Phosphate Binding with Sevelamer Preserves Mechanical Competence of Bone Despite Acidosis in Advanced Experimental Renal Insufficiency

Abstract

IntroductionPhosphate binding with sevelamer can ameliorate detrimental histomorphometric changes of bone in chronic renal insufficiency (CRI). Here we explored the effects of sevelamer-HCl treatment on bone strength and structure in experimental CRI.MethodsForty-eight 8-week-old rats were assigned to surgical 5/6 nephrectomy (CRI) or renal decapsulation (Sham). After 14 weeks of disease progression, the rats were allocated to untreated and sevelamer-treated (3% in chow) groups for 9 weeks. Then the animals were sacrificed, plasma samples collected, and femora excised for structural analysis (biomechanical testing, quantitative computed tomography).ResultsSevelamer-HCl significantly reduced blood pH, and final creatinine clearance in the CRI groups ranged 30%-50% of that in the Sham group. Final plasma phosphate increased 2.4- to 2.9-fold, and parathyroid hormone 13- to 21-fold in CRI rats, with no difference between sevelamer-treated and untreated animals. In the femoral midshaft, CRI reduced cortical bone mineral density (-3%) and breaking load (-15%) (p<0.05 for all versus Sham), while sevelamer increased bone mineral density (+2%) and prevented the deleterious changes in bone. In the femoral neck, CRI reduced bone mineral density (-11%) and breaking load (-10%), while sevelamer prevented the decrease in bone mineral density (+6%) so that breaking load did not differ from controls.ConclusionsIn this model of stage 3–4 CRI, sevelamer-HCl treatment ameliorated the decreases in femoral midshaft and neck mineral density, and restored bone strength despite prevailing acidosis. Therefore, treatment with sevelamer can efficiently preserve mechanical competence of bone in CRI.

Comparing the effect of sevelamer carbonate and sevelamer hydrochloride on plasma pH, bicarbonate and gastrointestinal complications in patients undergoing maintenance hemodialysis

“…Meanwhile, Yang et al indicated that, in comparison with sevelamer carbonate, sevelamer hydrochloride can significantly reduce blood bicarbonate levels (14). Moreover, Jokihaara et al, following of nine weeks of treatment with various drugs, including sevelamer hydrochloride, showed that sevelamer hydrochloride significantly reduced blood pH and lowered the bicarbonate level (15). In a review article by Pham et al showed that sevelamer hydrochloride can significantly reduce the level of blood bicarbonate too (16).…”

Comparison between calcium and non-calcium-based phosphate binders concerning acid-base status and electrolytes in Hemodialysis patients in ALHYAT hospital.

“…The role of sevelamer in inducing MA was supported by animal studies that showed reduced urinary PH, increased urinary calcium and ammonium excretion in animals treated with sevelamer indicating increased net acid excretion. Chronic MA is associated with several hazardous complications including risks of CVD, BMD as well as associated electrolytes disturbance, most seriously hyperkalemia (Jokihaara et al, 2016).…”