Effect of lipid reduction on the progression of renal disease: A meta-analysis

Statins frequently are used to prevent cardiovascular events. Several recent studies suggest that statins also may have renal benefits, although this is controversial. This systematic review and meta-analysis were performed to assess the effect of statins on change in kidney function and urinary protein excretion. Medline, EMBASE, the Cochrane Central Register of Controlled Trials, conference proceedings, and the authors' personal files were searched. Published or unpublished randomized, controlled trials or crossover trials of statins that reported assessment of kidney function or proteinuria were included, and studies of individuals with ESRD were excluded. Data were extracted for study design, subject characteristics, type of statin and dose, baseline/change in cholesterol levels, and outcomes (change in measured or estimated GFR [eGFR] and/or urinary protein excretion). Weighted mean differences were calculated for the change in GFR between statin and control groups using a random-effects model. A random-effects model also was used to calculate the standardized mean difference for the change in urinary protein excretion between groups. Twenty-seven eligible studies with 39,704 participants (21 with data for eGFR and 20 for proteinuria or albuminuria) were identified. Overall, the change in the weighted mean differences for eGFR was statistically significant (1.22 ml/min per yr slower in statin recipients; 95% confidence interval [CI] 0.44 to 2.00). In subgroup analysis, the benefit of statin therapy was statistically significant in studies of participants with cardiovascular disease (0.93 ml/min per yr slower than control subjects; 95% CI 0.10 to 1.76) but was NS for studies of participants with diabetic or hypertensive kidney disease or glomerulonephritis. The standardized mean difference for the reduction in albuminuria or proteinuria as a result of statin therapy was statistically significant (0.58 units of SD greater in statin recipients; 95% CI 0.17 to 0.98). Statin therapy seems to reduce proteinuria modestly and results in a small reduction in the rate of kidney function loss, especially in populations with cardiovascular disease.

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Statins for Improving Renal Outcomes: A Meta-Analysis

Background
Statins have uncertain benefits in chronic kidney disease (CKD) as individual trials may have insufficient power to determine whether treatment effects differ with severity of CKD.

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Benefits and harms of statin therapy for persons with chronic kidney disease: a systematic review and meta-analysis.

Background
Cardiovascular disease (CVD) is the most frequent cause of death in people with early stages of chronic kidney disease (CKD), for whom the absolute risk of cardiovascular events is similar to people who have existing coronary artery disease. This is an update of a review published in 2009, and includes evidence from 27 new studies (25,068 participants) in addition to the 26 studies (20,324 participants) assessed previously; and excludes three previously included studies (107 participants). This updated review includes 50 studies (45,285 participants); of these 38 (37,274 participants) were meta-analysed.

Objectives
To evaluate the benefits (such as reductions in all-cause and cardiovascular mortality, major cardiovascular events, MI and stroke; and slow progression of CKD to end-stage kidney disease (ESKD)) and harms (muscle and liver dysfunction, withdrawal, and cancer) of statins compared with placebo, no treatment, standard care or another statin in adults with CKD who were not on dialysis.

Search methods
We searched the Cochrane Renal Group's Specialised Register to 5 June 2012 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.

Selection criteria
Randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of statins with placebo, no treatment, standard care, or other statins, on mortality, cardiovascular events, kidney function, toxicity, and lipid levels in adults with CKD not on dialysis were the focus of our literature searches.

Data collection and analysis
Two or more authors independently extracted data and assessed study risk of bias. Treatment effects were expressed as mean difference (MD) for continuous outcomes (lipids, creatinine clearance and proteinuria) and risk ratio (RR) for dichotomous outcomes (major cardiovascular events, all-cause mortality, cardiovascular mortality, fatal or non-fatal myocardial infarction (MI), fatal or non-fatal stroke, ESKD, elevated liver enzymes, rhabdomyolysis, cancer and withdrawal rates) with 95% confidence intervals (CI).

Main results
We included 50 studies (45,285 participants): 47 studies (39,820 participants) compared statins with placebo or no treatment and three studies (5547 participants) compared two different statin regimens in adults with CKD who were not yet on dialysis. We were able to meta-analyse 38 studies (37,274 participants).

The risk of bias in the included studies was high. Seven studies comparing statins with placebo or no treatment had lower risk of bias overall; and were conducted according to published protocols, outcomes were adjudicated by a committee, specified outcomes were reported, and analyses were conducted using intention-to-treat methods. In placebo or no treatment controlled studies, adverse events were reported in 32 studies (68%) and systematically evaluated in 16 studies (34%).

