Treatment of dyslipidemia in chronic kidney disease: Effectiveness and safety of statins

Abstract

Several cardiovascular (CV) risk factors may explain the high rate of CV death among patients with chronic kidney disease (CKD). Among them both traditional and uremia-related risk factors are implicated and, moreover, the presence of kidney disease represents "per se" a multiplier of CV risk. Plasma lipid and lipoprotein profiles are changed in quantitative, but above all in qualitative, structural, and functional ways, and lipoprotein metabolism is influenced by the progressive loss of renal function. Statin therapy significantly reduces cholesterol synthesis and both CV morbidity and mortality either directly, by reducing the lipid profile, or via pleiotropic effects; it is supposed to be able to reduce both the progression of CKD and also proteinuria. These observations derive from a post-hoc analysis of large trials conducted in the general population, but not in CKD patients. However, the recently published SHARP trial, including over 9200 patients, either on dialysis or pre-dialysis, showed that simvastatin plus ezetimibe, compared with placebo, was associated with a significant low-density lipoprotein cholesterol reduction and a 17% reduction in major atherosclerotic events. However, no benefit was observed in overall survival nor in preserving renal function in patients treated. These recent data reinforce the conviction among nephrologists to consider their patients at high CV risk and that lipid lowering drugs such as statins may represent an important tool in reducing atheromatous coronary disease which, however, represents only a third of CV deaths in patients with CKD. Therefore, statins have no protective effect among the remaining two-thirds of patients who suffer from sudden cardiac death due to arrhythmia or heart failure, prevalent among CKD patients. The safety of statins is demonstrated in CKD by several trials and recently confirmed by the largest SHARP trial, in terms of no increase in cancer incidence, muscle pain, creatine kinase levels, severe rhabdomyolysis, hepatitis, gallstones and pancreatitis; thus confirming the handiness of statins in CKD patients. Here we will review the latest data available concerning the effectiveness and safety of statin therapy in CKD patients.

Increased HDL Size and Enhanced Apo A‐I Catabolic Rates Are Associated With Doxorubicin‐Induced Proteinuria in New Zealand White Rabbits

“…Therefore, large (HDL2b and HDL2a) and medium-sized (HDL3a) particles were enriched in triacylglycerols during proteinuria in rabbits, whereas the cholesterol content of HDL subclasses remained unchanged. These data are consistent with the elevated cholesterol and triacylglycerol plasma levels frequently reported in patients with chronic kidney disease [32][33][34], particularly in patients with nephrotic syndrome; these patients are characterized by an increased apo A-I FCR [34], likewise observed in the present study. The increased catabolism of apo A-I in these patients has been associated with a loss of cholesterol acyltransferase (LCAT) activity via urine [35], and it has been also observed in other LCAT deficiencies [36].…”

Serum Beta Hydroxybutyrate Concentrations in Cats with Chronic Kidney Disease, Hyperthyroidism, or Hepatic Lipidosis

“…Hypercholesterolemia is a well‐documented complication of CKD in dogs, with 55% of dogs with CKD having increased serum cholesterol levels 12. Dyslipidemia is a common finding in human patients with CKD of various etiologies, although this does not always result in an increased total serum cholesterol, but rather changes in the distribution of high, low, and very low density lipoproteins 13. Further studies could be indicated to determine if hypercholesterolemia is a repeatable finding in cats with CKD since information in the literature is limited for this species.…”

Identifying Patient Candidates for IL-1 Inhibition: Lessons From Real-World Cases

“…Reports suggest that CKD is a chronic inflammatory disease, as it is now recognized that rapid kidney function loss in CKD is independently associated with increased baseline levels of CRP and soluble tumor necrosis factor receptor-2 [41]. Therefore, the attenuation of the inflammatory response to renal injury on vascular structures induced by statin therapy may explain the renoprotective actions of these agents in patients with CKD [42], and suggests that inflammation represents an important target for pathogenetic interventions both in AKI and the progression of CKD. Recent evidence suggests that interleukin-1 (IL-1), a proinflammatory cytokine, plays a major role in mediating gouty arthritis inflammation [6,24,[43][44][45][46].…”