Abstract
BackgroundNephrotic syndrome (NS) is characterized by dyslipidemia which is a well-known risk factor for atherogenesis. Atherosclerosis in childhood is mostly subclinical and endothelial dysfunction is known to precede this. Evidence for screening for endothelial dysfunction and cardiovascular risk factors and early identification of premature onset of atherosclerosis in childhood NS remains tenuous in the absence of well-designed prospective studies addressing cardiovascular comorbidity in NS. The objective of our study is to examine endothelial dysfunction and short-term cardiovascular outcomes in a carefully phenotyped cohort of patients with Nephrotic syndrome as compared to healthy controls.MethodsIn a multi-centric prospective cohort study, 70 Steroid Resistant NS (SRNS), 70 Steroid Sensitive (SSNS) patients along with 70 Healthy Controls are being recruited. After a baseline assessment of functional and structural status of heart (2D Echocardiography), arteries (Carotid Doppler and Intima Media Thickness measurements) and microcirculation [a combination of 2D Echocardiography, Laser Doppler Flowmetry (LDF) and Brachial Artery Flow mediated dilation (FMD) and Nail Fold Capillaroscopy (NFC)], the patients are being investigated for endothelial dysfunction. Venous blood sample (15 ml) is being collected for routine investigations and assay of biochemical endothelial markers through Flow Cytometry. The patients will be followed up at 12 months and 24 months after the recruitment to look for any change from baseline period.DiscussionThis study will able to provide a better understanding of the epidemiology of endothelial dysfunction and associated subclinical cardiovascular co-morbidity in childhood NS. Findings on characterization of prevalence of endothelial dysfunction and subclinical markers may be used to design future randomized controlled trials for evaluating the efficacy of preventive and therapeutic interventions in reducing the incidence of cardiovascular disease.
Highlights
Nephrotic syndrome (NS) is characterized by dyslipidemia which is a well-known risk factor for atherogenesis
Apart from hyperlipidemia, a well-known risk factor for coronary artery disease (CAD) and a defining hallmark of NS, these children get exposed to other risk factors associated with impaired endothelial function and adverse cardiovascular outcomes like high oxidative stress, frequent infections, sustained proteinuria, hypoalbuminemia, thromboembolism, toxicity of steroids and non-steroidal drugs like calcineurin inhibitors
This study aims to provide a better understanding of the epidemiology of endothelial dysfunction and associated subclinical cardiovascular co-morbidity in childhood NS
Summary
Nephrotic syndrome (NS) is characterized by dyslipidemia which is a well-known risk factor for atherogenesis. The objective of our study is to examine endothelial dysfunction and short-term cardiovascular outcomes in a carefully phenotyped cohort of patients with Nephrotic syndrome as compared to healthy controls. Apart from hyperlipidemia, a well-known risk factor for coronary artery disease (CAD) and a defining hallmark of NS, these children get exposed to other risk factors associated with impaired endothelial function and adverse cardiovascular outcomes like high oxidative stress, frequent infections, sustained proteinuria, hypoalbuminemia, thromboembolism, toxicity of steroids and non-steroidal drugs like calcineurin inhibitors (hyperlipidemia,vasculotoxic and nephrotoxic effects). While hyperlipidemia is usually intermittent and transient in steroid sensitive nephrotic syndrome (SSNS), dyslipidemia and other abnormalities may be persistent in patients with frequent relapses (FRNS) or steroid resistant (SRNS) cases [6]. Occurrence of hemostatic abnormalities and generalized edema in NS attest to the wide ranging effects related to vascular endothelial dysfunction
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