Compared with placebo, statin therapy consistently prevented major cardiovascular events (13 studies, 36,033 participants; RR 0.72, 95% CI 0.66 to 0.79), all-cause mortality (10 studies, 28,276 participants; RR 0.79, 95% CI 0.69 to 0.91), cardiovascular death (7 studies, 19,059 participants; RR 0.77, 95% CI 0.69 to 0.87) and MI (8 studies, 9018 participants; RR 0.55, 95% CI 0.42 to 0.72). Statins had uncertain effects on stroke (5 studies, 8658 participants; RR 0.62, 95% CI 0.35 to 1.12).

Potential harms from statin therapy were limited by lack of systematic reporting and were uncertain in analyses that had few events: elevated creatine kinase (7 studies, 4514 participants; RR 0.84, 95% CI 0.20 to 3.48), liver function abnormalities (7 studies, RR 0.76, 95% CI 0.39 to 1.50), withdrawal due to adverse events (13 studies, 4219 participants; RR 1.16, 95% CI 0.84 to 1.60), and cancer (2 studies, 5581 participants; RR 1.03, 95% CI 0.82 to 130).

Statins had uncertain effects on progression of CKD. Data for relative effects of intensive cholesterol lowering in people with early stages of kidney disease were sparse. Statins clearly reduced risks of death, major cardiovascular events, and MI in people with CKD who did not have CVD at baseline (primary prevention).

Authors' conclusions
Statins consistently lower death and major cardiovascular events by 20% in people with CKD not requiring dialysis. Statin-related effects on stroke and kidney function were found to be uncertain and adverse effects of treatment are incompletely understood. Statins have an important role in primary prevention of cardiovascular events and mortality in people who have CKD.

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HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis.

In 13 of 15 randomized studies involving 1384 patients, statins reduced albuminuria and proteinuria. Since these outcomes were not the primary goals of the 15 clinical trials, we need larger trials...

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Meta-analysis: the effect of statins on albuminuria.

Effects of pravastatin on lipid levels, in vitro oxidizability of non-HDL lipoproteins and microalbuminuria in IDDM patients'

Effects of lipid-lowering drugs on the in vitro oxidizability of lipoproteins in diabetes

Song Zhen, Anxin Zhang, Jie Luo, Guanghai Xiong, Haibo Peng, Rang Zhou, Yuanfeng Li, Hongqiang Xu, Zhen Li, Wei Zhao, and Haoxiang Zhang. Prevalence of high-altitude polycythemia and hyperuricemia and risk factors for hyperuricemia in high-altitude immigrants. High Alt Med Biol. 00:000-000, 2023. Background: Few studies have investigated the epidemiology of chronic mountain sickness (CMS) in high-altitude immigrants. This study evaluated the prevalence of polycythemia and hyperuricemia (HUA) and risk factors for HUA in high-altitude immigrants. Methods: A cross-sectional study was conducted with 7,070 immigrants 15-45 years of age living on the Tibetan Plateau between January and December 2021. Information from routine physical examinations was obtained from each participant. Binary logistic regression analysis was performed to determine the correlation of several risk factors for HUA. Results: The prevalence of high-altitude polycythemia (HAPC) and HUA was 25.8% (28.7% in males and 9.4% in females) and 54.2% (59.9% in males and 22.5% in females), respectively. The highest prevalence of HAPC in males and females was observed in participants 26-30 and 21-25 years of age, respectively. The highest prevalence of HUA in both males and females was observed in participants 26-30 years of age. Binary logistic regression analysis showed that age, sex, and hemoglobin (Hb) concentration were risk factors for HUA, among which age was a negative factor and male sex and Hb concentration were positive factors. Conclusions: Immigrants are more susceptible to HAPC and HUA. The high prevalence of CMS of immigrants may be associated with Hb concentration, age, and sex.

Prevalence of High-Altitude Polycythemia and Hyperuricemia and Risk Factors for Hyperuricemia in High-Altitude Immigrants.

Relationship Between Weight-Adjusted Waist Index and Osteoporosis in the Senile in the United States from the National Health and Nutrition Examination Survey, 2017-2020.

A. Zhang

Papers

Effects of pravastatin on lipid levels, in vitro oxidizability of non-HDL lipoproteins and microalbuminuria in IDDM patients'

Effects of lipid-lowering drugs on the in vitro oxidizability of lipoproteins in diabetes

Prevalence of High-Altitude Polycythemia and Hyperuricemia and Risk Factors for Hyperuricemia in High-Altitude Immigrants.

Relationship Between Weight-Adjusted Waist Index and Osteoporosis in the Senile in the United States from the National Health and Nutrition Examination Survey, 2017-2020.