Dietary hydroxyproline induced calcium oxalate lithiasis and associated renal injury in the porcine model.
OBJECTIVE
We previously reported hyperoxaluria and calcium oxalate calculi in adult pigs (sows) fed hydroxyproline (HP). The purpose of this study was to grossly and histopathologically characterize intrarenal effects in this model.


METHODS
In the swine facility at our campus, we maintained 21 gestating sows, of which 15 received daily treatment (5% HP mixed with dry feed) and 6 received no treatment (controls). Nine were sacrificed at 21 d (three control, six HP). All kidneys were extracted and examined grossly and for radiographic evidence of stones (GE CT scanner, 80kV, 400MA, 1 sec rotation, 0.625 mm slices). Papillary and cortical samples were processed for histologic analysis.


RESULTS
Kidneys from treated sows showed significant calculi distributed within the renal papilla on CT, appeared mottled in the renal cortex and papillary areas, and had less distinct corticomedullary borders. Tiny crystals and mucinous debris lined the papillary tips, calices, and pelvis in kidneys from four of six treated sows, and multiple stones were noted at the papillary tips. Hematoxylin and eosin stain revealed crystals in collecting tubules and papillary tips in treated kidneys and none in controls. Yasue staining confirmed crystals in proximal periglomerular tubules of treated but not control animals. Tubular dilation and inflammatory/fibrotic changes were identified in kidneys from treated animals; none of these changes were evident in control kidneys.


CONCLUSIONS
We report renal damage as a result of dietary-induced hyperoxaluria in adult sows. Specifically, we found crystalluria in proximal periglomerular tubules and collecting ducts, with tubular damage at all segments.
1 Department of Urology, University of Wisconsin School of Medicine and Public Health , Madison, Wisconsin.
Sri
S
Sivalingam
Stephen Y
SY
Nakada
Priyanka D
PD
Sehgal
Thomas D
TD
Crenshaw
Kristina L
KL
Penniston
D000821:Animal Feed; D000818:Animals; D002129:Calcium Oxalate / Q000378:metabolism*; D004032:Diet / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D006909:Hydroxyproline / Q000008:administration & dosage / Q000633:toxicity*; D006959:Hyperoxaluria / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D007669:Kidney Calculi / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013552:Swine
D002129:Calcium Oxalate; D006909:Hydroxyproline