Serum citrulline levels as a marker of enterocyte function in patients after allogeneic hematopoietic stem cells transplantation - a pilot study.

BACKGROUND: Citrulline is an amino acid produced by enterocytes. Serum citrulline concentration has been proposed as a marker of enterocyte mass and function. Our study focused on evaluation of citrulline levels in patients with diarrhea related to toxic intestinal damage (mucositis), intestinal graft versus host disease (GVHD), and other etiology of diarrhea (e.g., dysmicrobia) after allogeneic stem cells transplantation (SCT). MATERIAL AND METHODS: This was a prospective study in 11 adults (18 blood samples) with diarrhea developed after allogeneic SCT in 4/2011-1/2012 compared to twenty healthy control samples. RESULTS: The median (interquartile range) of citrulline levels was significantly lower in the transplanted patients group compared to healthy controls: 9.3 (3.62-15.38) vs. 33.3 (26.82-36.23) µmol/L, p<0.0001. The median values of citrulline in patients with post-transplant toxic intestinal mucositis (n=8, days 1-22 post-transplant) vs. intestinal GVHD (n=7, day 43-142) vs. other etiology of diarrhea (e.g., dysmicrobia) (n=3, day 120-127) were: 9.55 (2.95-12.03) vs. 5 (3.85-9.05) vs. 15.6 (15.45-18.3) mol/L resp. Serum citrulline levels were significantly higher in other (eg, dysmicrobic) etiology of diarrhea in comparison with mucositis (p=0.0336) and GVHD (p=0.0152). CONCLUSIONS: Citrulline levels are very low shortly after the myeloablative FLU/MEL or BuCY2 conditioning allogeneic SCT due to the toxic intestinal damage. Significantly low levels of citrulline were also in patients with intestinal GVHD later on. Other observations in larger groups of patients are necessary before any specific recommendation for citrulline levels monitoring in intestinal GVHD can be made.

High ferritin, but not hepcidin, is associated with a poor immune response to an influenza vaccine in hemodialysis patients.

BACKGROUND: The immune response to vaccination in hemodialysis (HD) patients can be influenced by disorders of iron metabolism, iron overload or chronic inflammatory state. Elevated levels of hepcidin are considered a new marker of iron metabolism impairment and anemia of inflammation in HD patients. METHODS: We studied the effects of hepcidin, other markers of iron status and intravenous iron (Fe(iv)) on the response to an influenza vaccine (Influvac(R) subunit 2008/2009) in 40 HD patients. The immune response of HD patients was compared with that of 46 controls without renal disease according to serum antihemagglutinin antibody titer (anti-HA). RESULTS: A total of 31 HD patients (responders) attained seroconversion (at least a 4-fold increase in anti-HA) to at least 1 of 3 vaccine strains; 9 patients (nonresponders) did not respond to any strain. Responders did not differ from nonresponders in hepcidin [99 microg/l (36-200) vs. 97 microg/l (23-216), p = 0.97]. Responders had lower ferritin (571 +/- 291 vs. 821 +/- 309 microg/l, p = 0.031) and were administered higher doses of Fe(iv) within the last 12 weeks prior to vaccination [625 mg (312-625) vs. 312 mg (0-625), p = 0.029]. The seroconversion to A(H1N1), A(H3N2) and B strains was noted in 20, 52 and 40% of HD and in 11, 39 and 48% of controls, respectively (HD vs. controls, p = nonsignificant). The rates of seroprotection (anti-HA > or =40) to vaccine strains in HD (27, 85 and 95%) and controls (24, 96 and 98%) were also comparable. CONCLUSION: Antibody production following influenza vaccination in HD patients may be suppressed by very high ferritin levels. Hepcidin does not correlate with immune response and high levels of hepcidin may reflect its retention in HD patients. Fe(iv) administration was not associated with a poorer immune response. The immunogenicity of the A(H1N1) strain was inadequate in HD patients and controls alike.

Relationship between hepcidin and ferritin in haemodialysed patients.

BACKGROUND: Hepcidin is a key regulator of iron metabolism. It binds to ferroportin and causes the trapping of iron in cells, rendering it unavailable for erythropoiesis. The synthesis of hepcidin is upregulated by high iron stores and inflammation. Haemodialysed patients suffer from anaemia and impaired iron management, the cause of which is multifactorial. Our aim was to describe the relationship between hepcidin and other parameters of iron metabolism, erythropoiesis, and inflammation. PATIENTS, MATERIALS AND METHODS: Complete blood cell counts, hepcidin, parameters of iron metabolism, and inflammation were measured in samples from 164 dialysed patients and 37 control healthy volunteers. Patients were subdivided according to the time of dialysis session. RESULTS: According to the time of haemodialysis, iron levels showed an insignificant tendency for diurnal variability, whereas hepcidin levels were markedly different. Non-parametric correlations showed a weak, but statistically significant correlation between parameters of iron metabolism and inflammation in the entire group of patients. No correlation was found between hepcidin and other biochemical parameters in controls. Non-parametric correlations were also performed in the time subgroups of patients. CONCLUSION: It seems that the influence of inflammation on hepcidin levels in haemodialysed patients is not crucial and other factors (e.g. hepcidin retention) are involved.