A randomized trial of a 6-week course of celecoxib on proteinuria in diabetic kidney disease.
BACKGROUND
Preclinical data suggest that cyclooxygenase 2 inhibitors decrease proteinuria and preserve glomerular structure in animal models of diabetic nephropathy. The objective of this study is to compare the efficacy and safety of celecoxib with placebo for decreasing proteinuria in patients with diabetic nephropathy.


METHODS
Placebo-controlled double-blinded crossover design.


METHODS
24 patients with type 1 or 2 diabetes mellitus, proteinuria with protein of 500 mg/d or greater, and serum creatinine level of 3.0 mg/dL or less.


METHODS
Patients were randomly assigned to: (1) 6 weeks of celecoxib followed by a 3-week washout period, followed by 6 weeks of placebo followed by another 3-week washout; or (2) 6 weeks of placebo followed by a 3-week washout, followed by 6 weeks of celecoxib followed by another 3-week washout period. All patients were administered quinapril, 20 to 40 mg/d, or irbesartan, 150 to 300 mg/d. All patients were administered aspirin, 81 mg/d.


METHODS
Proteinuria was assessed by means of protein-creatinine ratio. Data were analyzed using the mixed-effect statistical model.


RESULTS
There was no significant difference in urinary proteinuria after 6 weeks of treatment with placebo or celecoxib (proteinuria ratio, celecoxib versus placebo, 1.041; 95% confidence interval, 0.846 to 1.282). Celecoxib had no significant effect on potassium or estimated glomerular filtration rate. Frequencies of adverse events were similar between the placebo and celecoxib treatments.


CONCLUSIONS
This pilot study was not designed to evaluate the safety or long-term clinical effects of celecoxib.


CONCLUSIONS
Celecoxib, 200 mg/d, for 6 weeks did not alter proteinuria. Few adverse events were noted in this high-risk population.
Rush University Medical Center, Chicago, IL 60607, USA. marvin_v_sinsakul@rush.edu
Marvin
M
Sinsakul
Mohammed
M
Sika
Roger
R
Rodby
John
J
Middleton
Yu
Y
Shyr
Heidi
H
Chen
Ernest
E
Han
Ruediger
R
Lehrich
Stephen
S
Clyne
Gerald
G
Schulman
Raymond
R
Harris
Julia
J
Lewis
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D000068579:Celecoxib; D003404:Creatinine / Q000097:blood; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D003928:Diabetic Nephropathies / Q000150:complications* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D008875:Middle Aged; D015233:Models, Statistical; D010865:Pilot Projects; D011507:Proteinuria / Q000188:drug therapy* / Q000209:etiology* / Q000652:urine; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077583:Quinapril; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D044005:Tetrahydroisoquinolines; D003404:Creatinine; D000068579:Celecoxib; D001241:Aspirin; D000077583:Quinapril