Renal effects of aspirin and low dose methotrexate in rheumatoid arthritis.

Seideman, P; Müller-Suur, R

doi:10.1136/ard.52.8.613

Cited by 44 publications

(42 citation statements)

References 8 publications

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“…For ibuprofen and naproxen, studies showed conflicting results [33][34][35] . Four studies evaluating high-dose ASA (1.3-4.5 g/day) reported an increase of serum concentration of MTX [45][46][47][48] (Level of evidence 4).…”

Section: Resultsmentioning

confidence: 99%

Canadian Recommendations for Use of Methotrexate in Patients with Rheumatoid Arthritis

Katchamart¹,

Bourré‐Tessier²,

Donka³

et al. 2010

J Rheumatol

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Objective.To develop recommendations for the use of methotrexate (MTX) in patients with rheumatoid arthritis.Methods.Canadian rheumatologists who participated in the international 3e Initiative in Rheumatology (evidence, expertise, exchange) in 2007–2008 formulated 5 unique Canadian questions. A bibliographic team systematically reviewed the relevant literature on these 5 topics. An expert committee consisting of 26 rheumatologists from across Canada was convened, and a set of recommendations was proposed based on the results of systematic reviews combined with expert opinions using a nominal group consensus process.Results.The 5 questions addressed drug interactions, predictors of response, strategies to reduce non-serious side effects, variables to assess clinical response, and incorporating patient preference into decision-making. The systematic review retrieved 93 pertinent articles; this evidence was presented to the expert committee during the interactive workshop. After extensive discussion and voting, a total of 9 recommendations were formulated: 2 on drug interactions, 1 on predictors of response, 2 on strategies to reduce non-serious side effects, 3 on variables to assess clinical response, and 1 on incorporating patient preferences into decision-making. The level of evidence and the strength of recommendations are reported. Agreement among panelists ranged from 85% to 100%.Conclusion.Nine recommendations pertaining to the use of MTX in daily practice were developed using an evidence-based approach followed by expert/physician consensus with high level of agreement.

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Section: Resultsmentioning

confidence: 99%

Canadian Recommendations for Use of Methotrexate in Patients with Rheumatoid Arthritis

Katchamart¹,

Bourré‐Tessier²,

Donka³

et al. 2010

J Rheumatol

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“…Low dose, which was thought to be safe to the kidney, has been shown to be nephrotoxic in patients with rheumatoid arthritis. Glomerular function and tubular function are reported to be altered after low-dose MTX therapy in patients with rheumatoid arthritis [16,17] . The potential toxicity of high-dose MTX can be prevented by vigorous hydration and alkalinization of the patient.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Infiltration and Oxidative Stress May Play a Critical Role in Methotrexate-Induced Renal Damage

Kolli¹,

Abraham²,

Isaac

et al. 2009

Chemotherapy

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Background: Nephrotoxicity is one of the adverse side effects of methotrexate (MTX) chemotherapy. The mechanism of renotoxicity of MTX is not fully understood. It is essential to understand the mechanism of nephrotoxicity of MTX in order to diminish the side effects and hence maximize the benefits of chemotherapy. Objectives: The aim of the study was to verify whether oxidative stress and neutrophil infiltration play a role in MTX-induced renal damage using a rat model. Methods: Adult male rats were administered MTX at the dose of 7 mg/kg body weight intraperitoneally for 3 consecutive days and sacrificed 12 or 24 h after the last dose. Vehicle-treated rats served as controls. The kidneys were removed and used for light microscopic and biochemical studies. Myeloperoxidase activity, a marker of neutrophil infiltration was measured in kidney homogenates along with the markers of oxidative damage including protein carbonyl content, protein thiol and malondialdehyde. The activities of the antioxidant enzymes, namely glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase, were also assayed. Results: MTX treatment induced damage to the glomeruli and tubules. Plasma creatinine levels in the MTX-treated rats were significantly elevated compared with controls. A significant increase in myeloperoxidase activity (p < 0.05) was observed in the kidneys of MTX-treated rats. Protein carbonyl content and malondialdehyde, sensitive and reliable markers of oxidative damage to proteins and lipids, respectively, were significantly elevated (p < 0.01) in the kidneys of MTX-treated rats compared with controls. The activities of the antioxidant enzymes, namely, superoxide dismutase and glutathione peroxidase, were significantly elevated (p < 0.01 and p < 0.05, respectively) in kidneys of rats following MTX treatment. Conclusion: The results of the present study provide evidence for the role of neutrophil infiltration and oxidative stress in MTX-induced renal damage. Administration of inhibitors of myeloperoxidase or scavenging hypochlorous acid, the product of myeloperoxidase, by supplementation with antioxidants as an adjuvant therapy may be promising in alleviating the renal side effect of MTX.

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“…In contrast, plasma clearance studies [12] indi cated that low-dose MTX can indeed provoke significant nephrotoxicity in man involving tubules and glomeruli.…”

Section: Discussionmentioning

confidence: 94%

“…Miescher et al [11] also stated that no unequivocal signs of renal toxicity could be detected in kidney biopsy specimens after prolonged treatment with MTX. However, the recent clearance studies of Seideman et al [12] showed significant renal effects in man follow ing treatment with low-dose MTX.…”

Section: Introductionmentioning

confidence: 99%

Nephrotoxicity of Low-Dose Methotrexate in Guinea Pigs: An Ultrastructural Study

Ma²,

Hm³

et al. 1996

Nephron

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The nephrotoxicity of low-dose methotrexate (MTX) and the rescue effect of leucovorin were studied by electron-microscopic examination of the kidney of guinea pigs. One group received MTX as a single weekly dose of 10 mg/kg, i.p.; a second group received a similar dose divided into three equal fractions. The third group received MTX rescued with an equal dose of leucovorin. The distal convoluted tubule showed cell swelling, fragmentation of the endoplasmic reticulum and loss of mitochondrial cristae and matrix. Leucovorin minimized these changes. The proximal tubule and the glomerulus were not affected. Low-dose MTX induced a nephrotoxicity in the distal convoluted tubule which could be minimized by leucovorin. Mild myelosuppression was also observed.

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Renal effects of aspirin and low dose methotrexate in rheumatoid arthritis.

Cited by 44 publications

References 8 publications

Canadian Recommendations for Use of Methotrexate in Patients with Rheumatoid Arthritis

Canadian Recommendations for Use of Methotrexate in Patients with Rheumatoid Arthritis

Neutrophil Infiltration and Oxidative Stress May Play a Critical Role in Methotrexate-Induced Renal Damage

Nephrotoxicity of Low-Dose Methotrexate in Guinea Pigs: An Ultrastructural Study

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