NDT Advance Access originally published online on February 6, 2007
Nephrology Dialysis Transplantation 2007 22(3):964; doi:10.1093/ndt/gfm053
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Reply
Email: L.T.W.de.Jong-van.den.Berg{at}rug.nlSir,
In response to our report, that in the PREVEND study statins were not found to improve GFR decline over time, Athyros et al. [1] ask whether the presence or absence of such an effect may depend on the type of statin used, the extent of the hypolidaemic effect and the patient category.
With respect to the type of statin used, Athyros refers in his letter to studies in which a favourable effect on GFR was found for pravastatin and for atorvastatin. In our randomized controlled trial (RCT) we used pravastatin, and in the observational cohort, simvastatin, atorvastatin and pravastatin were used. We found no difference between the three statins: in none of the groups did the statin had a favourable effect, neither a rise in GFR nor a fall in urinary albumin excretion (UAE).
The second option, whether the effect of the statin on renal function is dependent on the hypolipidaemic effect, is an interesting one. With this in mind, we already studied the effect of the dose of the statin in relation to the renal effect. This aspect could not be studied in the RCT, as we used a fixed dose regimen [2]. In the observational cohort however, we did not find a dose-dependent effect of the statin on the change in GFR. With respect to the effect of the statin on UAE, there was dose dependency, indicating that a higher dose was associated with a greater rise (instead of a fall) in UAE than the lower dose. To answer this question more precisely, we additionally tested whether the change in total cholesterol in both the RCT and the observational cohort was related to the change in GFR and/or the change in UAE. In both studies, the change in GFR and the change in UAE were not associated with the change in cholesterol.
The last option, that the effect of statins on kidney function is dependent on the patient category, can of course never be excluded. We found modest differences between subjects participating in the RCT (who were treated with statins because they had an elevated albuminuria while plasma cholesterol was never >8.0 mmol/l) and subjects of the observational cohort (who were treated because the general practitioner found statins indicated according to general guidelines). In none of the studies did we, find an improvement in GFR or a fall in UAE. As we already emphasized in our discussion, our subjects had a relatively well-preserved GFR, with only 8.2% of the subjects having a stage 3 or 4 GFR. This does not allow us to conclude that the effects in those subjects would be different. We thus cannot draw conclusions on the potentially beneficial effects of statins on GFR in stage 3 and 4 subjects. We wished only to conclude that we, disappointingly, could not show beneficial effects of statins on the kidney in subjects with an elevated UAE.
Department of Nephrology and
Department of Pharmacoepidemiology
University of Groningen
The Netherlands
References
- Atthobari J, Brantsma AH, Gansevoort RT, et al. (2006) The effect of statins on urinary albumin excretion and glomerular filtration rate: results from both a randomized clinical trial and an observational cohort study. Nephrol Dial Transplant 21:3106–3114.
[Abstract/Free Full Text] - Asselbergs FW, Diercks GF, Hillege HL, et al. (2004) Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND IT) Investigators. Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation 110:2809–2816.
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