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The kidneys
Published in Martin Andrew Crook, Clinical Biochemistry & Metabolic Medicine, 2013
Tissue precipitation of calcium to phosphate may occur early in renal disease and is related to hyperphosphataemia and the calcium phosphate product (calcium concentration × phosphate concentration). This precipitation can be reduced by adequate fluid intake. Dietary phosphate restriction is used in the early stages of chronic renal dysfunction. If the plasma phosphate concentration is raised, phosphate-binding agents such as calcium acetate or carbonate may be indicated. When GFR is below 60 mL/min per 1.73 m2, secondary hyperparathyroidism with elevated PTH concentration occurs. Giving small doses of active vitamin D, such as calcitriol or alfacalcidol, reduces the serum PTH, and improves bone histology, and leads to increased bone mineral density and helps avoid renal osteodystrophy, hypocalcaemia and tertiary hyperparathyroidism (see Chapter 6).
An update on phosphate binders for the treatment of hyperphosphatemia in chronic kidney disease patients on dialysis: a review of safety profiles
Published in Expert Opinion on Drug Safety, 2022
Hiroaki Ogata, Akiko Takeshima, Hidetoshi Ito
Since the late 1980s, calcium-based phosphate binders, including calcium acetate and calcium carbonate, both of which are well tolerated and have a stable phosphate-lowering action, have been used for hyperphosphatemia in patients with CKD, instead of aluminum-containing phosphate binders [19,20]. However, the use of calcium-based phosphate binders can increase intestinal calcium absorption, which can lead to hypercalcemia. Hypercalcemia was more frequent when calcium acetate was used rather than calcium carbonate for treating hyperphosphatemia in dialysis patients [19,20]. They have long been suggested to be of serious concern, as the increased calcium load accelerates vascular calcification, which is significantly predictive of cardiovascular events [21]. This calcification might lead to higher all-cause death and cardiovascular risk as compared with non-calcium-based phosphate binders [22]. Therefore, the updated KDIGO clinical practice guidelines for CKD-MBD in 2017 recommend the restriction of calcium-based phosphate binder doses for hypercalcemia in patients with advanced CKD [3]. This issue will be discussed in detail in the Expert Opinion section.
An evaluation of roxadustat for the treatment of anemia associated with chronic kidney disease
Published in Expert Opinion on Pharmacotherapy, 2022
Yu Kurata, Tetsuhiro Tanaka, Masaomi Nangaku
After single oral administration of 100 mg roxadustat in healthy subjects, tmax is approximately 2 hours and t1/2 is approximately 12 hours [13,14]. Roxadustat is administered three times a week, and no accumulation is observed with this dosing regimen. Roxadustat is primarily metabolized by CYP2C8 and glucuronidated via UGT1A9 [15]. In patients with CKD, Cmax is comparable to normal subjects, whereas AUC is approximately two-fold larger than that in normal subjects [16]. In patients with moderate hepatic impairment (Child-Pugh B), Cmax and AUC were 16% lower and 23% higher compared with normal subjects, respectively [13]. Roxadustat is highly bound to protein, and its dialysis clearance is 3–4%. HD treatment had little effect on the PK of roxadustat. Sevelamer carbonate and calcium acetate decrease Cmax and AUC of roxadustat, whereas lanthanum carbonate hydrate does not affect the PK of roxadustat [17]. The reduction of Cmax and AUC by sevelamer carbonate and calcium acetate can be mitigated by shifting the timing of administration by at least one hour before or after roxadustat. Gemfibrozil, a CYP2C8 inhibitor, and probenecid, a UGT inhibitor, increase Cmax and AUC of roxadustat [18]. Therefore coadministration of these medications should be avoided. Roxadustat has no in vivo CYP enzyme inhibitory effect. Roxadustat showed limited effects on PK and pharmacodynamics (PD) of warfarin, CYP2C9 substrate [19]. Roxadustat also inhibits OATP1B1 and increases Cmax and AUC of simvastatin and rosuvastatin, substrates for OATP1B1.
A safety evaluation of sucroferric oxyhydroxide for the treatment of hyperphosphatemia
Published in Expert Opinion on Drug Safety, 2021
Stuart M. Sprague, Markus Ketteler
The efficacy of SFOH in pediatric patients with CKD and hyperphosphatemia was assessed by a multicenter, randomized, open-label Phase III study [26]. In total, 85 patients (age 2–18 years) were randomized to SFOH (n = 66) or calcium acetate oral solution (CaAc; Phoslyra®, n = 19) for up to 10 weeks of dose titration (Stage 1), followed by a 24-week safety extension (Stage 2). SFOH was provided in two different formulations: sachets of powder for oral suspension (125, 250, and 500 mg doses) for younger patients (age <6 years), and chewable tablets (250 and 500 mg) for patients ≥6 years of age. Treatment was initiated at an age-dependent dose and titrated by 125 to 500 mg/day, according to patient age. Adolescents (12–18 years) accounted for the majority of patients in the SFOH and CaAc groups (64.6% and 66.7%, respectively), with lower proportions in the 6–<12 years (26.2% and 26.7%) and 2–<6 years (9.2% and 6.7%) age categories.