Heba Mostafa Ahmed,1 Emad El-Deen Ameen,1 Mohammad Shafiq Awad,2 Osama Ezzat Botrous1
1Division of Pediatrics, School of Medication, Beni-Suef College, Beni Suef, Egypt; 2Division of Cardiology, School of Medication, Beni- Suef College, Beni Suef, Egypt
Correspondence: Heba Mostafa Ahmed
Division of Pediatrics, School of Medication, Beni- Suef College, Beni-Suef, Egypt
Electronic mail [email protected]
Background: Youngsters with nephrotic syndrome (NS) are at a higher threat of atherosclerosis on account of recurrent exposures to hyperlipidemia, hypertension, and immunosuppressive drugs. CIMT (carotid intima media thickness) is a dependable marker for evaluation of atherosclerosis of huge and medium-sized blood vessels; endothelial dysfunction and elevated CIMT often precede the event of cardiovascular ailments. Some manifestations of NS, like proteinuria and hyperlipidemia, are related to an elevated threat of cardiac morbidity and mortality. The intention of the present research was to guage the carotid intima media thickness and LVM (left ventricular mass) thickness in kids with nephrotic syndrome.
Topics and Strategies: Eighty-one kids with nephrotic syndrome and 100 wholesome kids as controls have been enrolled within the research. The inclusion standards have been: illness length of minimal of 12 months, glomerular filtration charge > 60mL/min/1.73m 2 and youngsters aged two years or extra on the time of research. CIMT and left ventricular mass index, lipid profile, protein/creatinine ratio in urine and kidney operate exams have been achieved for instances and controls after approval of inner moral committee.
Outcomes: The imply CIMT (mm) was considerably increased in NS (0.51± 0.12) in comparison with controls (0.42± 0.09) (P < 0.001). LVM and LVM Index have been considerably increased in NS than controls (p< 0.001, for each). Subsequently, CIMT was considerably correlated to length of the illness (p< 0.001), LVM index was considerably correlated with length of the illness, physique mass index (BMI), blood pressures and triglycerides stage (p< 0.05).
Conclusion: Youngsters with NS are at growing threat to develop atherosclerosis as measured by CIMT. LVM was considerably increased in NS and positively correlated to BP, illness length, triglyceride ranges and BMI.
Key phrases: nephrotic syndrome, kids, left ventricular hypertrophy, carotid intima media thickness, dyslipidemia
Nephrotic syndrome (NS) is taken into account one of many commonest sorts of renal issues in kids.1 The medical options of NS embrace large proteinuria, hypoalbuminemia, in addition to generalized edema ensuing from destruction of the glomerular basement membrane.2 Hyperlipidemia can be a traditional characteristic present in sufferers with NS.1 Proteinuria was reported as a exceptional threat issue for cardiovascular issues. A number of metabolic abnormalities equivalent to hypercholesterolemia, hypertriglyceridemia, and hypercoagulable states are associated to the severity of proteinuria and contribute to the event of cardiovascular ailments. Different elements as hypertension, renal insufficiency, and corticosteroids therapy may contribute to the event of cardiovascular ailments(CVD).3 Regardless of hyperlipidemia is usually intermittent and non permanent in steroid-sensitive nephrotic syndrome (SSNS); but, dyslipidemia together with different abnormalities may be persistent in sufferers struggling regularly relapsing (FRNS) or steroid-resistant (SRNS) nephrotic syndrome.4 Ultrasound evaluation of the carotid intima media thickness (CIMT) was used as a marker of atherosclerosis of the coronary arteries. Elevated CIMT and plaque formation within the carotid arteries are exceptional indicators for cardiovascular ailments within the common inhabitants.5 The intention of this research was to guage CIMT and left ventricular mass (LVM) in kids with idiopathic nephrotic syndrome.
