Skip to main content

Advertisement

SpringerLink
Log in

Multimodal lipid-lowering treatment in pediatric patients with homozygous familial hypercholesterolemia—target attainment requires further increase of intensity

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

Abstract

Background

Familial hypercholesterolemia (FH) causes premature cardiovascular disease (CVD). Lipoprotein apheresis (LA) is recommended as first-line lipid-lowering treatment (LLT) for homozygous (ho) FH.

Methods

Efficacy of multimodal LLT including lifestyle counseling, drug treatment, and LA was analyzed in 17 pediatric hoFH or compound heterozygous (c-het) FH patients, who commenced chronic LA in Germany before the age of 18.

Results

At time of diagnosis, mean low-density lipoprotein cholesterol (LDL-C) concentration was 19.6 mmol/l (756 mg/dl). Multimodal LLT resulted in 73% reduction of mean LDL-C concentration including a 62% contribution of LA. Only three children (18%) achieved mean LDL-C concentrations below the recommended pediatric target of 3.5 mmol/l (135 mg/dl). In 13 patients (76%) during chronic LA, neither cardiovascular events occurred nor was CVD progression detected clinically or by routine imaging techniques. In four patients (24%), cardiovascular events documented progression of CVD despite weekly LA, including one death due to coronary and cerebrovascular CVD which was not stabilized after commencing LA. Based on the mutational status, only 6 out of the 17 children were candidates for proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibition. Two already responded with further LDL-C decrease by 40%.

Conclusions

Next to drug therapy, regular LA is an essential component of LLT for approaching LDL-C targets in children with hoFH or c-hetFH, which was successful only in a minority of children. Progression of CVD morbidity and resulting mortality remain unresolved issues. Early and intensified multimodal LLT guided by risk factors beyond LDL-C concentration is needed to improve outcome.

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.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, Wiklund O, Hegele RA, Raal FJ, Defesche JC, Wiegman A, Santos RD, Watts GF, Parhofer KG, Hovingh GK, Kovanen PT, Boileau C, Averna M, Borén J, Bruckert E, Catapano AL, Kuivenhoven JA, Pajukanta P, Ray K, Stalenhoef AF, Stroes E, Taskinen MR, Tybjærg-Hansen A, Panel EASC (2013) Familial hypercholesterolemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease. Eur Heart J 34:3478–3490

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Santos RD, Gidding SS, Hegele RA, Cuchel MA, Barter PJ, Watts GF, Baum SJ, Catapano AL, Chapman MJ, Defesche JC, Folco E, Freiberger T, Genest J, Hovingh GK, Harada-Shiba M, Humphries SE, Jackson AS, Mata P, Moriarty PM, Raal FJ, Al-Rasadi K, Ray KK, Reiner Z, Sijbrands EJ, Yamashita S, International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel (2016) Defining severe familial hypercholesterolaemia and the implications for clinical management: a consensus statement from the International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel. Lancet Diabetes-Endocrinol 4:850–861

    Article  PubMed  Google Scholar 

  3. Cuchel M, Bruckert E, Ginsberg HN, Raal FJ, Santos RD, Hegele RA, Kuivenhoven JA, Nordestgaard BG, Descamps OS, Steinhagen-Thiessen E, Tybjærg-Hansen A, Watts GF, Averna M, Boileau C, Borén J, Catapano AL, Defesche JC, Hovingh GK, Humphries SE, Kovanen PT, Masana L, Pajukanta P, Parhofer KG, Ray KK, Stalenhoef AF, Stroes E, Taskinen MR, Wiegman A, Wiklund O, Chapman MJ, European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia (2014) Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J 35:2146–2157

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Sjouke B, Meeike Kusters D, Kindt I, Besseling J, Defesche JC, Sijbrands EJ, Roeters van Lennep JE, Stalenhoef AF, Wiegman A, de Graaf J, Fouchier SW, Kastelein JJ, Hovingh GK (2015) Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: prevalence, genotype–phenotype relationship, and clinical outcome. Eur Heart J 36:560–565

