title: Mineral adaptations following kidney transplantation.
abstract: Klotho is predominantly expressed in the kidney and reported to have antioxidant and antifibrotic 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. Incident kidney transplant recipients (KTRs) were prospectively evaluated pretransplantation, 1, 12 and 52 weeks post-transplantation. Basic biochemistry, sKl and intact FGF23 were 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. 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. Modest increase in sKl is observed one-year postkidney transplantation with excellent early graft function suggesting factors beyond renal capacity may influence circulating sKl. FGF23 normalization 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.
authors.affiliation: Department of Nephrology, The Royal Melbourne Hospital, Parkville, Vic., Australia.|Department of Medicine, The University of Melbourne, Parkville, Vic., Australia.
authors.forename: Sven-Jean
authors.initials: SJ
authors.lastname: Tan
authors.affiliation: Department of Medicine, The University of Melbourne, Parkville, Vic., Australia.|Department of Nephrology, Austin Hospital, Heidelberg, Vic., Australia.
authors.forename: Amy
authors.initials: A
authors.lastname: Crosthwaite
authors.affiliation: Department of Nephrology, Northern Hospital, Epping, Vic., Australia.
authors.forename: David
authors.initials: D
authors.lastname: Langsford
authors.affiliation: Department of Endocrinology, St Vincent's Hospital Melbourne, Fitzroy, Vic., Australia.
authors.forename: Varuni
authors.initials: V
authors.lastname: Obeysekere
authors.affiliation: Department of Medicine, The University of Melbourne, Parkville, Vic., Australia.|Department of Nephrology, St Vincent's Hospital Melbourne, Fitzroy, Vic., Australia.|Victorian Kidney Transplantation Collaborative, Melbourne, Vic., Australia.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Ierino
authors.affiliation: Victorian Kidney Transplantation Collaborative, Melbourne, Vic., Australia.|Eastern Health Clinical School, Monash University, Box Hill, Vic., Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Roberts
authors.affiliation: Department of Nephrology, The Royal Melbourne Hospital, Parkville, Vic., Australia.|Department of Medicine, The University of Melbourne, Parkville, Vic., Australia.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Hughes
authors.affiliation: Department of Nephrology, The Royal Melbourne Hospital, Parkville, Vic., Australia.|Department of Medicine, The University of Melbourne, Parkville, Vic., Australia.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Hewitson
authors.affiliation: Department of Medicine, The University of Melbourne, Parkville, Vic., Australia.|Department of Nephrology, St Vincent's Hospital Melbourne, Fitzroy, Vic., Australia.|Victorian Kidney Transplantation Collaborative, Melbourne, Vic., Australia.|School of Medicine, Deakin University, Geelong, Vic., Australia.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Dwyer
authors.affiliation: Department of Nephrology, The Royal Melbourne Hospital, Parkville, Vic., Australia.|Department of Medicine, The University of Melbourne, Parkville, Vic., Australia.
authors.forename: Nigel D
authors.initials: ND
authors.lastname: Toussaint
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D015331:Cohort Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D008903:Minerals / Q000097:blood
chemical_list: C000717427:FGF23 protein, human; D008903:Minerals; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: fibroblast growth factor-23; kidney transplant recipient; phosphate; soluble Klotho