This research was carried out within the interval from April 2019 until August 2020. Eighty-one kids with idiopathic NS following up on the pediatric-nephrology outpatient clinic have been included within the research. Sufferers have been categorized in line with their response to steroid therapy into steroid-sensitive (SSNS), steroid-dependent (SDNS), and steroid-resistant (SRNS). One-hundred age and sex-matched wholesome kids chosen from the final outpatient clinic have been included within the research as a management group. The inclusion standards have been: age greater than two years on the time of enrollment within the research, steady or interrupted therapy for at least 12 months earlier than enrollment, glomerular filtration charge greater than 60 mL/min/1.73m2, being freed from acute an infection within the earlier three months earlier than the research. The exclusion standards have been: household historical past of early atherosclerosis, cerebrovascular accidents or familial hyperlipidemia, sufferers receiving lipid-lowering brokers, systemic vasculitis in exercise, coexisting cardiac anomalies, kids with persistent kidney illness, presence of extreme edema at time of examination, congenital or rheumatic coronary heart illness, and excessive CRP on the time of the research. All sufferers have been subjected to detailed historical past taken together with previous medical and drug historical past, medical knowledge of nephrotic sufferers stressing on age at prognosis, length of the illness, response to steroid therapy, frequency of relapses, immunosuppressive drugs, and full medical evaluation together with measurement of weight, top, physique mass index (BMI), arterial blood stress (BP), examination for edema and cardiac examination to make sure none of our sufferers had congenital or rheumatic coronary heart illness. Laboratory investigations together with ranges of blood urea, creatinine, albumin, spot protein/creatinine in urine (PCR), serum Na, serum Okay, and blood urea. All kids underwent a whole lipid profile consisting of complete ldl cholesterol, high-density lipoproteins-cholesterol (HDL), low-density lipoproteins-cholesterol (LDL), and triglycerides (TG). Ldl cholesterol and TG have been measured by means of 2 steps: 1) using the enzymatic endpoint technique to precipitate LDL utilizing phosphotungstic acid/magnesium adopted by the removing of HDL. 2) LDL ldl cholesterol was calculated by Friedwald’s method
Measurement of CIMT was performed according to Mannheim’s Consensus Guideline 20116 by an skilled heart specialist who was blinded to the affected person’s standing. The ultrasound measurement was obtained utilizing a single ultrasound machine (VIVID SS) with a linear high-frequency transducer (7.5 MHz). The sufferers have been mendacity within the supine place and had head turned barely to the contralateral aspect with slight overextension of the neck. After resting for ten minutes, to acquire the arterial diameter measurements, the arterial wall phase was assessed within the longitudinal view, firmly at a proper angle to the ultrasound beam, with each partitions clearly seen. It’s manufactured from two parallel strains representing the 2 structural boundaries: the intima lining the lumen and media-adventitia. Measurements have been obtained from the far wall of the left frequent carotid artery 10–20 mm proximal to the bifurcation. Photographs of the thickest CIMT have been taken and measurements have been taken on it whereas the calipers positioned on a zoomed frequent carotid artery picture. Photographs have been attained at passive end-expiration to scale back total cardiac motion from the usual parasternal long-axis and apical planes. The usual views have been used to acquire the left ventricle (LV) dimensions. Modified Simpson’s technique was used to calculate the left ventricle end-systolic and end-diastolic volumes after which they have been used to calculate the ejection fraction. The LVM index was calculated utilizing the Devereux’s method by the next equation: Left Ventricular Mass (LVM) = 0.80 [1.04 × (interventricular septal thickness + posterior wall thickness + end-diastolic diameter) 3 – (end-diastolic diameter) 3] + 0.6. LVMI is calculated as LVM/floor space.
Relapse: 24 hours urinary proteins greater than 40 mg/m2/h or urinary proteins greater than 3+ by dipstick in spot pattern for no less than three consecutive days.
Remission: 24 hours’ urinary proteins lower than 4 mg/m2/h, nil or hint by dipstick for no less than three consecutive days
Frequent relapses: Two or extra relapses inside 6 months of steroid-induced remission; 4 or extra relapses in any 12 months.
Steroid dependence: no less than 2 consecutive relapses throughout therapy cortisone with or inside 2 weeks of its withdrawal.
