Background/aim: Acute and chronic kidney diseases are a major contributor to morbidity and mortality worldwide, with no specific treatments currently available for these. To enable understanding the pathophysiology of and testing novel treatments for acute and chronic kidney disease, a suitable in vivo model of kidney disease is essential. In this article, we describe two reliable rodent models (rats and mice) of efficacious kidney injury displaying acute to chronic kidney injury progression, which is also reversible through novel therapeutic strategies such as ischemic preconditioning (IPC).
View Article and Find Full Text PDFIntroduction: The Campath, Calcineurin inhibitor (CNI) reduction, and Chronic allograft nephropathy (3C), a study comparing alemtuzumab versus basiliximab induction immunosuppression in kidney transplants, has found lower acute rejection rate with alemtuzumab but same graft survival. The aim of the current study is to evaluate the effect of induction immunosuppression (thymoglobulin, alemtuzumab, basiliximab) on the outcome of kidneys of donors after circulatory death (DCD).
Methods: Data of the 274 DCD patients of the 3C obtained from the sponsor were compounded with the 140 DCD patients who received thymoglobulin in a single center with the same entry criteria as the 3C, giving 414 patients on 3 induction regimes.
Ischemic preconditioning (IPC) is effective in limiting subsequent ischemic acute kidney injury in experimental models. MicroRNAs are an important class of post-transcriptional regulator and show promise as biomarkers of kidney injury. We evaluated the time- and dose-dependence of benefit from IPC in a rat model of functional (bilateral) ischemia-reperfusion injury (IRI).
View Article and Find Full Text PDFAim: We aimed to analyse the efficacy of the Thymoglobulin dose used for induction in controlled DCD kidneys, and its initial impact on blood cell and CD3 count, as predictors of efficacy.
Methods: 140 DCD patients who received ATG induction, were analysed. Intended dose was 1.
Hyaluronidase (HYAL)-2 is a weak, acid-active, hyaluronan-degrading enzyme broadly expressed in somatic tissues. Aberrant HYAL2 expression is implicated in diverse pathology. However, a significant proportion of HYAL2 is enzymatically inactive; thus the mechanisms through which HYAL2 dysregulation influences pathobiology are unclear.
View Article and Find Full Text PDFPredicting immediate and subsequent graft function is important in clinical decision-making around kidney transplantation, but is difficult using available approaches. Here we have evaluated urinary microRNAs as biomarkers in this context. Profiling of 377 microRNAs in the first urine passed post-transplantation identified 6 microRNAs, confirmed to be upregulated by RT-qPCR in an expanded cohort (miR-9, -10a, -21, -29a, -221, and -429, n = 33, P < 0.
View Article and Find Full Text PDFHypothermic machine perfusion is effective in improving outcome following kidney transplantation. Molecular analyses of hypothermic machine perfusate (HMP) have the potential to identify biomarkers of organ viability prior to transplantation, offering significant advantages to the transplant surgeon, and leading to a potential increase in the organ donor pool. MicroRNAs are emerging as important biomarkers in the context of kidney injury and transplantation.
View Article and Find Full Text PDFObjectives: We evaluated a continuous, immediate, localized ischemic preconditioning regimen in a rat model of ischemia-reperfusion injury and assessed whether it attenuated injury at the histologic and molecular levels.
Materials And Methods: Fifteen adult male Lewis rats received sham operation, left unilateral warm ischemia (45 minutes of cross-clamping of the renal pedicle; ischemia-reperfusion injury group), or 15 minutes of ischemia followed by a 20-minute reperfusion period, 45 minutes of ischemia-reperfusion injury, and subsequent reperfusion (ischemic preconditioning/ischemia-reperfusion injury group). Kidney tissue was retrieved 48 hours later, sectioned, stained with hematoxylin and eosin, and examined.
Introduction: To expand the donor pool, kidney transplants are being performed using donors who were previously considered unacceptable. We applied the United Network for Organ Sharing criteria to define expanded criteria donors (ECD) within the donation after cardiac death (DCD) and donation after brain stem death (DBD) cohorts. We compared outcomes of DCD and DBD transplants with and without (standard criteria donor [SCD]) the ECD criteria.
View Article and Find Full Text PDFBackground: Delayed graft function (DGF) and acute rejection (AR) exert an adverse impact on graft outcomes after kidney transplantation using organs from donation after brain-stem death (DBD) donors. Here, we examine the impact of DGF and AR on graft survival in kidney transplants using organs from donation after cardiac death (DCD) donors.
Methods: We conducted a single-center retrospective study of DCD and DBD donor kidney transplants.
We previously demonstrated that chronic hyperglycemia has a detrimental influence on neurovascular coupling in the brain-an effect linked to an alteration in the protein kinase C (PKC)-mediated phosphorylation pattern. Moreover, the activity of PKC was increased, in diabetic rat brain, in a tissue fraction composed primarily of the superficial glia limitans and pial vessels, but trended toward a decrease in cerebral cortical gray matter. However, that study did not examine the expression patterns of PKC isoforms in the rat brain.
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