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

Background and Aim: Anemia is an important factor in surviving chronic kidney disease (CKD). Anemia in CKD is associated with various factors, such as inadequate production of erythropoietin and the availability of iron and its binding protein. Reduced total iron-binding capacity (TIBC) and iron concentrations may be related to their urinary loss along with proteinuria. This study aimed to determine the urinary loss of iron and transferrin (TF) in relation to the degree of proteinuria. Materials and Methods: The study was performed on 37 dogs with CKD. Dogs were divided according to the severity of proteinuria into two groups based on the mean of urinary protein-creatinine (UPC) ratio into UPC ratio <4 and UPC ratio >4. The hematocrit (HCT), blood chemistries, plasma iron, plasma TF, UPC ratio, urinary iron per creatinine ratio (U-Iron/CR), and urinary TF per creatinine ratio (U-TF/CR) were evaluated. Results: Anemia was associated with the severity of renal impairment as demonstrated by reduction of HCT when staging of CKD was higher. Dogs with UPC ratio >4 had higher urinary loss of both U-Iron/CR (p < 0.01) and U-TF/CR (p < 0.001) with lower plasma TIBC (p < 0.001). The UPC ratio was positively correlated with both U-Iron/CR (r = 0.710, p < 0.001) and U-TF/CR (r = 0.730, p < 0.001) but negatively with TIBC (r = -0.462, p < 0.01). Conclusion: Proteinuria was associated with urinary loss of both iron and TF which may contribute to anemia in CKD.

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

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 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.

Heart rate variability and plasma norepinephrine concentration in diabetic dogs at rest.

Cardiac autonomic neuropathy in dogs with diabetic mellitus (DM) was evaluated using measurement of heart rate variability (HRV) and plasma norepinephrine (NE) concentration. Dogs were divided into 2 groups; the control non-DM group (n = 13) and the diabetic group (n = 22) which was further divided into the well-controlled DM (n = 11) and the poorly-controlled DM subgroups (n = 11) according to their fasting plasma fructosamine concentrations. The electrocardiogram (ECG) was recorded continuously for at least 30 min to yield HRV. The results showed that in the poorly-controlled DM subgroup, the average of normal R-R interval (mean N-N), SD of the mean of all 5-min segments of normal RR intervals (SDANN) were lower than the control group while heart rate was higher (P < 0.05). The NNA, SDNN, SDNN index and pNN50% were significantly lower when compared with the well-controlled DM subgroup (P < 0.05). The high frequency (HF) and total power were significantly lower while the ratio of low to high frequency (LF/HF) was higher (P < 0.05) when compared with the well-controlled DM subgroup. Moreover, in the poorly-controlled DM subgroup, plasma NE concentration was lower than the control group (210 ± 37 vs. 479 ± 74 pg/ml, P < 0.05). There was a significantly negative correlation between plasma NE and plasma fructosamine concentrations. It is concluded that cardiac autonomic neuropathy occurred in poorly-controlled DM dogs. The sympathetic activity was suppressed as shown by decrease in both plasma NE concentration and LF component.

Oxidative stress and intraerythrocytic concentrations of sodium and potassium in diabetic dogs.

Oxidative stress parameters; thiobarbituric acid reaction substances (RBC-TBARS), catalase (RBC-CAT) and reduced glutathione (RBC-GSH) and the intraerythrocytic concentrations of electrolytes; sodium and potassium (RBC-Na and RBC-K) were determined in 18 well- controlled (WC) and 22 poorly-controlled diabetic mellitus (DM). Dogs with DM had significant higher blood glucose concentration (P < 0.001), haemoglobin A1c (P < 0.01) and fructosamine (P < 0.001) compared to normal healthy dogs (n = 19). Diabetic dogs in both groups had higher RBC-CAT (P < 0.05) while RBC-TBARS were higher significantly only in poorly-controlled DM group (P < 0.05). The RBC-K was significantly higher in both DM groups (P < 0.001). No changes in RBC-GSH and RBC-Na were found between DM and control healthy dogs. By linear regression analysis, the relationship were found between degree of diabetic mellitus and RBC-CAT, RBC-TBARS, RBC-Na and RBC-K. The relationship was also found between oxidative stress parameters and intraerythrocytic K+. The results suggest that in diabetic dogs, oxidative stress occurs which related to the severity of disease and may affect potassium homeostasis.