The homocysteine confusion: now, more is better?

To the Editor: After reading the paper by Wrone et al in a recent issue of Kidney International regarding methylenetetrahydrofolate reductase (MTHFR) variant and cardiovascular disease (CVD) in renal patients1 we have some concerns we would like to express. First, it is troubling to accept that the TT genotype is bad, but high serum homocysteine is good. The sentences "TT genotype is associated with hyper-homocysteinemia" and "suggests a lifetime of abnormal homocysteine metabolism," are confirmed in studies measuring homocysteinemia before any vitamin supplementation, as in our 136 patients Figure 1a. Therefore, if Wrone et al conclude that patients "with the TT genotype may benefit the most from homocysteine reduction," it seems unacceptable to conclude that another goal is to keep high homocysteinemia to prevent CVD, as drawn from a logistic regression analysis in which a single determination of a parameter changing over time should not be used2, and crucial parameters such as phosphorus and parathyroid hormone are missing3. Second, the duration of dialysis of their patients (3.5 4 to .9 4.7 years) is probably too short to allow the conclusion that "The presence of TT genotype impairs survival in [end-stage renal disease] ESRD patients." This assumption is not confirmed in our patients who have had a longer duration of dialysis Figure 1b. As MTHFR mutation might be related to longevity4, its role in ESRD has not yet been clarified. Finally, only if the MTHFR variant confer risks by a phenotype different from homocysteinemia could the cost incurred in the recommendation of the screening for this polymorphism ($270) instead of homocysteine ($5.60) be routinely extended.