Díaz-De la Cruz Elodia Nataly, Cerrillos-Gutiérrez José Ignacio, García-Sánchez Andrés, Prado-Nevárez Carlos Gerardo, Andrade-Sierra Jorge, Jalomo-Martínez Basilio, Banda-López Adriana, Rojas-Campos Enrique, Miranda-Díaz Alejandra Guillermina
Department of Physiology, University Health Sciences Center, Universidad de Guadalajara, Guadalajara, Mexico.
Department of Nephrology and Organ Transplant Unit, National Western Medical Centre, Mexican Institute of Social Security, Specialties Hospital, Guadalajara, Mexico.
Front Med (Lausanne). 2021 Nov 25;8:714205. doi: 10.3389/fmed.2021.714205. eCollection 2021.
Patients with end-stage renal disease (ESRD) present alterations in mineral and bone metabolism. Hyperphosphatemia in ESRD is considered an independent risk factor for cardiovascular disease (CVD), increasing morbidity, and mortality. Sevelamer hydrochloride is a calcium-free, non-absorbable phosphate-chelating polymer. Calcium carbonate chelator is helpful in controlling serum phosphate levels. There is insufficient information on the influence of sevelamer hydrochloride and calcium carbonate on the behavior of oxidative stress (OS) markers and inflammation in patients on hemodialysis (HD). A randomized open clinical trial was carried out on patients to evaluate sevelamer hydrochloride and calcium carbonate influence at 6 months of study follow-up. Levels of oxidants (LPO, NO, and 8-isoprostanes), antioxidants (SOD and TAC), oxidative DNA damage (8-OHdG and hOGG1), pro-inflammatory cytokines (IL-6 and TNF-α), and inflammation markers (ferritin and C-reactive protein) were measured with colorimetric and ELISA methods. We found a significant increase in oxidants LPO and NO, and antioxidants SOD and TAC, and downregulation of IL-6 and TNF-α. Ferritin decrease at 6 months follow-up in the sevelamer hydrochloride group. Increase in C-reactive protein was found in the group of patients treated with calcium carbonate. In conclusion, we found an oxidative state imbalance with increase in LPO and NO oxidants. The activity of the antioxidant enzymes (SOD and TAC) was also found to increase, suggesting a compensatory effect in the face of increase in oxidants. The same phenomenon was observed with increase in the oxidative damage marker to DNA and the increase in the DNA repair enzyme, suggesting a compensatory effect. Pro-inflammatory cytokines were predominantly downregulated by TNF-α in the group that ingested sevelamer hydrochloride in the final determination at 6 months of follow-up. Serum ferritin levels decreased significantly at the end of follow-up in patients on HD in the sevelamer hydrochloride group. The management of hyperphosphatemia with sevelamer hydrochloride appears to have obvious anti-inflammatory and antioxidant benefits.
终末期肾病（ESRD）患者存在矿物质和骨代谢改变。ESRD患者的高磷血症被认为是心血管疾病（CVD）的独立危险因素，会增加发病率和死亡率。盐酸司维拉姆是一种无钙、不可吸收的磷酸盐螯合聚合物。碳酸钙螯合剂有助于控制血清磷水平。关于盐酸司维拉姆和碳酸钙对血液透析（HD）患者氧化应激（OS）标志物行为和炎症的影响，目前信息不足。对患者进行了一项随机开放临床试验，以评估在6个月的研究随访中盐酸司维拉姆和碳酸钙的影响。采用比色法和酶联免疫吸附测定法测量氧化剂（脂质过氧化产物、一氧化氮和8-异前列腺素）、抗氧化剂（超氧化物歧化酶和总抗氧化能力）、氧化性DNA损伤（8-羟基脱氧鸟苷和人8-氧鸟嘌呤糖苷酶1）、促炎细胞因子（白细胞介素-6和肿瘤坏死因子-α）以及炎症标志物（铁蛋白和C反应蛋白）的水平。我们发现氧化剂脂质过氧化产物和一氧化氮、抗氧化剂超氧化物歧化酶和总抗氧化能力显著增加，白细胞介素-6和肿瘤坏死因子-α下调。盐酸司维拉姆组在6个月随访时铁蛋白降低。在碳酸钙治疗组患者中发现C反应蛋白升高。总之，我们发现脂质过氧化产物和一氧化氮氧化剂增加导致氧化状态失衡。还发现抗氧化酶（超氧化物歧化酶和总抗氧化能力）的活性增加，表明面对氧化剂增加存在代偿作用。在DNA氧化损伤标志物增加和DNA修复酶增加时观察到相同现象，表明存在代偿作用。在6个月随访的最终测定中，摄入盐酸司维拉姆的组中促炎细胞因子主要被肿瘤坏死因子-α下调。盐酸司维拉姆组HD患者随访结束时血清铁蛋白水平显著降低。用盐酸司维拉姆治疗高磷血症似乎具有明显的抗炎和抗氧化益处。
