title: Increasing renal mass improves survival in anephric rats following metanephros transplantation.
abstract: Renal failure and end-stage renal disease are prevalent diseases associated with high levels of morbidity and mortality, the preferred treatment for which is kidney transplantation. However, the gulf between supply and demand for kidneys remains high and is growing every year. A potential alternative to the transplantation of mature adult kidneys is the transplantation of the developing renal primordium, the metanephros. It has been shown previously, in rodent models, that transplantation of a metanephros can provide renal function capable of prolonging survival in anephric animals. The aim of the present study was to determine whether increasing the mass of transplanted tissue can prolong survival further. Embryonic day 15 rat metanephroi were transplanted into the peritoneum of anaesthetized adult rat recipients. Twenty-one days later, the transplanted metanephroi were anastomosed to the recipient's urinary system, and 35 days following anastomosis the animal's native renal mass was removed. Survival times and composition of the excreted fluid were determined. Rats with single metanephros transplants survived 29 h longer than anephric controls (P < 0.001); animals with two metanephroi survived 44 h longer (P < 0.001). A dilute urine was formed, with low concentrations of sodium, potassium and urea; potassium and urea concentrations were elevated in terminal serum samples, but sodium concentration and osmolality were comparable to control values. These data show that survival time is proportional to the mass of functional renal tissue. While transplanted metanephroi cannot currently provide life-sustaining renal function, this approach may have therapeutic benefit in the future.
authors.affiliation: Faculty of Life Sciences, University of Manchester, 1.124 Stopford Building, Oxford Road, Manchester M13 9PT, UK. nick.ashton@manchester.ac.uk
authors.forename: Damian
authors.initials: D
authors.lastname: Marshall
authors.forename: Mark R
authors.initials: MR
authors.lastname: Dilworth
authors.forename: Marc
authors.initials: M
authors.lastname: Clancy
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Bravery
authors.forename: Nick
authors.initials: N
authors.lastname: Ashton
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D016332:Fetal Tissue Transplantation / Q000379:methods*; D006085:Graft Survival; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000196:embryology* / Q000502:physiology / Q000601:surgery*; D016030:Kidney Transplantation / Q000379:methods*; D009392:Nephrectomy; D038081:Organogenesis; D010537:Peritoneum / Q000601:surgery; D011188:Potassium / Q000097:blood / Q000652:urine; D051381:Rats; D011917:Rats, Inbred Lew; D012964:Sodium / Q000097:blood / Q000652:urine; D013997:Time Factors; D014508:Urea / Q000097:blood / Q000652:urine; D014513:Ureter / Q000601:surgery; D014554:Urination
chemical_list: D014508:Urea; D012964:Sodium; D011188:Potassium