Jørgen Frøkiær

Changes in cellular composition of kidney collecting duct cells in rats with lithium-induced NDI

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  • Department of Anatomy
  • Salt og vand
Lithium treatment for 4 wk caused severe polyuria, dramatic downregulation in aquaporin-2 (AQP-2) expression, and marked decrease in AQP-2 immunoreactivity with the appearance of a large number of cells without AQP-2 labeling in the collecting ducts after lithium treatment. Surprisingly, this was not all due to an increase in AQP-2-negative principal cells, because double immunolabeling revealed that the majority of the AQP-2-negative cells displayed [H(+)]ATPase labeling, which identified them as intercalated cells. Moreover, multiple [H(+)]ATPase-labeled cells were adjacent, which was never seen in control rats. Quantitation confirmed a significant decrease in the fraction of collecting duct cells that exhibited detectable AQP-2 labeling compared with control rats: in cortical collecting ducts, 40 +/- 3.4 vs. 62 +/- 1.8% of controls (P < 0.05; n = 4) and in inner medullary collecting ducts, 58 +/- 1.6 vs. 81 +/- 1.3% of controls (P < 0.05; n = 4). In parallel, a significant increase in the fraction of intercalated ([H(+)]ATPase-positive) cells was shown. Urine output, whole kidney AQP-2 expression, cellular organization, and the fractions of principal and intercalated cells in cortex and inner medulla returned to control levels after 4 wk on a lithium-free diet following 4 wk on a lithium-containing diet. In conclusion, lithium treatment not only decreased AQP-2 expression, but dramatically and reversibly reduced the fraction of principal cells and altered the cellular organization in collecting ducts. These effects are likely to be important in lithium-induced nephrogenic diabetes insipidus.
Original languageEnglish
JournalAmerican Journal of Physiology: Cell Physiology
Volume286
Issue4
Pages (from-to)C952-64
Number of pages13
ISSN0363-6143
DOIs
Publication statusPublished - 2004

    Research areas

  • Animals, Antibodies, Aquaporin 2, Aquaporin 4, Aquaporin 6, Aquaporins, Carrier Proteins, Diabetes Insipidus, Nephrogenic, Down-Regulation, Kidney Tubules, Collecting, Lithium, Membrane Transport Proteins, Microscopy, Immunoelectron, Proton-Translocating ATPases, Rats, Rats, Wistar, Recovery of Function, Urine

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