Hyperhomocysteinemia in Cyclosporine-Treated Renal Transplant Recipients1

Arnadottir, Margret; Hultberg, Björn; Vladov, V; Nilsson‐Ehle, Peter; Thysell, Hans

doi:10.1097/00007890-199602150-00034

Cited by 156 publications

(91 citation statements)

References 15 publications

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“…3,4 Several reports in RT also point out that hyperhomocysteinemia is present in RT patients, 9,10 -15 but limited data are available on the prevalence of hyperhomocysteinemia in stable RT recipients. 9,12,14,15 We have confirmed the presence of increased levels of tHcy, showing that 48.7% of our stable RT patients had hyperhomocysteinemia, mainly in males.…”

Section: Discussionsupporting

confidence: 62%

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Hyperhomocysteinemia in renal transplantation: preliminary results

Fonseca

Queirós

Santos

et al. 2000

Transplantation Proceedings

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C ARDIOVASCULAR disease (CVD) is a major cause of morbidity and mortality after renal transplantation (RT). 1,2 The excess risk of CVD in RT is due in part to a higher prevalence of established atherosclerotic risk factors, including hypertension, dyslipidemia, diabetes, obesity, and physical inactivity. 1,2 However, some renal-related risk factors like immunosuppressive medication and residual renal insufficiency also contribute to this excess CVD risk and may complicate the management of dyslipidemia and hypertension in this population. 1,2 Accordingly, there is a compelling need to identify and safely manage other putative CVD risk factors among RT patients. Elevated plasma homocysteine is emerging as an important risk factor for cardiovascular disease in general populations. 3,4 Some studies have demonstrated that hyperhomocysteinemia is present in patients with impaired renal function and is associated with CVD. 5-7 Only a small number of studies are available on the prevalence and determinants of hyperhomocysteinemia in renal transplant recipients. 8 -15 We undertook this study to 1. estimate the prevalence of hyperhomocysteinemia in renal transplant recipients; 2. examine the relationships between plasma total homocysteine (tHcy) and its metabolic determinants vitamin B 6 , vitamin B 12 , and folic acid; and 3. identify other determinants of tHcy. MATERIALS AND METHODSA cross-sectional study was conducted in 202 stable RT recipients (113 male, 89 female), selected from 633 RT patients with functioning allografts of our Renal Transplant Unit. All recipients received grafts from cadaver donors. The eligibility criteria were: age over 18 years, first renal allograft, time since RT of at least 6 months, and stable plasma creatinine values during 3 months prior to study. Patients with diagnosis of any kind of cancer, clinical or analytical evidence of liver disease, and chronic alcoholism were also excluded. None of the selected RT recipients were taking B vitamin.The mean age was 44 Ϯ 11 years (range, 21 to 71; median, 43). The mean duration after renal transplantation was 58.5 Ϯ 37.2 months (range, 17 to 192; median, 50.6). Patients had been on dialysis for an average of 42.7 Ϯ 37.5 months (range, 0 to 221; median, 30.5) before transplantation. Mean serum creatinine value was 1.5 Ϯ 0.6 mg/dL (range, 0.6 to 4.7; median, 1.4) at the time blood was drawn for this study. Immunosuppression protocol of the 202 RT patients is described on Table 1.The Ethics Committee of Santo Antonio Hospital approved the study protocol, and all participants provided written informed consent. Biochemical DeterminationsOvernight fasting blood samples were collected from each participant. Total fasting homocysteine levels were determined by polarized immunofluorescence on an automated Abbott IMx analyzer. Hyperhomocysteinemia was considered if plasma levels of fasting tHcy were higher than 15 mol/L. Plasma pyridoxal 5Ј-phosphate was determined by high performance liquid chromatography with fluorescence detection. Plasma vitamin B 12...

