Lene Heickendorff a , Lars Frost b , Jens K. Madsen b , Erling B. Pedersen b
17 December 2008
Cyclosporine, Azathioprine, Procollagen I, Procollagen III, Collagen metabolism, Transplantation, Fibrosis
Chronic cyclosporine nephrotoxicity is characterized morphologically by cortical interstitial fibrosis. The most important collagens involved in renal fibrosis are collagen types I and III. In order to estimate the synthesis of type III and type I collagens, we analyzed serum levels of the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal propeptide of type I procollagen (PICP) in 11 renal transplant recipients receiving cyclosporine (group CY) and a comparable group of 16 renal transplant recipients treated with azathioprine (group AZ). In addition, 27 healthy subjects and 15 patients with chronic renal disease and reduced renal function (group CRD) were examined. The cyclosporine-treated patients had serum PIIINP and PICP similar to the azathioprine-treated patients. Both groups of renal transplant recipients had significantly increased serum PIIINP compared to healthy controls (2p < 0.01) and serum PIIINP levels similar to group CRD in which serum PIIINP was also elevated compared to healthy controls (2p < 0.01). Mean serum PIIINP levels were: group CY 0.81 U/l (n = 11); group AZ 0.98 U/l (n = 16); controls 0.62 U/l (n = 27); and group CRD 1.06 U/l (n = 15). The renal graft recipients – both cyclosporine- and azathioprine-treated patients – had significantly increased PICP serum levels compared to healthy controls, but the patients with chronic renal disease had serum PICP levels which did not differ from that of healthy controls. Mean serum PICP levels were: group CY 174 μg/l; group AZ 151 μg/l; controls 106 μg/l; and group CRD 119 μg/l. A significant positive correlation was seen between serum creatinine and serum PIIINP in the renal graft recipients (r = 0.51, p < 0.01), but not in the patients with chronic renal disease (r =-0.009, p = 0.49). The data point to an increased synthesis of type I and III collagens in renal transplant recipients. The graft is most likely the source of the increased serum PIIINP and PICP levels. It is suggested that the increased serum levels of propeptides derived from collagen metabolism may reflect continuous immunological destruction of renal tissue causing inflammation and fibrosis.
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