MO1012: Variability of Klotho and FGF-23 Levels After Kidney Transplantation Depending on the Glomerular Filtration Rate

Abstract

BACKGROUND AND AIMS Klotho is a transmembrane protein expressed mainly in distal tubular epithelial cells of the kidneys. Its gene expression and soluble form levels play a crucial role in the interaction of the aging-inflammation binomial and act as a co-receptor for the phosphaturic fibroblast growth factor 23 (FGF-23). Klotho deficiency, which is the norm in chronic kidney disease (CKD), has been reported as an independent risk factor for cardiovascular disease and subclinical atherosclerosis [1, 2]. This study investigates the evolution of Klotho and FGF-23 levels during the first 2 years after kidney transplantation and their variability depending on the glomerular filtration rate (GFR). METHOD Serum levels of Klotho and FGF-23 were determined in 42 patients right before kidney transplantation (KT) and at 3rd, 12th and 24th month after KT. The measurements were made by ELISA. The GFR of the kidney graft was performed by indirect methods (formula: MDRa and CKD-EPI) at each study visit. Variables were reported as mean ± SD, and a value of P < .05 was considered to be statistically significant for each test. RESULTS KT recipients were divided into two groups arbitrary: the first group with a GFR > 40 mL/min (n = 26) and the other one with a GFR ≤ 40 mL/min (n = 16). At the starting point, there was not found any statistical difference in Klotho and FGF-23 levels between groups (GFR > 40 mL/min: 462.65 ± 264.99 pg/mL and 786.84 ± 521.67 pg/mL, respectively; versus GFR ≤ 40 mL/min: 436.5 ± 189.33 and 779.02 ± 589.86). Those with better kidney function after KT significantly increased Klotho levels on 12th and 24th month of follow-up (baseline 462.65 ± 264.99 versus 12th month 561.96 ± 314.68 and 24th month 581.15 ± 350.10; P = .001), whereas KT recipients with a GFR ≤ 40 mL/min only proved an increase in Klotho levels at 12th month after a non-significant initial decrease at 3rd month (462 ± 204.91 versus 356.96 ± 177.07, respectively; P = .028). This trend was not confirmed at the 24th month (397.12 ± 182.05). Klotho levels were found significantly different at the 24th month between groups (P = .031). See Fig. 1. Figure 2 shows the changes in FGF-23 levels. There are significant differences in both groups from baseline to month 24. (P < .001 group GFR > 40 mL/min and P < .001 group GFR ≤ 40 mL/min). FGF-23 dropped significantly in both groups at the 3rd month (P = .018) and 12th months (P = .003). CONCLUSION Vascular disease and mineral metabolism malfunction are relevant abnormalities in patients with CKD as well as in KT recipients. This study shows that Klotho is increasingly produced after KT in those patients whose allografts achieve a better function. We failed to prove the same effect on those with a GFR < 40 mL/min. Nonetheless, FGF-23 production declines satisfactorily independently of GRF. These results suggest the promotion of cardiovascular health after KT, particularly in those with higher GFR. The clinical and prognostic value of these changes are yet to be determined.