Effects of Statins on Renal Outcome in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis

Abstract

BackgroundHMG CoA reductase inhibitors (statins) are known to prevent cardiovascular disease and improve lipid profiles. However, the effects of statins on renal outcomes, including decline in estimated glomerular filtration rate (eGFR) and proteinuria in patients with chronic kidney disease (CKD), are controversial. This meta-analysis evaluated the impact of statins on renal outcomes in patients with CKD.Materials and MethodsWe comprehensively searched the databases of MEDLINE, EMBASE, and Cochrane Databases. The inclusion criteria were published RCT and cohort studies comparing statin therapy to placebo or active controls in patients with CKD (eGFR <60 ml/min/1.73 m2) not requiring dialysis. The primary outcome was the differences in the change of eGFR. We also examined change of protein concentration in urine as a secondary outcome. A meta-analysis comparing statin and its control groups and a subgroup analysis examining intensity of statin were performed.ResultsFrom 142 full-text articles, 10 studies were included in the meta-analysis. Overall, there was a significant difference in rate of eGFR change per year favoring statin group (mean difference (MD) = 0.10 ml/min/1.73 m2, 95% CI: 0.09 to 0.12). In our subgroup analysis, those who received high-intensity statins had a significant difference in eGFR with a MD of 3.35 (95% CI: 0.91 to 5.79) ml/min/1.73 m2 compared to control. No significant change in eGFR was found with moderate- and low-intensity statin therapy. Compared with the control group, the statin group did not have a difference in reduction of proteinuria with MD in change of proteinuria of 0.19 gm/day (95% CI: -0.02 to 0.40).ConclusionOverall, there was a difference in change of eGFR between the statin and control group. High-intensity statins were found to improve a decline in eGFR in population with CKD not requiring dialysis compared with control, but moderate- and low-intensity statins were not. Statins were not found to decrease proteinuria in patients with CKD.

Effect of Statin Therapy on the Progression of Autosomal Dominant Polycystic Kidney Disease. A Secondary Analysis of the HALT PKD Trials

“…Clinical trials showing a benefit of pre-angiography statin administration to prevent contrast-induced acute kidney injury typically used high doses of a high-potency statin 51–53 . A meta-analysis of trials examining statin therapy to prevent progression of chronic kidney disease did not find a benefit of low-intensity statins, but subjects in the high-intensity study arms did have a significantly slower decline in eGFR compared to controls 54 . Among high-potency statins, atorvastatin may have better renoprotective effects than rosuvastatin, based on a direct comparison in the PLANET (Prospective Evaluation of Proteinuria and Renal Function in Diabetic Patients with Progressive Renal Disease) trials 55 .…”

Efficacy of Statin Treatment in Early-Stage Chronic Kidney Disease

“…Several studies have evaluated the mechanism by which statins affect CKD [3, 12–15, 21, 27, 28]. Statins not only lower lipid profiles, they also exert anti-proteinuric effects [13].…”

“…High-dose statin therapy ameliorated the decline in eGFR in CKD patients (eGFR <60 mL/min/1.73 m 2 ), while statin therapy had no effect on renal progression in patietns with low-dose prescriptions [3]. Hence, the renoprotective effect of statins may vary according to the dose and type of statin, as well as CKD stage.…”

“…Individuals with CKD have a higher risk of premature mortality related to cardiovascular disease (CVD) even during the early stages of disease; this represents a significant challenge for physicians [2]. Renal dysfunction increases inflammation, oxidative stress, platelet dysfunction, endothelial dysfunction, proteinuria, and electrolyte imbalances [3–6]. Moreover, these alterations may be related to a higher risk of CVD events [7].…”

Pediatric Statin Administration: Navigating a Frontier with Limited Data

“…For example, patients with sickle cell disease can develop oxidative stress and chronic inflammation to their distal vasculature as a result of transient vaso-occlusion and subsequent [196][197][198] Decrease decline in GFR Prevent contrast induced acute kidney injury Decrease risk of stroke Fracture injuries, bone healing, & osteoporosis [199][200][201][202][203][204] Promote mesenchymal cell differentiation to osteoblasts Protect osteoblasts from apoptosis Reduce osteoclast activity and bone resorption HIV [205][206][207][208][209][210][211] Slow progression of vascular disease on ART Improve flow-mediated vasodilation Implement immunomodulation Reduce all-cause mortality Immunomodulation [212][213][214] Inhibit interferon production Decrease T cell activation Infection [215][216][217][218] Reduce risk of mortality from bacterial and viral infection Lupus [219][220][221][222] Reduce C-reactive protein Reduce circulating chemokines Improve endothelial function Polycystic ovary syndrome [223][224][225] Reduce markers of inflammation Reduce androgenic steroid concentrations Rheumatoid arthritis [226][227][228][229][230][231] Reduce risk of mortality Reduce joint pain/swelling Reduce markers of inflammation Rotator cuff injury 232,233 Stimulate migration and adhesi...…”