No associations between prolactin concentrations and response to erythropoiesis-stimulating agents in hemodialysis patients.

BACKGROUND: The effect of serum prolactin levels on the response to erythropoiesis-stimulating agents (ESA) in patients on chronic hemodialysis is unknown. METHODS: We included 111 stable hemodialysis patients in this study and examined the association of serum prolactin concentrations with the response to ESA. Accordingly we implemented an ESA index as a measure of therapeutic efficacy. The two outcomes of this cohort study were the association of prolactin concentrations with response to ESA, both at baseline (cross-sectional component) and after 1-year of follow-up (prospective component), and the presence of macroprolactin. RESULTS: Two male patients, but none of the female patients, had serum prolactin concentrations within the reference range. Following precipitation with polyethylene glycol (PEG), 17 males (25.4%) and 9 females (20.6%) had serum prolactin concentrations within the reference range. Females had somewhat higher levels than males: 39.8 (IQR 32.3-64.5) versus 27.8 (IQR 23.4-47.8) ng/ml (p = 0.003). The ratio of prolactin(PEG)/prolactin(Native) was greater than 0.60 in 103 patients (92.8%), thus excluding significant amounts of macroprolactin. From uni- and multivariate analyses we did not find associations of serum prolactin concentrations with a response to ESA either at baseline or at follow-up. CONCLUSIONS: From this prospective study we provide evidence that elevated serum prolactin levels are not related to the presence of macroprolactin in chronic hemodialysis patients. Furthermore, serum prolactin concentrations are not associated with the response to erythropoietic therapy in these individuals.

Effect of TCN2 776C>G on vitamin B12 cellular availability in end-stage renal disease patients.

BACKGROUND: Transcobalamin II is a serum protein that transports vitamin B12 from the intestine to the tissues. This complex, holo-transcobalamin II, may reflect vitamin B12 availability in the body. Conflicting data exist with regard to the effect of a polymorphism in the gene coding for transcobalamin II, TCN2 776C>G, on transcobalamin II levels in the general population, which in turn may affect holo-transcobalamin II, vitamin B12, as well as total homocysteine (tHcy) plasma levels. The effect of TCN2 776C>G on vitamin B12 cellular availability in dialysis patients is unknown. METHODS: We examined the effect of TCN2 776C>G on holo-transcobalamin II, vitamin B12, and tHcy plasma concentrations in 120 dialysis patients. RESULTS: Holo-transcobalamin II levels were normal or supranormal in all patients and showed a linear association with albumin (r = 0.205, P = 0.025) and with vitamin B12 (r = 0.778, P = 0.001), but not with age, creatinine, body mass index, tHcy, ln-tHcy, vitamin B6, plasma folate, and red blood cell folate concentration. TCN2 776C>G showed no effect on holo-transcobalamin II, vitamin B12, and tHcy concentration [one-way analysis of variance (ANOVA), post-hoc Scheffe test]. Multiple linear regression analyses showed that albumin and B12 are independently associated with holo-transcobalamin II, whereas TCN2 776C>G and MTHFR 677C>T had no effect. Independent predictors of ln-tHcy included creatinine, red blood cell folate, and the MTHFR 677TT genotype. There was also an effect of the TCN2 776CC genotype on ln-tHcy levels in this multivariate analysis, however, that deserves cautious interpretation because there was no effect of TCN2 genotypes by ANOVA and Scheffe test [median ln-tHcy concentrations according to TCN2 genotypes (micromol/L): CC, 3.22; CG, 3.30; GG, 3.23]. CONCLUSION: TCN2 776C>G does not influence holo-transcobalamin II or vitamin B12 levels, and has no major effect on tHcy concentrations of end-stage renal disease patients.

Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: results of the Vienna multicenter study.

Homocysteine is associated with atherosclerosis and enhanced cardiovascular risk. In previous studies, treatment with folic acid up to 15 mg/d failed to correct hyperhomocysteinemia in the majority of end-stage renal disease patients. A dose of 30 or 60 mg of folic acid per day was compared with 15 mg/d in an attempt to normalize hyperhomocysteinemia in 150 hemodialysis patients. In a randomized, double-blind, multicenter study, 144 patients completed the 4-wk treatment period and 121 patients completed the 6-mo follow-up. Total homocysteine plasma levels were reduced by 32.1% (15 mg/d), 29. 9% (30 mg/d), or 37.8% (60 mg/d) with no significant differences found between the three treatment groups. Baseline total homocysteine plasma concentration was an independent predictor of the response to folic acid therapy (P = 0.0001), whereas the 5, 10-methylenetetrahydrofolate reductase polymorphisms (MTHFR 677C --> T and 1298A --> C) had no influence. Nevertheless, patients with the MTHFR 677TT genotype more frequently attained normal total homocysteine plasma levels than patients with the CC or CT genotype (P = 0.025). In response to 60 mg of folic acid per day, TT genotype patients had lower folate plasma levels compared to CC or CT genotype patients (P = 0.016). After completion of the 4-wk treatment period with 30 or 60 mg of folic acid per day, there was a marked rebound of total homocysteine plasma levels at the end of the follow-up in patients with the MTHFR 677TT genotype, which even exceeded baseline values in several patients (P = 0.0001). This study clearly demonstrates that doses of 30 or 60 mg of folic acid per day are not more effective than 15 mg/d in reducing hyperhomocysteinemia in regular hemodialysis patients. Patients with the MTHFR 677TT genotype are more likely to realize normal total homocysteine plasma levels. Folic acid at 30 or 60 mg/d but not 15 mg/d results in a rebound of total homocysteine plasma concentrations when treatment is stopped.