부산대학교 도서관

Kidney transplantation is the treatment of choice for end-stage CKD. In the last decades, graft and patient survival have dramatically improved. However, at 10 years after transplantation, 25-35% of patients present graft failures and the necessity of renal replacement therapy. In addition to this, 30% of patients dying with a functioning graft die from a cardiovascular cause. These data are consistent between different series and registries. Our hypothesis is that early allograft subclinical inflammation can contribute to chronic graft dysfunction and promote systemic inflammation, what could be linked to the high cardiovascular risk in this population. The aim of this study is to evaluate whether allograft subclinical inflammation during the first year after transplantation modulates the progression of fibrosis, is related to the development of de novo DSA and to systemic inflammation as measured by C reactive protein. Patients with standard immunological risk receiving a single kidney transplantation at Oslo University Hospital Rikshospitalet between 2009 and 2012, with a surveillance graft biopsy at six weeks and at one year after transplantation, were studied. In a first study, the association between subclinical inflammation at six weeks and the progression of fibrosis at one year was evaluated. We also analyzed the association between early inflammation and de novo DSA at one year after transplantation. Early subclinical inflammation, when associated with chronic changes –IFTA-, together with clinical episodes of acute rejection, was an independent predictor of the progression of fibrosis at one year after transplantation. Early inflammation, alone or associated with chronic changes, was associated to an increased risk of development of de novo DSA at one year after transplantation. A second study was performed including patients with a stable clinical situation and a C-reactive protein determination at the time of one year biopsy. Patients were grouped into quartiles according to C reactive protein levels. One year biopsies were classified according to tubule-interstitial inflammation as normal, borderline or subclinical rejection. The diagnosis of suclinical rejection was an independent predictor of increased Creactive protein levels at one year after transplantation, together with BMI and the presence of an urinary tract infection some days before the biopsy. In conclusión, this thesis shows that early subclinical inflammation is a significant lesión. It is directly associated with the progression of fibrosis and with the development of de novo DSA, being probably one of the causes of elevation of C-reactive protein levels, marker of systemic inflammation and, therefore, probably associated with the high cardiovascular risk in this population.