NDT Advance Access originally published online on December 8, 2007
Nephrology Dialysis Transplantation 2008 23(4):1460-1461; doi:10.1093/ndt/gfm856
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Cinacalcet, fetuin-A and interleukin-6
E-mail: nigiot{at}inwind.itSir,
We read with interest the article by Messa et al., demonstrating that cinacalcet increases osteoprotegerin (OPG) and decreases fetuin-A serum levels, with no changes of interleukin-6 (IL-6) values [1].
Fetuin-A is downregulated in the presence of acute or chronic inflammation, with an inverse relationship to C-reactive protein (CRP) [2].
Haemodialyzed patients have reduced serum fetuin-A levels compared with the normal population; moreover, serum fetuin-A levels are decreased during a single haemodialysis session [3].
IL-6 is an acute phase protein, which can be involved in the vascular calcification process, IL-6 being the main stimulant for the hepatic production of CRP.
The half-life of IL-6 is only 2–4 h and is also more variable, while on the other hand, the greater stability of the concentrations and longer half-life (
20 h) of CRP probably contribute to the greater predictive value of this protein for cardiovascular risk.
It would be interesting to know the blood levels of CRP not reported in this article.
The authors also state that no significant changes were made to dosages of concomitant medications.
However, Table 1 shows a 20% reduction in vitamin D mean dose, an 8% reduction in sevelamer dosage and an 8.6% increase of calcium carbonate.
In previous studies, sevelamer was shown to decrease CRP levels and also to attenuate the progression of calcifications [4]. On the other hand, vitamin D inhibits the synthesis of IL-6 and other inflammatory cytokines, and slows the inflammatory process, thereby limiting the increase of hepatic synthesis of CRP [5].
Therefore, a reduction of vitamin D and sevelamer intake could contribute per se to the calcification process, due to the reduced capacity to inhibit CRP synthesis. Also, the single haemodialysis session can significantly reduce fetuin-A levels, but no information can be drawn from this article about dialysis modalities.
Based on these considerations, we could argue that the observed changes in OPG and fetuin-A levels are attributable to the various modifications of the therapeutic approach, rather than to the single introduction of cinacalcet.
Only with further experimental research and controlled clinical trials we could better define the correlation between cinacalcet therapy and proteins involved in the vascular calcification process.
Conflict of interest statement. None declared.
Nephrology and Dialysis Unit, Department of Medicine, Cardinal Massaja Hospital, ASL 19 Asti, Asti (AT), 14100, Italy
References
- Messa P, Alberti L, Como G, et al. Calcimimetic increases osteoprotegerin and decreases fetuin-A levels in dialysis patients. Nephrol Dial Transplant (2007) 22:2724–2725.
[Free Full Text] - Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med (1999) 340:448–454.
[Free Full Text] - Cozzolino M, Galassi A, Biondi ML, et al. Decreased serum fetuin-A levels after a single haemodialysis session. Nephrol Dial Transplant (2007) 22:290–291.
[Free Full Text] - Ferramosca E, Burke S, Chasan-Taber S, et al. Potential anti-atherogenic and anti-inflammatory properties of sevelamer in maintenance hemodialysis patients. Am Heart J (2005) 149:820–825.[CrossRef][Web of Science][Medline]
- Timms PM, Mannan N, Hitman GA, et al. Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? QJM (2002) 95:787–796.
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