Fat malabsorption induced by gastrointestinal lipase inhibitor leads to an increase in urinary oxalate excretion.
BACKGROUND
Unabsorbed fat and bile acids may react with calcium in the intestinal lumen, limiting the amount of free calcium binding with oxalate and thereby raising intestinal oxalate absorption leading to hyperoxaluria. The aim of the present study was to determine whether orlistat (Xenical), a gastrointestinal lipase inhibitor, might increase urinary oxalate in an experimental rat model.


METHODS
Thirty-nine male adult Wistar rats were fed a standard diet alone (controls) or supplemented with either 2% sodium oxalate (NaOx) or 3.2 mL of soy oil, or with both (NaOx + soy oil) for 4 weeks (diet period). Orlistat (16 mg/day) was added to the diet from the 5th to the 8th week (diet + orlistat period). Urinary oxalate (uOx), calcium (uCa), magnesium (uMg), and citrate (uCit) were determined and the ion-activity product of calcium oxalate [AP (CaOx) index(rat)] was estimated.


RESULTS
Compared to baseline uOx significantly increased after diet + orlistat in controls (0.64 +/- 0.1 mg/24 hours vs. 0.56 +/-0.1 mg/24 hours), soy oil (0.80 +/- 0.3 mg/24 hours vs. 0.49 +/-0.2 mg/24 hours), and NaOx (2.48 +/- 0.8 mg/24 hours vs. 0.57 +/- 0.2 mg/24 hours), but the most marked increase occurred in NaOx + soy oil (3.87 +/- 0.7 mg/24 hours vs. 0.47 +/- 0.1 mg/24 hours). All groups except controls presented a significant reduction in uCa and uMg. Orlistat induced a significant increase in AP (CaOx) index(rat) compared, respectively, to baseline and to the diet period in NaOx (4.52 +/- 2.34 mg/24 hours vs. 0.94 +/- 0.86 and 1.53 +/- 0.93 mg/24 hours) and NaOx + soy oil (6.49 +/- 4.03 mg/24 hours vs. 0.54 +/- 0.17 and 1.76 +/- 1.32 mg/24 hours).


CONCLUSIONS
These data suggest that the use of lipase inhibitors, especially under a diet rich in oxalate alone or associated with fat, leads to a significant and marked increase in urinary oxalate and a slight reduction in uCa and uMg that, taken together, resulted in an increase in AP (CaOx) index(rat), elevating the risk of stone formation.
Ferraz
Renato Ribeiro Nogueira
RR
Nephrology Division, Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil.
Tiselius
Hans-Göran
HG
Heilberg
Ita Pfeferman
IP
Heiberg
Ita Pfeferman
IP
D000818:Animals; D001835:Body Weight; D002129:Calcium Oxalate / Q000652:urine*; D004041:Dietary Fats / Q000493:pharmacokinetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005243:Feces / Q000737:chemistry; D007669:Kidney Calculi / Q000453:epidemiology / Q000209:etiology / Q000652:urine*; D007783:Lactones / Q000494:pharmacology; D008049:Lipase / Q000037:antagonists & inhibitors*; D008286:Malabsorption Syndromes / Q000139:chemically induced / Q000453:epidemiology / Q000652:urine*; D008297:Male; D000077403:Orlistat; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors
D004041:Dietary Fats; D004791:Enzyme Inhibitors; D007783:Lactones; D002129:Calcium Oxalate; D000077403:Orlistat; D008049:Lipase