ABSTRACT
The role of C5a receptors (C5aR1 and C5L2) in renal ischemia-reperfusion injury (IRI) is uncertain. We generated an in vitro model of hypoxia/reoxygenation with human proximal tubule epithelial cells to mimic some IRI events. C5aR1, membrane attack complex (MAC) and factor H (FH) deposits were evaluated with immunofluorescence. Quantitative polymerase chain reaction evaluated the expression of C5aR1, C5L2 genes as well as genes related to tubular injury, inflammation, and profibrotic pathways. Additionally, C5aR1 and C5L2 deposits were evaluated in kidney graft biopsies (KB) from transplant patients with delayed graft function (DGF, n = 12) and compared with a control group (n = 8). We observed higher immunofluorescence expression of C5aR1, MAC and FH as higher expression of genes related to tubular injury, inflammatory and profibrotic pathways and of C5aR1 in the hypoxic cells; whereas, C5L2 gene expression was unaffected by the hypoxic stimulus. Regarding KB, C5aR1 was detected in the apical and basal membrane of tubular epithelial cells, whereas C5L2 deposits were observed in endothelial cells of peritubular capillaries (PTC). DGF-KB showed more frequently diffuse C5aR1 staining and C5L2 compared to controls. In conclusion, C5aR1 expression is increased by hypoxia and IRI, both in vitro and in human biopsies with an acute injury. C5L2 expression in PTC could be related to endothelial cell damage during IRI.
ABSTRACT
Vancomycin has usually been associated with nephrotoxicity. Generally, this toxicity is presented as proximal tubular cells injury with or without necrosis and as acute interstitial nephritis. However, development of both lesions is uncommonly described in literature. We present a case of vancomycin-induced nephrotoxicity resulting in both acute interstitial nephritis and tubular cells damage confirmed by renal biopsy. Peak and trough levels of 77.11 and 63.60 µg/mL, respectively, were obtained at the first plasma determination. After 8 more plasma determinations and several hemodialysis sessions, vancomycin levels were undetectable 1 month after therapy was stopped. To our knowledge, this is the case report with the highest vancomycin trough levels developing both lesions and describing total vancomycin washout after a biopsy-proven vancomycin toxicity. In conclusion, early vancomycin therapeutic drug monitoring should be performed in order to avoid toxicities where, as seen in our patient, antibiotic exposure could last around 1 month after last dose administration.
ABSTRACT
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