Experimental induction of calcium oxalate nephrolithiasis in mice

Saeed R. Khan, Patricia A. Glenton

Research output: Contribution to journalArticle

Abstract

Purpose: The availability of various transgenic and knockout mice provides an excellent opportunity to better understand the pathophysiology of calcium oxalate stone disease. However, attempts to produce calcium oxalate nephrolithiasis in mice have not been successful. We hypothesized that calcium oxalate nephrolithiasis in mice requires increasing urine calcium and oxalate excretion, and experimentally induced hyperoxaluria alone is not sufficient. To provide evidence we induced hyperoxaluria by administering hyperoxaluria inducing agents in normocalciuric and hypercalciuric mice, and investigating various aspects of nephrolithiasis. Materials and Methods: We administered ethylene glycol, glyoxylate or hydroxyl proline via diet in male and female normocalciuric B6 mice, and in hypercalciuric sodium phosphate co-transporter type 2 a -/- mice for 4 weeks. We collected 24-hour urine samples on days 0, 3, 7, 14, 21 and 28, and analyzed them for pH, creatinine, lactate dehydrogenase calcium and oxalate. Kidneys were examined using light microscopy. Urine was examined for crystals using light and scanning electron microscopy. Results: Hypercalciuric mice on hydroxyl proline did not tolerate treatment and were sacrificed before 28 days. All mice on ethylene glycol, glyoxylate or hydroxyl proline became hyperoxaluric and showed calcium oxalate crystalluria. No female, normocalciuric or hypercalciuric mice showed renal calcium oxalate crystal deposits. Calcium oxalate nephrolithiasis developed in all mice on glyoxylate and in some on ethylene glycol. In all mice the kidneys showed epithelial injury. Male mice particularly on glyoxylate had more renal injury and inflammatory cell migration into the interstitium around the crystal deposits. Conclusions: Results confirm that hyperoxaluria induction alone is not sufficient to create calcium oxalate nephrolithiasis in mice. Hypercalciuria is also required. Kidneys in male mice are more prone to injury than those in female mice and are susceptible to calcium oxalate crystal deposition. Perhaps epithelial injury promotes crystal retention. Thus, calcium oxalate nephrolithiasis in mice is gender dependent, and requires hypercalciuria and hyperoxaluria.

Original languageEnglish (US)
Pages (from-to)1189-1196
Number of pages8
JournalJournal of Urology
Volume184
Issue number3
DOIs
StatePublished - Sep 2010
Externally publishedYes

Fingerprint

Calcium Oxalate
Hyperoxaluria
Ethylene Glycol
Kidney
Proline
Hydroxyl Radical
Hypercalciuria
Wounds and Injuries
Calcium Oxalate Nephrolithiasis
Urine
Sodium-Phosphate Cotransporter Proteins
Symporters
Light
Nephrolithiasis
L-Lactate Dehydrogenase
Knockout Mice
Electron Scanning Microscopy
Transgenic Mice
Cell Movement
Microscopy

Keywords

  • hypercalciuria
  • hyperoxaluria
  • kidney
  • mice, knockout
  • nephrolithiasis

ASJC Scopus subject areas

  • Urology
  • Medicine(all)

Cite this

Experimental induction of calcium oxalate nephrolithiasis in mice. / Khan, Saeed R.; Glenton, Patricia A.

In: Journal of Urology, Vol. 184, No. 3, 09.2010, p. 1189-1196.

Research output: Contribution to journalArticle

Khan, Saeed R. ; Glenton, Patricia A. / Experimental induction of calcium oxalate nephrolithiasis in mice. In: Journal of Urology. 2010 ; Vol. 184, No. 3. pp. 1189-1196.
@article{a827f6f9c65a4482ba8666e243e13c85,
title = "Experimental induction of calcium oxalate nephrolithiasis in mice",
abstract = "Purpose: The availability of various transgenic and knockout mice provides an excellent opportunity to better understand the pathophysiology of calcium oxalate stone disease. However, attempts to produce calcium oxalate nephrolithiasis in mice have not been successful. We hypothesized that calcium oxalate nephrolithiasis in mice requires increasing urine calcium and oxalate excretion, and experimentally induced hyperoxaluria alone is not sufficient. To provide evidence we induced hyperoxaluria by administering hyperoxaluria inducing agents in normocalciuric and hypercalciuric mice, and investigating various aspects of nephrolithiasis. Materials and Methods: We administered ethylene glycol, glyoxylate or hydroxyl proline via diet in male and female normocalciuric B6 mice, and in hypercalciuric sodium phosphate co-transporter type 2 a -/- mice for 4 weeks. We collected 24-hour urine samples on days 0, 3, 7, 14, 21 and 28, and analyzed them for pH, creatinine, lactate dehydrogenase calcium and oxalate. Kidneys were examined using light microscopy. Urine was examined for crystals using light and scanning electron microscopy. Results: Hypercalciuric mice on hydroxyl proline did not tolerate treatment and were sacrificed before 28 days. All mice on ethylene glycol, glyoxylate or hydroxyl proline became hyperoxaluric and showed calcium oxalate crystalluria. No female, normocalciuric or hypercalciuric mice showed renal calcium oxalate crystal deposits. Calcium oxalate nephrolithiasis developed in all mice on glyoxylate and in some on ethylene glycol. In all mice the kidneys showed epithelial injury. Male mice particularly on glyoxylate had more renal injury and inflammatory cell migration into the interstitium around the crystal deposits. Conclusions: Results confirm that hyperoxaluria induction alone is not sufficient to create calcium oxalate nephrolithiasis in mice. Hypercalciuria is also required. Kidneys in male mice are more prone to injury than those in female mice and are susceptible to calcium oxalate crystal deposition. Perhaps epithelial injury promotes crystal retention. Thus, calcium oxalate nephrolithiasis in mice is gender dependent, and requires hypercalciuria and hyperoxaluria.",
keywords = "hypercalciuria, hyperoxaluria, kidney, mice, knockout, nephrolithiasis",
author = "Khan, {Saeed R.} and Glenton, {Patricia A.}",
year = "2010",
month = "9",
doi = "10.1016/j.juro.2010.04.065",
language = "English (US)",
volume = "184",
pages = "1189--1196",
journal = "Journal of Urology",
issn = "0022-5347",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Experimental induction of calcium oxalate nephrolithiasis in mice

AU - Khan, Saeed R.

