MO947: Evaluation of Bone Metabolism Markers in Kidney Transplant Recipients

Abstract BACKGROUND AND AIMS Immunosuppressive therapies, pre-existing renal osteodystrophy, de novo hyperparathyroidism, and other traditional risk factors influence Mineral and Bone Disorder (MBD) after kidney transplantation. However, little is known about their effect on bone metabolism biomarkers. Therefore, we aimed to understand how kidney transplant affects bone metabolism markers in comparison to patients on hemodialysis and healthy individuals. METHOD This is a cross-sectional study with 57 kidney transplant patients, 36 patients on hemodialysis, and 31 healthy controls. Plasma concentrations of Dickkopf-related protein 1 (DKK1), osteoprotegerin (OPG), osteocalcin (OC), osteopontin (OPN), sclerostin (SOST) and fibroblast growth factor 23 (FGF-23) were measured using the Luminex-based microbead assay (HBNMAG-51K,  Millipore, Billerica, MA) in these three groups. Associations between the measurements of these molecules with clinical, demographic, and laboratory data were evaluated. For variables without Gaussian distribution, Mann–Whitney test was used to compare two groups and the Kruskal–Wallis test for comparisons between more than two groups. For variables with normal distribution, comparisons between two groups were made by unpaired Student's t-test and for more than two groups by analysis of variance followed by Bartlett’s post-test. Pearson or Spearman tests were adopted to evaluate correlations according to the variables’ distribution. All statistical tests were two-tailed with a significance level of P  < 0.05. RESULTS Transplant recipients had significantly lower levels of DKK1 (P  < 0.001), OPG (P  < 0.001), OC (P  < 0.001), OPN (P = 0.001), OST (P  < 0.001) and FGF-23 (P  < 0.001) when compared with patients on hemodialysis. In comparison to healthy controls, transplant recipients also presented lower levels of DKK1 (P = 0.019), OPG (P  < 0.001), OC (P = 0.027), SOST (P  < 0.001) and FGF-23 (P = 0.043) (Figure 1). Regarding demographic data, women presented lower plasma SOST levels when compared with men in the hemodialysis group (P = 0.012). Different correlations between the human bone metabolism components were detected in transplant recipients and hemodialysis patients. In the transplant group, DKK1 was positively correlated with SOST (r = 0.484, P = 0.001), OPN (r = 0.420, P = 0.005) and OPG (r = 0.521, P  < 0.001). In the same group, SOST levels were positively correlated with FGF-23 (r = 0.424, P = 0.027, Figure 2D) and OPG (r = 0.703, P  < 0.001), while OC only positively correlated with OPN (r = 0.572, P  < 0.001). By contrast, patients on hemodialysis only showed positive correlations between OPN and DKK1 (r = 0.420, P = 0.005) and between SOST and OPG (r = 0.757, P  < 0.001). Concerning laboratory parameters and their correlations with human bone metabolism molecules, both transplant recipients and hemodialysis patients showed a negative correlation between 25(OH)vitamin D levels and FGF-23. On the other hand, ALP levels were positively correlated with different molecules in the two groups. In transplant patients, ALP levels positively correlated with OPN (r = 0.572, P  < 0.001), while, in hemodialysis patients, the positive correlation was with OPG (r = 0.548, P = 0.012). CONCLUSION Our findings showed a reduction in bone metabolism markers, DKK1, OPG, OC, OPN and SOST after kidney transplantation. The first years after kidney transplantation modulate MBD markers, revealing a significant improvement of MBD associated with end-stage kidney disease.