    Article  PubMed  Google Scholar 

  5. Wiegman A, Gidding SS, Watts GF, Chapman MJ, Ginsberg HN, Cuchel M, Ose L, Averna M, Boileau C, Borén J, Bruckert E, Catapano AL, Defesche JC, Descamps OS, Hegele RA, Hovingh GK, Humphries SE, Kovanen PT, Kuivenhoven JA, Masana L, Nordestgaard BG, Pajukanta P, Parhofer KG, Raal FJ, Ray KK, Santos RD, Stalenhoef AF, Steinhagen-Thiessen E, Stroes ES, Taskinen MR, Tybjærg-Hansen A, Wiklund O, European Atherosclerosis Society Consensus Panel (2015) Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J 36:2425–2437

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Gautschi M, Pavlovic M, Nuoffer JM (2012) Fatal myocardial infarction at 4.5 years in a case of homozygous familial hypercholesterolaemia. JIMD Rep 2:45–50

    Article  PubMed  Google Scholar 

  7. Gidding SS, Champagne MA, de Ferranti SD, Defesche J, Ito MK, Knowles JW, McCrindle B, Raal F, Rader D, Santos RD, Lopes-Virella M, Watts GF, Wierzbicki AS, American Heart Association Atherosclerosis, Hypertension, and Obesity in Young Committee of Council on Cardiovascular Disease in Young, Council on Cardiovascular and Stroke Nursing, Council on Functional Genomics and Translational Biology, and Council on Lifestyle and Cardiometabolic Health (2015) The agenda for familial hypercholesterolemia. A scientific statement from the American Heart Association. Circulation 132:2167–2192

    Article  PubMed  Google Scholar 

  8. Nemati MH, Astaneh B, Joubeh A (2009) Triple coronary artery bypass graft in a 10-year-old child with familial hypercholesterolemia. Gen Thorac Cardiovasc Surg 57:94–97

    Article  PubMed  Google Scholar 

  9. Tissot C, da Cruz E, Aggoun Y (2007) Rescue left main coronary artery stenting for acute myocardial ischemia after coronary angiography in a 7-year-old girl with homozygous familial hypercholesterolemia. Catheter Cardiovasc Interv 69:243–247

    Article  PubMed  Google Scholar 

  10. Widhalm K, Binder CB, Kreissl A, Aldover-Macasaet E, Fritsch M, Kroisboeck S, Geiger H (2011) Sudden death in a 4-year-old boy: a near-complete occlusion of the coronary artery caused by an aggressive low-density lipoprotein receptor mutation (W556R) in homozygous familial hypercholesterolemia. J Pediatr 158:167

    Article  PubMed  Google Scholar 

  11. Thompson GR, Blom DJ, Marais AD, Seed M, Pilcher GJ, Raal FJ (2017) Survival in homozygous familial hypercholesterolemia is determined by the on-treatment level of serum cholesterol. Eur Heart J. https://doi.org/10.1093/eurheartj/ehx317

  12. Raal FJ, Pilcher GJ, Panz VR, van Deventer HE, Brice BC, Blom DJ, Marais AD (2011) Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy. Circulation 124:2202–2207

    Article  PubMed  CAS  Google Scholar 

  13. Khera AV, Emdin CA, Drake I, Natarajan P, Bick AG, Cook NR, Chasman DI, Baber U, Mehran R, Rader DJ, Fuster V, Boerwinkle E, Melander O, Orho-Melander M, Ridker PM, Kathiresan S (2016) Genetic risk, adherence to a healthy lifestyle, and coronary disease. N Engl J Med 375:2349–2358

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Thompson GR, Miller JP, Breslow JL (1985) Improved survival of patients with homozygous familial hypercholesterolaemia treated with plasma exchange. Brit Med J 291:1671–1673

    Article  CAS  Google Scholar 

  15. Chourdakis M, Buderus S, Dokoupil K, Oberhoffer R, Otfried Schwab KO, Wolf M, Zimmer KP, Koletzko B; for the German Society of Pediatrics (2015) S2k-guideline for diagnosis and treatment of dyslipidemias in children. Published online 2015 at www.awmf.org: AWMF-registry no 027-068 (document in German). http://www.awmf.org/leitlinien/detail/ll/027-068.html. Accessed 12 December 2017

  16. France M, Rees A, Datta D, Thompson G, Capps N, Ferns G, Ramaswami U, Seed M, Neely D, Cramb R, Shoulders C, Barbir M, Pottle A, Eatough R, Martin S, Bayly G, Simpson B, Halcox J, Edwards R, Main L, Payne J, Soran H, for HEART UK Medical Scientific and Research Committee (2016) HEART UK. Statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom. Atherosclerosis 255:128–139