Steroid resistance: Failure to realize remission after 4–8 weeks of each day oral prednisolone remedy at a dose of two mg/kg/day.7
The SPSS software program (Statistical Bundle for the Social Sciences, model 22.0, SPSS Inc, Chicago, IL, USA) was used for evaluation. Comparability between qualitative knowledge was carried out utilizing the chi-square and values have been expressed as numbers and percentages. Parametric quantitative unbiased teams have been examined utilizing the t-test or the Mann–Whitney check and values have been expressed as imply ± customary deviation. A method Anova check was used to check steady variables between the three illness teams. Correlations between the research’s steady variables have been achieved utilizing the Pearson correlation coefficient check. Common linear multivariate evaluation was achieved to substantiate vital correlations between threat elements and each CIMT and LVM index. P-value was set at lower than 0.05 for vital outcomes.
This research included 81 kids with nephrotic syndrome and 100 age and sex-matched wholesome kids as controls. The included kids have been stratified in line with their age into 3 teams: G1; ≤5 years (19 sufferers and 37 controls), G2; 6–10 years (33 sufferers, 38 controls), and G3; >10 years (29 sufferers and 25 controls). The age at illness onset within the sufferers was 4.9 ± 2.6 (vary 1.2–12 years). Within the sufferers’ group, 31 (38.3%) sufferers have been steroid-sensitive nephrotic syndrome (SSNS), 36 (44.4%) have been steroid-dependent nephrotic syndrome (SDNS) and14 (17.3%) have been steroid-resistant nephrotic syndrome (SRNS). The imply variety of relapses amongst sufferers was 2.1± 1.9 (vary 0–7) and imply illness length of three.6 ±2.6 (vary 1–11 years). Amongst sufferers with SDNS and SRNS, 35 sufferers had achieved renal biopsy; 28 sufferers had minimal change illness (MCD), 6 sufferers had focal segmental glomerulosclerosis (FSGS) and one affected person had mesangial-proliferative glomerulonephritis (MesPGN). Amongst our sufferers, 42% of them had obtained immunosuppressive remedy fairly than steroids. 19.7% of our sufferers obtained cyclophosphamide, 24.7% obtained calcineurin inhibitors (CNI), 6.2% obtained mycophenolate mofetil (MMF) and 6% obtained mixed remedy (CNI+MMF). The medical and laboratory traits of the research teams are proven in (Table 1). Ten of our sufferers (12.3%) have been hypertensive on the time of research enrollment and 17 sufferers (21%) confirmed hypertriglyceridemia versus 4 (5%) kids within the management group (p=0.023) and was positively correlated to systolic blood stress (r=0.38, p=0.021). On evaluating the 2 research teams relating to the CIMT and LV parameters, all have been considerably increased in sufferers as in comparison with controls throughout the three age teams (Table 2). On stratification of the sufferers in line with their response to steroids, sufferers with SRNS had considerably increased blood pressures, PCR, and TG ranges as in comparison with SSNS sufferers. LVM was considerably increased in SRNS. Quite the opposite, there have been no vital variations between the three teams as relating to different echo findings (Table 3). In evaluating sufferers with MCD and FDGS in line with renal biopsy there have been no vital variations between the 2 teams relating to demographic, medical, and laboratory knowledge aside from PCR (0.346± 0.59 versus 3.75 ± 7.84 mg/gm in MCD and FSGS, respectively, p=0.024). Then again, the LVM index was considerably increased within the FSGS group as in comparison with MCD (Table 4). Correlations between the echocardiographic knowledge and different medical and laboratory knowledge are proven in (Table 5). CMIT was considerably correlated to illness length, whereas there have been no vital correlations with systolic blood stress, diastolic blood stress, or lipid profile. LVM was considerably correlated to illness length, BMI, systolic and diastolic blood pressures, TG, and HDL ldl cholesterol stage. The outcomes of multivariate evaluation had confirmed these associations (Table 6).
