Association of hepcidin‐25 with survival after kidney transplantation

Abstract

BackgroundHepcidin 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 methodsSerum 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.ResultsWe 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).ConclusionsIn 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.

Serum Hepcidin-25 and Risk of Mortality in Patients on Peritoneal Dialysis

“…Several researchers have evaluated the association between serum hepcidin level and mortality risk in CKD patients, but the results are controversial. Some studies have shown the association of hepcidin-25 with increased CV mortality risk in HD patients (15) or with all-cause mortality in diabetic CKD patients (30), while Eisenga et al have not found a predictive role of hepcidin-25 in mortality among patients with kidney transplantation (31). Until now, there has no study to investigate the relationship between serum hepcidin level and mortality in PD patients.…”

Iron deficiency after kidney transplantation

“…Inflammation induces hepcidin expression in the liver through cytokines including interleukin (IL)-6 and bone morphogenetic protein (BMP) [ 17 ]. In particular, BMP6, a modulator of the renal response to injury, is a major hepcidin-inducing factor through stimulation of hepatocellular Suppressor against Mothers Against Decapentaplegic (SMAD) production [ 4 ].…”