    Article  PubMed  CAS  Google Scholar 

  17. Klaus G, Pape L, Schmitt CP (2010) SOP Kinderdialyse: LDL-Apherese; Arbeitskreis Kinderdialyse der Gesellschaft für Pädiatrische Nephrologie (GPN) (document in German)

  18. Kroon AA, van’t Hof MA, Demacker PN, Stalenhoef AF (2000) The rebound of lipoproteins after LDL-apheresis. Kinetics and estimation of mean lipoprotein levels. Atherosclerosis 152:519–526

    Article  PubMed  CAS  Google Scholar 

  19. Julius U, Metzler W, Pietzsch J, Faßbender T, Klingel R (2002) Intraindividual comparison of two extracorporeal LDL apheresis methods: Lipidfiltration and HELP. Int J Artif Organs 25:1180–1188

    Article  PubMed  CAS  Google Scholar 

  20. Heigl F, Hettich R, Lotz N, Reeg H, Pflederer T, Osterkorn D, Osterkorn K, Klingel R (2015) Efficacy, safety, and tolerability of long-term lipoprotein apheresis in patients with LDL- or Lp(a) hyperlipoproteinemia: findings gathered from more than 36,000 treatments at one center in Germany. Atheroscler Suppl 18:154–162

    Article  PubMed  Google Scholar 

  21. Leigh SEA, Foster AH, Whittall RA, Hubbart CS, Humphries SE (2008) Update and analysis of the university college London low density lipoprotein receptor familial hypercholesterolemia database. Ann Hum Genet 72:485–498 updated at http://www.ucl.ac.uk/ldlr/LOVDv.1.1.0/. Accessed 12 December 2017

    Article  PubMed  CAS  Google Scholar 

  22. Schaefer JR, Kurt B, Sattler A, Klaus G, Soufi M (2012) Pharmacogenetic aspects in familial hypercholesterolemia with the special focus on FHMarburg (FH p.W556R). Clin Res Cardiol Suppl 7:2–6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Schatz U, Illigens BMW, Siepmann T, Arneth B, Siegert G, Siegels D, Heigl F, Hettich R, Ramlow W, Prophet H, Bornstein SR, Julius U (2015) TIDILAP: Treatment of iron deficiency in lipoprotein apheresis patients. Atheroscler Suppl 18:199–208

    Article  PubMed  CAS  Google Scholar 

  24. Thompson GR, Barbir M, Davies D, Dobral P, Gesinde M, Livingston M, Mandry P, Marais AD, Matthews S, Neuwirth C, Pottle A, le Roux C, Scullard D, Tyler C, Watkins S (2010) Efficacy criteria and cholesterol targets for LDL apheresis. Atherosclerosis 208:317–321

    Article  PubMed  CAS  Google Scholar 

  25. Cholesterol Treatment Trialists Collaboration (CTT) (2015) Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174 000 participants in 27 randomised trials. Lancet 385:1397–1405

    Article  CAS  Google Scholar 

  26. Palcoux JB, Atassi-Dumont M, Lefevre P, Hequet O, Schlienger JL, Brignon P, Roussel B (2008) Low-density lipoprotein apheresis in children with familial hypercholesterolemia: follow-up to 21 years. Ther Apher Dial 12:195–201

    Article  PubMed  CAS  Google Scholar 

  27. Taylan C, Schlune A, Meissner T, Ažukaitis K, Udink Ten Cate FE, Weber LT (2016) Disease control via intensified lipoprotein apheresis in three siblings with familial hypercholesterolemia. J Clin Lipidol 10:1303–1310

    Article  PubMed  Google Scholar 

  28. Raal FJ, Sjouke B, Hovingh GK, Isaac BF (2016) Phenotype diversity among patients with homozygous familial hypercholesterolemia: a cohort study. Atherosclerosis 248:238–244

    Article  PubMed  CAS  Google Scholar 

  29. Fernández-Friera L, Penalvo JL, Fernandez-Ortiz A, Ibañez B, López-Melgar B, Laclaustra M, Oliva B, Mocoroa A, Mendiguren J, Martínez de Vega V, García L, Molina J, Sánchez-González J, Guzmán G, Alonso-Farto JC, Guallar E, Civeira F, Sillesen H, Pocock S, Ordovás JM, Sanz G, Jiménez-Borreguero LJ, Fuster V (2015) Prevalence, vascular distribution, and multiterritorial extent of subclinical atherosclerosis in a middle-aged cohort. The PESA (Progression of Early Subclinical Atherosclerosis) Study. Circulation 131:2104–2113