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Section: Discussionsupporting

confidence: 62%

“…9 But, as in other studies, we didn't find any correlation between tHcy levels and dose and plasma levels of cyclosporine. 10 -15 …”

Section: Discussioncontrasting

confidence: 49%

Hyperhomocysteinemia in renal transplantation: preliminary results

Fonseca

Queirós

Santos

et al. 2000

Transplantation Proceedings

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“…8,10,12 A smaller literature in renal transplantation also points a substantial risk of hyperhomocysteinemia contributing to the increased risk of early cardiovascular disease. [17][18][19][20][21] Whereas small retrospective studies are often subject to various biases, prospective studies generally provide a more robust estimate of association. Data from prospective stud-ies among populations with primary and secondary cardiovascular risk have shown that tHcy concentrations are inversely related with survival.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies suggest as well that hyperhomocysteinemia is a cardiovascular risk factor in these recipients. [17][18][19][20][21][22] In the present study, we prospectively followed a cohort of 202 recipients for 5 years to examine the impact of fasting homocysteinemia on long-term patient and renal allograft survival.…”

mentioning

confidence: 99%

Impact of Homocysteinemia on Long-Term Renal Transplant Survival

Fonseca

Martins

Queirós

et al. 2005

Transplantation Proceedings

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Aim. We prospectively followed a cohort of 202 renal transplant recipients for 5 years to examine the impact of fasting homocysteinemia on long-term patient and renal allograft survival. Methods. Cox proportional hazards regression analysis was used to identify independent predictors of all-cause mortality and graft loss. Results. Hyperhomocysteinemia (tHcy Ͼ15 mol/L) was present in 48.7% of the 202 patients, predominantly among men (55.8%) as opposed to women (37.1%). At the end of the follow-up period, 13 (6.4%) patients had died including 10 from cardiovascular disease, and 23 had (11.4%) had lost their grafts. Patient death with a functioning allograft was the most prevalent cause of graft loss (13 recipients). Levels of tHcy were higher among patients who died than among survivors (median 23.9 vs 14.3 mol/L; P ϭ .005). Median tHcy concentration was also higher among the patients who had lost their allografts than those who did not (median 19.0 vs 14.1 mol/L; P ϭ .001). In a Cox regression model including gender, serum creatinine concentration, transplant duration, traditional cardiovascular risk factors, and associated conditions, such as past cardiovascular disease, only tHcy concentration (ln) (HR ϭ 5.50; 95% CI, 1.56 to 19.36; P ϭ .008) and age at transplantation (HR ϭ 1.07; 95% CI, 1.02 to 1.13; P ϭ .01) were independent predictors of patient survival. After censoring data for patient death, tHcy concentration was not a risk factor for graft loss.Conclusions. This prospective study shows that tHcy concentration is a significant predictor of mortality, but not of graft loss, after censoring data for patient death.S HORT-AND LONG-TERM GRAFT and patient survivals after renal transplantation have improved considerably over the past three decades. However, life expectancy beyond 10 years is still considerably less than in the general population, mainly due to cardiovascular events. In fact, an accelerated form of atherosclerosis commonly occurs in these patients. Cardiovascular disease is the leading cause of morbidity and mortality in renal transplant recipients, accounting for approximately 40% of all deaths. 1,2 Classic cardiovascular risk factors (eg, dyslipidemia, hypertension, and diabetes) as well as nonmodifiable risk factors such as age, gender, and family history do not fully explain the cardiovascular disease. Among other predictors of atherosclerotic disease, attention has been drawn to the association between homocysteine and cardiovascular events. Clinical and epidemiological studies have shown that homocysteine measured in serum or plasma is a strong predictor of cardiovascular risk. 3,4 The results of early cross-sectional and case-control studies strongly support this hypothesis. 5,6 Prospective studies of patient populations known to be at high risk of cardiovascular events, including renal patients, consistently report strong associations between homocysteine and cardiovascular as well as all-cause mortality. [7][8][9][10][11][12][13][14][15][16] Elevated levels of fasting total ...

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“…Plasma separation was performed within one hour after blood collection for Hcy quantitation, according to the liquid chromatography/sequential mass spectrometry (LC-MS/MS) method 19 . Hcy concentrations >15µmol/ml were considered as characterizing hyperhomocysteinemia 20 .…”

Section: Biochemical Analysismentioning

confidence: 99%