Protection Against Nephropathy in Diabetes with Atorvastatin (PANDA): a randomized double-blind placebo-controlled trial of high- vs. low-dose atorvastatin(1)

Diabet Med. 2011 Jan;28(1):100-8. doi: 10.1111/j.1464-5491.2010.03139.x.

Abstract

Aims: To compare the renal effects of low- vs. high-dose atorvastatin in patients with Type 2 diabetes mellitus and optimally managed early renal disease.

Methods: We compared the 2-year progression of nephropathy in a double-blind randomized controlled trial of atorvastatin 80 mg/day (n = 60) vs. 10 mg/day (n = 59) in patients with Type 2 diabetes with microalbuminuria or proteinuria [mean (sd): age 64 years (10 years); HbA(1c) 7.7% (1.3%), 61 mmol/mol (10 mmol/mol); blood pressure 131/73 mmHg; renin-angiotensin system blocker use > 80%; dual blockade > 67%] recruited from diabetes clinics in Greater Manchester.

Results: Over (mean) 2.1 years of follow-up, the Modification of Diet in Renal Disease estimated glomerular filtration rate declined by 3 ml min(-1) 1.73 m(-2) in the combined group. The mean (95% CI) between-group difference during follow-up was not significant [2.2 ml min(-1) 1.73 m(-2) (-1.1 to 5.4 ml min(-1) 1.73: m(-2) ), P = 0.20] after adjusting for baseline differences in renal function; positive difference favours 80 mg dose. Similarly, there was no significant difference in creatinine clearance by Cockcroft and Gault [2.5 ml/min (-2.4 to 7.3 ml/min), P = 0.32]; serum creatinine/24-h urine collections [4.0 ml/min (-4.8 to 12.7 ml/min), P = 0.38]; cystatin C (P = 0.69); or 24-h urine protein or albumin excretion (P = 0.92; P = 0.93). We recorded no significant between-group differences in deaths or adverse events.

Conclusions: In patients with Type 2 diabetes with early renal disease, we found no statistical difference in renal function between those taking high- or low-dose atorvastatin over 2 years. We cannot exclude a beneficial effect of < 1.6 ml min(-1) 1.73 m(-2) year(-1) on Modification of Diet in Renal Disease estimated glomerular filtration rate, or if blood pressure management or if renin-angiotensin system blocker use had not been optimized.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / metabolism
  • Anticholesteremic Agents / administration & dosage*
  • Atorvastatin
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Nephropathies / chemically induced
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / metabolism
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Glomerular Filtration Rate
  • Heptanoic Acids / administration & dosage*
  • Humans
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney Failure, Chronic / chemically induced
  • Kidney Failure, Chronic / metabolism
  • Male
  • Middle Aged
  • Placebos
  • Pyrroles / administration & dosage*
  • Treatment Outcome
  • United Kingdom

Substances

  • Anticholesteremic Agents
  • Heptanoic Acids
  • Placebos
  • Pyrroles
  • Atorvastatin