CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Charles F. Harper, MD* and
Terry A. Jacobson, MD
* Department of Medicine, Emory University Faculty Building, 49 Jesse Hill Jr. Drive SE, Atlanta, Georgia 30303 (Email: charper{at}emory.edu).
We appreciate the comments from Drs. Kassimatis and Konstantinopoulos concerning our review (1). The pre-clinical evidence suggesting that statins may cause renal fibrosis, mediated by transforming growth factor-beta signaling, is interesting but does not negate other pre-clinical studies suggesting reno-protection. When examining the randomized controlled clinical trial evidence (the gold standard), the totality of evidence does not indicate a statin-induced deleterious effect (2,3). A detailed discussion of pre-clinical trials was beyond the scope of our review, and it was our goal to provide some balance and perspective to the inordinate amount of attention focused on statin-induced proteinuria after the introduction of rosuvastatin.
We acknowledge that some pre-clinical trials indicate statins may have an immunomodulatory role; however, prospective randomized controlled trials to date do not demonstrate a clinically significant effect. In the 4D (Die Deutsche Diabetes Dialyse Studie) trial with diabetic hemodialysis patients, there was no significant difference in fatal infections in the atorvastatin arm (n = 60) compared with that in the placebo arm (n = 68) (4). The ALERT (Assessment of Lescol in Renal Transplantation Trial) study was comprised of renal transplant patients with varying degrees of renal insufficiency who were immunocompromised due to cyclosporine and other immunosuppressant drugs, yet fluvastatin and placebo infection rates were not significantly different (fluvastatin [n = 25], placebo [n = 26]) (5).
Finally, we do not advocate the use of statins as renoprotective agents; however, we do not believe there is sufficient evidence to discourage the use of these agents in chronic kidney disease (CKD) patients who are at high risk of developing coronary heart disease (1). In fact, the National Kidney Foundation clinical practice guidelines state that CKD patients should be placed in the "highest risk" category for cardiovascular disease (6). The real question is not whether statins are a double-edged sword; rather, are they an underutilized weapon in the battle to prevent coronary heart disease in CKD patients?
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1. Harper CR, Jacobson TA. Managing dyslipidemia in chronic kidney disease J Am Coll Cardiol 2008;51:2375-2384.[Abstract/Free Full Text]2. Tonelli M, Isles C, Craven T, et al. Effect of pravastatin on rate of kidney function loss in people with or at risk for coronary disease Circulation 2005;112:171-178.[Abstract/Free Full Text] 3. Sandhu S, Wiebe N, Fried LF, Tonelli M. Statins for improving renal outcomes: a meta-analysis J Am Soc Nephrol 2006;17:2006-2016.[Abstract/Free Full Text] 4. Wanner C, Krane V, Marz W, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis N Engl J Med 2005;353:238-248(erratum in N Engl J Med 2005;353:1640).[Abstract/Free Full Text] 5. Holdaas H, Fellstrom B, Jardine AG, et al. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial Lancet 2003;361:2024-2031.[CrossRef][Web of Science][Medline] 6. K/DOQI clinical practice guidelines Am J Kidney Dis 2003;41(Suppl 3)S1–237.
Related Article
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Statins in Patients With Chronic Kidney Disease: A Double-Edged Sword?
- Theodoros I. Kassimatis and Panagiotis A. Konstantinopoulos
J. Am. Coll. Cardiol. 2008 52: 1679.
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