AU - Glenton, Patricia A.

PY - 2010/9

Y1 - 2010/9

N2 - Purpose: The availability of various transgenic and knockout mice provides an excellent opportunity to better understand the pathophysiology of calcium oxalate stone disease. However, attempts to produce calcium oxalate nephrolithiasis in mice have not been successful. We hypothesized that calcium oxalate nephrolithiasis in mice requires increasing urine calcium and oxalate excretion, and experimentally induced hyperoxaluria alone is not sufficient. To provide evidence we induced hyperoxaluria by administering hyperoxaluria inducing agents in normocalciuric and hypercalciuric mice, and investigating various aspects of nephrolithiasis. Materials and Methods: We administered ethylene glycol, glyoxylate or hydroxyl proline via diet in male and female normocalciuric B6 mice, and in hypercalciuric sodium phosphate co-transporter type 2 a -/- mice for 4 weeks. We collected 24-hour urine samples on days 0, 3, 7, 14, 21 and 28, and analyzed them for pH, creatinine, lactate dehydrogenase calcium and oxalate. Kidneys were examined using light microscopy. Urine was examined for crystals using light and scanning electron microscopy. Results: Hypercalciuric mice on hydroxyl proline did not tolerate treatment and were sacrificed before 28 days. All mice on ethylene glycol, glyoxylate or hydroxyl proline became hyperoxaluric and showed calcium oxalate crystalluria. No female, normocalciuric or hypercalciuric mice showed renal calcium oxalate crystal deposits. Calcium oxalate nephrolithiasis developed in all mice on glyoxylate and in some on ethylene glycol. In all mice the kidneys showed epithelial injury. Male mice particularly on glyoxylate had more renal injury and inflammatory cell migration into the interstitium around the crystal deposits. Conclusions: Results confirm that hyperoxaluria induction alone is not sufficient to create calcium oxalate nephrolithiasis in mice. Hypercalciuria is also required. Kidneys in male mice are more prone to injury than those in female mice and are susceptible to calcium oxalate crystal deposition. Perhaps epithelial injury promotes crystal retention. Thus, calcium oxalate nephrolithiasis in mice is gender dependent, and requires hypercalciuria and hyperoxaluria.

AB - Purpose: The availability of various transgenic and knockout mice provides an excellent opportunity to better understand the pathophysiology of calcium oxalate stone disease. However, attempts to produce calcium oxalate nephrolithiasis in mice have not been successful. We hypothesized that calcium oxalate nephrolithiasis in mice requires increasing urine calcium and oxalate excretion, and experimentally induced hyperoxaluria alone is not sufficient. To provide evidence we induced hyperoxaluria by administering hyperoxaluria inducing agents in normocalciuric and hypercalciuric mice, and investigating various aspects of nephrolithiasis. Materials and Methods: We administered ethylene glycol, glyoxylate or hydroxyl proline via diet in male and female normocalciuric B6 mice, and in hypercalciuric sodium phosphate co-transporter type 2 a -/- mice for 4 weeks. We collected 24-hour urine samples on days 0, 3, 7, 14, 21 and 28, and analyzed them for pH, creatinine, lactate dehydrogenase calcium and oxalate. Kidneys were examined using light microscopy. Urine was examined for crystals using light and scanning electron microscopy. Results: Hypercalciuric mice on hydroxyl proline did not tolerate treatment and were sacrificed before 28 days. All mice on ethylene glycol, glyoxylate or hydroxyl proline became hyperoxaluric and showed calcium oxalate crystalluria. No female, normocalciuric or hypercalciuric mice showed renal calcium oxalate crystal deposits. Calcium oxalate nephrolithiasis developed in all mice on glyoxylate and in some on ethylene glycol. In all mice the kidneys showed epithelial injury. Male mice particularly on glyoxylate had more renal injury and inflammatory cell migration into the interstitium around the crystal deposits. Conclusions: Results confirm that hyperoxaluria induction alone is not sufficient to create calcium oxalate nephrolithiasis in mice. Hypercalciuria is also required. Kidneys in male mice are more prone to injury than those in female mice and are susceptible to calcium oxalate crystal deposition. Perhaps epithelial injury promotes crystal retention. Thus, calcium oxalate nephrolithiasis in mice is gender dependent, and requires hypercalciuria and hyperoxaluria.

KW - hypercalciuria

KW - hyperoxaluria

KW - kidney

KW - mice, knockout

KW - nephrolithiasis

UR - http://www.scopus.com/inward/record.url?scp=77956634474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956634474&partnerID=8YFLogxK

U2 - 10.1016/j.juro.2010.04.065

DO - 10.1016/j.juro.2010.04.065

M3 - Article

C2 - 20663521

AN - SCOPUS:77956634474

VL - 184

SP - 1189

EP - 1196

JO - Journal of Urology

JF - Journal of Urology

SN - 0022-5347

IS - 3

ER -