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Preemptive treatment with mesenchymal stem cells (MSCs) can attenuate cisplatin-induced acute kidney injury (AKI). However, it is uncertain whether MSC treatment after the development of renal dysfunction prevents AKI progression or if MSC immunomodulatory properties contribute to MSC therapy. In this study, human umbilical cord blood (hUCB)- derived MSCs were used to compare the effects and mechanisms of early and late MSC therapy in a murine model. After cisplatin injection into C57BL/6 mice, hUCB-MSCs were administered on day 1 (early treatment) or day 3 (late treatment). With early treatment, cisplatin nephrotoxicity was attenuated as evidenced by decreased blood urea nitrogen (BUN) and reduced apoptosis and tubular injury scores on day 3. Early treatment resulted in downregulation of intrarenal monocyte chemotactic protein-1 and IL-6 expression and upregulation of IL-10 and VEGF expression. Flow cytometric analysis showed similar populations of infiltrated immune cells in both groups; however, regulatory T-cell (Treg) infiltration was 2.5-fold higher in the early treatment group. The role of Tregs was confirmed by the blunted effect of early treatment on renal injury after Treg depletion. In contrast, late treatment (at a time when BUN levels were 2-fold higher than baseline levels) showed no renoprotective effects on day 6. Neither the populations of intrarenal infiltrating immune cells (including Tregs) nor cytokine expression levels were affected by late treatment. Our results suggest that early MSC treatment attenuates renal injury by Treg induction and immunomodulation, whereas a late treatment (i.e., after the development of renal dysfunction) does not prevent AKI progression or alter the intrarenal inflammatory micromilieu. [ABSTRACT FROM AUTHOR]

Inflammatory process mediated by innate and adaptive immune systems is a major pathogenic mechanism of renal ischemia-reperfusion injury (IRI). There are concerns that organ recipients may be at increased risk of developing IRI after receiving kidneys from elder donors. To reveal the effects of aging on the development of renal IRI, we compared the immunologic micromilieu of normal and postischemic kidneys from mice of three different ages (9 wk, 6 mo, and 12 mo). There was a higher number of total T cells, especially effector memory CD4/CD8 T cells, and regulatory T cells in the normal kidneys of old mice. On day 2 after IRI, the proportion of necrotic tubules and renal functional changes were comparable between groups although old mice had a higher proportion of damaged tubule compared with young mice. More T cells, but less B cells, trafficked into the postischemic kidneys of old mice. The infiltration of NK T cells was similar across the groups. Macrophages and neutrophils were comparable between groups in both normal kidneys and postischemic kidneys. The intrarenal expressions of TNF-α and VEGF were decreased in normal and postischemic kidneys of aged mice. These mixed effects of aging on lymphocytes and cytokines/chemokines were not different between the two groups of old mice. Our study demonstrates that aging alters the intrarenal micromilieu but has small effects on the development of initial renal injury after IRI. Further study investigating aging-dependent differences in the repair process of renal IRI may be required. [ABSTRACT FROM AUTHOR]

Human umbil-ical cord blood-derived mesenchymal stem cells (HUCB-MSCs) have been studied in several models of immune-mediated disease because of their unique immunomodulatory properties. We hypothesized that HUCB-MSCs could suppress the inflammatory response in postisch-emic kidneys and attenuate early renal injury. In 8- to 10-wk-old male C57BL/6 mice, bilateral ischemia-reperfusion injury (IRI) surgery was performed, and 1 X 106 HUCB-MSCs were injected intraperito-neally 24 h before surgery and during reperfusion. Renal functional and histological changes, HUCB-MSC trafficking, leukocyte infiltra-tion, and cytokine expression were analyzed. Renal functional decline and tubular injury after IRI were attenuated by HUCB-MSC treat-ment. PKH-26-labeled HUCB-MSCs trafficked into the postischemic kidney. Although numbers of CD45-positive leukocytes in the post-ischemic kidney were comparable between groups, the expression of interferon-7 in the postischemic kidney was suppressed by HUCB-MSC treatment. The rapid decrease in intrarenal VEGF after IRI was markedly mitigated by HUCB-MSC treatment. In inflammatory con-ditions simulated in a cell culture experiment, VEGF secretion from HUCB-MSCs was substantially enhanced. VEGF inhibitor abolished the renoprotective effect of HUCB-MSCs after IRI. Flow cytometry analysis revealed the decreased infiltration of natural killer T cells and increased number of regulatory T cells in postischemic kidneys. In addition, these effects of HUCB-MSCs on kidney infiltrating mono-nuclear cells after IRI were attenuated by VEGF inhibitor. HUCB-MSCs attenuated renal injury in mice in the early injury phase after IRI, mainly by humoral effects and secretion of VEGF. Our results suggest a promising role for HUCB-MSCs in the treatment of renal IRI. [ABSTRACT FROM AUTHOR]

Focuses on a study which investigated the hypothesis that hypokalemia might induce renal injury via a mechanism that involves subtle renal injury and alterations in local vasoactive mediators that would favor sodium retention. Methods of the study; Renal histology; Association of hypokalemic nephropathy with an alteration in vasoactive mediators that favors vasoconstriction.

Features a study which examined the prevention of hypertension through treatment with an angiogenic factor aimed at ameliorating microvascular and renal injury with a model of post-cyclosporin A with the vascular endothelial growth factor. Methodology; Results and discussion.