The kidneys play an important role in the metabolism of vitamin A and its transport proteins [5, 6, 18] and it is well documented that a reduced kidney function due to acute or chronic renal failure is associated with increased serum concentrations of ROH, RBP4 and TTR [5, 8, 9]. However, very little is known about changes in the vitamin A transport complex in serum of donors after LDKT, which represents a sudden loss of kidney function. Therefore, we investigated the concentrations of ROH, RBP4 and TTR in serum of donors and the respective recipients before and after transplantation.
The main clinical consequence of unilateral nephrectomy in donors was a decrease in eGFR to approximately 65% of pre-nephrectomy values, which remained decreased also 6 months after LDKT as also described by others before [19–21]. In allograft recipients, LDKT resulted in a general improvement of kidney function, indicated by an increase of eGFR and decrease of UP/UC as expected and confirming previous results of others [22–25].
In donors the ROH and RBP4 serum concentrations as well as relative amounts of apoRBP4 (RBP4 unbound to ROH) increased post-nephrectomy and remained increased during the follow-up period of 6 months. In addition, it could be demonstrated that the increase of all three parameters was paralleled by a decrease of the donor's eGFR and correlation analysis revealed a significant inverse association of eGFR with ROH, RBP4 and apoRBP4, respectively. These results confirmed and expanded the observations of Argiles et al. , who reported an increase of ROH and RBP4 serum concentration in donors seven days after LDKT.
The increase of ROH and RBP4 serum concentration and relative amounts of apoRBP4 is most likely explained by the essential role of the kidneys in vitamin A metabolism. Under physiological conditions the complex of ROH, RBP4 and TTR ensures the transport of vitamin A in the circulation. After the delivery of ROH to the target tissue, the remaining complex of apoRBP4 and TTR dissociates and the resulting free apoRBP4 is then filtered and degraded in the kidneys [5, 7]. Therefore, a reduction of kidney function is associated with an increase of apoRBP4 in serum [27, 28], as also seen in the donors of the present study. In this context, Gerlach and Zile  proposed, that apoRBP4 provides a positive feedback signal for the hepatic release of holoRBP4 (RBP4 in complex with ROH), resulting in an increase of ROH and an additional increase of RBP4 serum concentration. Therefore, the increased concentrations of ROH and RBP4 in serum of donors of the present study are most likely attributed to the decreased kidney function and the resulting increase of apoRBP4 may in turn trigger the increased secretion of holoRBP4 from the liver contributing the increase of ROH and RBP4 serum concentration. The inverse association of eGFR with ROH, RBP4 and apoRBP4 in the present study supports this hypothesis and emphasizes the importance of the kidneys in homeostasis of the vitamin A metabolism. However, these results also indicate that in donors the remaining kidney function after LDKT does not seem to be adequate to maintain a normal vitamin A metabolism.
The fact that TTR serum concentration of donors does not seem to be affected by nephrectomy in the present study underlines the lesser importance of kidneys to TTR metabolism . Nevertheless, although not significant, the TTR concentration in serum of donors tended to increase and a longer follow-up period may might have resulted in a significant increase of TTR as well.
In view of the vitamin A transport complex, the allograft recipients revealed a reduction of ROH, RBP4, and TTR serum concentration as well as apoRBP4 within 6 months after LDKT, which is in accordance to results previously reported by Kelleher et al. . The decrease in serum concentration of all four compounds was paralleled by an increase of eGFR and may be mainly explained by the restoration of kidney function by LDKT. Nevertheless, even 6 months after LDKT none of the components of the vitamin A transport complex decreased to values comparable to those of donors before LDKT, which emphasize the incomplete remission of kidney function with regard to vitamin A metabolism as suggested by Kelleher et al. .
The elevated concentrations of ROH and RBP4 in serum of donors after LDKT raise the question concerning the possible consequences. In principle, kidney donation has been associated with a low risk for donors with regard to surgery-associated as well as long-term complications such as hypertension, CKD, and overall mortality [1–3, 31]. However, evidence is accumulating that incipient renal failure indicated by a reduced eGFR is strongly associated with an increased risk for CVD . In fact, recent data indicate that the long-term risks associated with living-kidney donation are higher than previously thought  and that there is indeed a paucity of data concerning cardiovascular risk factors in donors after LDKT . The situation is exacerbated by the trend of accepting donors beyond the traditional rigorous inclusion criteria due to the increasing demand for kidney transplantations .
In this context, the increased concentrations of ROH and RBP4 in serum of donors might contribute to the risk of CVD, since elevated levels of both parameters have been associated with CVD [12, 13]. Furthermore, high ROH and RBP4 serum concentrations have been linked to increased intima-media thickness [14, 15] and RBP4 serum concentration to a higher fat content in vessel walls and atherosclerotic plaques . The underlying mechanisms for these associations remain to be elucidated, but lipid modulating activities of retinoids and retinol-binding proteins have been suggested as an important factor [14, 33].
In addition, an elevated serum concentration of RBP4 has been linked to insulin resistance  as well as subclinical inflammation . Thus, the nephrectomy-associated increase of RBP4 serum concentrations may explain the increased susceptibility of living-kidney donors for insulin resistance as "described by Shehab-Eldin et al. . However, since the present study was an observational study, which primary aim was to analyze the nephrectomy-associated changes in ROH, RBP4 and TTR in living-kidney donors, the association of the vitamin A transport complex with CVD and insulin resistance remains speculative and should be a matter of future research.