Desk 1 Scientific and Investigational Knowledge of Circumstances and Controls
Desk 2 Carotid Intima Media Thickness, LVM and LVM Index In response to Age Teams in Circumstances and Controls
Desk 3 Scientific and Investigational Knowledge of the Three Nephrotic Teams
Desk 4 Comparability Between Sufferers with MCD (n=28) and FSGS (n=6) as Regard CIMD and Echo Findings
Desk 5 Correlations Between the Echocardiography Findings and Different Scientific and Laboratory Knowledge. Values are Expressed as p (r)
Desk 6 Common Linear Multivariate Mannequin for Analyzing the Impact of Threat Elements on CIMT and LVM Index
Endothelial dysfunction is an preliminary reversible part within the pathogenesis of atherosclerosis and may predict cardiovascular ailments. CIMT is an oblique indicator of atherosclerosis and focused organ destruction in adults. Its implication in kids continues to be below estimation nonetheless there are rising numbers of research on kids with threat elements for vascular harm.8 Impaired endothelial operate was reported within the lively part of idiopathic nephrotic syndrome. Earlier research had reported vital correlations between CIMT and illness length and response to therapy in kids with NS.9 This research was designed to research and assess the CIMT and left ventricular mass in idiopathic NS. There was a big improve in weight and BMI in NS sufferers in comparison with controls. Related outcomes have been reported by different research.10–12 Within the research by Youssef et al,13 they reported that physique weight and BMI have been considerably increased in NS sufferers than controls (p<0.001). This discovering could be defined by the surplus weight acquire throughout steroid remedy which may persist even after termination of steroids and often related to dyslipidemia that may improve the cardiovascular threat.14 We additionally famous that top was considerably decrease in sufferers than controls, comparable findings have been reported by Candan et al.15 This discovering could be defined by the adverse impact of steroids on linear development by means of the suppression of osteoblastogenesis and the induction of osteocyte and osteoblast apoptosis which result in a lower in bone formation.16 Serum ldl cholesterol, LDL ldl cholesterol, and protein/creatinine in urine have been considerably increased in sufferers than controls whereas serum albumin and HDL ldl cholesterol have been considerably decrease in sufferers in comparison with controls. Related outcomes have been reported by different research.9,13 Sufferers with NS have the next threat for myocardial infarction and coronary vascular accidents in comparison with regular populations. Hyperlipidemia, hypoalbuminemia, and hypercoagulable states are relative threat elements specifically LDL ldl cholesterol which might be assumed to extend the oxidative stress by means of the synthesis of atherogenic elements.17,18 CIMT is a marker for the analysis of atherosclerosis of huge and medium-sized blood vessels secondary to threat elements as hypertension, hyperlipidemia, and endothelial dysfunction.19 Within the present research, CIMT was considerably increased in kids with NS compared to controls throughout the three age teams particularly within the age group 6–10 years. Related outcomes have been documented within the research by Hooman et al20 who declared that frequent carotid artery CIMT within the sufferers group (0.42 ±.14) was increased than that of the management group (0.37 ±.08, p<0.05). Correspondingly, Mehta et al21 of their research carried out on 66 kids with NS and 128 age and intercourse matched wholesome controls, discovered that CIMT was considerably increased in NS particularly within the age above 4 years. Nevertheless, in contrast to our outcomes, Kniazewska et al9 discovered no vital variations in CIMT between 30 kids beforehand handled for nephrotic syndrome versus 30 wholesome kids. On this research, the inclusion within the research required being in remission freed from steroids for no less than 4 years in opposite to our research which included kids with SDNS and SRNS on present remedy with steroids or different immunotherapies. We didn’t discover a vital distinction within the CIMT between totally different steroid response teams or kids with MCD and FSGS. Related findings have been reported by Rahul et al12 who discovered no vital distinction in CIMT between sufferers with IFRNS, FRNS, SDNS, and SRNS however they didn’t research the distinction between sufferers in line with their histopathology. Additionally, Youssef et al13 didn’t state a distinction between response subgroups or sufferers in remission and exercise as regards the CIMT. CIMT was considerably correlated to illness length. Just like our outcomes, Hooman