Study of pro-hepcidin level and renal functions in nephrotic syndrome, chronic renal failure and hemodialysis patients

ABSTRACT

Anemia is associated with worse outcomes in patients with chronic kidney disease [CKD]. Hepcidin is a recently discovered protein produced mainly by the hepatocytes as a pre-prohormone, pre-prohepcidin. It is a key regulator of iron metabolism in different iron disorders. To study serum pro-hepcidin levels in nephrotic syndrome [NS], chronic renal failure [CRF], and hemodialysis [HD] patients. The study included 4 groups. Group I 20 patients with NS, group II 20 patients with CRF on conservative treatment, group III 20 patients on regular HD, and group IV 20 healthy subjects as a control group. All groups were age and sex matched, and subjected to physical examination, abdominal ultrasound, and laboratory investigations including Complete blood cell count, serum iron, iron indices, serum pro-hepcidin, serum high sensitivity C-reactive protein [hs-CRP], renal functions, liver functions, and other necessary tests. CRF and HD patients had a statistically significant higher mean serum pro-hepcidin than NS patients and controls [P <0.001], with no statistically significant difference between the NS and control groups. All patient groups had a statistically significant higher serum hs-CRP, and a significantly lower hemoglobin concentration, serum iron, and transferrin saturation compared with controls [P<0.001]. The mean serum ferritin was statistically significantly increased in the HD group only [P <0.001]. Serum pro-hepcidin showed a statistically significant positive correlation with serum hs-CRP [a marker of inflammation], serum ferritin, blood urea and serum creatinine in all patient groups, with serum uric acid in NS and CRE patients, and with serum albumin only in NS patients. It showed a statistically significant inverse correlation with serum iron and transferrin saturation in all patient groups, with hemoglobin concentration and creatinine clearance in NS and CRF patients [HD patients were anuric], and with urinary albumin excretion only in NS patients probably due to increased pro-hepcidin loss with the proteinuria. In patients with CKD, the presence of a chronic inflammatory status offsets the inhibitory effect of anemia on pro-hepcidin production with a net increase in serum pro-hepcidin levels. This inflammation related dysregulation of pro-hepcidin might result in a functional iron deficiency, thus aggravating the anemia. Pro-hepcidin is unlikely to be beneficial in monitoring anemia of CKD. However, it could be a future therapeutic target in managing anemia in these patients