Continuous infusion of oxalate by minipumps induces calcium oxalate nephrocalcinosis.
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 micromol/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 microFTIR. Oxalate excretion was significantly elevated in all KOx rats (P < or = 0.005). CaOx crystalluria was most persistent in the 240-360 micromol/day KOx rats, but even 60 micromol/day KOx rats showed sporadic crystalluria. One hundred percent of KOx rats had CaOx nephrocalcinosis as confirmed by microFTIR. 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 micromol/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.
Department of Urology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106-4931, USA. srm10@case.edu
Susan Ruth
SR
Marengo
Daniel H-C
DH
Chen
Andrew P
AP
Evan
Andre J
AJ
Sommer
Nicholas T
NT
Stowe
Donald G
DG
Ferguson
Martin I
MI
Resnick
Gregory T
GT
MacLennan
D000818:Animals; D002097:C-Reactive Protein / Q000032:analysis; D002129:Calcium Oxalate / Q000378:metabolism*; D003460:Crystallization; D015918:Infusion Pumps, Implantable; D007668:Kidney / Q000378:metabolism; D008297:Male; D009397:Nephrocalcinosis / Q000139:chemically induced*; D010070:Oxalates / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010070:Oxalates; D002129:Calcium Oxalate; D002097:C-Reactive Protein