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Pediatric Nephrology

, Volume 33, Issue 7, pp 1199–1208 | Cite as

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

  • Günter Klaus
  • Christina Taylan
  • Rainer Büscher
  • Claus Peter Schmitt
  • Lars Pape
  • Jun Oh
  • Joenna Driemeyer
  • Matthias Galiano
  • Jens König
  • Carsten Schürfeld
  • Ralf Spitthöver
  • Juergen R. Schaefer
  • Lutz T. Weber
  • Andreas Heibges
  • Reinhard KlingelEmail author
Original Article

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.

Keywords

Children Familial hypercholesterolemia LDL-cholesterol Lipoprotein apheresis prevention Treatment 

Notes

Acknowledgements

Supported by German Society for Pediatric Nephrology (GPN)

Authors’ 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.

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.

Compliance with ethical standards

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.

Supplementary material

467_2018_3906_MOESM1_ESM.docx (28 kb)
ESM 1 (DOCX 28 kb)
467_2018_3906_MOESM2_ESM.docx (18 kb)
ESM 2 (DOCX 17 kb)

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Copyright information

© IPNA 2018

Authors and Affiliations

  • Günter Klaus
    • 1
  • Christina Taylan
    • 2
  • Rainer Büscher
    • 3
  • Claus Peter Schmitt
    • 4
  • Lars Pape
    • 5
  • Jun Oh
    • 6
  • Joenna Driemeyer
    • 6
  • Matthias Galiano
    • 7
  • Jens König
    • 8
  • Carsten Schürfeld
    • 9
  • Ralf Spitthöver
    • 10
  • Juergen R. Schaefer
    • 1
  • Lutz T. Weber
    • 2
  • Andreas Heibges
    • 11
  • Reinhard Klingel
    • 11
    Email author
  1. 1.Renal UnitKfH Pediatric Kidney Centre, and Centre for Undiagnosed and Rare DiseasesMarburgGermany
  2. 2.Pediatric Nephrology, Children’s and Adolescents’ HospitalUniversity Hospital of CologneCologneGermany
  3. 3.Pediatric Nephrology, Center for Pediatrics and Adolescent MedicineEssen University HospitalEssenGermany
  4. 4.Pediatric NephrologyUniversity Hospital for Pediatric and Adolescent MedicineHeidelbergGermany
  5. 5.Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine and DermatologyHannover Medical SchoolHannoverGermany
  6. 6.Center for Obstetrics and Pediatrics, Department of PediatricsUniversity Medical Center Hamburg-Eppendorf (UKE)HamburgGermany
  7. 7.Pediatric Nephrology, Center for Pediatrics and Adolescent MedicineErlangen University HospitalErlangenGermany
  8. 8.Pediatric Nephrology, Center for Pediatrics and Adolescent MedicineMünster University HospitalMünsterGermany
  9. 9.Center for Nephrology and DialysisSaarlouisGermany
  10. 10.Dialysis and Lipid Center North RhineEssenGermany
  11. 11.Apheresis Research InstituteCologneGermany

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