title: The Natural History of Kidney Graft Cortical Microcirculation Determined by Real-Time Contrast-Enhanced Sonography (RT-CES).
abstract: BACKGROUND
  Kidney transplantation is the therapy of choice for end-stage kidney disease. Graft's life span is shorter than expected due in part to the delayed diagnosis of various complications, specifically those related to silent progression. It is recognized that serum creatinine levels and proteinuria are poor markers of mild kidney lesions, which results in delayed clinical information. There are many investigation looking for early markers of graft damage. Decreasing kidney graft cortical microcirculation has been related to poor prognosis in kidney transplantation. Cortical capillary blood flow (CCBF) can be measured by real-time contrast-enhanced sonography (RT-CES). Our aim was to describe the natural history of CCBF over time under diverse conditions of kidney transplantation, to explore the influence of donor conditions and recipient events, and to determine the capacity of CCBF for predicting renal function in medium term.
  
  
  METHODS
  RT-CES was performed in 79 consecutive kidney transplant recipients during the first year under regular clinical practice. Cortical capillary blood flow was measured. Clinical variables were analyzed. The influence of CCBF has been determined by univariate and multivariate analysis using mixed regression models based on sequential measurements for each patient over time. We used a first-order autoregression model as the structure of the covariation between measures. The post-hoc comparisons were considered using the Bonferroni correction.
  
  
  RESULTS
  The CCBF values varied significantly over the study periods and were significantly lower at 48 h and day 7. Brain-death donor age and CCBF levels showed an inverse relationship (r: -0.62, p<0.001). Living donors showed higher mean CCBF levels than brain-death donors at each point in the study. These significant differences persisted at month 12 (54.5 ± 28.2 vs 33.7 ± 30 dB/sec, living vs brain-death donor, respectively, p = 0.004) despite similar serum creatinine levels (1.5 ± 0.3 and 1.5 ± 0.5 mg/dL). A sole rejection episode was associated with lower overall CCBF values over the first year. CCBF defined better than level of serum creatinine the graft function status at medium-term.
  
  
  CONCLUSIONS
  RT-CES is a non-invasive tool that can quantify and iteratively estimate cortical microcirculation. We have described the natural history of cortical capillary blood flow under regular clinical conditions.
authors.affiliation: Department of Nephrology, Research Unit, University Hospital La Paz, IdiPAZ, IRSIN, REDinREN, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Jiménez
authors.affiliation: Department of Nephrology, Research Unit, University Hospital La Paz, IdiPAZ, IRSIN, REDinREN, Madrid, Spain.
authors.forename: María Ovidia
authors.initials: MO
authors.lastname: López
authors.affiliation: Department of Nephrology, University Hospital Donostia. Donostia. Spain.
authors.forename: Amaia
authors.initials: A
authors.lastname: Ros
authors.affiliation: Department of Nephrology, Research Unit, University Hospital La Paz, IdiPAZ, IRSIN, REDinREN, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Aguilar
authors.affiliation: Department of Nephrology, Research Unit, University Hospital La Paz, IdiPAZ, IRSIN, REDinREN, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Menendez
authors.affiliation: Department of Nephrology, Research Unit, University Hospital La Paz, IdiPAZ, IRSIN, REDinREN, Madrid, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Rivas
authors.affiliation: Department of Nephrology, Research Unit, University Hospital La Paz, IdiPAZ, IRSIN, REDinREN, Madrid, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Santana
authors.affiliation: Department of Nephrology, Research Unit, University Hospital La Paz, IdiPAZ, IRSIN, REDinREN, Madrid, Spain.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Vaca
authors.affiliation: Department of Nephrology, Research Unit, University Hospital La Paz, IdiPAZ, IRSIN, REDinREN, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Escuin
authors.affiliation: Department of Biostatistics, University Hospital La Paz, Madrid, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Madero
authors.affiliation: Department of Nephrology, Research Unit, University Hospital La Paz, IdiPAZ, IRSIN, REDinREN, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Selgas
mesh_terms: D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors / Q000633:toxicity; D003287:Contrast Media; D003404:Creatinine / Q000097:blood; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007672:Kidney Cortex / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000473:pathology / Q000502:physiology; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009336:Necrosis; D011237:Predictive Value of Tests; D014463:Ultrasonography
chemical_list: D065095:Calcineurin Inhibitors; D003287:Contrast Media; D003404:Creatinine; D019703:Calcineurin