The relationship of plasma S100A12 levels and carotis intima media thickness and athosclerosis in pediatric patients who have peritoneal dialysis due to chronic renal failure

AIM:End Stage Renal Failure (ESRD) is one of the serious causes of morbidity and mortality in pediatric patients, in which only 10-15% of normal kidney functions can be achieved with renal replacement therapies such as peritoneal dialysis (PD) and hemodialysis (HD). Since atherosclerotic cardiovascular diseases are among the leading causes of mortality and morbidity in these patients, it is very important to identify carefully and treat the causes that can be contribute to this process. Chronic inflammation, oxidative stress and endothelial dysfunction due to advanced glycation end products (AGE-RAGE) are among the identified risk factors. S100A12, which is one of the advanced glycation end products formed by the glycation of proteins and lipids in peritoneal dialysis patients; macrophage, it can be overexpressed on the surface of lymphocytes and endothelial cells and cause atherosclerosis with AGE-RAGE mediated proinflammatory cytokine response. Increased carotid intima media thickness and high S100A12 level, which is considered as an indicator of cardiovascular diseases, have been demonstrated in adult peritoneal dialysis patients. In this study, we aimed to investigate the effect of S100A12 levels on inflammation biomarkers and carotid intimamedia thickness (CIMT) and to evaluate its relationship with atherosclerosis. MATERIALS AND METHODS:In the study, 36 pediatric patients who had undergone peritoneal dialysis for at least 3 months for ESRD and a similar protocol as a control group for comparative analysis were performed in the same age group, admitted to the pediatric outpatient clinic. Thirty-eight healthy children with no known serious or chronic diseasewere evaluated withlaboratory parameters, carotid intima media thickness (CIMT) and S100A12 level. Information about the patients' age, gender, height, weight, body mass index, BMI and ESRD diagnosis (CRF etiology, presence of residual renal function (RRF), peritoneal dialysis modality and duration), blood pressure stages and antihypertensive treatments, supportive treatments (phosphorus binding therapy, anemia therapy), CIMT thickness, S100A12 level with simultaneous urea, creatinine, albumin, phosphorus, calcium, alkaline phosphatase (ALP), total cholesterol, triglyceride, LDL, HDL, parathormone (PTH), ferritin, C -reactive protein (CRP), leukocyte count, hemoglobin level, absolute neutrophil count (ANS), absolute lymphocyte count (ALS), platelet count) information were used.Bilateral carotid artery intima-media thickness (CIMT) was performed by a single trained pediatric cardiologist to all participants with a live E9 XD with 11 MHz 11L-D vascular probe with a Clear 4D (GE Electronic, USA) echocardiography device measured by real-time ultrasonography.Concentrations of S100A12 (pg/mL) were measured from samples that were plasma separated and frozen (at -70°C) with the commercially available ELISA Kit according to the manufacturer's instructions. (Human S100A12(Protein S100-A12)- ELISA Kit. Wuhan Fine Biotech Co., Ltd.) Statistical aAnalyzes were performed with IBM SPSS (Statistics Package Program for Social Sciences) version 26.0 (IBM Corporation, Armonk, NY, USA). Statistical significance level was accepted as p<0.05. RESULTS:Patient and control groups; It consisted of 36 patients (20 girls, 16 boys) with chronic peritoneal dialysis and 38 healthy children, 22 girls and 16 boys, as the control group. While the mean age (as months) of the patient group with chronic PD was 133.61±46.33, the mean age (as months) of the control group was 127.76±43.92. While there was no significant difference between the control group and the patient group in terms of age (months) and gender (p=0.579 and p=0.839, respectively), the pathological weight sds, height sds and BMI sds levels in the patient group were significantly higher than the control group. (p<0.001, p<0.001 and p<0.001, respectively). While 92.1% in the control group had normal blood pressure