Mineral adaptations following kidney transplantation

Background Klotho is predominantly expressed in the kidney and reported to have anti-oxidant and anti-fibrotic properties. Soluble-Klotho (sKl), the circulating protein cleaved from membrane-bound Klotho, is reduced significantly with kidney disease and inversely associated with mortality. sKl has not been thoroughly evaluated prospectively after kidney transplantation. Methods Incident kidney transplant recipients (KTRs) were prospectively evaluated pre-transplantation, 1-week, 12-weeks and 52-weeks post-transplantation. Basic biochemistry, sKl and intact FGF23 was measured. Within-subject comparisons were evaluated using repeat-measure ANOVA or Friedman's analysis. Effects of immunosuppression and biochemical parameters on sKl and FGF-23 over time were analysed using mixed effects modelling. Results Median serum creatinine (sCr) at 1-week was 116 (92-142)μmol/L and at 52-weeks, all 29 KTRs had a functioning graft with median sCr of 111 (97-131)μmol/L. Compared with baseline, sKl was increased at 52-weeks following an initial decline at 1-week (p<0.005 and p<0.01 respectively), while FGF23 was considerably reduced at 52 weeks (p<0.001). In a mixed effects model, an increased sKl was not associated with reduction in immunosuppression or evaluated biochemical parameters. Conclusions Modest increase in sKl is observed one-year post kidney transplantation with excellent early graft function suggesting factors beyond renal capacity may influence circulating sKl. FGF23 normalisation was observed. Longer-term evaluation in transplantation, specifically addressing the effects of immunosuppression, is required to understand the pathophysiology of the sKl/FGF23 axis and potential for modification. This article is protected by copyright. All rights reserved.