Skip to main content

Advertisement

SpringerLink
Log in

Augmentation index, a predictor of cardiovascular events, is increased in children and adolescents with primary nephrotic syndrome

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

Arterial stiffness is associated with an increased risk of cardiovascular diseases. Augmentation index (AIx@75), a measure of arterial stiffness and wave reflection, has not been evaluated in patients with primary nephrotic syndrome (PNS). We investigated whether central and peripheral vascular profiles, hemodynamic parameters, and biochemical tests are associated with AIx@75 in PNS patients.

Methods

This observational study involved 38 children and adolescents with PNS (12.14 ± 3.65 years) and 37 healthy controls (13.28 ± 2.80 years). Arterial stiffness and vascular and hemodynamic parameters were measured noninvasively using the Mobil-O-Graph® (IEM, Stolberg, Germany). In the PNS group, biochemical tests and corticosteroid dosage/treatment time were analyzed.

Results

Peripheral and central systolic blood pressure (SBPp, SBPc) Z-scores were significantly higher in the PNS patients. AIx@75 was significantly higher in the PNS patients (25.14 ± 9.93%) than in controls (20.84 ± 7.18%). In the control group, AIx@75 negatively correlated with weight (r = − 0.369; p = 0.025), height (r = − 0.370; p = 0.024), and systolic volume/body surface (r = − 0.448; p = 0.006). In the PNS group, a univariate linear correlation showed that AIx@75 negatively correlated with weight (r = − 0.360; p = 0.027), height (r = 0.381; p = 0.18), and systolic volume/body surface (r = − 0.447; p < 0.002) and positively with the Z-score of SBPp (r = 0.407; p = 0.011), peripheral diastolic blood pressure (DBPp, r = 0.452; p = 0.004), SBPc (r = 0.416; p = 0.009), DBPc (r = 0.407; p = 0.011), triglycerides (r = 0.525; p = 0.001), and cholesterol [total (r = 0.539; p < 0.001), LDLc (r = 0.420; p = 0.010), and non-HDLc (r = 0.511; p = 0.001)].

Conclusions

Early abnormalities of AIx@75 and vascular parameters suggest that patients with PNS, even in stable condition, present subclinical indicators for the development of cardiovascular disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

AIx:

augmentation index

AIx@75:

AIx normalized to heart rate of 75 bpm

AP:

augmentation pressure

ACEI:

angiotensin-converting enzyme inhibitors

ARB:

angiotensin receptor blockers

BF:

body fat

BMI:

body mass index

CKD:

chronic kidney disease

CVD:

cardiovascular disease

DBPc:

central diastolic blood pressure

DBPp:

peripheral diastolic blood pressure

GFR:

glomerular filtration rate

HDLc:

High -density lipoprotein cholesterol

HR:

heart rate

LDLc:

low-density lipoprotein cholesterol

MAP:

mean arterial pressure

Non-HDLc:

non-high-density lipoprotein cholesterol

PedsQL™:

Pediatric Quality of Life Inventory

PNS:

primary or idiopathic nephrotic syndrome

PPc:

central pulse pressure

PPp:

peripheral pulse pressure

PTN4h:

24-h proteinuria

PWV:

pulse wave velocity

SBPc:

central systolic blood pressure

SBPp:

peripheral systolic blood pressure

TVR:

total vascular resistance

References

  1. Niaudet P, Boyer O (2016) Idiopathic nephrotic syndrome in children; clinical aspects. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N (eds) Pediatric nephrology. 7th ed. Springer-Verlag, Berlin Heidelberg, pp 839–882

    Chapter  Google Scholar 

  2. Gadegbeku CA, Gipson DS, Holzman L, Ojo AO, Song PX, Barisoni L, Sampson MG, Kopp JB, Lemley KV, Nelson PJ, Lienczewski CC, Adler SG, Appel GB, Cattran DC, Choi MJ, Contreras G, Dell KM, Fervenza FC, Gibson KL, Greenbaum LA, Hernandez JD, Hewitt SM, Hingorani SR, Hladunewich M, Hogan MC, Hogan SL, Kaskel FJ, Lieske JC, Meyers KE, Nachman PH, Nast CC, Neu AM, Reich HN, Sedor JR, Sethna CB, Trachtman H, Tuttle KR, Zhdanova O, Zilleruelo GE, Kretzler M (2013) Design of the Nephrotic Syndrome Study Network (NEPTUNE) to evaluate primary glomerular nephropathy by a multi-disciplinary approach. Kidney Int 83:749–756

