title: Oxidative stress and 'monocyte reprogramming' after kidney transplant: a longitudinal study.
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.
authors.affiliation: Department of Nephrology, Dialysis and Transplant, St. Bortolo Hospital, Vicenza, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: de Cal
authors.forename: Sandra
authors.initials: S
authors.lastname: Silva
authors.forename: Dinna
authors.initials: D
authors.lastname: Cruz
authors.forename: Flavio
authors.initials: F
authors.lastname: Basso
authors.forename: Valentina
authors.initials: V
authors.lastname: Corradi
authors.forename: Paolo
authors.initials: P
authors.lastname: Lentini
authors.forename: Federico
authors.initials: F
authors.lastname: Nalesso
authors.forename: Daniela
authors.initials: D
authors.lastname: Dissegna
authors.forename: Volker
authors.initials: V
authors.lastname: Goepel
authors.forename: Stefano
authors.initials: S
authors.lastname: Chiaramonte
authors.forename: Claudio
authors.initials: C
authors.lastname: Ronco
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000276:immunology; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018384:Oxidative Stress / Q000276:immunology*; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000601:surgery; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus