Treatment of hyperhomocysteinemia with folic acid reduces oxidative stress in renal transplant recipients.

BACKGROUND: We conducted a prospective, uncontrolled, open study to assess the relationship between homocysteine (tHcy) and oxidative stress in chronic, stable, renal transplant recipients (RTR). METHODS: Included in the study were 17 chronic, stable RTR. All the patients received folic acid (5 mg/day). tHcy and total antioxidant capacity (TAOC) were measured before and at the end of the study period. RESULTS: Mean tHcy concentration was 26+/-10 micromol/L. tHcy significantly decreased during the study period (26+/-10 vs. 18+/-7 micromol/L; P<0.001). There was a significant inverse relationship between TAOC and tHcy (r= -0.33; P=0.01). TAOC significantly increased during the study period (1.49+/-0.23-1.78+/-0.6; P<0.001). There was an inverse relationship between the variation in tHcy and the variation in TAOC (r= -0.44; P=0.01). CONCLUSION: Our results demonstrate that hyperhomocysteinemia contributed to increased oxidative stress in RTR. tHcy-lowering treatment with folic acid may lower oxidative stress.

C-reactive protein and cardiovascular disease in peritoneal dialysis patients.

BACKGROUND: Elevated plasma concentrations of C-reactive protein (CRP) is a risk factor for cardiovascular disease (CVD) in the general population and in hemodialysis patients. The prognostic value of CRP is less well known in peritoneal dialysis (PD) patients. We examined the association between CRP and cardiovascular event (CVE) in a large population of PD patients. METHODS: Two hundred and forty patients starting PD were enrolled in this prospective study. The role of CRP was analyzed with respect to other known cardiovascular risk factors. RESULTS: The patients were followed for a mean duration of 41 +/- 21 months; the median value of CRP was 7 mg/L. Eighty-nine cardiovascular events (CVE; 37.1%) occurred in 84 patients and the CRP levels were higher in patients who experienced CVE (27 +/- 14 vs. 6 +/- 8 mg/L; P < 0.0001). In the Cox model, patients in the three lower quartiles of the CRP levels had a decreased risk of CVE compared with those in the highest quartile. Cox regression analysis also revealed that age, a previous history of cardiovascular disease, hyperhomocysteinemia and hypoalbuminemia were risk factors for CVE. CRP levels were higher in patients who died during the study period (25 +/- 12 vs. 5 +/- 8 mg/L; P = 0.003). In the Cox model, patients with CRP levels above the median had an increased risk of death compared with those in the lowest quartile. CONCLUSIONS: Chronic inflammation, as reflected by elevated CRP levels, is frequent in patients starting PD and independently contributes to an increased incidence of CVE in this population.

Homocysteine, nutritional status and insulin in renal transplant recipients.

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for the development of cardiovascular conditions in chronic stable renal-transplant recipients (RTR). Major determinants of plasma total homocysteine (tHcy) in RTR are renal function and folate levels. The data dealing with the possible regulation of the tHcy metabolism by insulin and nutritional status is conflicting in non-transplant populations. METHODS: We examined the relationship between tHcy, insulin and nutritional status in 103 chronic, stable RTR. Demographic, clinical, and biochemical parameters were assessed for each patient. RESULTS: Mean tHcy was 19.7+/-9.2 micro mol/l (range 8.6-53). The tHcy was strongly related to creatinine clearance (r=0.55, P<0.0001). Fasting tHcy levels were negatively related to folate concentrations (r=-0.32, P=0.01). There was a positive relationship between tHcy and LDL-cholesterol (r=0.34, P=0.03) and a significant negative correlation between tHcy and insulin (r=-0.38, P=0.01). Fasting tHcy concentrations were significantly higher in the lower quartile of insulin concentration than in the upper quartile (27.7+/-12.7 vs 15.9+/-9.5, P=0.01). In multivariate analysis, tHcy was associated with serum creatinine (P=0.001), insulin (P=0.02) and folate concentration (P=0.03). Patients with the highest IGF-1 concentration had lower tHcy than patients with the lowest IGF-1 concentration (16.8+/-5.7 vs 23.3+/-11 micro mol/l, P=0.01). CONCLUSION: We observed an inverse relationship between insulin and tHcy in chronic, stable RTR.