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Continuous infusion of oxalate by minipumps induces calcium oxalate nephrocalcinosis

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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 papillar 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.

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Acknowledgements

This manuscript is dedicated to the late Nicholas T. Stowe, without whose assistance this work could not have been completed. Appreciation is expressed to SE Brown for editorial assistance. This work was supported by NIH-NIDDK:DK55528 (SRM), DK62073 (SRM), NIH PO1 DK56788 (APE) and the Jim & Eilleen Dicke Research Endowment.

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Authors and Affiliations

  1. Department of Urology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106-4931, USA

    Susan Ruth Marengo, Daniel H. -C. Chen & Martin I. Resnick

  2. Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA

    Andrew P. Evan

  3. Department of Chemistry and Biochemistry, Miami University, Oxford, OH, USA

    Andre J. Sommer

  4. Department of Surgery, School of Medicine, Case Western Reserve University, Cleveland, OH, USA

    Nicholas T. Stowe

  5. Department of Anatomy, School of Medicine, Case Western Reserve University, Cleveland, OH, USA

    Donald G. Ferguson

  6. Institute of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA

    Gregory T. MacLennan

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  1. Susan Ruth Marengo
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  2. Daniel H. -C. Chen
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Correspondence to Susan Ruth Marengo.

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Marengo, S.R., Chen, D.H.C., Evan, A.P. et al. Continuous infusion of oxalate by minipumps induces calcium oxalate nephrocalcinosis. Urol Res 34, 200–210 (2006). https://doi.org/10.1007/s00240-006-0043-7

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