Each connection was formed by maximally 4 RCTs. We found no evidence for inconsistency in the network for eGFR decline and proteinuria using global tests p-value for inconsistency 0.
We found that almost all statins performed better than control Fig. The size of the nodes represents the number of RCTs for each treatment ranging from 1 to 30; 30 for control intervention.
The width of the connections represents the number of RCTs for each individual comparison ranging from 1 to 5. Effect of different statins compared to control treatment on annual eGFR decline.
Effects are presented as weighted mean differences. Positive values represent a slower eGFR decline. Prediction intervals represent the expected range of true effects of future similar studies and is suitable to assess the variability of an effect across different settings. Figure 4B shows the network plot for all statin treatments regarding proteinuria. Globally, there was no evidence for inconsistency p-value 0. Effect of different statins compared to control treatment on annual change in proteinuria.
Effects are presented as standardized mean differences SMD. Negative values represent a reduction of proteinuria. Prediction intervals represent the expected range of true effects in future similar studies and is suitable to assess the variability of effect across different settings.
Since we included RCTs with seven different types of statin treatments with one or more different dosages, networks of subgroups had only few closed loops. Therefore, estimates were based mostly on either direct or indirect evidence, but not on mixed evidence.
Since only a small number of RCTs with small sample sizes studied the effect of statins on proteinuria, we could not perform the aforementioned sensitivity analyses.
In this network meta-analysis, we showed that there are no substantial differences in the efficacy of seven different statins and dosages, with or without ezetimibe, regarding slowing down eGFR decline or reducing proteinuria.
In the pairwise meta-analysis we showed that use of statins lowered the rate of annual kidney function decline by 0. Our results are in line with a recent meta-analysis Su et al. The small difference in outcomes between the present study and Su et al.
In contrast to the study of Su et al. Including also treatments combining statins with ezetimibe, results in a more complete review of existing literature on lipid-lowering therapy by statins. Finally, we found that the beneficial effect of statins on eGFR decline was weaker in RCTs with a higher mean systolic blood pressure. Taken together, these results suggest that a high systolic blood pressure modifies the effect of statins on eGFR decline. Hypertension is most likely a stronger risk factor for kidney function decline compared to hypercholesteremia.
Therefore, we speculate that the positive effect of statins on kidney function decline is overwhelmed in the presence of high blood pressure. In our network meta-analysis, we specifically investigated the efficacy of individual statins and different dosages, using both direct and indirect evidence. We showed that each different statin compared to placebo had a beneficial effect on the annual eGFR decline and reduced proteinuria.
However, confidence intervals were broad for individual treatment comparisons in our network, due to the small number of RCTs contributing to each comparison. Su et al. However, they pooled for each statin all dosages. The validity of these comparisons may be limited, considering the clear differential effects of different dosages 8 , However, this result was strongly influenced by the study of Kinouchi et al.
We found that the second most efficacious statin on both renal endpoints was high dose atorvastatin, which improved the annual eGFR decline by 1. Statins also may have pleiotropic effects favourable for reducing CKD progression, such as lowering oxidative stress, reducing inflammation, and stabilizing atherosclerotic plaques 7 , The main strength of the current study is that we performed a network meta-analysis, in addition to a pairwise meta-analysis, to investigate differential effects of different statins with or without ezetimibe.
We only included RCTs because they are more likely to provide unbiased information. This network meta-analysis has several limitations. The I 2 statistic represents statistical heterogeneity, rather than clinically relevant heterogeneity, and is most strongly affected by the sample size of the individual studies.
Deciding whether it is valid to pool studies, should be based on the clinical relevance of any present heterogeneity, rather than solely on the I 2 statistic We used random effects models to take heterogeneity into account. Second, we found an asymmetric funnel plot regarding proteinuria, which may be an indication of publication bias. On the other hand, larger compared to smaller RCTs showed a weak but opposite effect.
Thus, the asymmetry may also be the consequence of inclusion of smaller RCTs with lower quality. Therefore, we cannot rule out that the beneficial effect of statins on proteinuria is an overestimation. Small studies therefore had a large impact on the network meta-analysis estimates, introducing inconsistencies especially in loops comprising small numbers of RCTs.
The advantage of a network analysis is that it takes both direct and indirect effects into account, reducing the impact of single studies with a small sample size. The much smaller effect of statins compared to control in double blind compared to open-label RCTs may suggest bias due to the lack of blinding in the open-label RCTs.
Since 17 out of 30 RCTs were open-label, we may have overestimated the beneficial effect on eGFR decline of statins compared to control. Third, due to the low number of RCTs contributing to each connection in the network meta-analyses, there was insufficient power to detect differences between statins.
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Corresponding author. Corresponding author: Eun Seok Kang. Abstract Background Although the beneficial effects of statin treatment in dyslipidemia and atherosclerosis have been well studied, there is limited information regarding the renal effects of statins in diabetic nephropathy. Methods We enrolled patients with diabetes who received statin treatment for more than 12 months.
Results In both statin treatment groups, patients showed improved serum lipid levels and significantly reduced eGFRs from Conclusion These results suggest that a moderate-intensity dose of atorvastatin has fewer detrimental effects on renal function than that of rosuvastatin. Keywords: Atorvastatin calcium, Rosuvastatin calcium, Diabetes mellitus, Renal insufficiency, chronic.
METHODS Study design and population In this study, subjects were identified by reviewing patient case notes using the electronic medical records at Severance Hospital, a tertiary university hospital in Korea. Clinical and laboratory parameters Clinical parameters, including age, sex, height, weight, duration of DM, history of hypertension and cardiac disease, and statin treatment information, were collected by carefully reviewing electronic medical records.
Open in a separate window. Variable Atorvastatin Rosuvastatin P value Crude 1 reference 1. References 1. Taming the chronic kidney disease epidemic: a global view of surveillance efforts. Kidney Int. US renal data system annual data report. Am J Kidney Dis.
Park CW. Diabetic kidney disease: from epidemiology to clinical perspectives. Diabetes Metab J. Renal effects of atorvastatin and rosuvastatin in patients with diabetes who have progressive renal disease PLANET I : a randomised clinical trial. Lancet Diabetes Endocrinol. Current challenges in diabetic nephropathy: early diagnosis and ways to improve outcomes. Endocrinol Metab Seoul ; 31 — Cholesterol: a renal risk factor in diabetic nephropathy? Dyslipidemia associated with chronic kidney disease.
Open Cardiovasc Med J. Eligibility for statin treatment in Korean subjects with reduced renal function: an observational study. Koo BK. Statin for the primary prevention of cardiovascular disease in patients with diabetes mellitus. Campese VM, Park J. HMG-CoA reductase inhibitors and the kidney. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR trial.
Effects of atorvastatin and rosuvastatin on renal function: a meta-analysis. Int J Cardiol. Liao JK. Safety and efficacy of statins in Asians. Am J Cardiol. A new equation to estimate glomerular filtration rate. Ann Intern Med.
Determinants of decline in glomerular filtration rate in nonproteinuric subjects with or without diabetes and hypertension. Clin J Am Soc Nephrol. Progression of kidney dysfunction in the community-dwelling elderly. Factors associated with the decline of kidney function differ among eGFR strata in subjects with type 2 diabetes mellitus. Int J Endocrinol. Diamond Analogous pathobiologic mechanisms in glomerulosclerosis and atherosclerosis.
Kidney Int Suppl. Renal injury of diet-induced hypercholesterolemia in rats. Early mechanisms of renal injury in hypercholesterolemic or hypertriglyceridemic rats. J Am Soc Nephrol. Inhibitory effect of pravastatin on transforming growth factor beta1-inducible gene h3 expression in a rat model of chronic cyclosporine nephropathy.
Am J Nephrol. Preventive effect of cerivastatin on diabetic nephropathy through suppression of glomerular macrophage recruitment in a rat model. Role of hyperlipidemia in progressive renal disease: focus on diabetic nephropathy. Methods: We searched Medline, the international medical database, to conduct a systematic review of the literature on the efficacy and tolerability of statins in CKD and renal transplant patients and on specific recommendations for dosage adjustments in this population.
Results: The efficacy of statins in decreasing total cholesterol and LDL-cholesterol levels in dialysis and renal transplant patients is similar to that in the general population. On the other hand, large-scale randomized clinical trials among CKD 4D and renal transplant ALERT patients do not demonstrate that statins significantly decrease rates of cardiovascular disease. They have a beneficial effect on proteinuria and lower the rate of kidney function deterioration in patients with dyslipidemia.
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