title: Renal effects of atorvastatin and rosuvastatin in patients with diabetes who have progressive renal disease (PLANET I): a randomised clinical trial.
abstract: 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.
  
  
  RESULTS
  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%).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  AstraZeneca.
authors: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands. Electronic address: d.de.zeeuw@umcg.nl.
authors: Dick
authors: D
authors: de Zeeuw
authors: AstraZeneca, Wilmington, DE, USA.
authors: Deborah A
authors: DA
authors: Anzalone
authors: AstraZeneca, Wilmington, DE, USA.
authors: Valerie A
authors: VA
authors: Cain
authors: Cardiovascular/Metabolic Unit, Covance, Princeton, NJ, USA (formerly AstraZeneca, Wilmington, DE, USA).
authors: Michael D
authors: MD
authors: Cressman
authors: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
authors: Hiddo J Lambers
authors: HJ
authors: Heerspink
authors: Department of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Bruce A
authors: BA
authors: Molitoris
authors: AstraZeneca, Wilmington, DE, USA.
authors: John T
authors: JT
authors: Monyak
authors: Department of Medical Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Faculty of Health Science, Aarhus University, Aarhus, Denmark.
authors: Hans-Henrik
authors: HH
authors: Parving
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
authors: Giuseppe
authors: G
authors: Remuzzi
authors: Diabetes and Cardiovascular Center, University of Missouri, Columbia, MO, USA.
authors: James R
authors: JR
authors: Sowers
authors: Department of Nephrology and Hypertension, Cleveland Clinic, Cleveland, OH, USA.
authors: Donald G
authors: DG
authors: Vidt
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000069059:Atorvastatin; D003404:Creatinine / Q000652:urine; D048909:Diabetes Complications / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005060:Europe; D005464:Fluorobenzenes / Q000494:pharmacology / Q000627:therapeutic use*; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D009656:North America; D011507:Proteinuria; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013020:South America; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D005464:Fluorobenzenes; D006538:Heptanoic Acids; D008055:Lipids; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D003404:Creatinine