Patients with hypertension-associated thrombotic microangiopathy may present with complement abnormalities

Sjoerd A. M. E. G. Timmermans, Myrurgia A. Abdul-Hamid, Joris Vanderlocht, Jan G. M. C. Damoiseaux, Chris P. Reutelingsperger, Pieter van Paassen*, Limburg Renal Registry

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Thrombotic microangiopathy (TMA) is a pattern of endothelial damage that can be found in association with diverse clinical conditions such as malignant hypertension. Although the pathophysiological mechanisms differ, accumulating evidence links complement dysregulation to various TMA syndromes and in particular the atypical hemolytic uremic syndrome. Here, we evaluated the role of complement in nine consecutive patients with biopsy-proven renal TMA attributed to severe hypertension. Profound hematologic symptoms of TMA were uncommon. In six Out of nine patients, we found mutations C3 in three, CFI in one, CD46 in one, and/or CFH in two patients either with or without the risk CFH-H3 haplotype in four patients. Elevated levels of the soluble C5b-9 and renal deposits of C3c and C5b-9 along the vasculature and/or glomerular capillary wall, confirmed complement activation in vivo. In contrast to patients without genetic defects, patients with complement defects invariably progressed to end-stage renal disease, and disease recurrence after kidney transplantation seems common. Thus, a subset of patients with hypertension-associated TMA falls within the spectrum of complement-mediated TMA, the prognosis of which is poor. Hence, testing for genetic complement abnormalities is warranted in patients with severe hypertension and TMA on renal biopsy to adopt suitable treatment options and prophylactic measures.

Original languageEnglish
Pages (from-to)1420-1425
Number of pages6
JournalKidney International
Volume91
Issue number6
DOIs
Publication statusPublished - Jun 2017

Keywords

  • atypical hemolytic uremic syndrome
  • complement dysregulation
  • genetics
  • malignant hypertension
  • thrombotic microangiopathy
  • HEMOLYTIC-UREMIC SYNDROME
  • FACTOR-H
  • RENAL-TRANSPLANTATION
  • INHIBITOR ECULIZUMAB
  • CLINICAL PHENOTYPE
  • GENE-MUTATIONS
  • C3 MUTATION
  • AHUS
  • ACTIVATION
  • RECURRENCE

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