Do statins reduce the risk of diabetic kidney disease?

Do statins reduce the risk of diabetic kidney disease?

Among patients with type 2 diabetes, initiation of statin therapy is associated with significantly lower risks of incident diabetic kidney disease (DKD) and kidney function decline, the data suggest. These results differ from those of larger studies, however.

In a retrospective multicenter cohort study including nearly 20,000 patients with type 2 diabetes, initiation of statin therapy was associated with a 28% reduction in the risk of DKD.

“These results suggest that statin initiation may be an effective and reasonable approach to prevent kidney disease in patients with type 2 diabetes,” writes study author Shiyu Zhou, a student at Southern Medical University in Guangzhou, in China, and coauthors. “The similar results in multiple sensitivity analyzes assessing reverse causality and unmeasured confounders also suggest that the results of the present study are robust.”

The data was published online on May 29 CMJ extension.

“Robust” bindings.

To examine the relationship between statin initiation and renal outcomes in patients with type 2 diabetes, the researchers analyzed data from the China Renal Data System. Eligible patients had type 2 diabetes and were hospitalized between January 1, 2000 and May 26, 2021.

The mean age of the participants was 62.2 years and 55.5% were men. In all, 7,272 participants were statin initiators and 12,586 were not. The mean duration of follow-up was 1.6 years.

The primary outcome measure of the study was DKD, defined as a composite of renal dysfunction and sustained proteinuria for at least 90 days. Secondary outcomes included decline in renal function, defined as a sustained > 40% reduction in estimated glomerular filtration rate.

Statin initiation was associated with lower risks of DKD (hazard ratio [HR], 0.72) and decline in renal function (HR, 0.60). “These associations were robust, being unaffected by differences in clinical features or pattern of dyslipidemia,” the authors write.

Compared with participants with inadequate lipid control (low-density lipoprotein cholesterol [LDL-C] 3.4 mmol/L), those with intensive control (LDL-C < 1.8 mmol/L) had the lowest risk of developing DKD (HR, 0.51).

The researchers also evaluated the relationships between various types of statins and renal outcomes. The HR for DKD ranged from 0.65 to 0.88 for patients taking lipophilic statins (such as simvastatin, pitavastatin, fluvastatin, and atorvastatin) and from 0.46 to 0.75 for patients taking hydrophilic statins (such as pravastatin and rosuvastatin).

Finally, the researchers found a significant positive association between statin initiation and increased use of oral hypoglycemic drugs (odds ratio [OR]1.75).

Although current Chinese guidelines recommend statin therapy for all patients with type 2 diabetes aged 40 years and older, 36.6 percent of eligible participants were prescribed statins during the study period,” which is less than [the rates] in Canada (54.0% for males and 45.3% for females) and the United States (41.6%),” the authors write. “Suboptimal compliance with this recommendation could contribute to the higher risk of progression of renal disease that we observed in our study population. Our findings suggest that there is an urgent need to promote guideline-compliant care in real-world clinical practice in China.”

Monitor blood sugar

Commenting on the results for Medscape Medical News, Ishak Mansi, MD, a professor of internal medicine at the University of Central Florida College of Medicine in Orlando, said “much stronger data points to the opposite of the findings in this study.” Notably, Mansi pointed to a meta-analysis of randomized controlled trials that reported that, compared with no use, statin use was associated with an increased risk of renal failure (OR, 1.14).

“Randomized controlled trials are considered the gold standard for evaluating drug efficacy,” Mansi said. He and his colleagues published a large observational study that also found a higher rate of kidney disease progression in statin users than in nonusers (OR, 1.16).

“Statins should be prescribed to reduce cardiovascular disease … not to prevent kidney disease,” Mansi said. He suggested that the findings of the current study could be related to study size or different confounding factors. “For example, statin users may be more health-conscious individuals and, therefore, may have better outcomes because of their health awareness, not necessarily because of statins. Or the other way around: statin users may be more sick, that’s why their doctors prescribed statins. So, the worse outcomes may be because they were sicker, not because of the statins.”

Finally, Mansi pointed out that the US Food and Drug Administration and Health Canada have issued warnings about the association of statin use with increases in blood glucose and A1c levels. “Physicians should ask their patients to test their blood sugar more often when starting or escalating statins. In an article we recently published, we discussed this issue. Our personal non-evidence-based recommendations were to check hemoglobin A1c 3 to 6 months after starting statins and annually thereafter”.

The study was supported by grants from the National Key R&D Program of China and the National Natural Science Foundation of China. The work was also supported by the Outstanding Youths Development Scheme of Nanfang Hospital, Southern Medical University. Zhou and Mansi reported no relevant financial dealings.

CMJ extension. Published May 29, 2023. Full text

Kate Johnson is a Montreal-based freelance medical journalist who has written on all areas of medicine for more than 30 years.

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