Statins Reduce Proteinuria, Mortality in CKD Patients

The drugs do not appear to prevent progression to ESRD, new meta-analysis finds.
The drugs do not appear to prevent progression to ESRD, new meta-analysis finds.

Statins improve survival and other outcomes in patients with chronic kidney disease (CKD), but they do not appear to slow progression to end-stage renal disease (ESRD), a new meta-analysis finds.

Since previous research yielded inconsistent results, Zhenhong Zhang, MD, Pinsheng Wu, MD, and colleagues at Southern Medical University in China, pooled data from 23 randomized controlled trials (1995–2014) including 39,419 participants for an updated meta-analysis. The causes of CKD included diabetes, hypertension, glomerulonephritis, autosomal dominant polycystic kidney disease, idiopathic membranous nephropathy, and metabolic syndrome. Eight types of statins were examined.

According to results published in Pharmacological Research, statins improved proteinuria, reducing urinary protein excretion to 682.68 mg daily. Statin treatment also reduced all-cause mortality by 22%.

“Statins unquestionably reduce the risk of death in populations with, or at low risk of cardiovascular disease,” the researchers stated. “Our study further indicated that statins had the same effect on non-end stage CKD.” Statins lower lipid levels, protect the vascular endothelium, stabilize plaques, and suppress inflammation.

Drs. Zhang, Wu, and colleagues were less certain about statins' effect on microalbuminuria. Statin use lowered the urine albumin excretion ratio to 26.73 µg/min. Despite this statistical improvement, a paucity of good-quality studies call for future investigation. Statins provide podocyte protection, prevent tuberinterstitial injury, and improve endothelial dysfunction, the investigators noted, but use of statins at large doses may raise microalbuminuria due to reduced protein trafficking across tubular cells.

Notably, statins did not reduce renal health events including kidney failure leading to dialysis or transplantation, a doubling of creatinine level, or a halving of glomerular filtration rate (GFR). One study, Study of Heart and Renal Protection (SHARP), accounted for most of the finding, so future research is still needed.

“These findings support the recommendations in the present guidelines for the use of statins in hyperlipidaemic early stage CKD patients,” the researchers concluded. Several recent meta-analyses support this finding. For example, statin therapy reduced major cardiovascular events by 18% in CKD patients with coronary diseases and by 23% in those with CKD only, according to a 2013 analysis by Wanyin Hou, MD, and colleagues published in the European Heart Journal (2013;34:1807-1817). A 2008 study by Giovanni F. M. Strippoli, MD, and colleagues published in BMJ (2008;336:645-651) similarly indicated that statins reduce fatal and non-fatal cardiovascular events by 19% and 23%, respectively. Evidence for renoprotective effects have been mixed. 

Among the limitations of the current analysis, variation in populations and interventions, such as the type of statin and dosage, may have influenced the results.

Source

  1. Zhang Z, Wu P, Zhang J, Wang S, and Zhang G. The Effect of Statins on Microalbuminuria, Proteinuria, Progression of Kidney Function, and All-cause Mortality in Patients With Non-end Stage Chronic Kidney Disease: A Meta-analysis. Pharmacol Res. doi:10.1016/j.phrs.2016.01.005. 
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