Assessment of subclinical atherosclerosis and cardiovascular disease in children and adolescents with nephrotic syndrome: a systematic review and meta-analysis.

backgroundChildren with nephrotic syndrome (NS) are frequently exposed to chronic inflammation, hypertension, and multiple metabolic abnormalities, such as hyperlipidemia, that may contribute to early development of atherosclerosis and cardiovascular disease. However, the extent of subclinical cardiovascular involvement remains unclear.

objectivesThis systematic review and meta-analysis aimed to investigate the presence of subclinical atherosclerosis and cardiovascular disease in pediatric patients with NS, using carotid intima-media thickness (cIMT), carotid-femoral pulse wave velocity (c-f PWV), and left ventricular mass (LVM) index as surrogate markers. DATA SOURCES: A systematic literature search was conducted in PubMed/MEDLINE, Scopus, and Cochrane Library databases from their inception until December 20, 2024. STUDY ELIGIBILITY CRITERIA: Eligible studies included observational studies that evaluated early markers of atherosclerosis and cardiovascular disease in children with NS. PARTICIPANTS AND

interventionsChildren and adolescents with NS under the age of 18 years were compared to healthy controls. Surrogate markers included cIMT, PWV, and LVI index. Blood pressure was evaluated as a cardiovascular risk factor. STUDY APPRAISAL AND SYNTHESIS

methodsThe Newcastle-Ottawa Scale was used to assess study quality. The mean difference with 95% confidence intervals was used for continuous outcomes. Statistical significance was set at p < 0.05. Sensitivity and subgroup analyses and meta-regression were conducted for further exploration of the outcomes. Statistical analyses were performed using R software (Version 4.3.2).

resultsSixteen studies with a total of 1461 participants (668 patients with NS and 793 healthy controls) met inclusion criteria. Children with NS had significantly increased cIMT compared to controls (MD = 0.06 mm; 95% CI: 0.05-0.07; p < 0.001), with substantial heterogeneity across studies. No statistically significant differences were observed for c-f PWV and LVM index. Moderate correlations were found between cIMT and disease duration (r = 0.47) and number of relapses (r = 0.45). A small positive correlation was observed between cIMT and triglycerides, but not with total or LDL cholesterol. LIMITATIONS: This meta-analysis is limited by the observational and predominantly cross-sectional nature of the included studies, substantial heterogeneity across studies, and the highly diverse study population. Furthermore, in many studies, the phenotypes of NS were poorly characterized, or grouped together, and insufficient data were provided for treatment regimens, limiting interpretation of the results. CONCLUSIONS AND IMPLICATIONS OF KEY

findingsChildren with NS exhibit increased cIMT, which may be associated with increased future cardiovascular risk. However, prospective longitudinal studies are needed to determine whether these surrogate markers can predict such an association.