Recipient age and weight affect chronic allograft nephropathy in rats
In summary, our results demonstrate that recipient age and body weight profoundly influence the long-term renal allograft outcome in our rat model. Increased recipient age and body weights are detrimental to the graft, implicating the importance of recipient functional demand in the development of chronic allograft nephropathy. By contrast, donor kidney weight did not significantly affect the late allograft injury. Only in old recipients groups, increase in donor age is associated with the progression of chronic allograft nephropathy, suggesting that increased recipient functional demand may also augment the influence of donor- aging-related nephron loss in late allograft failure. Nephron dose and immune response change with age. Thus, age is a potential risk factor for graft survival after kidney transplantation. The aim of the current study was to determine whether age-related differences are of importance for the long-term outcome after renal transplantation. Kidneys of Fisher (F344) rats were orthotopically transplanted into nephrectomized Lewis (LEW) rats. Kidneys were transplanted in donors and recipients of three age levels: young (Y: 8 weeks old), adult (A: 16 weeks old), and old (O: 40 weeks old). Rats were harvested 24 weeks after transplantation and functional, morphological, and molecular evaluations were performed. Recipient rather than donor age determined graft survival. No significant correlation was found between donor kidney weight at the day of transplantation and morphological results. Advanced recipient age was associated with reduced creatinine clearance, more severe histological injuries including extended glomerular sclerosis, interstitial fibrosis, vascular lesions, more pronounced cellular infiltration, as well as a higher expression of TGF-b, and PDGF A and B chain. However, while we observed no significant correlation between donor age or kidney weight at the day of transplantation and morphological results, there was a significant correlation between recipient body weight at the day of transplantation and allograft injury. Therefore, recipient age and weight affect chronic allograft nephropathy. Renal allografts may benefit from young recipient age but may deteriorate in old recipients, suggesting effects of recipient functional demand on long-term outcome.