et al20 discovered that CIMT was correlated with illness length longer than 2 years (P = 0.04, 95% confidence interval, 0.002 to 0.12). Even after excluding kids with a glomerular filtration charge lower than 90 mL/min/1.73m2, this correlation remained vital (P = 0.03). We had not discovered any correlation of CIMT with blood stress, and this might be as a result of solely 12.2% of our NS kids have been hypertensive. Just like our outcomes, Mehta et al21 reported no vital correlation between CIMT and blood stress. Furthermore, there have been no vital correlations between CIMT and lipid profile in our sufferers. Related findings have been reported by different research.13,20,22 In our research, LVM and LVMI have been considerably increased within the NS group than controls. Additionally, LVM index was considerably increased in SRNS and in sufferers with FSGS in comparison with MCD. Just like our research, Candan et al15 discovered that LVM index values have been increased in NS than wholesome kids of their research carried out on 37 NS sufferers to evaluate the presence of understated heart problems (CVD) in kids with SRNS. In our research, there have been vital constructive correlations between LVM index and illness length, BMI, systolic BP, and TG and on multivariate evaluation illness length, BMI, BP and TG have been unbiased threat elements for LVH. Within the research by Candan et al,15 the one unbiased threat issue for LVH was BMI and so they did not elicit vital correlation between LVM index and different laboratory and medical parameters. The limitation of their research was the small variety of sufferers, which can alter the rationality of the multivariate evaluation. Systemic hypertension is a substantial threat issue for the event of renal harm and heart problems and irregular BP was previously famous in sufferers with persistent kidney illness.23 In our research, each systolic and diastolic blood pressures have been considerably increased in sufferers than controls and in SRNS than SSNS and have been positively correlated to LVM index. Within the research by Frishberg et al24 on 30 kids with SRNS, they documented that the evaluation of consecutive echocardiograms of their sufferers revealed delicate to extreme LVH on the onset of SRNS and reported an extra improve in LVH throughout observe up, parallel with the acquirement of considerable hypertension. Equally, Hooman et al20 reported that echocardiographic measurements confirmed LVH in a single (1.9%) of the management group versus 19 (50%) of the NS group (p worth<0.001) and there was a constructive correlation between LVH and systolic hypertension (p-value=0.019). Regardless of there was no vital distinction between sufferers and controls as regards the imply TG ranges however the frequency of hyperlipidemia was considerably increased in nephrotic sufferers and it was considerably correlated to each blood stress and LVMI indicating the function of dyslipidemia as a threat issue for hypertension and LVH. In our research, the HDL-cholesterol was considerably decrease in sufferers than controls and there was a big inverse correlation between LVMI and HDL-cholesterol. The identical discovering was reported by Giuseppe et al25 signifying that HDL-cholesterol might have a defending function in opposition to LVH. Along with the induction of reverse ldl cholesterol transport, HDL additionally has antioxidant actions and anti inflammatory properties and protects in opposition to endothelial dysfunction by binding to scavenger receptor B1 to activate endothelial nitric oxide synthase.26 Throughout NS, there may be dysregulation of a number of key proteins leading to irregular construction and performance of HDL-cholesterol in addition to deficiency of lecithin ldl cholesterol acyltransferase on account of its loss in urine.27
Limitations of our research have been lack of long-term observe as much as see the adjustments in CIMT over a time period and lack of learning the impact of corticosteroids cumulative dose on CIMT.
CIMT was elevated in kids with NS and there was vital constructive correlation with illness length. Equally, LVM index was increased in instances than controls and was considerably positively correlated with BMI, BP, illness length and TG ranges. Youngsters with NS are at extra threat for atherosclerosis as measured by CIMT and LVH as measured by LVM index in comparison with wholesome kids. Due to this fact, follow-up and early administration of threat elements equivalent to correct management of hypertension to keep up the blood stress on the 50% for age and intercourse, management of dyslipidemia by wholesome vitamin and correct management of the nephrotic state and proteinuria are strongly really useful for these sufferers.