stages, the rate of stage 1 hypertension in the patient group was 30.6% and the rate of stage 2 hypertension was 19.4% (p<0.001). While the PD type of the patients in our study was automated peritoneal dialysis (APD) in 80.6% and continuous ambulatory peritoneal dialysis (SAPD) in 19.4%. The mean duration of PD was 32.2 (3-130.1) months. The duration of dialysis was 0-12 months in 22.2% of the patients, 12-36 months in 30.5%, and 12-36 months in 47.2% of them. The etiology was glomerular diseases in 33.3% of the patients, urological anomaly in 22.2%, cystic kidney disease in 13.9% and hereditary diseases in 11.1%. While 47.2% of the patients received erythropoietin treatment, 11.1% received oral iron treatment, 37.9% received erythropoietin combined with oral iron treatment, 2.8% did not receive any iron replacement treatment. Considering the antihypertensive drug treatment; 22.2% of patients were undersingle drug, 41.7% of the patients were undertwo drugs, 27.8% of the patients were under three or more drugs.The rate of patients who received only calcium carbonate or calcium acetate (OFB) treatment was 72.2%, the rate of patients who received sevelamer with a phosphorus-binding drug was 19.4%. In the comparisons between the patient and control groups; LDL cholesterol, urea and creatinine, ferritin, PTH, ALP values were found to be significantly higher in the patient group than the control group (p<0.001, p<0.001p<0.001, p<0.001, p<0.001, p=0.043), respectively. Likewise, right CIMT, left CIMT and S100A12 values in the patient group [respectively0.58±0.09, .57±0.07, 564.09±164.91], compared to the control group [respectively0.49±0.05, 0.48±0.04, 483.90±134.18] were found to be at significantly higher levels (p<0.001, p<0.001, p=0.024, respectively). Hemoglobin, platelet count ,albumin level andcalcium phosphorus multiplier levels in the patient group [respectively8.91±1.53, 281.05±98.95, 32.5 (4.2-40), 43.28±13.09], compared to the control group [respectively12.93±0.77, 323.55±66.33, 43 (39-49),45.42±8.09] were found to be at significantly lower (p<0.001, p<0.001, p<0.001, respectively, p=0.398).In our study, when CIMT and S100A12 parameters were compared with blood pressure stages in the patient group, patients with stage 1 and stage 2 hypertension had higher CIMT than normotensive patients(p= 0.013, p=0.021). When the duration of peritoneal dialysis and laboratory parameters were compared with CIMT and S100A12 levels, right CIMT values were found higher who underwent peritoneal dialysis for more than 36 months compared with patients who underwent peritoneal dialysis for 12-36 months and 0-12 months (p=0.001 and p=0.043), and mean values of CIMT were found to be significantlyhigherwhen compared patients with the duration for more than36 monthsof PD with patients who have PD for 0-12 months. (p=0.002). Statistically S100A12 levels were not associated with PD duration and blood pressure stages (respectively p=0.998,p= 0.73). In addition, a positive, moderately strong and significant correlation was found between right CIMT, left CIMT, mean CIMT values and parathormone levels (r=0.483, p=0.003, r=0.425, p=0.013 and r=0.546, p=0.001, respectively).). CONCLUSION: In terms of cardiovascular risk factors, right CIMT, left CIMT and serum S100A12 levels were found to be high in pediatric patients with end-stage renal disease who underwent peritoneal dialysis. Left CIMT was found to be increased in PD patients with stage 1 and stage 2 hypertension compared with patients normal blood pressure. It was determined that the mean CIMT values were increased with the prolonged follow-up period in dialysis and with high level of parathormone. With these findings, patients with PD should be followed closely in terms of cardiovascular system risk factors. We believe that effective dialysis, appropriate control and treatment of parathormone levels, effective hypertension treatment can be effective in preventing morbidity and mortality that may occur due to CVS diseases. Keywords:Childhood, Chronic kidney failure, Peritoneal dialysis, S100A12 level, Carotid intima media thickness (CIMT)