels and coronary artery disease in south Indian males. Indian Heart J. 2001;53:44-7.
BKS Sastry, N Indira, B Anand, Kedarnath, B Surya Prabha, B Soma Raju. A Case-Control Study of Plasma Homocysteine Levels in South Indians With and Without Coronary Artery disease. Indian Heart J. 2001;53(6):749-53.