Novel kidney stone inhibitors
doi:10.1038/nindia.2013.11 Published online 25 January 2013
Researchers have identified three novel proteins in human kidney stones that could inhibit the formation of these very stones in kidneys and urinary tract1. These proteins are also capable of protecting kidney epithelial cells from stone-induced injury.
These findings may yield new therapies to alleviate urolithiasis, the formation of stones in the urinary tract.
Such stone-induced diseases affect people globally, including residents from the north-western states of India. Proteins in the stones inhibit or promote stone formation, and studies have thrown light on the roles of negatively charged proteins in such stones. However, no studies have investigated the functions of positively charged proteins in stone formation.
To pin down the roles of such proteins, the researchers isolated human calcium oxalate-containing kidney stones. They prepared various protein fractions from these stones and studied the effects of the protein fraction on calcium oxalate stone formation.
Sophisticated spectroscopic analyses identified positively charged proteins that inhibit stone formation. The researchers detected three new proteins - histone-lysine N-methyltransferase, inward rectifier K channel and protein Wnt-2.
These proteins were purified and their effects on calcium oxalate stone formation and stone-induced injury to dog kidney epithelial cells were studied. Purified proteins showed significant inhibition of calcium oxalate crystal nucleation and growth and showed protective effects toward the cell injury caused by oxalate.
During cell damage, levels of lactose dehydrogenase (LDH), a protein increased in various body tissues including heart, liver, kidney, muscles, brain, blood cells and lungs. Exposure to purified proteins significantly reduced the release of LDH in stone-injured epithelial cells showing that the purified proteins can stop stone-induced cell injury.
The authors of this work are from: Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, and Department of Urology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.