Iron status and erythropoiesis response to darbepoetin alfa in dogs with chronic kidney disease

Abstract

Iron metabolism, hepcidin and some blood profiles were investigated in 13 healthy and 31 chronic kidney disease (CKD) dogs. The study consisted of 2 experiments, experiment I included healthy dogs (CONT) and CKD dogs (stage 2, 3 and 4), while experiment II consisted of anemic CKD dogs subjected to 28-day darbepoetin alfa treatment. The response to darbepoetin alfa could divide anemic CKD dogs into responder (RP) and non-responder (NRP) subgroups. The results from experiment I showed that packed cell volume (PCV) and plasma albumin concentration were significantly lower in 2 CKD dogs of all stages while the total iron binding capacity (TIBC) was lower in only CKD stage 3 and 4 compared with dogs in CONT group. The PCV was related to both TIBC and albumin when considering among all dogs or only in CKD dogs. The hepcidin concentration in CKD dogs with anemia was lower than those without anemia (P<0.05). In experiment II before darbepoetin alfa treatment, RP subgroup had significantly higher iron and TIBC compared with NRP subgroup (P<0.05), the iron concentration was decreased only in RP subgroup after darbepoetin alfa treatment (P<0.05). The percent increase in PCV was correlated with initial TIBC (P<0.01). Plasma hepcidin concentration was not different between CONT and CKD groups and between RP and NRP subgroups both before and after darbepoetin alfa treatment. It is concluded that TIBC and plasma iron concentration play role on anemia and erythropoietic response to darbepoetin alfa treatment in CKD dogs.

The first study on urinary loss of iron and transferrin in association with proteinuria in dogs with chronic kidney disease

“…Plasma ALB concentration was negatively correlated with HCT. The results were similar to the previous study in CKD and control healthy dogs [ 14 ]. This association was also found in patients with diabetic nephrosclerosis [ 23 ].…”

“…Thus, heavy proteinuria could alter erythrocyte metabolism resulting in enhanced erythrocyte death and anemia [ 24 ]. Moreover, many anemic dogs with CKD failed to respond to the EPO treatment and iron supplementation [ 13 , 14 ]. It is likely that iron metabolism is one of important factors affecting anemia in patients with CKD.…”

“…Some studies recommended TF determination using immunologic-based techniques rather than TIBC, although genetic variation in TF was found in some populations [ 25 ]. The level of iron in dogs of all groups was lower than those measured from control healthy dogs [ 14 ]. The TIBC was lower in UPC ratio >4 group than UPC ratio <4 groups, and TIBC was negatively correlated with UPC ratio.…”

“…Thus, TIBC was affected by the degree of proteinuria. Lower TIBC and HCT were found in both dogs and cats with CKD than in healthy control [ 14 , 26 ]. Unfortunately, proteinuria was not evaluated in both studies.…”

“…For anemia treatment response in dogs with CKD, baseline hematocrit (HCT), iron supplementation, dosage of darbepoetin, severity of azotemia, age, or comorbidities of dogs showed no correlation with darbepoetin treatment responses [ 13 ]. While in another study, low iron and TIBC were associated with the degree of anemia and the erythropoietic response to darbepoetin treatment with iron supplementation in dogs with CKD [ 14 ]. Thus, alteration in iron metabolism and bone marrow status could significantly impact erythropoiesis in dogs with CKD, even with EPO treatment and iron supplementation.…”