Association Between Side of Living Kidney Donation and Post-Transplant Outcomes.

Background: Right-sided living donor kidneys have longer renal arteries and shorter veins that make vascular anastomosis more challenging. We sought to determine whether recipients of right-sided living donor kidneys have worse outcomes than left-sided kidney recipients. Methods: An observational analysis of the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) was undertaken. We used adjusted logistic regression to determine the association between side and delayed graft function (DGF) and time-stratified adjusted cox regression models for graft and patient survivals. Results: Between 2004 and 2018, 4,050 living donor kidney transplants were conducted with 696 (17.2%) using right kidneys. With reference to left kidneys, the adjusted OR (95% CI) for DGF was 2.01 (1.31-3.09) for recipients with right kidneys. Within 30 days, 46 allografts (1.4%) were lost, with major causes of overall graft loss being technical, primary non-function and death. Recipients of right donor kidneys experienced a greater risk of early graft loss (aHR 2.02 [95% CI 1.06-3.86], p = 0.03), but not beyond 30 days (aHR 0.97 [95% CI 0.80-1.19], p = 0.8]). Conclusion: Technical challenge is the most common cause of early graft loss. The risk of early graft loss among recipients who received right kidneys is doubled compared to those who received left living donor kidneys.

Encapsulation of OZ439 into Nanoparticles for Supersaturated Drug Release in Oral Malaria Therapy.

Malaria poses a major burden on human health and is becoming increasingly difficult to treat due to the development of antimalarial drug resistance. The resistance issue is further exacerbated by a lack of patient adherence to multi-day dosing regimens. This situation motivates the development of new antimalarial treatments that are less susceptible to the development of resistance. We have applied Flash NanoPrecipitation (FNP), a polymer-directed self-assembly process, to form stable, water-dispersible nanoparticles (NPs) of 50-400 nm in size containing OZ439, a poorly orally bioavailable but promising candidate for single-dose malaria treatment developed by Medicines for Malaria Venture (MMV). During the FNP process, a hydrophobic OZ439 oleate ion paired complex was formed and was encapsulated into NPs. Lyophilization conditions for the NP suspension were optimized to produce a dry powder. The in vitro release rates of OZ439 encapsulated in this powder were determined in biorelevant media and compared with the release rates of the unencapsulated drug. The OZ439 NPs exhibit a sustained release profile and several-fold higher release concentrations compared to that of the unencapsulated drug. In addition, XRD suggests the drug was stabilized into an amorphous form within the NPs, which may explain the improvement in dissolution kinetics. Formulating OZ439 into NPs in this way may be an important step toward developing a single-dose oral malaria therapeutic, and offers the possibility of reducing the amount of drug required per patient, lowering delivery costs, and improving dosing compliance.