The role of claudin 16 protein in the molecular etiology of stone disease in children

Childhood urinary system stone disease is a disease with an increasing prevalence with many morbidities and complications. It has been shown that the presence of metabolic causes, which is the most common factor in the etiology of this disease, causes the clinical course of the disease to progress more seriously. The role of Claudin-16, one of the tight junction proteins in the kidney epithelium, in the etiology of urinary stone disease has not been clarified yet. The study was carried out between 50 healthy children under 18 years of age who applied to Manisa Celal Bayar University Pediatrics Polyclinic between July 2021 and July 2022 and 50 patients followed up in Manisa Celal Bayar University Hospital Pediatric Nephrology Polyclinic with the diagnosis of primary hypercalciuric urinary system stone disease. All statistical analyzes were performed using the SPSS 23.0. There was no statistically significant difference in sociodemographic characteristics such as age, gender, body weight, height, BMI, week of birth between the patient and control groups (p>0.05). Spot urine Ca/Cr, Uric acid/Cr, Na/K values were statistically significantly higher in the patient group compared to the control group; Spot urine Mg/Cr and citrate / Cr values were statistically significantly lower (p<0.05). As a result of the CLDN16 gene panel, Arg55Ser/Ala56LeufsTer16 compound heterozygous mutation was seen in the patient and control groups. Due to the high frequency of this mutation in the healthy control group (9%), this mutation was accepted as a polymorphism. The frequency of this polymorphism was statistically significantly higher in the patient group than in the control group (p<0.05). There was no statistically significant difference between the patient group with polymorphism and the patient group without polymorphism in terms of age, gender, body weight, height, BMI, week of birth, history of hospitalization in the neonatal period, presence of stone disease in the family, and consanguinity between parents (p>0, 0). 05). Although spot urine ca / cr was higher in the patient group with polymorphism than in the patient group without polymorphism, this difference was not statistically significant (p>0.05). Spot urine Na / K was significantly higher in the patient group with polymorphism compared to the patient group without polymorphism (p<0.05). In our study, Arg55Ser/Ala56LeufsTer16 combined heterozygous polymorphism in the Claudin-16 gene was found to be statistically significantly higher in the patient group than in the healthy control group. Therefore, we concluded that the presence of this polymorphism may predispose to hypercalciuric stone disease. Future studies with larger sample groups may clarify the relationship of Claudin 16 with Hypercalciuric URTI. In this way, complications can be prevented with early diagnosis and early treatment for urinary system stone disease.