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.

α-Klothoʼs effects on mineral homeostasis are fibroblast growth factor-23 dependent

“…There is good evidence from clinical and experimental studies that both acute and chronic renal failure are associated with reduced expression of Klotho in the kidney, and with reduced sKlotho levels in the blood [ 43 ▪▪ , 44 – 47 ]. In agreement with these data, kidney transplantation in CKD patients results in a rapid rise in circulating sKlotho, and a decline in circulating FGF23 levels [ 48 ▪ , 49 ▪ ]. Conversely, treatment of mice with sKlotho improves outcome in acute and chronic renal injury models [ 50 ▪▪ ].…”

Serum iFGF-23, sKlotho, and 1,25 (OH)&lt;sub&gt;2&lt;/sub&gt; D&lt;sub&gt;3&lt;/sub&gt; Vitamin Levels in Kidney Transplant

“…On the other hand, in a study covering pretransplantation and posttransplantation periods, it was found that sKlotho levels declined at 1w following transplantation and started increasing gradually afterward. At 12 w it exceeded the pretransplant level and at 52 w it was still increasing [23].…”

Serum Klotho in Living Kidney Donors and Kidney Transplant Recipients: A Meta-Analysis

“…Eighteen of these were excluded from the full-length review as they did not report the outcome of interest, while six articles were excluded because they were not observational studies. Thus, 15 studies (10 cohort studies [ 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ] with a total of 431 KTx recipients and 5 cohort studies [ 68 , 69 , 70 , 71 , 72 ] with a total of 108 living kidney donors) were included. The literature retrieval, review, and selection process are demonstrated in Figure 1 .…”

“…In addition, living donor KTx provides greater allograft longevity than those transplanted from a deceased donor [ 57 ]. However, changes in serum klotho levels and the impact of klotho on outcomes among KTx recipients and kidney donors remain unclear [ 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ]. Thus, we conducted this systematic review and meta-analysis to assess serum klotho levels and the impact of klotho on outcomes among KTx recipients and kidney donors…”