The Natural History of Kidney Graft Cortical Microcirculation Determined by Real-Time Contrast-Enhanced Sonography (RT-CES)

PLoS One. 2016 Mar 7;11(3):e0150384. doi: 10.1371/journal.pone.0150384. eCollection 2016.

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.

Patients and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcineurin / metabolism
  • Calcineurin Inhibitors / toxicity
  • Contrast Media*
  • Creatinine / blood
  • Female
  • Graft Rejection
  • Humans
  • Kidney Cortex / blood supply*
  • Kidney Cortex / diagnostic imaging*
  • Kidney Cortex / pathology
  • Kidney Cortex / physiology
  • Kidney Function Tests
  • Kidney Transplantation* / adverse effects
  • Male
  • Microcirculation*
  • Middle Aged
  • Necrosis
  • Predictive Value of Tests
  • Ultrasonography

Substances

  • Calcineurin Inhibitors
  • Contrast Media
  • Creatinine
  • Calcineurin

Grants and funding

Funded by Genzyme and Novartis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.