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

Abstract

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 homeostasis, recycling and vulnerability in the stressed kidney: A neglected dimension of iron‐deficient heart failure

“…In fact, experimental heart failure is accompanied by decreases in megalin-mediated endocytosis, 89 and urinary excretion of megalin is closely associated with the loss of iron in the urine. 90 Proteinuria (present in nearly half of patients with heart failure 91 ) can cause urinary loss of iron-rich transferrin 92,93 (whose reabsorption is megalin-dependent 21,22 ), and the loss of urinary transferrin is correlated with the severity of hypoferraemia in experimental chronic kidney disease 94 and with anaemia in patients with heart failure. 95 Interestingly, heart failure is accompanied by decreased expression of DMT1 and ferroportin in cardiomyocytes and of DMT1 in duodenal enterocytes 96,97 ; a similar change in DMT1 expression in the proximal renal tubule would be expected to further enhance urinary losses of iron.…”