Article

Heart and iron deficiency anaemia in rats with renal insufficiency: the role of hepcidin.

Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina.
Nephrology (impact factor: 1.31). 09/2008; 13(7):636-45. DOI:10.1111/j.1440-1797.2008.01019.x pp.636-45
Source: PubMed

ABSTRACT Anaemia is prevalent in chronic kidney disease (CKD) and induces significant changes in heart and kidney. In this study, we evaluated the relationship between iron metabolism, hepcidin and inflammation focusing on left ventricular (LV) function, in a remnant kidney rat model.
Rats with 5/6 subtotal nephrectomy (STNx) and sham operation. Haemoglobin (Hb), serum iron (SI), fractional shortening (FS%) by echocardiograms were evaluated. Six months after STNx, the heart and kidney were processed by immunohistochemistry with antibodies against hypoxia-inducible factors (HIF)-1alpha, erythropoietin (EPO), pro-hepcidin, caspase-3, tumour necrosis factor (TNF)-alpha and interleukin (IL)-6.
Hb (g/dL) STNx: 10.8 +/- 0.8, sham: 14.7 +/- 0.6 (P < 0.01); SI (microg/dL) STNx: 154.5 +/- 24.5, sham: 287.5 +/- 32.1 (P < 0.01); heart weight (g) STNx: 2.21 +/- 0.15, sham: 1.12 +/- 0.12 (P < 0.01); FS% STNx: 28.4 +/- 2.5, sham: 45.1 +/- 4.1 (P < 0.01). There was a correlation between Hb and FS% (r = 0.95; P < 0.01) and between SI and FS% (r = 0.86; P < 0.01) in the STNx group. Tissue ferritin was reduced in heart and in kidney in the STNx group (P < 0.01). HIF-1alpha was expressed in cardiomyocytes (positive cells/area) STNx: 32 +/- 5, sham: 4 +/- 1; and tubular cells in STNx group: 70 +/- 16, sham: 10 +/- 3, P < 0.01. Hepcidin (% staining/area) in heart STNx: 6.6 +/- 0.8, sham: 0.8 +/- 0.1; in kidney STNx: 9.7 +/- 2.6, sham: 3.7 +/- 0.9, P < 0.01. EPO (% staining/area) in heart STNx: 2.6 +/- 0.4, sham: 0.8 +/- 0.2; in kidney STNx: 10.2 +/- 1.4, sham: 1.2 +/- 0.6; P < 0.01. In STNx group positive caspase-3, TNF-alpha and IL-6 were detected in heart and renal cells.
Low LV performance is associated with iron deficiency anaemia in rats with CKD. Furthermore, overproduction of HIF-1alpha and the activation of caspase-3 seem to be associated with iron deficiency and with inflammatory markers. Hepcidin seems to plays a key role in this mechanism.

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    Ewa A Jankowska, Piotr Rozentryt, Agnieszka Witkowska, Jolanta Nowak, Oliver Hartmann, Beata Ponikowska, Ludmila Borodulin-Nadzieja, Waldemar Banasiak, Lech Polonski, Gerasimos Filippatos, John J V McMurray, Stefan D Anker, Piotr Ponikowski
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    European Heart Journal 08/2010; 31(15):1872-80. · 10.48 Impact Factor
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Keywords

% staining/area
 
5/6 subtotal nephrectomy
 
chronic kidney disease
 
FS% STNx
 
heart STNx
 
induces significant changes
 
inflammatory markers
 
iron deficiency
 
iron deficiency anaemia
 
iron metabolism
 
kidney STNx
 
Low LV performance
 
positive cells/area
 
remnant kidney rat model
 
renal cells
 
serum iron
 
STNx group
 
STNx group positive caspase-3
 
tubular cells
 
tumour necrosis factor
 

Jorge Eduardo Toblli