Cardiovascular outcomes of Nephrotic syndrome in childhood (CVONS) study: a protocol for prospective cohort study

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.

Disease-Associated Systemic Complications in Childhood Nephrotic Syndrome: A Systematic Review

“… ● Significantly decreased PON11 and lecithin:cholesterol acyltransferase activity resulted in increased oxidation of LDL, thus accelerating atherosclerosis. Patnaik et al 35 India To define the extent of endothelial dysfunction by noninvasive evaluation for impairment of macrovascular and microvascular endothelial function in children with NS versus healthy controls by assessment of brachial artery, flow-mediated dilation, and cutaneous postocclusive reactive hyperemia Total of 70 steroid-resistant NS (SRNS) 70 steroid-sensitive (SSNS) patients, and 70 healthy controls aged 1–18 years ● Prospective cohort study with ● two phases: recruitment and baseline assessment of biomarkers of endothelial dysfunction (phase 1) and prospective follow-up and cardiovascular outcome assessment (phase 2). ● After baseline assessment of functional and structural status of the heart, arteries, patients were investigated for endothelial dysfunction.…”

Hypertension in Childhood Nephrotic Syndrome

“…Future research is needed to better understand the relationship between the human microbiome and virome in BP regulation in children with NS. Currently, a multi-centric prospective cohort study of 70 steroid-resistant, 70 steroid-sensitive, and 70 healthy controls are being recruited to better understand the epidemiology of endothelial dysfunction and associated subclinical cardiovascular co-morbidity in childhood NS (68).…”

Prevalence and determinants of peripheral arterial disease in children with nephrotic syndrome

“…High rate of PAD in children with steroid resistant NS has been previously documented by Mohammed et al [4] The higher risk of PAD in steroid resistant NS may be attributed to persistence of proteinuria and progression to chronic kidney disease which is an established risk factor for PAD. [8,38] Chronic kidney disease leads to development of PAD through persistent proteinuria, endothelial dysfunction and chronic inflammatory state thereby enhancing plaque formation in the lumen of vessels. [12] In the current study occurrence of PAD was found to increase with age albeit not significant.…”

“…[7] Peripheral arterial disease has been established to be prevalent among children with chronic kidney disease, especially children with NS, with a prevalence as high as 80% documented in Egypt by Mohammed et al [4] The development of PAD can become progressive and associated with a significant increase in cardiovascular related events like cardiac arrest, arrhythmias, transient ischaemic attack and sudden cardiac death that can occur in children. [8,9] There is a paucity of data on the burden of PAD in children with NS, with the few studies reporting a high prevalence of PAD, above 80%. [4,8] Thus, with a prevalence of PAD in children with NS as high as 80% compared to 9% in apparently healthy controls in an African study done in Egypt by Mohammed et al [4] the need for prompt screening of children with NS for PAD cannot be overemphasized.…”

“…[9,[16][17][18][19][20] Hyperlipidaemia is a known risk factor for the development of atherosclerosis, and is a major component of NS that predisposes to vascular damage and, as a result, poses a risk for the development of PAD, particularly in children with NS. [8,11] A valid and reliable screening tool in detecting PAD is the ankle brachial index (ABI). The ABI is proven to be a sensitive, noninvasive, user friendly, readily available, and cost-effective screening tool for PAD that can be used in children.…”