title: Early Macrophage Infiltration and Sustained Inflammation in Kidneys From Deceased Donors Are Associated With Long-Term Renal Function.
abstract: Kidney transplants from living donors (LDs) have a better outcome than those from deceased donors (DDs). Different factors have been suggested to justify the different outcome. In this study, we analyzed the infiltration and phenotype of monocytes/macrophages and the expression of inflammatory and fibrotic markers in renal biopsy specimens from 94 kidney recipients (60 DDs and 34 LDs) at baseline and 4 months after transplantation. We evaluated their association with medium- and long-term renal function. At baseline, inflammatory gene expression was higher in DDs than in LDs. These results were confirmed by the high number of CD68-positive cells in DD kidneys, which correlated negatively with long-term renal function. Expression of the fibrotic markers vimentin, fibronectin, and α-smooth muscle actin was more elevated in biopsy specimens from DDs at 4 months than in those from LDs. Gene expression of inflammatory and fibrotic markers at 4 months and difference between 4 months and baseline correlated negatively with medium- and long-term renal function in DDs. Multivariate analysis point to transforming growth factor-β1 as the best predictor of long-term renal function in DDs. We conclude that early macrophage infiltration, sustained inflammation, and transforming growth factor-β1 expression, at least for the first 4 months, contribute significantly to the difference in DD and LD transplant outcome.
authors: Molecular Biology Laboratory, Fundació Puigvert, Barcelona, Spain.|UAB, REDinREN, Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Institut Investigació Biosanitaria Sant Pau, Barcelona, Spain.
authors: E
authors: E
authors: Guillén-Gómez
authors: UAB, REDinREN, Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Institut Investigació Biosanitaria Sant Pau, Barcelona, Spain.|Nephrology Department, Fundació Puigvert, Barcelona, Spain.
authors: I
authors: I
authors: Dasilva
authors: UAB, REDinREN, Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Institut Investigació Biosanitaria Sant Pau, Barcelona, Spain.|Renal Transplant Unit, Fundació Puigvert, Barcelona, Spain.
authors: I
authors: I
authors: Silva
authors: UAB, REDinREN, Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Institut Investigació Biosanitaria Sant Pau, Barcelona, Spain.|Pathology Laboratory, Fundació Puigvert, Barcelona, Spain.
authors: Y
authors: Y
authors: Arce
authors: UAB, REDinREN, Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Institut Investigació Biosanitaria Sant Pau, Barcelona, Spain.|Renal Transplant Unit, Fundació Puigvert, Barcelona, Spain.
authors: C
authors: C
authors: Facundo
authors: Molecular Biology Laboratory, Fundació Puigvert, Barcelona, Spain.|UAB, REDinREN, Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Institut Investigació Biosanitaria Sant Pau, Barcelona, Spain.
authors: E
authors: E
authors: Ars
authors: UAB, REDinREN, Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Institut Investigació Biosanitaria Sant Pau, Barcelona, Spain.|Urology Department, Fundació Puigvert, Barcelona, Spain.
authors: A
authors: A
authors: Breda
authors: IIS-Fundación Jiménez Díaz/UAM, REDinREN, Madrid, Spain.
authors: A
authors: A
authors: Ortiz
authors: UAB, REDinREN, Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Institut Investigació Biosanitaria Sant Pau, Barcelona, Spain.|Renal Transplant Unit, Fundació Puigvert, Barcelona, Spain.
authors: L
authors: L
authors: Guirado
authors: UAB, REDinREN, Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Institut Investigació Biosanitaria Sant Pau, Barcelona, Spain.|Nephrology Department, Fundació Puigvert, Barcelona, Spain.
authors: J A
authors: JA
authors: Ballarín
authors: UAB, REDinREN, Fundación Renal Iñigo Álvarez de Toledo (FRIAT), Institut Investigació Biosanitaria Sant Pau, Barcelona, Spain.|Nephrology Department, Fundació Puigvert, Barcelona, Spain.
authors: M M
authors: MM
authors: Díaz-Encarnación
mesh_terms: D000328:Adult; D002102:Cadaver; D051799:Delayed Graft Function; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology* / Q000473:pathology; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000601:surgery; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D014019:Tissue Donors; D009927:Tissue and Organ Procurement / Q000379:methods*
keywords: basic (laboratory) research/science; biopsy; donors and donation; fibrosis; graft survival; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; molecular biology; translational research/science