    Article  PubMed  PubMed Central  Google Scholar 

  3. Vidianty J, Pardede SO, Hendarto A, Akib AAP (2010) Obesity in children with frequent relapse and steroid dependent nephrotic syndrome. PaediatricaIndonesiana 50:139–143

    Google Scholar 

  4. Hooman N, Isa TR, Otukesh H, Mostafavi S, Hallaji F (2013) Carotid artery function in children with idiopathic nephrotic syndrome. Nefrologia 33:650–656

    PubMed  Google Scholar 

  5. Eneman B, Levtchenko E, Van den Heuvel B, Van Geet C, Freson K (2016) Platelet abnormalities in nephritic syndrome. Pediatr Nephrol 31:1267–1279

    Article  PubMed  Google Scholar 

  6. Tkaczyk M, Czupryniak A, Owczarek D, Lukamowicz J, Nowicki M (2008) Markers of endothelial dysfunction in children with idiopathic nephrotic syndrome. Am J Nephrol 28:197–202

    Article  CAS  PubMed  Google Scholar 

  7. Rahul I, Krishnamurthy S, Satheesh S, Biswal N, Bobby Z, Lakshminarayanan S (2015) Brachial artery flow-mediated dilatation and carotid intima medial thickness in pediatric nephrotic syndrome: a cross-sectional case-control study. Clin Exp Nephrol 19:125–132

    Article  CAS  PubMed  Google Scholar 

  8. Candan C, Canpolat N, Gökalp S, Yıldız N, Turhan P, Taşdemir M, Sever L, Çalışkan S (2014) Subclinical cardiovascular disease and its association with risk factors in children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 29:95–102

    Article  PubMed  Google Scholar 

  9. Savant JD, Furth SL, Meyers KEC (2014) Arterial stiffness in children: pediatric measurement and considerations. Pulse 2:69–80

    Article  PubMed  Google Scholar 

  10. Avolio AP, Van Bortel LM, Boutouyrie P, Cockcroft JR, McEniery CM, Protogerou AD, Roman MJ, Safar ME, Segers P, Smulyan H (2009) Role of pulse pressure amplification in arterial hypertension: experts’ opinion and review of the data. Hypertension 54:375–383

    Article  CAS  PubMed  Google Scholar 

  11. Blaim MR, Skrzypczyk P, Wawer Z (2013) Pulse wave analysis in children with glomerulopathies. J Nephrol Ther 3:134

    Google Scholar 

  12. Mohamed SM, Elmazary A, Taha HT (2013) Ankle brachial index in children with steroid-resistant nephrotic syndrome. Sultan Qaboos Univ Med J 13:88–92

    Article  PubMed  PubMed Central  Google Scholar 

  13. Covic A, Mardare N, Gusbeth-Tatomir P, Brumaru O, Gavrilovici C, Munteanu M, Prisada O, Goldsmith DJ (2006) Increased arterial stiffness in children on haemodialysis. Nephrol Dial Transplant 21:729–735

    Article  PubMed  Google Scholar 

  14. Briese S, Claus M, Querfeld U (2008) Arterial stiffness in children after renal transplantation. Pediatr Nephrol 23:2241–2245

    Article  PubMed  Google Scholar 

  15. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis (2012) Kidney Int Suppl 1:139–274

    Google Scholar 

  16. Mendonça ACQ, Oliveira EA, Fróes BP, Faria LD, Pinto JS, Nogueira MM, Lima GO, Resende PI, Assis NS, Simões E, Silva AC, Pinheiro SV (2015) A predictive model of progressive chronic kidney disease in idiopathic nephrotic syndrome. Pediatr Nephrol 30:2011–2020

    Article  PubMed  Google Scholar 

  17. Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kavey RW, Simons-Morton DG, de Jesus JM, Editors S (2011) Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics 128(Suppl 5):S213–S256

    Google Scholar 

  19. Fryar CD, Gu Q, Ogden CL, Flegal KM (2016) Anthropomeric reference data for children and adults: United States, 2011–2014. National Center for Health Statistics. Vital Health Stat 23:1–46

