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

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.

• Authors: M K Rutter, H R Prais, V Charlton-Menys, M Gittins, C Roberts, R R Davies, A Moorhouse, P Jinadev, M France, P G Wiles, J M Gibson, J Dean, P A Kalra, J K Cruickshank, P N Durrington
• Journal: Diabetic medicine : a journal of the British Diabetic Association (Diabet Med) Vol. 28 Issue 1 Pg. 100-8 (Jan 2011) ISSN: 1464-5491 [Electronic] England
• PMID: 21166851 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 The Authors. Diabetic Medicine © 2010 Diabetes UK.

Chemical References

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

Topics

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