We appreciate the editorial comment by Dr. Khan, whose great work on the significance of oxidative stress or the production of reactive oxygen species in nephrolithiasis has been well recognized. 1 Khan S.R. Reactive oxygen species as the molecular modulators of calcium oxalate kidney stone formation: evidence from clinical and experimental investigations. J Urol. 2013; 189: 803-811 Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar , 2 Khan S.R. Is oxidative stress, a link between nephrolithiasis and obesity, hypertension, diabetes, chronic kidney disease, metabolic syndrome?. Urol Res. 2012; 40: 95-112 Crossref PubMed Scopus (120) Google Scholar , 3 Khan S.R. Hyperoxaluria-induced oxidative stress and antioxidants for renal protection. Urol Res. 2005; 33: 349-357 Crossref PubMed Scopus (153) Google Scholar , 4 Thamilselvan S. Khan S.R. Menon M. Oxalate and calcium oxalate mediated free radical toxicity in renal epithelial cells: effect of antioxidants. Urol Res. 2003; 31: 3-9 PubMed Google Scholar As Dr. Khan described in detail, oxidative stress extensively affects or modulates a number of functional proteins, enzymes, and other biochemical parameters, which might play critical roles in renal cell injury and stone formation. Our numerous data searches also prompted us to believe that oxidative stress could be a major cellular or biochemical event inducing or facilitating kidney stone formation. Experimentally, CaOx crystal deposition, induced by EG, has been markedly prevented or reduced by various antioxidants, 4 Thamilselvan S. Khan S.R. Menon M. Oxalate and calcium oxalate mediated free radical toxicity in renal epithelial cells: effect of antioxidants. Urol Res. 2003; 31: 3-9 PubMed Google Scholar , 5 Thamilselvan S. Menon M. Vitamin E therapy prevents hyperoxaluria-induced calcium oxalate crystal deposition in the kidney by improving renal tissue antioxidant status. BJU Int. 2005; 96: 117-126 Crossref PubMed Scopus (90) Google Scholar , 6 Lee H.J. Jeong S.J. Lee H.J. et al. 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose reduces renal crystallization and oxidative stress in a hyperoxaluric rat model. Kidney Int. 2011; 79: 538-545 Crossref PubMed Scopus (28) Google Scholar , 7 Itoh Y. Yasui T. Okada A. et al. Preventive effects of green tea on renal stone formation and the role of oxidative stress in nephrolithiasis. J Urol. 2005; 173: 271-275 Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar , 8 Ghodasara J. Pawar A. Deshmukh C. et al. Inhibitory effect of rutin and curcumin on experimentally-induced calcium oxalate urolithiasis in rats. Pharmacognosy Res. 2010; 2: 388-392 Crossref PubMed Scopus (29) Google Scholar suggesting a pivotal role of oxidative stress in such CaOx nephrolithiasis that could yet be abolished with certain antioxidants. Editorial CommentUrologyVol. 82Issue 2PreviewExposure to CaOx and calcium phosphate crystals results in the production of reactive oxygen species (ROS) and the development of oxidative stress, leading to injury of the renal epithelial cells.1 Activation of the renin angiotensin system and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase occurs. Exposure to CaOx also leads to oxidatively modified mitochondrial proteome.2 The production of crystallization modulators, osteopontin, bikunin, matrix-GLA-protein, α1-microglobulin, inter-α-inhibitor, prothrombin fragment-1; secondary mediators, such as isoprostanes, cytoplasmic phospholipase A2, prostaglandins; and inflammatory molecules, such as monocyte chemoattractant protein-1, are also increased. Full-Text PDF