Data Suggest Statins May Protect Kidney

SAN DIEGO -- Patients with statin-treated dyslipidemia had about one third fewer kidney stones as compared with nonusers, according to results of a large cohort study.

Overall, statin use was associated with a 50% reduction in the risk of nephrolithiasis. After controlling for concomitant medication use, statin users had a 70% lower risk of kidney stones.

The benefit associated with statin was more than twice as great in women, James Masterson, MD, of the Naval Medical Center in San Diego, reported here at the American Urological Association meeting.

"This analysis suggests that hyperlipidemic patients with stone disease should consider treatment with statin medications in addition to dietary modification and increased exercise," Masterson and colleagues concluded in a poster presentation.

In a separate study reported at the AUA meeting, statin use was associated with significantly better survival after surgery for renal cell carcinoma (RCC).

The two studies add to the evidence supporting a beneficial effect of the lipid-modifying drugs in noncardiovascular conditions, for which the drugs were originally developed. Therapeutic effects beyond lipid modification have been ascribed to statins' pleiotropic activities, which include anti-inflammatory effects and modification of endothelial dysfunction.

Statins' documented efficacy in coronary atherosclerosis provided a rationale for examining the drugs' effects on nephrolithiasis, which some research has indicated might have a vascular etiology, Masterson noted. To study the relationship, investigators retrospectively reviewed 60,000 randomly selected records of outpatients from the year 2000. After excluding 7,816 pediatric patients, the adult cohort comprised 52,814 patients who had mean age of 31 at enrollment.

The records showed that 702 patients developed nephrolithiasis during a mean follow-up of 61.7 months. Multivariate analysis identified hypertension (P<0.001), hyperlipidemia (P=0.04), obesity (P<0.001), and tobacco use (P=0.04) as risk factors for nephrolithiasis.

Of the total cohort, 7,743 patients had hyperlipidemia. During follow-up, 887 of those patients initiated treatment with hydrochlorothiazide and 88 started potassium citrate (known risks factors for nephrolithiasis). Exclusion of those patients left 6,768 patients for the final analysis (3,684 men and 3,084 women).

The hyperlipidemic subgroup had a mean age of 45 at enrollment and a mean follow-up of 96.4 months. Masterson reported that 4,167 hyperlipidemic patients used statins during follow-up, and 228 patients developed nephrolithiasis, including 107 statin users. Men and women had an identical nephrolithiasis incidence of 3.4%.

By univariate analysis, statin use was associated with a nephrolithiasis hazard ratio of 0.5 versus nonusers (P<0.001). Multivariate analysis showed that statin use was an independent predictor of stone risk in hyperlipidemic patients, associated with a hazard ratio of 0.3 versus nonusers (P<0.001). Factors that significantly increased the risk of nephrolithiasis were hypertension (P<0.001), coronary artery disease (P=0.006), and obesity (P=0.002).

In the second study, Samuel Kaffenberger, MD, of Vanderbilt University in Nashville, Tenn., investigated the relationship between statin use and RCC.

Investigators retrospectively reviewed medical records for 967 patients who underwent partial or total nephrectomy for RCC from 1995 through 2010 and for whom statin use could be ascertained.

After a median follow-up of 42.9 months, statin users had a 3-year disease-specific survival of 90% compared with 83% for patients who did not receive statins (P=0.045). A multivariable analysis that included 620 patients showed that statin use remained an independent predictor of improved overall survival (OR 0.60, P=0.005) and disease-specific survival (OR 0.48, P=0.007).

Although the anti-cancer mechanisms of statins remain unclear, that should not stand in the way of clinical evaluation, Kaffenberger said during an AUA press briefing.

"I think there has been enough of an accumulation of evidence for improved survival with statins in various cancers -- including renal cell carcinoma -- that I think it's absolutely reasonable to start a prospective trial to see whether it will help with cancer survival," he said. "It's a pretty safe drug. Severe complications are pretty rare, and we have better ways to know who is going to have severe complications among people who are on statins."

Others cautioned about over-interpreting the results, including Peter Clark, MD, also of Vanderbilt.

"It is not reasonable to tell people right now that if they get a diagnosis of kidney cancer they should go on a statin," added Clark, who was a senior investigator in the study. "That's way, way, way premature."

Source: www.medpagetoday.com