Association of hepcidin-25 with survival after kidney transplantation

Abstract

Background: Hepcidin is considered the master regulator of iron homoeostasis. Novel hepcidin antagonists have recently been introduced as potential treatment for iron-restricted anaemia. Meanwhile, serum hepcidin has been shown to be positively associated with cardiovascular disease and inversely with acute kidney injury. These properties may lead to contrasting effects, especially in renal transplant recipients (RTR), which are prone to cardiovascular diseases and graft failure. To date, the role of serum hepcidin in RTR is unknown. We, therefore, prospectively determined the association of serum hepcidin with risk of graft failure, cardiovascular mortality and all-cause mortality in RTR.

Materials and methods: Serum hepcidin was assessed in an extensively phenotyped RTR cohort by dual-monoclonal sandwich ELISA specific immunoassay. Statistical analyses were performed using univariate linear regression followed by stepwise backward linear regression. Cox proportional hazard regression models were performed to determine prospective associations.

Results: We included 561 RTR (age 51 ± 12 years). Mean haemoglobin (Hb) was 8·6 ± 1·0 mM. Median [IQR] serum hepcidin was 7·2 [3·2-13·4] ng/mL. Mean estimated glomerular filtration rate was 47 ± 16 mL/min/1·73 m² . In univariate Cox regression analyses, serum hepcidin was not associated with risk of graft failure, cardiovascular mortality or all-cause mortality. Notably, after adjustment for high sensitivity C-reactive protein and ferritin, serum hepcidin became negatively associated with all-cause mortality (hazard ratio 0·89; 95% confidence interval 0·80-0·99, P = 0·03).

Conclusions: In this study, we did not find an association between serum hepcidin and outcomes, that is graft failure, cardiovascular mortality or all-cause mortality. Based on our results, it is questionable whether serum hepcidin may be used to predict a beneficial effect of hepcidin antagonists.

Keywords: Determinants; graft failure; hepcidin; mortality; renal transplantation.

Figure 1

Determinants of serum hepcidin. (a) The interaction between high sensitivity C‐reactive protein (hs‐CRP) and serum ferritin on hepcidin is shown. hs‐CRP and ferritin levels were divided in tertiles. (b) The interaction between serum insulin levels and serum ferritin on serum hepcidin is shown. Insulin and ferritin levels were divided in tertiles.

Figure 2

Association between serum hepcidin and risk of graft failure (a) of cardiovascular (b) and all‐cause mortality (c) according to model 3, Table 3. The line in the graph represents the hazard ratio. The grey area represents the 95% confidence interval of the hazard ratio.