Ethics Approval and Consent to Take part
This research was carried out in accordance with the Declaration of Helsinki. It was authorised by the Ethics Committee of Beni-Suef College, School of drugs and the Ethic Code was FMBSUREC/05032019. FWA00015574. The aims of this research have been defined for all dad and mom by the researcher and knowledgeable consent was obtained from the dad and mom earlier than initiation.
The authors wish to thank the entire kids who participated within the research and their dad and mom.
All authors made a big contribution to the work reported, whether or not that’s within the conception, research design, execution, acquisition of knowledge, evaluation and interpretation, or in all these areas; took half in drafting, revising or critically reviewing the article; gave ultimate approval of the model to be printed; have agreed on the journal to which the article has been submitted; and comply with be accountable for all elements of the work.
The authors report no conflicts of curiosity on this work.
1. Safaei A, Maleknejad S. Spectrum of childhood nephrotic syndrome in Iran: a single middle research. Indian J Nephrol. 2009;19(3):87–90. doi:10.4103/0971-4065.57103
2. Ishikura Okay, Matsumoto S, Sako M, et al. Scientific apply guideline for pediatric idiopathic nephrotic syndrome, medical remedy. Clin Exp Nephrol. 2015;19(1):6–33. doi:10.1007/s10157-014-1030-x
3. Chaubey S, Singh KV, Singh P, Mittal M, Singh Abhishek Okay, Kushwaha KP. A research on intima-media thickness of carotid artery in kids with nephrotic syndrome: a cross sectional research. J Pediatr Rev. 2017;4(02):91–101.
4. Zhang Q, Zeng C, Fu Y, Cheng Z, Zhang J, Liu Z. Biomarkers of endothelial dysfunction in sufferers with main focal segmental glomerulosclerosis. Nephrology. 2012;17(4):338–345. doi:10.1111/j.1440-1797.2012.01575.x
5. Szeto CC, Chow KM, Woo KS, et al. Carotid intima media thickness predicts cardiovascular ailments in Chinese language predialysis sufferers with persistent kidney illness. J Am Soc Nephrol. 2007;18(6):1966–1972. doi:10.1681/ASN.2006101184
6. Touboul P-J, Hennerici MG, Meairs S, et al. Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An replace on behalf of the advisory board of the third, 4th and fifth watching the chance symposia, on the thirteenth, fifteenth and twentieth European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011. Cerebrovasc Dis. 2012;34(4):290–296. doi:10.1159/000343145
7. Srivastava RN, Bagga A. Nephrotic Syndrome. ch. 12.
8. Adhikari MC, Guin A, Chakraborty S, et al. Subclinical atherosclerosis and endothelial dysfunction in sufferers with early rheumatoid arthritis as evidenced by measurement of carotid intima-media thickness and flow-mediated vasodilatation: an observational research. Semin Arthritis Rheum. 2012;5:669–675. doi:10.1016/j.semarthrit.2011.08.003
9. Kniazewska MH, Obuchowicz AK, Wielkoszyn´Oski T, et al. Atherosclerosis threat elements in younger sufferers previously handled for idiopathic nephrotic syndrome. Pediatr Nephrol. 2009;24:549–554. doi:10.1007/s00467-008-1029-1
10. Kuźma-Mroczkowska E, Pańczyk-Tomaszewska M, Skrzypczyk P, et al. Physique weight adjustments in kids with idiopathic nephrotic syndrome. Dev Interval Med. 2016;20:16–22.
11. El-Mashad GM, El-Hawy MA, El-Hefnawy SM, et al. Bone mineral density in kids with idiopathic nephrotic syndrome. J Pediatr (Rio J). 2016;16:237–266.
12. Rahul I, Krishnamurthy S, Satheesh S, et al. Brachial artery flow-mediated dilatation and carotid intima medial thickness in pediatric nephrotic syndrome: a cross-sectional case-control research. Clin Exp Nephrol. 2015;19:125–132. doi:10.1007/s10157-014-0958-1
13. Youssef DM, Gomaa MA, El-Akhras A, et al. Brachial artery flow-mediated dilatation and carotid intima-media thickness in kids with idiopathic nephrotic syndrome. IJKD. 2018;12:331–340.
