Administration of EPO as a single dose before the onset of ischaemia produced a significant reduction in tubular injury, which was accompanied by a marked amelioration of renal functional impairment. The cytoprotective action of EPO against I/R injury seems to be associated with its anti-apoptotic action. Moreover, transcription factor NF-kappaB is likely to play a pivotal role in the pathophysiology of I/R renal injury and might have a key role in EPO-mediated protective effects.
End stage renal disease (ESRD) engenders detrimental effects in the Immune system, manifested as quantitative alterations of lymphocyte subpopulations, akin, albeit not identical to those observed during the ageing process. We performed dimensionality reduction of an extended lymphocyte phenotype panel of senescent and exhaustion related markers in ESRD patients and controls with Principal Component Analysis (PCA) and Uniform Manifold Approximation and Projection (UMAP). The plane defined by the first two principal components of PCA showed two fuzzy clusters, for patients and controls, respectively, with loadings of non-senescent markers pointing towards the controls’ centroid. Naive lymphocytes were reduced in ESRD patients compared to controls (CD4+CD45RA+CCR7+ 200(150-328) vs. 426(260-585cells/μl respectively, P = 0.001, CD19+IgD+CD27- 54(26-85) vs. 130(83-262)cells/μl respectively, P < 0.001). PCA projections of the multidimensional ESRD immune phenotype suggested a more senescent phenotype in hemodialysis compared to hemodiafiltration treated patients. Lastly, clustering based on UMAP revealed three distinct patient groups, exhibiting gradual changes for naive, senescent, and exhausted lymphocyte markers. Machine learning algorithms can distinguish ESRD patients from controls, based on their immune-phenotypes and also, unveil distinct immunological groups within patients’ cohort, determined possibly by dialysis prescription.
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