The effect of statins on urinary albumin excretion and glomerular filtration rate: results from both a randomized clinical trial and an observational cohort study.
BACKGROUND
Statins improve cardiovascular outcome, but less is known on the renal outcome. We, therefore, studied the relationship between the use of statins and urinary albumin excretion (UAE) and glomerular filtration rate (GFR) in two settings: a randomized controlled trial (RCT) and an observational cohort study, in which patients were included to study the impact of an elevated UAE on renal and cardiovascular prognosis.


METHODS
We used data from the Prevention of REnal and Vascular ENd-stage Disease Intervention trial (PREVEND-IT) and the PREVEND cohort study. The PREVEND-IT subjects (788 with a UAE 15-300 mg/day) received pravastatin 40 mg/day vs placebo and/or fosinopril 20 mg/day vs placebo in a 2x2 factorial-RCT design. Of the 3440 cohort subjects, 469 used statins during the 4-year follow-up period. Multivariate-regression adjusted for confounding factors and the propensity score was used to estimate the relation between statin use and UAE and GFR.


RESULTS
In the RCT, pravastatin did not change UAE or GFR, neither in fosinopril yes/no subgroups. In the observational cohort, statin use was associated with a rise in UAE (+12.1%), compared with statin non-use (+3.6%, P<0.001). This rise was most pronounced in those on statins prior to the first screening [+24.8% (95% CI: 11.9-39.2)], those using statins>3 years [+18.5% (7.3-30.8)] and those with >1 or >2 defined daily doses (+15.7 and +17.3%, respectively). These differences remained significant after adjustment for relevant variables and propensity score. The rise in UAE could not be attributed to a higher dose or a specific statin. GFR fell in 4 years in both statin users and non-users (4.6+/-13.5 and 2.4+/-11.2, respectively). The fall in GFR between groups was not different after adjustment (P=0.11).


CONCLUSIONS
We conclude from the RCT data that statins do not lower UAE in subjects selected because of an elevated UAE instead of hyperlipidaemia. In the observational cohort study, the use of statins similarly was not associated with a fall in UAE; UAE instead increased. Statin treatment was not associated with a significant change in GFR in these subjects with only modestly impaired GFR.
Atthobari
Jarir
J
Department of Social Pharmacy, Pharmacoepidemiology & Pharmacotherapy, Groningen University for Drug Exploration (GUIDE), Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Brantsma
Auke H
AH
Gansevoort
Ron T
RT
Visser
Sipke T
ST
Asselbergs
Folkert W
FW
van Gilst
Wiek H
WH
de Jong
Paul E
PE
de Jong-van den Berg
Lolkje T W
LT
D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000188:drug therapy* / Q000652:urine; D002318:Cardiovascular Diseases / Q000503:physiopathology / Q000517:prevention & control / Q000652:urine; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000503:physiopathology / Q000517:prevention & control / Q000652:urine; D007678:Kidney Glomerulus / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011446:Prospective Studies
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors