Articles
Renal effects of atorvastatin and rosuvastatin in patients with diabetes who have progressive renal disease (PLANET I): a randomised clinical trial

https://doi.org/10.1016/S2213-8587(14)70246-3Get rights and content

Summary

Background

The role of lipid-lowering treatments in renoprotection for patients with diabetes is debated. We studied the renal effects of two statins in patients with diabetes who had proteinuria.

Methods

PLANET I was a randomised, double-blind, parallel-group trial done in 147 research centres in Argentina, Brazil, Bulgaria, Canada, Denmark, France, Hungary, Italy, Mexico, Romania, and the USA. We enrolled patients with type 1 or type 2 diabetes aged 18 years or older with proteinuria (urine protein:creatinine ratio [UPCR] 500–5000 mg/g) and taking stable angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or both. We randomly assigned participants to atorvastatin 80 mg, rosuvastatin 10 mg, or rosuvastatin 40 mg for 52 weeks. The primary endpoint was change from baseline to week 52 of mean UPCR in each treatment group. The study is registered with ClinicalTrials.gov, number NCT00296374.

Findings

We enrolled 353 patients: 118 were assigned to rosuvastatin 10 mg, 124 to rosuvastatin 40 mg, and 111 to atorvastatin 80 mg; of these, 325 were included in the intention-to-treat population. UPCR baseline:week 52 ratio was 0·87 (95% CI 0·77–0·99; p=0·033) with atorvastatin 80 mg, 1·02 (0·88–1·18; p=0·83) with rosuvastatin 10 mg, and 0·96 (0·83–1·11; p=0·53) with rosuvastatin 40 mg. In a post-hoc analysis to compare statins, we combined data from PLANET I with those from PLANET II (a similar randomised parallel study of 237 patients with proteinuria but without diabetes; registered with ClinicalTrials.gov, NCT00296400). In this analysis, atorvastatin 80 mg lowered UPCR significantly more than did rosuvastatin 10 mg (−15·6%, 95% CI −28·3 to −0·5; p=0·043) and rosuvastatin 40 mg (−18·2%, −30·2 to −4·2; p=0·013). Adverse events occurred in 69 (60%) of 116 patients in the rosuvastatin 10 mg group versus 79 (64%) of 123 patients in the rosuvastatin 40 mg group versus 63 (57%) of 110 patients in the atorvastatin 80 mg group; renal events occurred in nine (7·8%) versus 12 (9·8%) versus five (4·5%).

Interpretation

Despite high-dose rosuvastatin lowering plasma lipid concentrations to a greater extent than did high-dose atorvastatin, atorvastatin seems to have more renoprotective effects for the studied chronic kidney disease population.

Funding

AstraZeneca.

Introduction

The number of patients with declining renal function progressing to end-stage renal disease is rising worldwide, particularly as a result of atherosclerosis and type 2 diabetes.1 Lifestyle and dietary changes can reduce the risk of adverse renal outcomes, as can glucose-lowering and blood pressure-lowering drugs.2, 3, 4, 5, 6 Nevertheless, residual progressive renal function loss is high,7 and end-stage renal disease imposes enormous health and cost burdens on high-income countries.8

Cholesterol is thought to be an important risk factor for loss of renal function. Experimental studies have shown that cholesterol might have a role in renal disease progression, and lowering cholesterol concentrations with statins has renoprotective effects.9 However, in clinical studies, statins seem to have varying effects on renal function,10 and a recent large study with a renal hard outcome failed to show that a combination of simvastatin and ezetimibe had a renoprotective effect.11, 12 We did the Prospective Evaluation of Proteinuria and Renal Function in Diabetic Patients with Progressive Renal Disease (PLANET I) trial to assess the renal effects of two different statins on patients with diabetes and proteinuria.

Section snippets

Study design and participants

We did this randomised, double-blind, parallel-group trial at 147 research centres in Argentina, Brazil, Bulgaria, Canada, Denmark, France, Hungary, Italy, Mexico, Romania, and the USA. During an 8-week lead-in period, patients with diabetes and proteinuria were given dietary advice and underwent optimisation of existing hypertension treatment and stopped taking statins (if applicable). Eligible patients were aged 18 years or older and had type 1 or type 2 diabetes with proteinuria (urine

Results

We did PLANET I from Feb 8, 2006, to March 3, 2009. We screened 1642 patients, of whom we enrolled 353. 118 patients were assigned to rosuvastatin 10 mg, 124 to rosuvastatin 40 mg, and 111 to atorvastatin 80 mg. 325 patients constituted the intention-to-treat population (figure 1); 47 patients (14·5%) had type 1 diabetes and 278 (85·5%) had type 2 diabetes. Baseline demographic, clinical, and biochemical characteristics and concomitant treatments were balanced between treatment groups (table 1;

Discussion

The PLANET I study showed that urinary protein excretion was reduced during 1 year of treatment with atorvastatin 80 mg, with no significant changes in eGFR in patients with diabetes and proteinuria. In patients given rosuvastatin 40 mg, urinary protein excretion was not significantly different from baseline, but the patients did have a significant decrease from baseline in eGFR, and doubling of serum creatinine and acute renal failure were more common in this group. Although the study was not

References (29)

  • HH Parving et al.

    The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes

    N Engl J Med

    (2001)
  • BM Brenner et al.

    Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy

    N Engl J Med

    (2001)
  • EJ Lewis et al.

    Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes

    N Engl J Med

    (2001)
  • Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy

    Lancet

    (1997)
  • Cited by (0)

    Dr Vidt died in April, 2013

    View full text