Elsevier

Kidney International

Volume 53, Issue 1, January 1998, Pages 200-204
Kidney International

Original Article
Interactions between cyclosporine A and adenosine in kidney transplant recipients

https://doi.org/10.1046/j.1523-1755.1998.00727.xGet rights and content
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Interactions between cyclosporine A and adenosine in kidney transplant recipients. Adenosine is involved in a large number of physiological processes including immune response and vasomotor function. But its precise involvement in renal physiology is poorly understood. We have investigated the putative relationships between cyclosporine A (CsA) and adenosine (ADO) metabolism in kidney transplant recipients (KTR). We first compared ADO plasma levels in three groups of patients and in 10 controls: the first group (N = 14) was composed of CsA-treated KTR; the second group (N = 5) was KTR not treated with CsA, and the third (N = 6) was chronic kidney failure patients. We also measured ADO plasma level in two KTR treated with FK506, a CsA analog. ADO plasma levels in CsA-treated KTR were significantly higher (mean 0.76 μM ± 0.27) than in the control group (mean 0.31 ± 0.13; Mann-Whitney test, S = 8.5; P = 2.1 × 10-4) and than in the chronic kidney failure group (0.37 ± 0.16; Mann-Whitney, S = 5.5; P = 1.6 × 10-3). In CsA-treated KTR, CsA and ADO plasma levels were significantly correlated (Spearman’s, r = 0.8, P = 1.9 × 10-3). No significant differences in ADO plasma levels were found between patients with chronic kidney failure and controls (P < 0.05). ADO plasma levels in KTR not treated with CsA were in the same range as those in controls. Finally, the ADO plasma level was increased in the two FK506-treated patients. We also investigated the action of CsA on ADO plasma degradation and uptake by erythrocytes in vitro. No interaction between adenosine deaminase and CsA was found because CsA, in the presence of adenosine deaminase, did not modify the plasma half-life of ADO. Conversely, in the presence of CsA (500 and 1000 ng/ml), the uptake of ADO by erythrocytes was significantly decreased in adenosine deaminase-free samples (analysis of variance, P = 1.8.10-3 and 1.2 × 10-4, respectively). We conclude that ADO plasma levels are significantly elevated and correlate with CsA blood level in CsA-treated KTR, and that these high levels are due to CsA inhibition of ADO uptake by red cells. Since ADO and metabolites have well known immunosuppressive and vascular effects, ADO is likely to participate in the immune defect and in the vasoconstriction induced by CsA.

Keywords

adenosine and CsA
cyclosporine
transplantation
kidney transplant recipients

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