Association of vascular endothelial growth factor and renal thrombotic microangiopathy-like lesions in patients with Castleman's disease

Nephrology (Carlton). 2020 Feb;25(2):125-134. doi: 10.1111/nep.13630. Epub 2019 Aug 5.

Abstract

Aim: Renal thrombotic microangiopathy (TMA) is a common pathological manifestation of Castleman's disease (CD)-associated renal lesions. Increased level of plasma vascular endothelial growth factor (VEGF) has been shown in single-case reports. We aimed to investigate the dysregulation of VEGF in the pathogenesis of CD-associated TMA-like lesions (CD-TMA) in a larger cohort.

Methods: Nineteen patients with clinico-pathologically diagnosed CD with renal involvement were enrolled. Ten patients with pregnancy TMA or TMA of unknown reasons were enrolled as TMA control group. The plasma levels of VEGF, soluble Flt-1 and interleukin-6 (IL-6) were detected using enzyme-linked immunosorbent assay kits. The expression of VEGF in the kidney biopsied tissue sections and the lymph node specimens were detected by immunostaining.

Results: The plasma levels of VEGF and IL-6 levels were the highest in CD-TMA group compared to TMA control group and healthy controls. The levels of plasma VEGF was positively correlated with that of IL-6, and increased expression of VEGF and IL-6 was also observed in the lymph nodes from CD-TMA patients. However, the expression of VEGF in the glomerular podocytes was significantly decreased in CD-TMA group as well as in the TMA control.

Conclusion: Our findings suggest that renal VEGF expression might be important in the pathogenetic mechanism of CD-associated TMA-like lesions.

Keywords: Castleman's disease; interleukin-6; podocyte; thrombotic microangiopathy-like lesions; vascular endothelial growth factor.

MeSH terms

  • Adult
  • Biopsy / methods
  • Castleman Disease* / immunology
  • Castleman Disease* / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Interleukin-6* / analysis
  • Interleukin-6* / blood
  • Kidney* / immunology
  • Kidney* / pathology
  • Lymph Nodes* / immunology
  • Lymph Nodes* / pathology
  • Male
  • Middle Aged
  • Podocytes / immunology*
  • Reproducibility of Results
  • Thrombotic Microangiopathies* / immunology
  • Thrombotic Microangiopathies* / pathology
  • Vascular Endothelial Growth Factor A* / analysis
  • Vascular Endothelial Growth Factor A* / blood
  • Vascular Endothelial Growth Factor Receptor-1* / analysis
  • Vascular Endothelial Growth Factor Receptor-1* / blood

Substances

  • Interleukin-6
  • Vascular Endothelial Growth Factor A
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1