Little is known about the long-term changes of mineral metabolism in living kidney donors and their significance. It has been shown that fibroblast growth factor 23 (FGF23) has an important role in mineral metabolism in chronic kidney disease (CKD), regulating serum phosphate level and vitamin D metabolism. FGF23 down-regulates sodium/phosphate co-transporter 2a (NaPi-2a) in kidney by binding with the fibroblast growth factor receptor 1 (FGFR1), where Klotho has an important role as a co-receptor. It has been shown that the impairment of kidney function during the CKD is associated with increased FGF23 serum level and decreased renal Klotho, FGFR1 and NaPi-2a levels1. Our aim was to show whether unilateral nephrectomy has a long-term impact on FGF23-Klotho axis in a rat model of living kidney donation.10 female Sprague-Dawley rats at 4 months of age were divided into two groups (N=5/per group): a) uninephrectomized, and b) naïve rats used as controls. At the time of inclusion, rats were anesthetized by intraperitoneal injection of 75 mg/kg of ketamine and 0,5 mg/kg od midazolam, and unilaterally nephrectomized or left intact, according to the group. Kidney samples were taken 12 months after the procedure (at age of 16 months). Klotho, FGFR1 and NaPi-2a co-transporter mRNA levels in kidney tissue were determined by real time PCR method, mRNA level was normalized to hypoxanthine phosphoribosyltransferase (HPRT) housekeeping gene and analyzed by REST 2009 (v 2.0.13, Qiagen, Hilden, Germany). Standard avidin-biotin complex method was used for immunohistochemical staining of kidney sections to show Klotho expression and distribution.Our results showed that there is a 3.6-fold down-regulation of Klotho gene (mean factor 0.277;SEM=0.132-0.651;p=0.014), 4.5-fold down-regulation of FGFR1 gene (mean factor 0.222;SEM=0.086-0.635;p=0.015) and 3.9-fold down-regulation of NaPi-2a gene (mean factor 0.256;SEM=0.160-0.537;p=0.005) in remnant kidneys of uninephrectomized rats compared to controls. Representative immunohistochemistry of kidney sections showed that Klotho is mainly expressed in renal distal and collecting tubules. When Klotho expression in kidney sections was compared between uninephrectomized and naïve rats, no qualitative difference has been seen.Down-regulation of Klotho, FGFR1 and NaPi-2a co-transporter gene in the remnant kidney, may be explained by nephron loss and renal dysfunction 12 months after the unilateral nephrectomy. These results are in line with our previous report on impaired kidney function 6 months after unilateral nephrectomy2. Taken together, our results suggest that unilateral nephrectomy does lead to certain long-term changes of FGF23-Klotho axis and mineral metabolism. Future studies are needed to show the importance of these changes on living donor kidney function and general health.