Donor Proteinuria and Allograft Function in Kidney Transplantation: Short- and Long-Term Results From a Retrospective Cohort Study.

Donor proteinuria (DP) is a common but rarely evaluated aspect of today's kidney transplant allocation process. While proteinuria after kidney transplantation is a risk factor for impaired graft function and survival, the long-term effects of DP in kidney transplantation have not yet been evaluated. Therefore, this study aims to investigate the impact of DP on the long-term outcome after kidney transplantation. A total of 587 patients were found to be eligible and were stratified into two groups: (1) those receiving a graft from a donor without proteinuria (DP-) and (2) those receiving a graft from a donor with proteinuria (DP+). At 36 months, there was no difference in the primary composite endpoint including graft loss and patient survival (log-rank test, p = 0.377). However, the analysis of DP+ subgroups showed a significant decrease in overall patient survival in the group with high DP (p = 0.017). DP did not adversely affect patient or graft survival over 36 months. Nevertheless, this work revealed a trend towards decreased overall survival of patients with severe proteinuria in the subgroup analysis. Therefore, the underlying results suggest caution in allocating kidneys from donors with high levels of proteinuria.

Microporous Polylactic Acid Scaffolds Enable Fluorescence-Based Perfusion Imaging of Intrinsic In Vivo Vascularization.

In vivo tissue engineering (TE) techniques like the AV loop model provide an isolated and well-defined microenvironment to study angiogenesis-related cell interactions. Functional visualization of the microvascular network within these artificial tissue constructs is crucial for the fundamental understanding of vessel network formation and to identify the underlying key regulatory mechanisms. To facilitate microvascular tracking advanced fluorescence imaging techniques are required. We studied the suitability of microporous polylactic acid (PLA) scaffolds with known low autofluorescence to form axial vascularized tissue constructs in the AV loop model and to validate these scaffolds for fluorescence-based perfusion imaging. Compared to commonly used collagen elastin (CE) scaffolds, the total number of vessels and cells in PLA scaffolds was lower. In detail, CE-based constructs exhibited significantly higher vessel numbers on day 14 and 28 (d14: 316 ± 53; d28: 610 ± 74) compared to the respective time points in PLA-based constructs (d14: 144 ± 18; d28: 327 ± 34; each p < 0.05). Analogously, cell counts in CE scaffolds were higher compared to corresponding PLA constructs (d14: 7661.25 ± 505.93 and 5804.04 ± 716.59; d28: 11211.75 + 1278.97 and 6045.71 ± 572.72, p < 0.05). CE scaffolds showed significantly higher vessel densities in proximity to the main vessel axis compared to PLA scaffolds (200-400 µm and 600-800 µm on day 14; 400-1000 µm and 1400-1600 µm on day 28). CE scaffolds had significantly higher cell counts on day 14 at distances from 800 to 2000 µm and at distances from 400 to 1600 µm on day 28. While the total number of vessels and cells in PLA scaffolds were lower, both scaffold types were ideally suited for axial vascularization techniques. The intravascular perfusion of PLA-based constructs with fluorescence dye MHI148-PEI demonstrated dye specificity against vascular walls of low- and high-order branches as well as capillaries and facilitated the fluorescence-based visualization of microcirculatory networks. Fluorophore tracking may contribute to the development of automated quantification methods after 3D reconstruction and image segmentation. These technologies may facilitate the characterization of key regulators within specific subdomains and add to the current understanding of vessel formation in axially vascularized tissue constructs.