Internalization of calcium oxalate crystals by renal tubular cells: a nephron segment-specific process?
BACKGROUND
Crystal retention in the kidney is caused by the interaction between crystals and the cells lining the renal tubules. These interactions involve crystal attachment, followed by internalization or not. Here, we studied the ability of various renal tubular cell lines to internalize calcium oxalate monohydrate (COM) crystals.


METHODS
Crystal-cell interactions are studied by light-, electron-, and confocal microscopy with cells resembling the renal proximal tubule [porcine kidney (LLC-PK1)], proximal/distal tubule [Madin-Darby canine kidney II (MDCK-II)], and distal tubule and/or collecting ducts [(Madin-Darby canine kidney I (MDCK-I), rat cortical collecting duct 1 (RCCD1)]. Crystal-binding strength and internalization are characterized and quantified with radiolabeled COM.


RESULTS
Microscopy studies showed that crystals were firmly embedded in the membranes of LLC-PK1 and MDCK-II cells to be subsequently internalized. On the other hand, crystals bound only loosely to MDCK-I and RCCD1 and were not taken up by these cells. Crystal uptake by LLC-PK1 and MDCK-II, expressed in microg/10(6) cells, is temperature-dependent and gradually increases from 0.88 and 0.15 in 30 minutes, respectively, to 4.70 and 3.85, respectively, after five hours, whereas these values never exceeded background levels in MDCK-I and RCCD1 cells.


CONCLUSIONS
The adherence of COM crystals to renal cells with properties of the proximal tubule is inevitable and actively followed by their uptake, whereas crystals attached to cells resembling the distal tubule and/or collecting duct are not internalized. Since crystal formation usually occurs in segments beyond the renal proximal tubule, crystal uptake may be of less importance in the etiology of idiopathic calcium oxalate stone disease.
Schepers
Marieke S J
MS
Department of Urology, Erasmus MC, Rotterdam, The Netherlands.
Duim
Ronald A J
RA
Asselman
Marino
M
Romijn
Johannes C
JC
Schröder
Fritz H
FH
Verkoelen
Carl F
CF
D000818:Animals; D002129:Calcium Oxalate / Q000737:chemistry / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D002460:Cell Line; D003460:Crystallization; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure; D005404:Fixatives; D006820:Hyaluronic Acid / Q000378:metabolism; D006821:Hyaluronoglucosaminidase; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism*; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008858:Microscopy, Phase-Contrast; D009399:Nephrons / Q000166:cytology / Q000378:metabolism*
D002250:Carbon Radioisotopes; D005404:Fixatives; D002129:Calcium Oxalate; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase