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Advisor(s)
Abstract(s)
Anemia is a common complication of chronic kidney disease (CKD) that develops early and its
severity increases as renal function declines. It is mainly due to a reduced production of erythropoietin
(EPO) by the kidneys; however, there are evidences that iron metabolism disturbances
increase as CKD progresses. Our aim was to study the mechanisms underlying the
development of anemia of CKD, as well as renal damage, in the remnant kidney rat model of
CKD induced by 5/6 nephrectomy. This model of CKD presented a sustained degree of renal
dysfunction, with mild and advanced glomerular and tubulointerstitial lesions. Anemia developed
3 weeks after nephrectomy and persisted throughout the protocol. The remnant kidney
was still able to produce EPO and the liver showed an increased EPO gene expression. In
spite of the increased EPO blood levels, anemia persisted and was linked to low serum iron
and transferrin levels, while serum interleukin (IL)-6 and high sensitivity C-reactive protein (hs-
CRP) levels showed the absence of systemic inflammation. The increased expression of duodenal
ferroportin favours iron absorption; however, serum iron is reduced which might be due
to iron leakage through advanced kidney lesions, as showed by tubular iron accumulation. Our
data suggest that the persistence of anemia may result from disturbances in iron metabolism
and by an altered activity/function of EPO as a result of kidney cell damage and a local inflammatory
milieu, as showed by the increased gene expression of different inflammatory proteins
in the remnant kidney. In addition, this anemia and the associated kidney hypoxia favour the
development of fibrosis, angiogenesis and inflammation that may underlie a resistance to EPO
stimuli and reduced iron availability. These findings might contribute to open new windows to
identify putative therapeutic targets for this condition, as well as for recombinant human EPO
(rHuEPO) resistance, which occurs in a considerable percentage of CKD patients.
Description
Keywords
Anemia Dysmetabolism Renal Hypoxia Inflammation Fibrosis
Citation
Patrícia Garrido, Sandra Ribeiro, João Fernandes, Helena Vala, Elsa Bronze-da-Rocha, Petronila Rocha-Pereira, Luís Belo, Elísio Costa, Alice Santos-Silva and Flávio Reis (2015). Iron-hepcidin dysmetabolism, anemia and renal hypoxia, inflammation and fibrosis in the remnant kidney rat model. PLOS ONEPONE-D-14-44540R1. 2015; 10(4): e0124048: 24pp
Publisher
McGill University