    Google Scholar 

  20. García-Ortiz L, Recio-Rodríguez JI, Mora-Simón S, Guillaumet J, Martí A-CC, Rodriguez-Sanchez E, Maderuelo-Fernandez JA, Ramos-Blanes R, Gómez-Marcos MA, MARK Group (2016) Vascular structure and function and their relationship with health-related quality of life in the MARK study. BMC Cardiovasc Disord 16:95

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Klatchoian DA, Len CA, Terreri MTRA, Silva M, Itamoto C, Ciconelli RM, Varni JW, Hilário MO (2008) Quality of life of children and adolescents from São Paulo: reliability and validity of the Brazilian version of the Pediatric Quality of Life Inventory version 4.0 generic core scales. J Pediatr 84:308–315

    Article  Google Scholar 

  22. Puolakka E, Pahkala K, Laitinen TT, Magnussen CG, Hutri-Kähönen N, Kähönen M, Lehtimäki T, Tossavainen P, Jokinen E, Sabin MA, Laitinen T, Elovainio M, Pulkki-Råback L, Viikari JSA, Raitakari OT, Juonala M (2017) Childhood socioeconomic status and arterial stiffness in adulthood: the Cardiovascular Risk in Young Finns Study. Hypertension 70:729–735

    Article  CAS  PubMed  Google Scholar 

  23. Associação Brasileira de Empresas de Pesquisa–ABEP (2014) São Paulo: Brasileira de Empresas e Pesquisas, 2014. http://www.abep.org/Servicos/Download.aspx?id=09. Accessed 07.25.2015

  24. Pini R, Cavallini MC, Palmieri V, Marchionni N, Di Bari M, Devereux RB, Masotti G, Roman MJ (2008) Central but not brachial blood pressure predicts cardiovascular events in an unselected geriatric population. J Am Coll Cardiol 51:2432–2439

    Article  PubMed  Google Scholar 

  25. Maas RJ, Deegens JK, Beukhof JR, Reichert LJ, TenDam MA, Beutler JJ, van den Wall Bake AWL, Rensma PL, Konings CJ, Geerse DA, Feith GW, Van Kuijk WH, Wetzels JF (2017) The clinical course of minimal change nephrotic syndrome with onset in adulthoodor late adolescence: a case series. Am J Kidney Dis 69:637–646

    Article  PubMed  Google Scholar 

  26. Deshmukh CT (2007) Minimizing side effects of systemic corticosteroids in children. Indian J Dermatol Venereol Leprol 73:218–221

    Article  CAS  PubMed  Google Scholar 

  27. Liu D, Ahmet A, Ward L, Krishnamoorthy P, Mandelcorn ED, Leigh R, Brown JP, Cohen A, Kim H (2013) A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol 9:30

    Article  PubMed  PubMed Central  Google Scholar 

  28. Par SJ, Il Shin J (2011) Complications of nephrotic syndrome. Korean J Pediatr 54:322–328

    Article  CAS  Google Scholar 

  29. Sakuragi S, Abhayaratna K, Gravenmaker KJ, O'Reilly C, Srikusalanukul W, Budge MM, Telford RD, Abhayaratna WP (2009) Influence of adiposity and physical activity on arterial stiffness in healthy children the lifestyle of our kids study. Hypertension 53:611–616

    Article  CAS  PubMed  Google Scholar 

  30. Hudson L, Kinra S, Wong I, Cole TJ, Deanfield J, Viner R (2017) Is arterial stiffening associated with adiposity, severity of obesity and other contemporary cardiometabolic markers in a community sample of adolescents with obesity in the UK? BMJ Paediatr Open 1:e000061

    Article  PubMed  PubMed Central  Google Scholar 

  31. Cote AT, Phillips AA, Harris KC, Sandor GGS, Panagiotopoulos C, Devlin AM (2015) Obesity and arterial stiffness in children systematic review and meta-analysis. Arterioscler Thromb Vasc Biol 35:1038–1044

    Article  CAS  PubMed  Google Scholar 

  32. Juonala M, Jarvisalo MJ, Maki-Torkko N, Kahonen M, Viikari JS, Raitakari OT (2005) Risk factors identified in childhood and decreased carotid artery elasticity in adulthood: the Cardiovascular Risk in Young Finns Study. Circulation 112:1486–1493

