Hyperhomocysteinemia Confers an Independent Increased Risk of Atherosclerosis in End-Stage Renal Disease and Is Closely Linked to Plasma Folate and Pyridoxine Concentrations

Robinson, Killian; Gupta, Anjan; Dennis, Vincent W.; Arheart, Kristopher L.; Chaudhary, Deepa; Green, Ralph; Vigo, P; Mayer, E; Selhub, Jacob; Kutner, Michael; Jacobsen, Donald W.

doi:10.1161/01.cir.94.11.2743

Cited by 310 publications

(200 citation statements)

References 37 publications

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“…Hyperhomocysteinemia is present in the vast majority of maintenance dialysis patients according to almost all descriptive and prevalent studies (5)(6)(7)(8)(9)(10)(11)(12). In most of such studies, including our current study, Ͼ90% of maintenance dialysis patients have hyperhomocysteinemia, and the mean and median values of tHcy are between 20 and 25 mol/L.…”

Section: Discussionsupporting

confidence: 48%

“…In maintenance hemodialysis (MHD) outpatients, however, the association between tHcy and clinical outcome is inconsistent and even paradoxical. Some studies have shown a poor outcome in MHD patients with hyperhomocysteinemia (5)(6)(7)(8)(9). However, a few recent studies have suggested that a decreased, not an increased, tHcy concentration is related to a higher prevalence of cardiovascular disease and poor outcome in these individuals (10 -12).…”

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confidence: 99%

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A Low, Rather than a High, Total Plasma Homocysteine Is an Indicator of Poor Outcome in Hemodialysis Patients

Kalantar-Zadeh

Block

Humphreys

et al. 2004

Journal of the American Society of Nephrology

153

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Abstract. An increased level of total plasma homocysteine (tHcy) is a risk factor for poor cardiovascular outcome in the general population. However, a decreased, rather than an increased, tHcy concentration may predict poor outcome in maintenance hemodialysis (MHD) patients, a phenomenon referred to as reverse epidemiology. Associations were examined between tHcy level and markers of malnutrition-inflammation complex syndrome and 12-mo prospective hospitalization and mortality in 367 MHD patients, aged 54.5 Ϯ 14.7 (mean Ϯ SD) years, who included 199 men and 55% individuals with diabetes. tHcy was 24.4 Ϯ 11.8 mol/L, and 94% of the patients had hyperhomocysteinemia (tHcy Ͼ13.5 mol/L). tHcy had weak to moderate but statistically significant bivariate and multivariate correlations with some laboratory markers of nutrition (serum albumin, prealbumin, creatinine, and urea nitrogen) but no significant correlation with serum C-reactive protein or two proinflammatory cytokines (IL-6 and TNF-␣).During 12 mo of follow-up, 191 MHD patients were hospitalized, 37 died, nine underwent renal transplantation, and 38 transferred out. Hospitalization rates were significantly higher in patients with lower tHcy levels. Mortality rate in the lowest tHcy quartile (17.4%) was significantly higher compared with other three quartiles (6.5 to 9.8%; Kaplan-Meier P ϭ 0.04). Relative risk of death for the lowest tHcy quartile, even after adjustment for case-mix and serum albumin, was 2.27 (95% confidence interval, 1.14 to 4.53; P ϭ 0.02). Hence, tHcy may be a more exclusive nutritional marker in MHD patients with no association with inflammatory measures. Despite a very high prevalence of hyperhomocysteinemia in MHD patients, lower values of tHcy are paradoxically associated with increased hospitalization and mortality. The lowest tHcy quartile confers a twofold increase in risk of death independent of hypoalbuminemia. The nutritional feature of tHcy in MHD patients may explain its reverse association with outcome.In the general population, an increased level of total plasma homocysteine (tHcy) is a risk factor for increased cardiovascular events and mortality (1-4). In maintenance hemodialysis (MHD) outpatients, however, the association between tHcy and clinical outcome is inconsistent and even paradoxical. Some studies have shown a poor outcome in MHD patients with hyperhomocysteinemia (5-9). However, a few recent studies have suggested that a decreased, not an increased, tHcy concentration is related to a higher prevalence of cardiovascular disease and poor outcome in these individuals (10 -12). This seems to be due to the empirical association between a low tHcy and protein-energy malnutrition, which is per se a known risk factor for poor clinical outcome in dialysis patients (11,13,14). This recently described paradoxical association between tHcy and clinical outcome in dialysis patients has now been referred to as a possible component of the reversal of the cardiovascular risks (15-17). It is believed that both inflammation and protei...

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Section: Discussionsupporting

confidence: 48%

mentioning

confidence: 99%

A Low, Rather than a High, Total Plasma Homocysteine Is an Indicator of Poor Outcome in Hemodialysis Patients

Kalantar-Zadeh

Block

Humphreys

et al. 2004

Journal of the American Society of Nephrology

153

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“…3,4 Some studies have demonstrated that hyperhomocysteinemia is present in patients with impaired renal function and is associated with CVD. [5][6][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.…”

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confidence: 99%

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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“…[16] An increased plasma homocysteine concentration is more among hemodialysis patients, [17,18] and also considered to be risk factor for atherosclerotic complications of ESRD. [19][20][21][22] CKD is associated with increase in triglyceride level, due to increase in VLDL, chylomicrons, and its remnants. Increase in triglycerides is due to delay in catabolism and the increase in triglyceride-rich lipoproteins from liver.…”

Section: Introductionmentioning

confidence: 99%

To Analyse the Pattern of Lipid Profile in Patients of Chronic Kidney Disease

Verma¹,

Singh²

2018

AIMDR

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Background: Chronic kidney disease (CKD), is a progressive and irreversible deterioration in the function of kidney over months to years,2 which is defined as"glomerular filtration rate (GFR) lesser than 60 ml/min with protenuria for 3 months".3 It leads to various biochemical disturbances and numerous clinical symptoms and signs.4Some of the associated changes are abnormalities in haematology parameters, heart related issues, disturbances of gastrointestinal tract, neurologic disorder, osteodystrophy, skin related problems and sexual dysfunction. Dyslipidemias are a common among CRF patients. The disturbances of lipoprotein metabolism are seen in early stages of CRF and can follow decrement pattern that follows the renal function deterioration. Aim and Objectives This study was aimed to analyse the pattern of lipid profile among the dif. Methods: The study was cross-sectional observational study conducted on 100 patients either attending or being admitted in the department of Internal Medicine, TMMC & RC, TMU , Moradabad, U.P., INDIA, which were in line with the inclusion criteria. Result & Conclusion: Our results indicated that patients undergoing CRF show important abnormalities of lipid metabolism which could contribute to atherosclerosis and cardiovascular disease and may increase the morbidity and mortality in these patients.

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Hyperhomocysteinemia Confers an Independent Increased Risk of Atherosclerosis in End-Stage Renal Disease and Is Closely Linked to Plasma Folate and Pyridoxine Concentrations

Abstract: A high total plasma homocysteine concentration is an independent risk factor for atherosclerotic complications of end-stage renal disease. Such patients may benefit from higher doses of B vitamins than those currently recommended.

Cited by 310 publications

References 37 publications

A Low, Rather than a High, Total Plasma Homocysteine Is an Indicator of Poor Outcome in Hemodialysis Patients

A Low, Rather than a High, Total Plasma Homocysteine Is an Indicator of Poor Outcome in Hemodialysis Patients

Hyperhomocysteinemia in renal transplantation: preliminary results

To Analyse the Pattern of Lipid Profile in Patients of Chronic Kidney Disease

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