Possible Association between Serum Hepcidin and Hemostatic Parameters in Chronic Renal Failure Rat Model: Influence of Inhibition of Angiotensin Converting Enzyme

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Category: Vol. 87, March 2019

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Possible Association between Serum Hepcidin and Hemostatic Parameters in Chronic Renal Failure Rat Model: Influence of Inhibition of Angiotensin Converting Enzyme, MAHA A. FATHY and NADINE A. RAAFAT

Abstract
Background: Chronic renal failure (CRF) is usually asso-ciated with abnormal coagulation profile. Hepcidin is a major regulator of iron metabolism and was reported to have an impact on anemia, insulin resistance, dyslipidemia, inflam-mation and oxidative stress which were all reported to play a potential role in CRF induced coagulopathy. Renin angi-otensin system (RAS) is involved in the pathophysiology of CRF and can affect coagulation profile.
Aim of Study: To evaluate changes in coagulation profile in a rat model of chronic renal failure and the possible asso-ciation of these changes with serum hepcidin level in relation to some metabolic, inflammatory and oxidative stress param-eters and to evaluate whether changes in these parameters induced by inhibition of angiotensin converting enzyme (ACE) can affect serum hepcidin level.
Material and Methods: Forty adult male albino rats divided into: Group I (n=8): Control group: Rats received subcutaneous injection with the vehicle (0.3M NaHCO3, 5ml/Kg) once weekly for 5 weeks. Group II (n=16): Chronic renal failure-induced group (CRF): Rats received subcutaneous injection with folic acid (300mg/kg in 5ml) once weekly (dissolved in 0.3M NaHCO3) for 5 weeks. Group III (n=16): (CRF + captopril): Chronic renal failure was induced by folic acid as in group II with concomitant administration of the ACE inhibitor; captopril in a daily dose of (100mg/kg/day) orally by gastric gavage. The following was measured in all groups: Blood pressure, Kidney function, haematological and haemo-static parameters, HOMA-IR, lipid profile, CRP, IL6, MDA, SOD and histopathological examination was made.
Results: There was a significant increase in serum hepcidin level in group II compared to control which was correlated positively with serum creatinine, blood urea and negatively with creatinine clearance, while its level decreased significantly in group III compared to group II. A significant increase in bleeding time, WBCT, PT, APTT, INR, FDPs, D dimer and protein C was found in group II compared to control with an increase in HOMA-IR, CRP, IL6, MDA, systolic and diastolic blood pressure and a significant decrease in Hb, MCV, MCH, platelet count, MPV and SOD. In group III, bleeding time, WBCT and protein C remained significantly elevated versus control and further increase in APTT was found versus group II. A significant decrease in FDPs and D dimer was found in group III versus group II with a significant decrease in HOMA-IR, TG, LDL, VLDL, CRP, IL6, MDA, systolic and diastolic BP.
Conclusion: Chronic renal failure induced significant increase in hepcidin level associated with an abnormal coag-ulation profile. Hepcidin can indirectly affect coagulation profile through its effect on anaemia, IR, oxidative stress and inflammatory mediators. Inhibition of ACE by captopril caused significant improvement of renal function with significant decrease in hepcidin level and significant decrease in hyper-coagulopathy.

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