A more novel link is reported in this month’s JASN: a manuscript by Betjes et al describes an association between ESRD patients with CMV-positivity and those with EPO resistance. It turns out that individuals infected with CMV have an altered profile of T-cells: they tend to have high percentages of CD4+ T-cells which lack the co-stimulatory molecule CD28, whereas patients who are CMV negative contain very small (less than 5%) numbers of these cells. These CD4+ CD28- cells apparently are very pro-inflammatory, capable of secreting large amounts of IFN-gamma and TNF-alpha, which the authors cite as a plausible mechanism to explain why CMV-positive dialysis patients tended to have higher EPO requirements (12,000 units versus 6,300 units per week) than CMV-negative dialysis patients.
The study is potentially significant in that it implicates a common virus in aspects of the chronic inflammatory state known to be associated with poor outcomes in CKD and ESRD, and even points towards antiviral medications as a potential therapy for preventing some of the cardiovascular complications of ESRD. Of course, the big caveat is that the association does not necessary reflect causality; for instance, it may be possible that “sicker”, more chronically-inflamed dialysis patients may simply be more susceptible to acquiring CMV seropositivity.
We discussed the Betjes et al paper in our journal club. The non-normal distribution of the Hb data in the CMV-ve group suggests numbers too small or too much missing data to make a conclusion as this is not seen in all major studies of Epo or IV iron. The p values of the regression analyses just make significance and they tellingly did not remove CMV status from their regression model to check their findings that CMV status impacted on Epo resistance. Finally the use of standard rather than hsCRP for a study claiming to look at factors affecting inflammation and Epo resistance is suspect. At best the evidence presented is insufficient to support the authors claims, at worst it is a retrospective analysis of transplant clinic data with some prospective flow cytometry work added in.