    Article  PubMed  Google Scholar 

  33. Nakamura A, Niimi R, Kurosaki K, Yanagawa Y (2010) Factors influencing cardiovascular risk following termination of glucocorticoid therapy for nephrotic syndrome. Clin Exp Nephrol 14:457–462

    Article  PubMed  Google Scholar 

  34. Hidvégi EV, Illyés M, Molnár FT, Cziráki A (2015) Influence of body height on aortic systolic pressure augmentation and wave reflection in childhood. J Hum Hypertens 29:495–401

    Article  PubMed  Google Scholar 

  35. Kniazewska MH, Obuchowicz AK, Wielkoszyński T, Zmudzińska-Kitczak J, Urban K, Marek M, Witanowska J, Sieroń-Stołtny K (2009) Atherosclerosis risk factors in young patients formerly treated for idiopathic nephrotic syndrome. Pediatr Nephrol 24:549–554

    Article  PubMed  Google Scholar 

  36. Dnyanesh S, Shenoy V (2014) A study of serum lipids in nephrotic syndrome in children. IOSR Journal of Dental and Medical Sciences 13:1–6

    Google Scholar 

  37. Riggio S, Mandraffino G, Sardo MA, Iudicello R, Camarda N, Imbalzano E, Alibrandi A, Saitta C, Carerj S, Arrigo T, Saitta A (2010) Pulse wave velocity and augmentation index, but not intima media thickness, are early indicators of vascular damage in hypercholesterolemic children. Eur J Clin Investig 40:250–257

    Article  CAS  Google Scholar 

  38. Ruggenenti P, Remuzzi G (2006) Time to abandon microalbuminuria? Kidney Int 70:1214–1222

    Article  CAS  PubMed  Google Scholar 

  39. Eriksen BO, Lochen M-L, Arntzen KA, Bertelsen G, Eilertsen B-AW, von Hanno T, Herder M, Jenssen TG, Mathisen UD, Melsom T, Njølstad I, Solbu MD, Toft I, Mathiesen EB (2014) Subclinical cardiovascular disease is associated with a high glomerular filtration rate in the nondiabetic general population. Kidney Int 86:146–153

    Article  CAS  PubMed  Google Scholar 

  40. Duyuler S, Bayir PT, Guray U, Yildiz A, Korkmaz A, Atilgan KG (2016) Association between central aortic pulsatility and glomerular filtration rate in patients with coronary artery disease. Anatol J Cardiol 16:784–790

    CAS  PubMed  Google Scholar 

  41. McGaughey TJ, Fletcher EA, Shah SA (2016) Impact of antihypertensive agents on central systolic blood pressure and augmentation index: a meta-analysis. Am J Hypertens 29:448–457

    Article  CAS  PubMed  Google Scholar 

  42. Cadnapaphornchai MA, Tkachenko O, Shchekochikhin D, Schrier RW (2014) The nephrotic syndrome: pathogenesis and treatment of edema formation and secondary complications. Pediatr Nephrol 29:1159–1167

    Article  PubMed  Google Scholar 

  43. Weiss W, Gohlisch C, Harsch-Gladisch C, Tölle M, Zidek W, van der Giet M (2012) Oscillometric estimation of central blood pressure: validation of the Mobil-O-Graph in comparison with the Sphygmo-Cor device. Blood Press Monit 17:128–131

    Article  PubMed  Google Scholar 

  44. Zocalo Y, Castro JM, Garcia-Espinosa V, Curcio S, Chiesa P, Giachetto G, Cabrera-Fischer EI, Bia D (2018) Forward and backward aortic components and reflection indexes in children and adolescents: determinants and role in high pressure states. Curr Hypertens Rev 14:137–153

    PubMed  Google Scholar 

  45. Elmenhorst J, Hulpke-Wette M, Barta C, Dalla Pozza R, Springer S, Oberhoffer R (2015) Percentiles for central blood pressure and pulse wave velocity in children and adolescents recorded with an oscillometric device. Atherosclerosis 238:9–16

    Article  CAS  PubMed  Google Scholar 

  46. Keenswijk W, Ilias MI, Raes A, Donckerwolcke R, Walle JV (2018) Urinary potassium to urinary potassium plus sodium ratio can accurately identify hypovolemia in nephrotic syndrome: a provisional study. Eur J Pediatr 177:79–84

