Abstract
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.
Highlights
Disorders of mineral and bone metabolism are frequent complications in patients with end-stage renal disease (ESRD)
Body weight was similar in both groups, 64.79 ± 19.1 kg of patients treated with sevelamer hydrochloride and 63.55 ± 22.46 kg of those treated with calcium carbonate
In the calcium carbonate group, the Body mass index (BMI) was normal in 71.4%, 14% of the patients were overweight, and 14.3% were obese. 74.2% of the patients in the sevelamer hydrochloride group and 71.4% of the patients treated with calcium carbonate had diabetes mellitus (DM). 32.3% of the patients treated with sevelamer hydrochloride and 19% of those treated with calcium carbonate had arterial hypertension (AH) (Table 1)
Summary
Disorders of mineral and bone metabolism are frequent complications in patients with end-stage renal disease (ESRD). Hyperphosphatemia is an inevitable consequence of ESRD, the presence of which is associated with increased morbidity and mortality [1]. Observational studies have reported that hyperphosphatemia is an independent risk factor for cardiovascular disease (CVD) capable of increased mortality in patients on dialysis [2]. New phosphate binders have made it possible to dispense with calcium in the formulation [4]. Sevelamer hydrochloride is a non-absorbable, calcium-free phosphatechelating polymer that has been available since 1998 [5]. Sevelamer hydrochloride is an anion exchange resin, allowing it to exchange negatively charged ions. Sevelamer hydrochloride has a high affinity for phosphate ions and exerts its therapeutic action in the intestine, exchanging chloride for phosphate and forming an insoluble compound that is excreted in feces [6]
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