Oxidative stress and 'monocyte reprogramming' after kidney transplant: a longitudinal study

Blood Purif. 2008;26(1):105-10. doi: 10.1159/000110575. Epub 2008 Jan 10.

Abstract

Uremia has been implicated in increased oxidative stress (OS) and decreased monocyte HLA-DR expression in chronic kidney disease (CKD) patients. Thus, one would expect normalization of these parameters after successful kidney transplant (KTx). Our aim was to describe patterns of OS and HLA-DR expression after KTx and to explore the effect of renal function and different immunosuppression regimens. 30 KTx patients (20 male; 48 +/- 11 years) were enrolled and compared with 20 healthy controls. We measured advanced oxidation protein products (AOPP) and the percentage of monocytes expressing HLA-DR (%DR+) before (preKTx) and after KTx (on days 2, 30, 90, 180 and after 1 year). Compared to controls, patients had a higher preKTx AOPP (152.6 vs. 69.3 micromol/l; p < 0.001). AOPP decreased at 48 h after KTx, achieving values similar to controls. Thereafter, it increased again and remained significantly higher compared to controls, returning to preKTx levels at 90 days. Prior to KTx there was a trend for lower %DR+ in KTx patients compared to controls (96 vs. 98%; NS). Following KTx, patients had a lower %DR+ in the 1st month; then it gradually returned to preKTx levels during the 1st year; at no time did it reach a value similar to controls. Cyclosporine (CyA)-treated patients had a significantly higher AOPP (161.5 vs. 99.5 micromol/l; p = 0.03) and a lower %DR+ (91.7 vs. 96.4; p < 0.05) at 30 days than patients on tacrolimus (FK). Patients on mycophenolate mofetil (MMF) showed a low AOPP (106.9 vs. 168.1 micromol/l; p = 0.05) and a high %DR+ (96.7 vs. 88.2%; p = 0.001) than those on everolimus. After 3 months, CyA-treated patients had a non-significant increase in AOPP levels, whereas those on FK showed a decrease (p < 0.05) as did those treated with MMF (p < 0.05). Successful KTx reduced but did not normalize AOPP, suggesting ongoing OS, perhaps due to persistent mild renal dysfunction and the effects of immunosuppression. HLA-DR expression remained low after KTx, which may be a possible contributing factor to infectious complications after transplantation. Immunosuppressive agents appear to have diverse effects on OS and HLA-DR expression.

MeSH terms

  • Adult
  • Cyclosporine / pharmacology
  • Female
  • HLA-DR Antigens / metabolism
  • Humans
  • Immunosuppression Therapy*
  • Immunosuppressive Agents / pharmacology*
  • Kidney / drug effects
  • Kidney / immunology
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / physiology*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / pharmacology
  • Oxidative Stress / immunology*
  • Prospective Studies
  • Renal Insufficiency / surgery
  • Tacrolimus / pharmacology

Substances

  • HLA-DR Antigens
  • Immunosuppressive Agents
  • Cyclosporine
  • Mycophenolic Acid
  • Tacrolimus