Endothelial cell plasticity in kidney fibrosis and disease.

Renal endothelial cells demonstrate an impressive remodeling potential during angiogenic sprouting, vessel repair or while transitioning into mesenchymal cells. These different processes may play important roles in both renal disease progression or regeneration while underlying signaling pathways of different endothelial cell plasticity routes partly overlap. Angiogenesis contributes to wound healing after kidney injury and pharmaceutical modulation of angiogenesis may home a great therapeutic potential. Yet, it is not clear whether any differentiated endothelial cell can proliferate or whether regenerative processes are largely controlled by resident or circulating endothelial progenitor cells. In the glomerular compartment for example, a distinct endothelial progenitor cell population may remodel the glomerular endothelium after injury. Endothelial-to-mesenchymal transition (EndoMT) in the kidney is vastly documented and often associated with endothelial dysfunction, fibrosis, and kidney disease progression. Especially the role of EndoMT in renal fibrosis is controversial. Studies on EndoMT in vivo determined possible conclusions on the pathophysiological role of EndoMT in the kidney, but whether endothelial cells really contribute to kidney fibrosis and if not what other cellular and functional outcomes derive from EndoMT in kidney disease is unclear. Sequencing data, however, suggest no participation of endothelial cells in extracellular matrix deposition. Thus, more in-depth classification of cellular markers and the fate of EndoMT cells in the kidney is needed. In this review, we describe different signaling pathways of endothelial plasticity, outline methodological approaches and evidence for functional and structural implications of angiogenesis and EndoMT in the kidney, and eventually discuss controversial aspects in the literature.

Longitudinal tracking of acute kidney injury reveals injury propagation along the nephron.

Acute kidney injury (AKI) is an important risk factor for chronic kidney disease (CKD), but the underlying mechanisms of failed tubule repair and AKI-CKD transition are incompletely understood. In this study, we aimed for dynamic tracking of tubule injury and remodeling to understand if focal injury upon AKI may spread over time. Here, we present a model of AKI, in which we rendered only half of the kidney ischemic. Using serial intravital 2-photon microscopy and genetic identification of cycling cells, we tracked dynamic tissue remodeling in post- and non-ischemic kidney regions simultaneously and over 3 weeks. Spatial and temporal analysis of cycling cells relative to initial necrotic cell death demonstrated pronounced injury propagation and expansion into non-necrotic tissue regions, which predicted tubule atrophy with epithelial VCAM1 expression. In summary, our longitudinal analyses of tubule injury, remodeling, and fate provide important insights into AKI pathology.

Impact of corneal donor lens status on two-year course and outcome of Descemet membrane endothelial keratoplasty (DMEK).

PURPOSE: Our purpose was to investigate the impact of lens status of corneal donors on the two-year course and clinical outcome of Descemet membrane endothelial keratoplasty (DMEK). METHODS: In 181 DMEK surgeries, 136 phakic and 45 pseudophakic donor corneas were grafted. In this retrospective audit we compared the lens status of corneal donors regarding the outcome measures best spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), and endothelial cell density (ECD) at 1, 3, 6, 12, and 24 months, as well as intra- and postoperative complication rates and graft detachment rates requiring re-bubbling. RESULTS: Comparing the use of phakic and pseudophakic donor tissue in DMEK surgery, BSCVA results revealed no significant differences during the two-year course (p ≥ 0.087). CCT showed significantly lower values at 1 month (553.8 ± 56 vs. 625.2 ± 119 µm; p < 0.001) and 6 months follow-up (530.6 ± 49.9 vs. 557.3 ± 47 µm; p = 0.026) for phakic donor tissue recipients, but were comparable later (p ≥ 0.173). ECD values were statistically higher 6 (1915 ± 390 vs. 1565 ± 420 cells/mm2; p < 0.001) and 24 months postoperatively (1772 ± 384 vs. 1375 ± 377 cells/mm2; p = 0.030) in phakic donor tissue recipients. Mixed regression analyses demonstrated a significant association between ECD results and donor lens status (p = 0.029) and donor ECD (p = 0.028), but donor age did not show significant influence (p = 0.241). CONCLUSION: ECD is higher in phakic corneal donors and appears to remain at a higher level during the course resulting in initially faster reduction of corneal edema compared to pseudophakic DMEK grafts. Nevertheless, pseudophakic transplants with high ECD seem to produce comparable functional results in recipients after a two year course.