    Article  PubMed  Google Scholar 

  30. Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, Hoes AW, Jennings CS, Landmesser U, Pedersen TR, Reiner Ž, Riccardi G, Taskinen MR, Tokgozoglu L, Verschuren WM, Vlachopoulos C, Wood DA, Zamorano JL, Task Force Members (2016) 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J 37:2999–3058

    Article  PubMed  Google Scholar 

  31. Nordestgaard BG, Langsted A (2016) Lipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology. J Lipid Res 57:1953–1975

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Roeseler E, Julius U, Heigl F, Spitthoever R, Heutling D, Breitenberger P, Leebmann J, Lehmacher W, Kamstrup PR, Nordestgaard BG, Maerz W, Noureen A, Schmidt K, Kronenberg F, Heibges A, Klingel R, Pro(a)LiFe-Study Group (2016) Lipoprotein apheresis for lipoprotein(a)-associated cardiovascular disease: prospective 5 years of follow-up and apolipoprotein(a) characterization. Arterioscler Thromb Vasc Biol 36:2019–2027

    Article  PubMed  CAS  Google Scholar 

  33. Pérez de Isla L, Alonso R, Mata N, Fernández-Pérez C, Muñiz O, Díaz-Díaz JL, Saltijeral A, Fuentes-Jiménez F, de Andrés R, Zambón D, Piedecausa M, Cepeda JM, Mauri M, Galiana J, Brea Á, Sanchez Muñoz-Torrero JF, Padró T, Argueso R, Miramontes-González JP, Badimón L, Santos RD, Watts GF, Mata P (2017) Predicting cardiovascular events in familial hypercholesterolemia. The SAFEHEART registry. Circulation 135:2133–2144

    Article  PubMed  Google Scholar 

  34. Zschocke J, Schaefer JR (2003) Homozygous familial hypercholesterolemia in identical twins. Lancet 361:1641

    Article  PubMed  CAS  Google Scholar 

  35. Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, Stroes ES, Langslet G, Raal FJ, El Shahawy M, Koren MJ, Lepor NE, Lorenzato C, Pordy R, Chaudhari U, Kastelein JJ, ODYSSEY LONG TERM Investigators (2015) Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 16:1489–1499

    Article  CAS  Google Scholar 

  36. Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, Ballantyne CM, Somaratne R, Legg J, Wasserman SM, Scott R, Koren MJ, Stein EA, Open-Label Study of Long-Term Evaluation against LDL Cholesterol (OSLER) Investigators (2015) Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 372:1500–1509

    Article  PubMed  CAS  Google Scholar 

  37. Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR, FOURIER Steering Committee and Investigators (2017) Evolocumab and clinical outcomes in patients with cardiovascular disease. New Engl J Med 376:1713–1722

    Article  PubMed  CAS  Google Scholar 

  38. Raal FR, Honarpour N, Blom DJ, Hovingh GK, Xu F, Scott R, Wasserman SM, Stein EA, TESLA Investigators (2015) Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet 385:341–350

    Article  PubMed  CAS  Google Scholar 

  39. Raal FJ, Hovingh GK, Blom D, Santos RD, Harada-Shiba M, Bruckert E, Couture P, Soran H, Watts GF, Kurtz C, Honarpour N, Tang L, Kasichayanula S, Wasserman SM, Stein EA (2017) Long-term treatment with evolocumab added to conventional drug therapy, with or without apheresis, in patients with homozygous familial hypercholesterolaemia: an interim subset analysis of the open-label TAUSSIG study. Lancet Diab Endocrinol 5:280–290

    Article  CAS  Google Scholar 

  40. Stefanutti C, Morozzi C, Di Giacomo S, Sovrano B2, Mesce D2, Grossi A (2016) Management of homozygous familial hypercholesterolemia in real-world clinical practice: a report of 7 Italian patients treated in Rome with lomitapide and lipoprotein apheresis. J Clin Lipidol 10:782–789

    Article  PubMed  Google Scholar 

  41. Bruckert E, Kalmykova O, Bittar R, Carreau V, Béliard S, Saheb S, Rosenbaum D, Bonnefont-Rousselot D, Thomas D, Emery C, Khoshnood B, Carrié A (2017) Long-term outcome in 53 patients with homozygous familial hypercholesterolaemia in a single centre in France. Atherosclerosis 257:130–137