14. Nakamura A, Niimi R, Kurosaki Okay, et al. Elements influencing cardiovascular threat following termination of glucocorticoid remedy for nephrotic syndrome. Clin Exp Nephrol. 2010;14(5):457–462. doi:10.1007/s10157-010-0317-9
15. Candan C, Canpolat N, Gökalp S, et al. Subclinical heart problems and its affiliation with threat elements in kids with steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2014;29(1):95–102. doi:10.1007/s00467-013-2608-3
16. Valavi E, Aminzadeh M, Amouri P, Rezazadeh A, Mousavi MB. Impact of prednisolone on linear development in kids with nephrotic syndrome. J De Pediatria (Versão Em Português). 2020;96(1):117–124. doi:10.1016/j.jpedp.2018.11.019
17. Pritchard KA, Groszek L, Smalley DM, et al. Native low-density lipoprotein will increase endothelial cell nitric oxide synthase technology of superoxide anion. Circ Res. 1995;77(3):510–518. doi:10.1161/01.RES.77.3.510
18. Dogra GK, Herrmann S, Irish AB, et al. Insulin resistance, dyslipidaemia, irritation and endothelial operate in nephrotic syndrome. Nephrol Dial Transplant. 2002;17:2220–2225. doi:10.1093/ndt/17.12.2220
19. Tkaczyk M, Czupryniak A, Owczarek D, et al. Markers of endothelial dysfunction in kids with idiopathic nephrotic syndrome. Am J Nephrol. 2008;28(2):197–202. doi:10.1159/000110088
20. Hooman N, Isa-Tafreshi R, Otukesh H, Mostafavi SH, Hallaji F. Carotid artery operate in kids with idiopathic nephrotic syndrome. Nefrologia. 2013;33:650–656. doi:10.3265/Nefrologia.pre2013.Might.12036
21. Mehta A, Mishra S, Ahmad Okay, Tiwari HC, Singh V, Singh A. Carotid intima media thickness in kids with nephrotic syndrome: an observational case management research. Sudan J Paediatr. 2019;19(2):110–116. doi:10.24911/SJP.106-1535804613
22. Dalmau SJ, Vitoria MI, Legarda TM, Muro VD, Sangüesa NC. Analysis of carotid intima-media thickness in familial hypercholesterolemia in childhood. An Pediatr. 2009;70(4):349–353. doi:10.1016/j.anpedi.2008.11.017
23. Mitsnefes M, Flynn J, Cohn S, et al. CKD Examine Group masked hypertension associates with left ventricular hypertrophy in kids with CKD. J Am Soc Nephrol. 2010;21(1):137–144. doi:10.1681/ASN.2009060609
24. Frishberg Y, Feinstein S, Rinat C, et al. The guts of kids with steroid-resistant nephrotic syndrome: is all of it podocin? J Am Soc Nephrol. 2006;17(1):227–231. doi:10.1681/ASN.2005060653
25. Giuseppe S, Gaetano V, Gianpaolo R, et al. Excessive-density lipoprotein ldl cholesterol and left ventricular hypertrophy in important hypertension. J Hypertens. 2001;19(12):2265–2270. doi:10.1097/00004872-200112000-00021
26. Birjmohun RS, van Leuven SI, Ranges JHM, et al. Excessive-density lipoprotein attenuates irritation and coagulation response on endotoxin problem in people. Arterioscler Thromb Vasc Biol. 2007;27:1153–1158. doi:10.1161/ATVBAHA.106.136325
27. Vaziri ND, Liang Okay, Parks JS. Acquired lecithin-cholesterol acyltransferase deficiency in nephrotic syndrome. Am J Physiol R En Physiol. 2001;28:F823–F828. doi:10.1152/ajprenal.2001.280.5.F823