Continuous infusion of oxalate by minipumps induces calcium oxalate nephrocalcinosis

Susan Ruth Marengo, Daniel H.C. Chen, Andrew P. Evan, Andre J. Sommer, Nicholas T. Stowe, Donald G. Ferguson, Martin I. Resnick, Gregory T. MacLennan

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

It is hypothesized that oxalate plays an active role in calcium oxalate (CaOx) nephrocalcinosis and oxalate driven nephrolithiasis by interacting with the kidney. We developed an adjustable, nonprecursor, continuous infusion model of hyperoxaluria and CaOx nephrocalcinosis to investigate this hypothesis. Minipumps containing PBS or KOx (60-360 μmol/day; n= 5-7/dose) were implanted subcutaneously in male Sprague-Dawley rats on D0 and D6. Rats were killed on D13. Oxalate excretion and CaOx crystalluria were monitored by 20+4 h urine collections. Localization and content of intrarenal crystals were determined on frozen sections using polarization and μFTIR. Oxalate excretion was significantly elevated in all KOx rats (P ≤ 0.005). CaOx crystalluria was most persistent in the 240-360 μmol/day KOx rats, but even 60 μmol/day KOx rats showed sporadic crystalluria. One hundred percent of KOx rats had CaOx nephrocalcinosis as confirmed by μFTIR. Most crystals were localized to the lumens of the corticomedullary collecting ducts. A few crystals are localized just under the papular urothelium. The minipump model is the first model of hyperoxaluria to provide continuous infusion of oxalate. It permits control of the levels of hyperoxaluria, crystalluria and CaOx nephrocalcinosis. The level of sustained hyperoxaluria and CaOx nephrocalcinosis induced by treatment with 360 μmol/day KOx for 13D models the conditions frequently observed in jejunoileal bypass patients. Adjustments in the length of treatment and level of hyperoxaluria may allow this model to also be used to study the oxalate driven CaOx-nephrolithiasis common in patients with hyperoxaluria due to other causes.

Original languageEnglish (US)
Pages (from-to)200-210
Number of pages11
JournalUrological Research
Volume34
Issue number3
DOIs
StatePublished - Jun 1 2006

Keywords

  • Calcium
  • Nephrocalcinosis
  • Nephrolithiasis
  • Oxalate
  • Oxalosis
  • Rat

ASJC Scopus subject areas

  • Urology

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    Marengo, S. R., Chen, D. H. C., Evan, A. P., Sommer, A. J., Stowe, N. T., Ferguson, D. G., Resnick, M. I., & MacLennan, G. T. (2006). Continuous infusion of oxalate by minipumps induces calcium oxalate nephrocalcinosis. Urological Research, 34(3), 200-210. https://doi.org/10.1007/s00240-006-0043-7