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Intestinal Phosphate Regulation in Chronic Kidney Disease.
Author(s) -
HoggCornejo Veronica,
Sutherland Eileen,
Dobrinskikh Evgenia,
Levi Moshe
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.969.10
Subject(s) - medicine , endocrinology , hyperphosphatemia , alport syndrome , kidney disease , ileum , kidney , creatinine , homeostasis , chemistry , biology , glomerulonephritis
Increase in serum phosphate (Pi) level (hyperphosphatemia) is a common clinical problem in chronic kidney disease (CKD). Systemic Pi homeostasis is balanced through three major mechanisms: intestinal uptake, retention or release from bone, and renal reabsorption. Sodium‐phosphate co‐transporter type 2b (NaPi2b) is a major phosphate transporter in the enterocytes of the small intestine. Alport syndrome is a genetic disorder characterized by CKD and hearing loss. We have studied Alport CKD model in mice that have a mutation in a COL4A3 gene on an SvEv129 background. Alport mice (males) have less body (19.6 ± 1.4 g compared to 25.6 ± 0.8 g in WT mice) and kidney weight (177.8 ± 10.4 mg compared to 216.8 ± 16.3 mg in WT mice). By the 9‐10 weeks of age Alport mice develop signs of CKD and hyperphosphatemia: they have increased level of the serum blood urea nitrogen (47.43 ± 7.45 mg/dl compared to 28.52 ± 3.02 mg/dl in wild type (WT) mice), serum creatinine (0.53 ± 0.08 mg/dl compared to 0.30 ± 0.04 mg/dl in WT mice) and elevated level of serum Pi (9.4 ± 1.21 mg/dl compared to 6.1 ± 0.38 mg/dl in WT mice). We have found by WB that there is an increase in intestinal NaPi‐2b protein abundance in the ileum of the Alport mice. Everted Sac studies revealed increased NaPi transport in the Alport Ileum compared to the WT littermate controls. Our study indicates an important role for increased intestinal Pi absorption and NaPi‐2b protein in hyperphosphatemia in CKD.