NDT Advance Access published online on October 12, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm671
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Development and functional capacity of transplanted rat metanephroi
1 Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK 2 Manchester Institute of Nephrology and Transplantation, Manchester Royal Infirmary, Manchester M13 9WL, UK 3 Intercytex Ltd, Innovation House, Crewe Road, Manchester M23 9QR, UK
Correspondence and offprint requests to: Correspondence and offprint requests to: Dr Mark R Dilworth, Faculty of Life Sciences, 1.124 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK. Tel: +44-161 275 5454; Fax: +44-161 275 3938; E-mail: m.r.dilworth{at}manchester.ac.uk
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Abstract |
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Background. Transplantation of embryonic kidneys (metanephroi) offers a potential solution to the problem of kidney donor shortage. The aim of this study was to characterise the haemodynamic capacity of transplanted rat metanephroi and to determine the number and maturity of the tubules.
Methods. Metanephroi from E15 Lewis rat embryos were transplanted adjacent to the abdominal aorta of uninephrectomised adult female syngeneic Lewis rats. Twenty-one days later, a single metanephros ureter was anastomosed to the host's urinary system. Three months later animals were prepared for standard clearance measurements.
Results. Effective renal blood flow (149 ± 33 µl min–1 per g kidney weight) and glomerular filtration rate (17 ± 9 µl min–1 per g kidney weight), standardised to kidney weight, were significantly lower in transplanted metane- phroi compared with control adult kidneys (P < 0.001); renal vascular resistance (934 ± 209 mmHg ml min–1 per g kidney weight) was significantly higher (P < 0.001). Nephron number in transplanted metanephroi was significantly greater than that of E21 kidneys (P < 0.01) but lower than that of postnatal day (PND) 1 kidneys (P < 0.001). Angiotensin II type 2 receptor mRNA expression, a marker of nephrogenesis, was markedly reduced in metanephroi. Aquaporins 1 and 2, epithelial Na channel and Na-K-2Cl cotransporter type 2 mRNA and protein were expressed in transplanted metanephroi; the urea transporters-A1, 2 and 3 were absent. Vascular markers (
-smooth muscle actin and CD31) were identified in metanephroi but their expression did not differ from that of E21 and PND 1 kidneys.
Conclusions. This study shows that metanephroi continue to develop post-transplantation but only reach a stage of development equivalent to that of a normal rat kidney at birth.
Keywords: aquaporin; metanephros; nephrogenesis; renal blood flow; transplantation; urea
Received for publication: 8. 6.07
Accepted in revised form: 3. 9.07