Tacrolimus and Nonsteroidal Anti-Inflammatory Drugs: An Association to Be Avoided

Vol. 25, No. 4, 2005

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Original Report: Laboratory Investigation

Tacrolimus and Nonsteroidal Anti-Inflammatory Drugs: An Association to Be Avoided
Rosa Maria C. Soubhia^a, Glória Elisa F. Mendes^a, Francine Zocoler Mendonça^a, Maria Alice S. Baptista^a, José Paulo Cipullo^b, Emmanuel A. Burdmann^a

^aDivision of Nephrology and
^bDivision of Internal Medicine, São José do Rio Preto Medical School, São Paulo, Brazil

Address of Corresponding Author

Am J Nephrol 2005;25:327-334 (DOI: 10.1159/000086569)

Key Words

Acute nephrotoxicity
Acute renal failure
Nonsteroidal anti-inflammatory drugs
Tacrolimus
Diclofenac
Rofecoxib
COX-1
COX-2
Selective cyclooxygenase inhibitors

Abstract

Background: Tacrolimus (FK) and nonsteroidal anti-inflammatory drugs (NSAIDs) can cause acute nephrotoxicity. The expanding use of tacrolimus and the intense consumption of NSAIDS increase the chances of their simultaneous use. Methods: Rats receiving a nonselective COX inhibitor (diclofenac, D) and FK or a selective COX-2 inhibitor (rofecoxib, RO) and FK were treated with FK (2 mg/kg/day), D (10 mg/kg/day), RO (3 mg/kg/day), FK+D, FK+RO and vehicle for 7 days on low-salt diet. Results: Both associations significantly impaired glomerular filtration rate (GFR; 0.63 ± 0.06 ml/min/100 g in FK+D, 0.83 ± 0.06 ml/min/100 g in FK+RO) which did not occur with single drug therapy (0.98 ± 0.03 ml/min/100 g in D, 1.06 ± 0.04 ml/min/100 g in RO, 0.99 ± 0.05 ml/min/ 100 g in FK) or vehicle (1.10 ± 0.05 ml/min/100 g). GFR decrease was significantly higher with FK+D. GFR impairment occurred without RBF or RVR major changes. Mild tubular vacuolization and dilatation and acute degenerative changes were observed in tubular cells. FK+D animals showed a marked weight loss, not observed in the other groups. FK+NSAIDs association decreased FK blood levels (1.73 ± 0.3 ng/ml in FK+D, 1.8 ± 0.3 ng/ml in FK+RO, 3.2 ± 0.4 ng/ml in FK, p < 0.05). Conclusions: The association of FK and nonselective or COX-2 selective NSAIDs in salt-depleted animals caused a significant GFR impairment and decreased FK blood levels.

Author Contacts

Emmanuel A. Burdmann, MD
Av. Brigadeiro Faria Lima 5416
São José do Rio Preto
15090-000 São Paulo (Brazil)
Tel. +55 17 32015712, Fax +55 17 2105712, E-Mail burdmann@famerp.br

Article Information

Received: March 18, 2005
Accepted: May 13, 2005
Published online: June 21, 2005
Number of Print Pages : 8
Number of Figures : 3, Number of Tables : 3, Number of References : 38

Medline Abstract (ID 15976495)

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