Delivery of human erythropoietin gene with an adeno-associated virus vector through parotid glands to treat renal anaemia in a swine model.

Abstract

Anaemia is a common complication of chronic kidney disease, for which there is presently no adequate treatment. The delivery of human erythropoietin (hEPO) cDNA to salivary glands reportedly increases red blood cell counts, haematocrit (HCT) and haemoglobin concentration, representing a potential new method of renal anaemia treatment. However, no studies have examined the effects of this method in an animal model of renal anaemia. Here we established a miniature pig animal model of renal anaemia through continuous feeding with adenine. In these animals, we delivered the AAV2hEPO gene to the parotid glands through Stensen's duct. As a control, we transferred AAVLacZ. Enzyme-linked immunosorbent assay was used to detect hEPO in serum and saliva. Red blood counts and serum biochemistry were used to evaluate how hEPO gene administration affected renal anaemia. Compared with the control group, we found increased hEPO concentrations in parotid saliva and serum, respectively, at 2 and 6 weeks after AAV2hEPO administration to the anaemic animals. HCT and haemoglobin were also increased after AAV2hEPO was delivered; most serum indicators of renal damage were not changed over the time span of the experiment, suggesting the adenine-induced kidney damage had not been completely reversed. However, blood urea nitrogen and B2 microglobulin levels showed small but significant improvement. Overall, our present findings suggest that adeno-associated virus 2 (AAV2)-mediated gene transduction of hEPO via the parotid gland is a promising potential alternative therapy for renal anaemia.