Presence of lipids in urine, crystals and stones: implications for the formation of kidney stones.
BACKGROUND
Cell membranes and their lipids play critical roles in calcification. Specific membrane phospholipids promote the formation of calcium phosphate and become a part of the organic matrix of growing calcification. We propose that membrane lipids also promote the formation of calcium oxalate (CaOx) and calcium phosphate (CaP) containing kidney stones, and become a part of their stone matrix.


METHODS
Human urine, crystals of CaOx and CaP produced in the urine of healthy individuals, and urinary stones containing struvite, uric acid, CaOx and CaP crystals for the presence of membrane lipids were analyzed. Crystallization of CaOx monohydrate at Langmuir monolayers of dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylserine (DPPS), dioleoylphosphatidylglycerol (DOPG), palmitoyloleoylphosphatidylglycerol (POPG) and dimyristoylphosphatidylglycerol (DMPG) was investigated to directly demonstrate that phospholipid assemblies can catalyze CaOx nucleation.


RESULTS
Urine as well as CaOx and CaP crystals made in the urine and various types of urinary stones investigated contained some lipids. Urine of both CaOx and uric acid stone formers contained significantly more cholesterol, cholesterol ester and triglycerides than urine of healthy subjects. However, urine of CaOx stone formers contained more acidic phospholipids. The organic matrix of calcific stones contained significantly more acidic and complexed phospholipids than uric acid and struvite stones. For each Langmuir monolayer precipitation was heterogeneous and selective with respect to the orientation and morphology of the CaOx crystals. Crystals were predominantly monohydrate, and most often grew singly with the calcium rich (10-1) face toward the monolayer. The number of crystals/mm2 decreased in the order DPPG> DPPC and was inversely proportional to surface pressure and mean molecular area/molecule.


CONCLUSIONS
Stone forming conditions in the kidneys greatly impact their epithelial cells producing significant differences in the urinary lipids between healthy and stone forming individuals. Altered membrane lipids promote face selective nucleation and retention of calcium oxalate crystals, and in the process become a part of the growing crystals and stones.
Khan
Saeed R
SR
Department of Pathology, University of Florida, Gainesville, Florida 32610, USA. khan@pathology.ufl.edu
Glenton
Patricia A
PA
Backov
Renal
R
Talham
Daniel R
DR
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000652:urine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002129:Calcium Oxalate / Q000737:chemistry / Q000652:urine; D003460:Crystallization; D005260:Female; D006801:Humans; D007669:Kidney Calculi / Q000737:chemistry* / Q000652:urine*; D008055:Lipids / Q000652:urine*; D008297:Male; D008560:Membrane Fluidity; D008875:Middle Aged; D010715:Phosphatidylglycerols / Q000652:urine; D010718:Phosphatidylserines / Q000652:urine
D008055:Lipids; D010715:Phosphatidylglycerols; D010718:Phosphatidylserines; D002129:Calcium Oxalate; D015060:1,2-Dipalmitoylphosphatidylcholine; C038694:dipalmitoylphosphatidylserine; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C043806:dioleoylphosphatidylthioglycerol; C002773:dimyristoylphosphatidylglycerol; C030345:1,2-dipalmitoylphosphatidylglycerol