Do statins have a beneficial effect on the kidney?
Do statins have a beneficial effect on the kidney?
Clinical studies indicate that lipid-lowering agents might inhibit the progression of kidney disease.
To ascertain whether statins improve renal outcomes.
The investigators conducted a systematic review and meta-analysis of studies that reported the effect of statins on kidney function or proteinuria. They searched EMBASE and MEDLINE (in March 2005), the Cochrane Controlled Trials Register, abstracts from large nephrology meetings, the metaRegister of Controlled Trials, article reference lists and their own libraries to identify suitable studies. No language restrictions were placed on the search and studies could be published or unpublished. Randomized controlled or randomized crossover trials in adults were included in the analysis; those that enrolled patients with end-stage renal disease were excluded. The overall differences in renal outcomes between the statin and control groups were calculated using random-effects models.
Annual change in estimated glomerular filtration rate (eGFR; the definition also included creatinine clearance) was the primary endpoint. Change in proteinuria or albuminuria was a secondary endpoint.
The analysis included 27 studies (n = 39,704; follow-up 3-73 months), of which 4 (15%) had a Jadad score >3. Among the 21 trials that reported eGFR, the rate of renal function decline was 76% lower in the statin groups than the control groups (weighted mean difference 1.22 ml/min per year; 95% CI 0.44-2.00 ml/min per year). When disease subgroups were analyzed separately, there remained a meaningful difference in eGFR between the statin and control groups in the 38,311 patients with cardiovascular disease (0.93 ml/min per year; 95% CI 0.10-1.76 ml/min per year), but not in the patients with diabetes (n = 122), glomerulonephritis (n = 222) or hypertension (n = 212). Restricting the analysis to trials with ≥1 year of follow-up did not substantially alter the findings. Univariate meta-regression analysis of factors including age, baseline serum cholesterol level, baseline eGFR and type of statin revealed that only the latter significantly influenced the effect of statins on eGFR, with atorvastatin-treated patients showing a reduction in renal function decline of 2.5 ml/min per year (95% CI 1.8-3.2 ml/min per year; P <0.001) compared with patients who received other statins. When the trials that reported proteinuria or albuminuria were combined (a total of 18 studies), the standardized mean difference in outcome between statin and control groups was meaningful (-0.58 SD; 95% CI -0.98 to -0.17 SD). Restricting the analysis to trials with ≥1 year of follow-up again did not markedly alter the results. None of the covariates examined showed a significant association with the effect of statins on urinary protein excretion. There was no difference in the impact of statins on proteinuria between any of the four disease subgroups.
Statins appear to have a small beneficial effect on the rate of kidney function decline (particularly in patients with cardiovascular disease), and proteinuria.
Synopsis
Background
Clinical studies indicate that lipid-lowering agents might inhibit the progression of kidney disease.
Objective
To ascertain whether statins improve renal outcomes.
Design and Intervention
The investigators conducted a systematic review and meta-analysis of studies that reported the effect of statins on kidney function or proteinuria. They searched EMBASE and MEDLINE (in March 2005), the Cochrane Controlled Trials Register, abstracts from large nephrology meetings, the metaRegister of Controlled Trials, article reference lists and their own libraries to identify suitable studies. No language restrictions were placed on the search and studies could be published or unpublished. Randomized controlled or randomized crossover trials in adults were included in the analysis; those that enrolled patients with end-stage renal disease were excluded. The overall differences in renal outcomes between the statin and control groups were calculated using random-effects models.
Outcome Measures
Annual change in estimated glomerular filtration rate (eGFR; the definition also included creatinine clearance) was the primary endpoint. Change in proteinuria or albuminuria was a secondary endpoint.
Results
The analysis included 27 studies (n = 39,704; follow-up 3-73 months), of which 4 (15%) had a Jadad score >3. Among the 21 trials that reported eGFR, the rate of renal function decline was 76% lower in the statin groups than the control groups (weighted mean difference 1.22 ml/min per year; 95% CI 0.44-2.00 ml/min per year). When disease subgroups were analyzed separately, there remained a meaningful difference in eGFR between the statin and control groups in the 38,311 patients with cardiovascular disease (0.93 ml/min per year; 95% CI 0.10-1.76 ml/min per year), but not in the patients with diabetes (n = 122), glomerulonephritis (n = 222) or hypertension (n = 212). Restricting the analysis to trials with ≥1 year of follow-up did not substantially alter the findings. Univariate meta-regression analysis of factors including age, baseline serum cholesterol level, baseline eGFR and type of statin revealed that only the latter significantly influenced the effect of statins on eGFR, with atorvastatin-treated patients showing a reduction in renal function decline of 2.5 ml/min per year (95% CI 1.8-3.2 ml/min per year; P <0.001) compared with patients who received other statins. When the trials that reported proteinuria or albuminuria were combined (a total of 18 studies), the standardized mean difference in outcome between statin and control groups was meaningful (-0.58 SD; 95% CI -0.98 to -0.17 SD). Restricting the analysis to trials with ≥1 year of follow-up again did not markedly alter the results. None of the covariates examined showed a significant association with the effect of statins on urinary protein excretion. There was no difference in the impact of statins on proteinuria between any of the four disease subgroups.
Conclusion
Statins appear to have a small beneficial effect on the rate of kidney function decline (particularly in patients with cardiovascular disease), and proteinuria.
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