Experimentally induced calcium oxalate crystals in the rabbit kidney - Meaning for human nephrolithiasis

Purpose: In the recent years various models of experimentally induced nephr olithiasis have been established. Aim of our investigations was to establis h a currently described approach involving tubular dysfunction in an animal model of calcium oxalate nephrolithiasis that assists perception of pathog enesis by enabling the investigation of histological and physico-chemical p arameters of stone formation that closely simulating the process in humans. Material and Methods: 15 rabbits (2.9-3.5 kg/KG) received gentamycin (40 mg /kg/KG) over a period of 8 days to induce proximal tubular dysfunction. Add itional ammoniumoxalate (2%) was administered from day 8 to 14. Glomerular filtration rate was determined on day 1 and 14, urinary calcium, oxalate, m agnesiume, citrate on the 1st, 8th and 14th days. Bisected kidneys were exa mined histologically to determine extent and localisation of intrarenal CaO x-deposits using a semiquantitative score. Results: Macroscopical investigations revealed plaques or CaOx-deposits at the papilla of the most kidneys. Microscopical analysis with HE staining sh owed in 85% papillary located deposits or microliths. Urinary-pH remained c onstant over the whole induction period. GFR decreased from 5.19 ml/h/kg to 1.48 ml/h/kg. Gentamycin administration resulted in hypercalciuria and hyp omagnesiuria with distinct increase of citrate. Administration of ammonium oxalate resulted in a further calcium increase and oxalate increase. Conclusions: Our investigations demonstrates the possibility of a stone mod el that closely simulating the process found in humans, resulting in intera ction with endogenous and exogenous inhibiting or promoting factors are res ponsible for crystal growth and agglomeration. In addition the model can be used as a basis for further investigations and the evaluation of therapeut ical approaches.