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Cited by 379Complement system in diseasesCoagulation, Bradykinin, Polyphosphates, and AngioedemaRenal Diseases and Glomerulopathies

The renaissance of complement therapeutics

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Ricklin, Daniel, Mastellos, Dimitrios C., Reis, Edimara S., Lambris, John D.·2018·Nature Reviews Nephrology
DOI 10.1038/nrneph.2017.156PMC PMC5805379
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Abstract

The increasing number of clinical conditions that involve a pathological contribution from the complement system - many of which affect the kidneys - has spurred a regained interest in therapeutic options to modulate this host defence pathway. Molecular insight, technological advances, and the first decade of clinical experience with the complement-specific drug eculizumab, have contributed to a growing confidence in therapeutic complement inhibition. More than 20 candidate drugs that target various stages of the complement cascade are currently being evaluated in clinical trials, and additional agents are in preclinical development. Such diversity is clearly needed in view of the complex and distinct involvement of complement in a wide range of clinical conditions, including rare kidney disorders, transplant rejection and haemodialysis-induced inflammation. The existing drugs cannot be applied to all complement-driven diseases, and each indication has to be assessed individually. Alongside considerations concerning optimal points of intervention and economic factors, patient stratification will become essential to identify the best complement-specific therapy for each individual patient. This Review provides an overview of the therapeutic concepts, targets and candidate drugs, summarizes insights from clinical trials, and reflects on existing challenges for the development of complement therapeutics for kidney diseases and beyond.

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Authors
Ricklin, D., Mastellos, D. C., Reis, E. S., & Lambris, J. D.
Affiliations
  • University of Basel (CH)
  • National Centre of Scientific Research "Demokritos" (GR)
  • University of Pennsylvania (US)
Corresponding author
  • Ricklin, Daniel
  • Lambris, John D.
ORCID
Venue
Nature Reviews Nephrology
Publisher
Springer Science and Business Media LLC
Published
2017-12-04
Volume
14
Issue
1
Pages
26-47
ISSN
  • 1745-8323 (ISSN-L)
  • 1759-5061
  • 1759-507X
DOI
10.1038/nrneph.2017.156
PMC
PMC5805379
OpenAlex
W2775288206
Cited by
379
References
145
Citations by year
2026: 14 · 2025: 22 · 2024: 25 · 2023: 36 · 2022: 37 · 2021: 73 · 2020: 68 · 2019: 63 · 2018: 41
FWCI
4.83
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Reviews Nephrology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (176104)
  • National Institutes of Health (n01ai30040-13-0-5)
  • National Institute of Allergy and Infectious Diseases (P01AI068730, N01 AI030040, R01AI030040)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
  • Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
  • Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
Keywords
complement therapeutics, complement system, complement inhibition, eculizumab, drug candidates, kidney disease, graft rejection, patient stratification, clinical trials
MeSH terms
Complement System Proteins, Complement Activation, Graft Rejection, Humans, Inflammation, Kidney Diseases, Complement Inactivating Agents, Drug Discovery, Molecular Targeted Therapy, Antibodies, Monoclonal, Humanized

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