Limits...
Ferric citrate hydrate as a phosphate binder and risk of aluminum toxicity.

Gupta A - Pharmaceuticals (Basel) (2014)

Bottom Line: Oral citrate solubilizes aluminum that is present in food and drinking water, and opens the tight junctions in the intestinal epithelium, thereby increasing aluminum absorption and urinary excretion.In healthy animals drinking tap water, oral citrate administration increased aluminum absorption and, over a 4-week period, increased aluminum deposition in brain and bone by about 2- and 20-fold, respectively.Renal excretion of aluminum is impaired in patients with chronic kidney disease, thereby increasing the risk of toxicity.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology and Hypertension, University of California Irvine Medical Center, Orange, CA 92868-3217, USA. ajayg1@uci.edu.

ABSTRACT
Ferric citrate hydrate was recently approved in Japan as an oral phosphate binder to be taken with food for the control of hyperphosphatemia in patients with chronic kidney disease (CKD). The daily therapeutic dose is about 3 to 6 g, which comprises about 2 to 4 g of citrate. Oral citrate solubilizes aluminum that is present in food and drinking water, and opens the tight junctions in the intestinal epithelium, thereby increasing aluminum absorption and urinary excretion. In healthy animals drinking tap water, oral citrate administration increased aluminum absorption and, over a 4-week period, increased aluminum deposition in brain and bone by about 2- and 20-fold, respectively. Renal excretion of aluminum is impaired in patients with chronic kidney disease, thereby increasing the risk of toxicity. Based on human and animal studies it can be surmised that patients with CKD who are treated with ferric citrate hydrate to control hyperphosphatemia are likely to experience enhanced absorption of aluminum from food and drinking water, thereby increasing the risk of aluminum overload and toxicity.

No MeSH data available.


Related in: MedlinePlus

Aluminum absorption during calcium citrate treatment in 26 subjects. Midpoint equals 19 ± 6 days; endpoint equals 38 ± 14 days. Data were derived from Nolan et al. [3].
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4210856&req=5

pharmaceuticals-07-00990-f002: Aluminum absorption during calcium citrate treatment in 26 subjects. Midpoint equals 19 ± 6 days; endpoint equals 38 ± 14 days. Data were derived from Nolan et al. [3].

Mentions: Citrate tri-anion reacts with aluminum to form a complex that is soluble over the wider pH range [15]. Furthermore, citrate chelates extracellular calcium causing disruption of the integrity of intestinal epithelial cell tight junctions (Figure 1), creating a paracellular pathway for the absorption of soluble aluminum citrate complexes [16]. Animal models suggest that citrate‑containing compounds augment absorption of aluminum from tap water and food, causing aluminum accumulation in bone and brain despite normal renal function [17]. Nolan and colleagues [3] measured aluminum levels in plasma and in 24-hour urine collections in 30 healthy women before and during treatment with calcium citrate (800 mg calcium and approximately 2500 mg citrate), administered daily in 2 divided doses (Figure 2). After approximately 2 weeks, plasma levels of aluminum increased from 87 ± 13 to 143 ± 22 nmol/L (p = 0.03), and the 24‑hour urinary aluminum excretion increased from 338 ± 51 to 655 ± 119 nmol/day (p = 0.002). This highly significant increase in urine and serum aluminum occurred despite a relatively low aluminum content of the municipal water (3.4 ± 1.2 µg/L). Notably, citrate administration had no effect on lead absorption. Alfrey and coworkers [18] concluded that citrate significantly increases absorption of aluminum from dietary sources. Animal models suggest that citrate-containing compounds augment absorption of aluminum from tap water and food, causing aluminum accumulation in bone and brain despite normal renal function [17].


Ferric citrate hydrate as a phosphate binder and risk of aluminum toxicity.

Gupta A - Pharmaceuticals (Basel) (2014)

Aluminum absorption during calcium citrate treatment in 26 subjects. Midpoint equals 19 ± 6 days; endpoint equals 38 ± 14 days. Data were derived from Nolan et al. [3].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4210856&req=5

pharmaceuticals-07-00990-f002: Aluminum absorption during calcium citrate treatment in 26 subjects. Midpoint equals 19 ± 6 days; endpoint equals 38 ± 14 days. Data were derived from Nolan et al. [3].
Mentions: Citrate tri-anion reacts with aluminum to form a complex that is soluble over the wider pH range [15]. Furthermore, citrate chelates extracellular calcium causing disruption of the integrity of intestinal epithelial cell tight junctions (Figure 1), creating a paracellular pathway for the absorption of soluble aluminum citrate complexes [16]. Animal models suggest that citrate‑containing compounds augment absorption of aluminum from tap water and food, causing aluminum accumulation in bone and brain despite normal renal function [17]. Nolan and colleagues [3] measured aluminum levels in plasma and in 24-hour urine collections in 30 healthy women before and during treatment with calcium citrate (800 mg calcium and approximately 2500 mg citrate), administered daily in 2 divided doses (Figure 2). After approximately 2 weeks, plasma levels of aluminum increased from 87 ± 13 to 143 ± 22 nmol/L (p = 0.03), and the 24‑hour urinary aluminum excretion increased from 338 ± 51 to 655 ± 119 nmol/day (p = 0.002). This highly significant increase in urine and serum aluminum occurred despite a relatively low aluminum content of the municipal water (3.4 ± 1.2 µg/L). Notably, citrate administration had no effect on lead absorption. Alfrey and coworkers [18] concluded that citrate significantly increases absorption of aluminum from dietary sources. Animal models suggest that citrate-containing compounds augment absorption of aluminum from tap water and food, causing aluminum accumulation in bone and brain despite normal renal function [17].

Bottom Line: Oral citrate solubilizes aluminum that is present in food and drinking water, and opens the tight junctions in the intestinal epithelium, thereby increasing aluminum absorption and urinary excretion.In healthy animals drinking tap water, oral citrate administration increased aluminum absorption and, over a 4-week period, increased aluminum deposition in brain and bone by about 2- and 20-fold, respectively.Renal excretion of aluminum is impaired in patients with chronic kidney disease, thereby increasing the risk of toxicity.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology and Hypertension, University of California Irvine Medical Center, Orange, CA 92868-3217, USA. ajayg1@uci.edu.

ABSTRACT
Ferric citrate hydrate was recently approved in Japan as an oral phosphate binder to be taken with food for the control of hyperphosphatemia in patients with chronic kidney disease (CKD). The daily therapeutic dose is about 3 to 6 g, which comprises about 2 to 4 g of citrate. Oral citrate solubilizes aluminum that is present in food and drinking water, and opens the tight junctions in the intestinal epithelium, thereby increasing aluminum absorption and urinary excretion. In healthy animals drinking tap water, oral citrate administration increased aluminum absorption and, over a 4-week period, increased aluminum deposition in brain and bone by about 2- and 20-fold, respectively. Renal excretion of aluminum is impaired in patients with chronic kidney disease, thereby increasing the risk of toxicity. Based on human and animal studies it can be surmised that patients with CKD who are treated with ferric citrate hydrate to control hyperphosphatemia are likely to experience enhanced absorption of aluminum from food and drinking water, thereby increasing the risk of aluminum overload and toxicity.

No MeSH data available.


Related in: MedlinePlus