Letters and Replies

Nephrol Dial Transplant (2011) 26: 2715–2719

Advance Access publication 19 May 2011

Statins and resistance to erythropoiesis-stimulating agents: are the two associated? In their recent paper in Nephrology Dialysis Transplantation, Panichi et al. brilliantly demonstrated a strong association between erythropoiesis-stimulating agent (ESA) resistance on the one hand, and mortality and cardiovascular events on the other hand in the RISCAVID cohort of haemodialysis patients [1]. Moreover, they showed that higher interleukin-6 (IL-6) levels and lower albumin and transferrin saturation (TSAT) values are independent risk factors for presenting a higher ESA resistance index (ERI). To the contrary, acetylsalicylic acid (ASA) and sevelamer usage were associated with a decreased risk of presenting a high ERI, even after controlling for other predictors. The authors attributed this latter finding to the anti-inflammatory actions of these drugs, although none of the drugs reported in the study (ASA, Sevelamer and statins) statistically significantly influenced IL-6 or C-reactive protein (CRP) levels (data not shown). However, we were disappointed that the authors did not display the proportion of patients taking statins in the different ERI quartiles of patients (Table 4). This would have been of utmost interest considering that these drugs have been demonstrated previously to reduce inflammatory markers

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Letters and Replies

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in chronic kidney disease patients [2, 3] and to further inhibit the production of IL-6 in response to CRP stimulation [4, 5]. Furthermore, preliminary data have suggested that statins could reduce prohepcidin (the precursor peptide of hepcidin, a keystone mediator of inflammatory anaemia) levels in endstage renal disease patients with anaemia [6]. Moreover, we were puzzled to read in the discussion section of the article that: ‘factors that influenced ERI were low-serum albumin, IL-6 as well as TSAT and therapy with Sevelamer, statins and ASA’. It would be of paramount scientific importance, in our opinion, that the authors include the data about the proportion of patients taking statins in each ERI quartile and that they clarify whether or not these drugs were significantly associated with resistance to ESAs.

Nephrol Dial Transplant (2011) production by isolated human monocytes from chronic kidney disease patients. Biomed Pharmacother 2007; 61: 360–365 4. Li JJ, Chen XJ. Simvastatin inhibits interleukin-6 release in human monocytes stimulated by C-reactive protein and lipopolysaccharide. Coron Artery Dis 2003; 14: 329–334 5. Liang YJ, Shyu KG, Wang BW et al. Simvastatin inhibits C-reactive protein-induced pro-inflammatory changes in endothelial cells by decreasing mevalonate pathway products. Cardiology 2008; 110: 182–190 6. Arabul M, Gullulu M, Yilmaz Y et al. Effect of fluvastatin on serum prohepcidin levels in patients with end-stage renal disease. Clin Biochem 2008; 41: 1055–1058

doi: 10.1093/ndt/gfr249

Conflict of interest statement. None declared.

1. Panichi V, Rosati A, Bigazzi R et al. Anaemia and resistance to erythropoiesis-stimulating agents as prognostic factors in haemodialysis patients: results from the RISCAVID study. Nephrol Dial Transplant 2011; 26: 2641–2648 2. Panichi V, Paoletti S, Mantuano E et al. In vivo and in vitro effects of simvastatin on inflammatory markers in pre-dialysis patients. Nephrol Dial Transplant 2006; 21: 337–344 3. Mantuano E, Santi S, Filippi C et al. Simvastatin and fluvastatin reduce interleukin-6 and interleukin-8 lipopolysaccharide (LPS) stimulated

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Department of Nephrology, Alexandre Granger Valle´e CHRU Montpellier, Bernard Canaud Montpellier, France E-mail: [email protected]