C-Reactive Protein Level in Dialysis Patients: Weak Genetic Influence and Nonspecific Clinical Meaning

In their interesting study, Zhang et al1 found a weak association between C-reactive protein (CRP) gene variation and CRP serum level at baseline and no association with longitudinal CRP level after the start of dialysis therapy in white patients with chronic kidney disease. Moreover, no association was found between haplotypes of the CRP gene and incident cardiovascular disease (CVD).1 Both findings, although apparently unexpected, are of importance.

As shown by several studies, including our own, intraindividual variation in serum CRP levels is remarkable in dialysis patients.2, 3 If genetic factors do not play the primary role, then the variability in CRP levels over time is caused mainly by environmental factors. Subclinical4 and full-blown5 infections, changes in dialysis conditions, and changes in comorbid conditions, such as diabetes, hypertension, atherosclerosis, congestive heart failure, and dyslipidemias, can cause fluctuations in CRP levels.6 All these factors should be taken into consideration when we estimate inflammation in this population.2, 6 However, the genetic influence seems to be weak.

The second negative finding in the study of Zhang et al,1 regarding CVD prediction based on variation in CRP gene, also is not surprising. For the same reasons, the predictive value of CRP level for incident CVD also is weaker than previously thought, and CRP gene polymorphisms are not associated with coronary events in the general population.7, 8, 9 Thus, both negative results in the study published in AJKD add essential new and confirmatory data serving our understanding about CRP level increase and clinical meaning in dialysis patients.