    Article  PubMed  CAS  Google Scholar 

  42. Hudgins LC, Kleinman B, Scheuer A, White S, Gordon BR (2008) Long-term safety and efficacy of low-density lipoprotein apheresis in childhood for homozygous familial hypercholesterolemia. Am J Cardiol 102:1199–1204

    Article  PubMed  CAS  Google Scholar 

  43. Makino H, Harada-Shiba M (2003) Long-term effect of low-density lipoprotein apheresis in patients with homozygous familial hypercholesterolemia. Ther Apher Dial 7:397–401

    Article  PubMed  CAS  Google Scholar 

  44. Graesdal A, Bogsrud MP, Holven KB, Nenseter MS, Narverud I, Langslet G, Brekke M, Retterstøl K, Arnesen KE, Ose L (2012) Apheresis in homozygous familial hypercholesterolemia: the results of a follow-up of all Norwegian patients. J Clin Lipidol 6:331–339

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Supported by German Society for Pediatric Nephrology (GPN)

Funding

Funding of this study was part of an unrestricted research grant from Diamed, Cologne, Germany, to Apheresis Research Institute, covering costs of ethics votes and personal costs. No other costs were accounted for this study project.

Author information

Authors and Affiliations

  1. Renal Unit, KfH Pediatric Kidney Centre, and Centre for Undiagnosed and Rare Diseases, Marburg, Germany

    Günter Klaus & Juergen R. Schaefer

  2. Pediatric Nephrology, Children’s and Adolescents’ Hospital, University Hospital of Cologne, Cologne, Germany

    Christina Taylan & Lutz T. Weber

  3. Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Essen University Hospital, Essen, Germany

    Rainer Büscher

  4. Pediatric Nephrology, University Hospital for Pediatric and Adolescent Medicine, Heidelberg, Germany

    Claus Peter Schmitt

  5. Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine and Dermatology, Hannover Medical School, Hannover, Germany

    Lars Pape

  6. Center for Obstetrics and Pediatrics, Department of Pediatrics, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany

    Jun Oh & Joenna Driemeyer

  7. Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Erlangen University Hospital, Erlangen, Germany

    Matthias Galiano

  8. Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Münster University Hospital, Münster, Germany

    Jens König

  9. Center for Nephrology and Dialysis, Saarlouis, Germany

    Carsten Schürfeld

  10. Dialysis and Lipid Center North Rhine, Essen, Germany

    Ralf Spitthöver

  11. Apheresis Research Institute, Stadtwaldguertel 77, 50935, Cologne, Germany

    Andreas Heibges & Reinhard Klingel

Authors
  1. Günter Klaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christina Taylan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rainer Büscher
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claus Peter Schmitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lars Pape
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Joenna Driemeyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Matthias Galiano
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jens König
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Carsten Schürfeld
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ralf Spitthöver
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Juergen R. Schaefer
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Lutz T. Weber
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Andreas Heibges
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Reinhard Klingel
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Günter Klaus, Reinhard Klingel, and Andreas Heibges were mainly involved in analyzing the data and writing the manuscript. All clinical investigators gathered, documented, and summarized data from patients at their respective clinical sites and contributed equally to preparing the manuscript.

Corresponding author

Correspondence to Reinhard Klingel.

Ethics declarations

Ethical approval for the study had been obtained for every study site. All parents or legal guardians of the participating children and adolescents gave their written informed consent.

Conflict of interest statement

AH and RK are employees of Apheresis Research Institute, which received research grants from Diamed, Cologne Germany, and Asahi Kasei Medical, Tokyo Japan. JRS is funded by the Reinfried Pohl foundation and has served as medical adviser for MSD Germany, AMGEN, and Sanofi-Genzyme. In addition, he has received lecture fees by MSD, Sanofi-Genzyme, Synlab Academie, Novartis, and Berlin Chemie. For all other authors, no conflict of interest is declared.

Electronic supplementary material

ESM 1

(DOCX 28 kb)

ESM 2

(DOCX 17 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Klaus, G., Taylan, C., Büscher, R. et al. Multimodal lipid-lowering treatment in pediatric patients with homozygous familial hypercholesterolemia—target attainment requires further increase of intensity. Pediatr Nephrol 33, 1199–1208 (2018). https://doi.org/10.1007/s00467-018-3906-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-018-3906-6

Keywords

Search

Navigation