Renal tubular alteration by crystalluria in stone disease-an experimental study by means of MDCK cells.
OBJECTIVE
Physicochemical properties of urine do not explain the formation of urinary stones. Clinical findings and results of animal experiments suggest that alteration to the renal tubular cell plays a key role in the initiation of urinary stone formation. It is not clear whether this is a primarily intracellular alteration of metabolic origin which, after lysis of the renal tubular cell in the lumen, presents a nucleus for the formation of concretions, or whether in the lumen it is tubular cell damage induced by crystalluria that triggers the formation of urinary stones.


METHODS
Using Madin-Darby canine kidney cells, the influence of crystalluria on the renal tubular cell was tested in cell cultures. The influence of parathyroid hormone, vitamin D(3), oxalate and calcium concentrations and the extent to which these processes can be inhibited by allopurinol and selenium were investigated.


RESULTS
Calcium oxalate monohydrate crystals produced reproducible damage to the renal tubular cell which was independent of parathyroid hormone and vitamin D(3). The crystalluria-induced effects were unrelated to the oxalate and calcium concentration or the pH. Allopurinol and selenium were able to inhibit the processes.


CONCLUSIONS
The results indicate secondary involvement of the renal tubular cell in lithogenesis as a result of luminal alteration caused by calcium oxalate crystals. Mechanical damage and interaction between crystal and tubular cell lead to the apposition of crystals. The nephroprotective effect of allopurinol and selenium as antioxidants might explain the benefit of allopurinol found clinically in terms of stone metaphylaxis.
Lahme
S
S
Department of Urology, University of Tübingen, Tübingen, Germany. sven.lahme@med.uni-tuebingen.de
Feil
G
G
Strohmaier
W L
WL
Bichler
K-H
KH
Stenzl
A
A
D000818:Animals; D003460:Crystallization; D004285:Dogs; D007684:Kidney Tubules / Q000166:cytology* / Q000378:metabolism*; D014545:Urinary Calculi / Q000209:etiology / Q000378:metabolism / Q000652:urine*