NDT Advance Access originally published online on February 22, 2005
Nephrology Dialysis Transplantation 2005 20(5):1015-1016; doi:10.1093/ndt/gfh681
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Statins and progression of renal failure: is a reconsideration of clinical practice guidelines justified?
Sir,In the 2002 and 2003 clinical practice guidelines (CPG) [1], it is stated that there is ‘insufficient evidence to recommend lipid-lowering therapy for the purpose of slowing the progression of chronic kidney disease (CKD)’. Recently, these guidelines were questioned on the basis of post hoc analyses of several large clinical trials, with cardiovascular disease (CVD) end-points, in the general population [2].
In the above-mentioned post hoc analyses, apart from the increased risk for type I errors [2], there are several limitations. Renal failure patients were excluded [1] and results regarding CKD progression are often based on fewer patients than initially included in the study [3]; glomerular filtration rate is indirectly estimated; adjustment for main factors influencing CKD progression is often incomplete and, when it is, changes the initial results [4], while data for albuminuria or microalbuminuria are frequently absent [5]. If the negative results of the ASCOT-LLA [6], VA-HIT [7] and ALERT [8] studies are added to these limitations, a motivated, based on post hoc analyses, reconsideration of the CPG seems, up to now, less urgent.
On the other hand, considering the impressive results achieved by statin treatment in studies with CVD end-points in the general population and taking into account the dyslipidaemia patterns in CKD patients, a few points of interest in this particular population are worth highlighting.
The main target, regarding lipids, in the majority of the studies in the general population, was elevated low-density lipoproteins (LDL) and total cholesterol (tChol). At initial stages of CKD, a similar dyslipidaemic pattern—due to nephrotic syndrome or to common causes of CKD such as diabetes, atherosclerosis, etc.—is frequently observed. Results based on studies in the general population can potentially be extrapolated (regarding hypolipidaemic treatment for CVD prevention) in CKD patients with a similar dyslipidaemic profile. The improvement of cardiovascular status—at least the haemodynamic benefit—should also be important for the stabilization or retardation of CKD progression. Furthermore, the pleiotropic effects of these drugs and specifically their actions on endothelial function, oxidative stress, inflammation, etc. might also be beneficial in slowing progression of CKD in this subgroup of patients.
In contrast, in patients with severe CKD in whom the dyslipidaemic pattern approaches that of patients with end-stage renal failure (ESRF) in renal replacement treatment (who usually have elevated triglycerides, low high-density lipoproteins and normal or low tChol and LDL), extrapolation of the general population study results might no longer be appropriate (mainly because this dyslipidaemic profile does not exist in the populations included in these studies). Furthermore, hypertriglyceridaemia is better treated with fibrates or hypolipidaemic drugs other than statins, which do not seem to have any beneficial effects on CKD progression [7]. Moreover, cholesterol lowering in this subgroup of CKD patients might even be inappropriate, especially if the ‘reverse epidemiology’, regarding the detrimental role of low tChol in ESRF patients' morbidity and mortality, is valid and also extended to the pre-dialysis population. Finally, malnutrition and aggravation of micro-inflammation, frequently observed in these late CKD stages, might be inter-related with dyslipidaemia and also have to be taken in consideration.
In any case, only studies in CKD populations (such as SHARP and PREVEND-IT [1]), with end-points related to renal function in time, can eventually give a definite answer to the question of whether lipid-lowering treatment is beneficial for the progression of CKD.
Conflict of interest statement. None declared.
1 Department of Nephrology General Hospital of Athens2 Department of Biopathology Eginition Hospital Medical School University of Athens3 Renal Unit Alexandra General Hospital Athens Greece Email: tsipg{at}hellasnet.gr
References
- Kidney Disease Outcomes Quality Initiative (K/DOQI) Group. K/DOQI clinical practice guidelines for management of dyslipidemias in patients with kidney disease. Am J Kidney Dis Suppl 2003; 41: S1–91
- Afzali B, Haydar AA, Vinen K, Goldsmith DJ. From Finland to fatland: beneficial effects of statins for patients with chronic kidney disease. J Am Soc Nephrol 2004; 15: 2161–2168
[Abstract/Free Full Text] - Tonelli M, Moye L, Sacks FM et al. Effect of pravastatin on loss of renal function in people with moderate chronic renal insufficiency and cardiovascular disease. J Am Soc Nephrol 2003; 14: 1605–1613
[Abstract/Free Full Text] - Muntner P, Coresh J, Smith JC et al. Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study. Kidney Int 2000; 58: 293–301[CrossRef][Web of Science][Medline]
- Collins R, Armitage J, Parish S et al. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003; 361: 2005–2016[CrossRef][Web of Science][Medline]
- Sever PS, Dahlof B, Poulter NR et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003; 361: 1149–1158[CrossRef][Web of Science][Medline]
- Tonelli M, Collins D, Robins S et al. Gemfibrozil for secondary prevention of cardiovascular events in mild to moderate chronic renal insufficiency. Kidney Int 2004; 66: 1123–1130[CrossRef][Web of Science][Medline]
- Fellström B, Holdaas H, Jardine AG et al. Effect of fluvastatin on renal end points in the Assessment of Lescol in Renal Transplant (ALERT) trial. Kidney Int 2004; 66: 1549–1555[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||