Use of normal saline and incidence of dyselectrolytaemia in children following kidney transplantation.

BACKGROUND: The use of hypotonic fluid, such as 0.45% saline, following kidney transplantation (KT) in children is associated with a high incidence of electrolyte imbalance, especially hyponatraemia. This can result in serious adverse events, such as cerebral oedema and seizures. The aim of this study was to investigate the incidence of electrolyte disturbance in children when 0.9% saline was the intravenous fluid used in the first 72 h following KT. METHODS: This is a retrospective, observational study of 50 consecutive KT undertaken between January 2017 and January 2019 at a single centre. RESULTS: The median age at KT was 9.2 years (IQR 4-14) and 16 (32%) were females. Thirty-two (64%) were living related donor (LRD) KT and 22 (44%) were carried out in children < 20 kg. The mean volume of fluid administered intra-operatively, and on Day 1, Day 2 and Day 3, were 73 ml/kg, 124 ml/kg, 97 ml/kg and 86 ml/kg, respectively. Hyponatraemia was noted in 4%, hypernatraemia in 18%, hyperkalaemia in 18%, hyperchloraemia in 68% and low bicarbonate was seen in 88%. Fifteen percent of the children had an episode of hyperglycaemia. None of the children developed symptomatic dyselectrolytaemia. There was delayed graft function (DGF) in 4 (8%) recipients - all deceased donor (DD) KT, including 2 who received donations after circulatory death. CONCLUSIONS: While the use of 0.9% saline is associated with a high incidence of electrolyte disturbances, including hyperkalaemia, it reduces the risk of hyponatraemia. None of the children developed a symptomatic electrolyte abnormality. A higher resolution version of the Graphical abstract is available as Supplementary information.

Azidothymidine Sensitizes Primary Effusion Lymphoma Cells to Kaposi Sarcoma-Associated Herpesvirus-Specific CD4+ T Cell Control and Inhibits vIRF3 Function.

Kaposi sarcoma-associated herpesvirus (KSHV) is linked with the development of Kaposi sarcoma and the B lymphocyte disorders primary effusion lymphoma (PEL) and multi-centric Castleman disease. T cell immunity limits KSHV infection and disease, however the virus employs multiple mechanisms to inhibit efficient control by these effectors. Thus KSHV-specific CD4+ T cells poorly recognize most PEL cells and even where they can, they are unable to kill them. To make KSHV-infected cells more sensitive to T cell control we treated PEL cells with the thymidine analogue azidothymidine (AZT), which sensitizes PEL lines to Fas-ligand and TRAIL challenge; effector mechanisms which T cells use. PELs co-cultured with KSHV-specific CD4+ T cells in the absence of AZT showed no control of PEL outgrowth. However in the presence of AZT PEL outgrowth was controlled in an MHC-restricted manner. To investigate how AZT sensitizes PELs to immune control we first examined BJAB cells transduced with individual KSHV-latent genes for their ability to resist apoptosis mediated by stimuli delivered through Fas and TRAIL receptors. This showed that in addition to the previously described vFLIP protein, expression of vIRF3 also inhibited apoptosis delivered by these stimuli. Importantly vIRF3 mediated protection from these apoptotic stimuli was inhibited in the presence of AZT as was a second vIRF3 associated phenotype, the downregulation of surface MHC class II. Although both vFLIP and vIRF3 are expressed in PELs, we propose that inhibiting vIRF3 function with AZT may be sufficient to restore T cell control of these tumor cells.