Efeito do polímero quitosana ferro (III) insolúvel na fosfatemia e no distúrbio mineral-ósseo em ratos urêmicos

Abstract

Introduction: The Chronic Kidney Disease (CKD) is characterized by multiple clinical and metabolic changes that lead to long-term high rates of morbidity and mortality. The CKD mineral and bone disorder (CKD-MBD) is characterized by abnormal laboratory results, bone metabolic variations and soft tissue calcifications. CKD-MBD requires a complex treatment based on phosphate binders substances. There are many options of phosphate binders available on market, however calcium-free formulations are preferable in order to provide a binding phosphate’s effect with lower risk of vascular calcification. A new class of calciumfree phosphate binders, in which iron is the main binder element, was recently introduced and has presented promising results. A new polymer of chitosan and iron was developed at Universidade do Vale do Itajaí Chemical’s Laboratory and have shown phosphate’s binder activity on primary tests in vivo and in vitro tests in animals with normal renal function. Objective: to evaluate the phosphate chelator effect of the chitosan-Fe III polymer (QTS-Fe III) and its activity in bone metabolism in animals with CKD. We evaluated 120 animals, divided equally into 5 groups: control, CKD, QTS-Fe III, CKD/QTS-Fe III and CKD/Calcium carbonate (CKD/CaCO3), over 7 weeks. We induced CKD by feeding animals with an adenine-enriched diet (0.75% in the first 4 weeks and 0.1% in the following 3 weeks) supplemented with 1% phosphorus. We administered 30mg/kg daily of the QTS-Fe III polymer and 500mg/kg daily of the CaCO3, by gavage, both from the third week until the end of the study. Eight animals from each group were submitted to euthanasia at weeks 4, 6 and 7 for collection of blood, urine and femur. By blood and urine tests we evaluated renal function and bone metabolic disorder, and by bone disease by bone histomorphometry. Results: The DRC group presented a significant elevation of creatinine in relation to the control (0.47 ± 0.25 vs 0.95 ± 0.21 mg / dl, p = 0.001), hyperphosphatemia (6.82 ± 0.52 vs 10.6 ± 2.49 mg/dl; p = 0.001), elevated excreted phosphorus fraction (FeP) (0.2 ± 0.17 vs 0.71 ± 0.2; p = 0.0001) and higher FGF23 (7.42 ± 1.96 vs. 81.36 ± 37.16 pg/ml, p = 0.011). The use of chelators provided significant reduction of FeP (Control: 0.71 ± 0.20, CKD/QTS-Fe III: 0.40 ± 0.16, CKD/CaCO3 : 0.34 ± 0.15, p = 0.001), without alteration of FGF23 levels. Histomorphometry showed a high turnover bone disease in uremic animals that was not altered with the use of chelators. Conclusion: QTS-Fe III reduced the phosphate overload, without causing changes in the FGF23 serum level or bone disease profile. These results corroborate to the QTS-Fe III activity as a potential calcium-free phosphate binder.