Effect of an Acute Oral Ibuprofen Intake on Urinary Aquaporin-2 Excretion in Healthy Humans

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Title: Effect of an Acute Oral Ibuprofen Intake on Urinary Aquaporin-2 Excretion in Healthy Humans
Authors: Pedersen, Robert Schou; Bentzen, Hans; Bech, Jesper Norgaard; Pedersen, Erling Bjerregaard
Publisher: Scandinavian Journal of Clinical and Laboratory Investigation
Date Published: January 01, 2001
Reference Number: 555
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Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the enzyme cyclooxygenase and thereby block the prostaglandin (PG) synthesis in the kidneys. In animals, PG interferes with the formation of aquaporin 2 in the distal renal tubules. The purpose was to measure the effect of ibuprofen on urinary excretion of aquaporin-2 (u-AQP2), urinary output, urinary osmolality (u-osm) and plasma concentration of vasopressin (AVP) in a dose-response study using placebo and ibuprofen 600mg and 1200mg. In 12 healthy subjects, urine was collected in 6 periods between 07.00 h and 13.00 h, and blood samples were drawn at 60-min intervals. The study medication was given 10 h and 1 h before the study. U-AQP2 and AVP were determined by radioimmunoassays. U-AQP2 decreased 33% in the placebo group and increased 47% in the ibuprofen groups. There was a highly significant difference between the placebo group, on the one hand, and the ibuprofen groups, on the other. There was a small but significant increase in AVP in the placebo group and the 600 mg ibuprofen group, but not in the 1200 mg ibuprofen group. Urinary output was at maximum after 2 h, with a 394%, 1020% and 714% increase for placebo, 600 mg ibuprofen and 1200 mg ibuprofen, respectively. U-osm decreased during the experiment in all three groups. Inhibition of renal prostaglandin synthesis by ibuprofen affects the distal part of the nephron by increasing u-AQP2. This increase was not related to changes in AVP, urinary output or urinary osmolality. We suggest that the increased excretion of AQP2 can be explained by an increase in the ratio of AQP2 that is shed into the urine because the endocytic retrieval of AQP2 from the apical membrane is impaired. This could not be revealed by changes in the osmoregulatory system by the low doses of ibuprofen used in the present study.

This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)

Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), reduces the amount of prostaglandin (PG) in the kidneys. PG interferes with aquaporin-2 (AQP2) formation in the cells of specific sections of the small tubes (tubules) found in the kidney. AQP2, deployed from the kidney collecting duct cell interior to its membrane as a result of the hormone, vasopressin (AVP), helps the kidney concentrate urine. Pedersen, et al., examined the effect of ibuprofen on:

  1. urinary excretion of aquaporin-2 (u-AQP2),
  2. the amount of AVP in the blood, and
  3. the concentration of naturally occurring particles in the blood and urine.

The researchers hypothesized that the reduction of PG due to ibuprofen interferes with AVP action on collecting duct cells because a reduction in PG would result in an increase in AQP2. This increase would be reflected in an increase in the amount of AQP2 excreted in the urine by those subjects ingesting ibuprofen.

The researchers divided 15 healthy human volunteers into three groups. One group was given placebos, another 600 mgs of ibuprofen, and the last 1200 mgs. Both placebo and ibuprofen were given in two doses. Measurements on 12 of the subjects (3 subjects had to be excluded) showed the u-AQP2 increased in the ibuprofen groups and decreased in the placebo group. However, urinary output increased and urine concentrations decreased in all three groups. There was a slight increase in AVP in the placebo group and the 600 mg group, but not in the 1200 mg group. The researchers determined that the changes in u-AQP2 were not related to the changes in AVP, urinary output or the relative concentration of the urine.

It might be expected that the greater abundance of AQP2s that occurs when PG formation is inhibited by ibuprofen would result in a decrease in urinary output and a more concentrated urine. The researchers suggest that this did not occur either because the AQP2 increase is too discrete, or the ratio of AQP2 shed in the urine is greater than the normal rate. They suggest that the increased u-AQP2 indicates the ibuprofen has a direct effect on the collecting ducts.