Dietary fructose inhibits intestinal calcium absorption and induces vitamin D insufficiency in CKD.
Renal disease leads to perturbations in calcium and phosphate homeostasis and vitamin D metabolism. Dietary fructose aggravates chronic kidney disease (CKD), but whether it also worsens CKD-induced derangements in calcium and phosphate homeostasis is unknown. Here, we fed rats diets containing 60% glucose or fructose for 1 mo beginning 6 wk after 5/6 nephrectomy or sham operation. Nephrectomized rats had markedly greater kidney weight, blood urea nitrogen, and serum levels of creatinine, phosphate, and calcium-phosphate product; dietary fructose significantly exacerbated all of these outcomes. Expression and activity of intestinal phosphate transporter, which did not change after nephrectomy or dietary fructose, did not correlate with hyperphosphatemia in 5/6-nephrectomized rats. Intestinal transport of calcium, however, decreased with dietary fructose, probably because of fructose-mediated downregulation of calbindin 9k. Serum calcium levels, however, were unaffected by nephrectomy and diet. Finally, only 5/6-nephrectomized rats that received dietary fructose demonstrated marked reductions in 25-hydroxyvitamin D(3) and 1,25-dihydroxyvitamin D(3) levels, despite upregulation of 1alpha-hydroxylase. In summary, excess dietary fructose inhibits intestinal calcium absorption, induces marked vitamin D insufficiency in CKD, and exacerbates other classical symptoms of the disease. Future studies should evaluate the relevance of monitoring fructose consumption in patients with CKD.
Douard
Veronique
V
Department of Pharmacology and Physiology, UMDNJ-New Jersey Medical School, Newark, NJ 07101-1709, USA.
Asgerally
Abbas
A
Sabbagh
Yves
Y
Sugiura
Shozo
S
Shapses
Sue A
SA
Casirola
Donatella
D
Ferraris
Ronaldo P
RP
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D000818:Animals; D015519:Bone Density; D002112:Calcifediol / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002908:Chronic Disease; D004040:Dietary Carbohydrates / Q000009:adverse effects / Q000494:pharmacology*; D004195:Disease Models, Animal; D005632:Fructose / Q000009:adverse effects / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects*; D007668:Kidney / Q000378:metabolism / Q000601:surgery; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014808:Vitamin D Deficiency / Q000209:etiology / Q000378:metabolism*
D004040:Dietary Carbohydrates; D010710:Phosphates; D005632:Fructose; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D005947:Glucose; D002112:Calcifediol; D002118:Calcium