Letter to the editor regarding the article “Serum paraoxonase-1 gene polymorphism and enzyme activity in patients with urolithiasis”

Sir,

We read with great interest the recently published manuscript by Atar et al.¹ entitled “Serum paraoxonase-1 gene polymorphism and enzyme activity in patients with urolithiasis”. The study was designed to investigate the relationship between urolithiasis and paraoxonase-1 (PON1) activity and PON1 Q192R polymorphisms. PON-1, which is an enzyme with esterase and lactonase activities, inhibits the LDL oxygenation process by reactive oxygen species (ROS) and therefore leads to a decrease in oxidized low-density lipoproteins. The authors propose that decreased activity of PON-1 might be associated with urinary stone formation. First of all, we congratulate the authors conducting a study to enhance our understanding of the possible mechanism of stone formation pathogenesis. However, several issues should be discussed further. The production of ROS and development of oxidative stress (OS) may be a common link between urolithiasis and PON-1 activity. Proinflammatory cytokines, acute inflammation markers, adhesion molecules, urinary microalbumin, myeloperoxidase, 8-hydroxydeoxyguanosine, 3-nitrotyrosine, and monocyte chemoattractant protein were found to be elevated in patients with urolithiasis.² Since PON1 is a serum high-density lipoprotein (HDL)-bound enzyme with an antioxidant function, the authors should also address the oxidant/antioxidant status of patients.

Lipid metabolism profiling including HDL, LDL, triglyceride, total cholesterol, and apolipoprotein AI levels should also be evaluated. Given that oxidative stress and chronic low-grade inflammation are major characteristics of obesity-related disorders and some studies^3,4 propose that metabolic syndrome is associated with urolithiasis, the present study, which evaluates an enzyme serving in lipid metabolism, should also include the status of metabolic disorders such as diabetes, obesity, dyslipidemia, and metabolic syndrome. According to the present study, PON1 L55M polymorphism was significantly higher in the urolithiasis group and PON1 192 RR homozygotes had significantly higher PON activity than QR and QQ genotypes. The present study provides useful knowledge about the association between PON-1 and urolithiasis, but it does not give us sufficient data regarding PON-1 polymorphisms in patients with urolithiasis accompanied by diabetes, metabolic syndrome, dyslipidemia, etc.

The present study also lacks an assessment of stone composition. As some studies propose that higher body mass index (BMI) is associated with increased urinary excretion of oxalate, sodium, uric acid, calcium, and phosphorous as well as lower pH and diabetics are associated with a reduction in renal ammonium production and low urinary pH, which could lead to the development of uric acid stones and oxalate calcium stones, the analysis of stone composition is necessary.^5,6

It is obvious that further studies will allow us to better understand the implications of PON-1 enzyme activities and polymorphisms in the pathogenesis of urinary stone formation and also trigger health care professionals to manage patients in order to encourage them to make lifestyle modifications for urinary tract stone recurrence and prevention.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.