Oral Presentation ESA-SRB Conference 2015

Effect of low dose glucocorticoid therapy on arginine metabolism in patients with rheumatoid arthritis (#188)

Anjana Radhakutty 1 2 , Brenda L Mangelsdorf 2 , Sophie M Drake 3 , Andrew Rowland 1 4 , Malcolm D Smith 1 5 , Arduino A Mangoni 1 4 , Campbell H Thompson 1 6 , Morton G Burt 1 2
  1. School of Medicine, Flinders University, Adelaide, SA, Australia
  2. Southern Adelaide Diabetes and Endocrine Services, Repatriation General Hospital, Adelaide, SA, Australia
  3. Southern Adelaide Diabetes and Endocrine Services, RGH, Adelaide, SA, Australia
  4. Department of Clinical Pharmacology, Flinders Medical Centre, Adelaide
  5. Department of Rheumatology, Repatriation General Hospital, Adelaide, SA, Australia
  6. Discipline of Medicine, The University of Adelaide, Adelaide, SA, Australia

Background: Low dose prednisolone therapy is associated with better endothelial function in patients with rheumatoid arthritis (1). This contrasts findings in hypopituitary patients, where an increase in glucocorticoid dose impaired endothelial function (2). In the endothelium arginine is converted by nitric oxide synthase to citrulline and nitric oxide, a potent vasodilator. However, arginine can also be converted to ornithine or homoarginine, reducing its availability. Furthermore, the arginine metabolites asymmetric dimethyl arginine (ADMA), N-mono methylated arginine (MMA) and symmetric dimethyl arginine (SDMA) inhibit nitric oxide synthase directly or indirectly and are associated with increased cardiovascular risk. We hypothesized that rheumatoid arthritis causes specific changes in arginine metabolism that influence the response to glucocorticoids.

Methods: Eighteen patients with rheumatoid arthritis who had not taken prednisolone for > 6 months (non-GC users), 18 patients taking continuous oral prednisolone (6.5±1.8 mg/day) for > 6 months (GC users) and 20 healthy controls were studied. Fasting serum concentrations of 7 key components of arginine metabolism (arginine, homoarginine, citrulline, ornithine, ADMA, MMA and SDMA) were measured by ultra-performance liquid-chromatography.

Results: There were no significant differences in age, sex and glomerular filtration rate between the groups (Table). Non-GC users had higher arginine (p=0.001), citrulline (p=0.002), ADMA (p=0.004) and MMA (p<0.001) than controls, with no significant difference in ornithine, homoarginine and SDMA (Table). ADMA (p=0.03) and SDMA (p=0.03) were lower in GC users than non-GC users, with no significant differences in other arginine metabolites between these two groups (Table).

Conclusions: Rheumatoid arthritis per se is associated with changes in arginine metabolism, including an increase in ADMA. Long term prednisolone treatment in rheumatoid arthritis is associated with lower levels of ADMA. The latter might account, at least partly, for the improved endothelial function observed in these patients

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  1. 1) Radhakutty A, et al. 57th Annual Scientific Meeting of ESA, 2015, Melbourne, Australia. 2) Petersons CJ, et al. J Clin Endocrinol Metab 2014;99:2269-76.