    Article  CAS  PubMed  Google Scholar 

  47. Kastl JT (2017) Renal function in the fetus and neonate e the creatinine enigma. Semin Fetal Neonatal Med 22:83–89

    Article  PubMed  Google Scholar 

  48. Coresh J, Hu JR, Bello AK, Feldman HI, Fogo AB, Ganji MR, Harris DC, Levey AS, Okpechi IG, Stengel B, Thomas B, Wiecek A, Gansevoort RT (2017) Endogenous markers for kidney function in children: a review. Kidney Int Suppl 7:63–70

    Article  Google Scholar 

  49. Selistre L, Rabilloud M, Cochat P, de Souza V, Iwaz J, Lemoine S, Beyerle F, Poli-de-Figueiredo CE, Dubourg L (2016) Comparison of the Schwartz and CKD-EPI equations for estimating glomerular filtration rate in children, adolescents, and adults: a retrospective cross-sectional study. PLoS Med 13:e1001979

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by the Fundação Educacional Lucas Machado (Feluma), Faculdade Ciências Médicas - Minas Gerais (FCM-MG), Pós-Graduação em Ciências da Saúde e Fundação de Amparo à Pesquisa do Estado de Minas Gerais (Fapemig). José Felippe Pinho and Giselle Santos Magalhães received support from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes). We are grateful to Isabel Cristina Gomes for assistance with statistical analysis.

Funding Source

There were no external funding sources for this study.

Author information

Authors and Affiliations

  1. Medical Sciences Faculty of Minas Gerais, Post-Graduation Program in Health Sciences, Belo Horizonte, MG, Brazil

    Cláudia Alves, José Felippe Pinho, Luzia Maria dos Santos, Giselle Magalhães & Maria Glória Rodrigues-Machado

  2. Department of Pediatrics, Pediatric Nephrourology Unit, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil

    Fernanda Luiza Fontes & Sérgio Pinheiro

  3. Mental Health Department, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil

    Sordaini Maria Caligiorne

  4. University Hospital of Medical Sciences, Belo Horizonte, MG, Brazil

    Cláudia Alves & Júnia Maria da Silva

Authors
  1. Cláudia Alves
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. José Felippe Pinho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luzia Maria dos Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Giselle Magalhães
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Júnia Maria da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fernanda Luiza Fontes
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sordaini Maria Caligiorne
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sérgio Pinheiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Maria Glória Rodrigues-Machado
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Cláudia Marotta Neves Alves conceived the study, performed all collection of data, carried out the initial analyses, interpreted the data, drafted the initial manuscript, and reviewed the manuscript.

José Felippe Pinho contributed to the collection of data, carried out the initial analyses, drafted the initial manuscript, and reviewed the manuscript.

Luzia Maria dos Santos contributed to selection of the control group and the collection of data, and reviewed the manuscript.

Giselle Santos Magalhães contributed to selection of the control group and the collection of data, edited, and reviewed the manuscript.

Júnia Maria da Silva, Fernanda Luiza Dias Fontes and Sordaini Maria Caligiorne contributed to the collection of data from medical records and retroactive quantification of corticosteroids and reviewed the manuscript.

Sérgio Veloso Brant Pinheiro selected all PNS patients, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content.

Maria Glória Rodrigues-Machado conceived and designed the study, coordinated and supervised data collection, analyzed and interpreted the data, drafted, edited and critically reviewed the manuscript for important intellectual content.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the research.

Corresponding author

Correspondence to Maria Glória Rodrigues-Machado.

Ethics declarations

Financial Disclosure

The authors have no financial relationships relevant to this article to disclose.

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ethics and Research Committee of the Faculdade Ciências Médicas-Minas Gerais (FCM-MG, CAAE 47152815.7.00005134) and the Ethics and Research Committee of the UFMG (CAAE 47152815.7.3001.5149) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alves, C., Pinho, J.F., dos Santos, L.M. et al. Augmentation index, a predictor of cardiovascular events, is increased in children and adolescents with primary nephrotic syndrome. Pediatr Nephrol 35, 815–827 (2020). https://doi.org/10.1007/s00467-019-04434-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-019-04434-0

Keywords

Search

Navigation