Pathological significance of urinary complement activation in diabetic nephropathy: A full view from the development of the disease

J Diabetes Investig. 2019 May;10(3):738-744. doi: 10.1111/jdi.12934. Epub 2018 Oct 13.

Abstract

Aims/introduction: The aim of the present study was to obtain a full view of the changes of urinary complement activation products in the development of diabetic nephropathy and explore their possible significance in the disease process.

Materials and methods: A total of 62 patients at different stages of diabetic nephropathy, 20 diabetes patients without nephropathy and 20 healthy persons were enrolled. Urinary complement activation products, including C3a, C5a and C5b-9, were measured, and their associations with the progression of the disease were analyzed.

Results: The urinary complement activation products increased markedly since the proteinuria stage, and were parallel with the progression of diabetic nephropathy. More severe renal tubular damage was observed in patients with higher levels of urinary complement activation products. The urinary complement activation products levels correlated closely with renal tubulointerstitial injury score and relative tubular interstitial volume. Multivariate regression analysis showed that elevated urinary complement activation products were independent risk factors for tubular injury in diabetic nephropathy patients.

Conclusions: Urinary complement activation might have a role in renal tubular interstitial injury in patients with diabetic nephropathy, especially in patients at a later stage of the disease.

Keywords: Diabetic nephropathy; Tubular injury; Urinary complement activation products.

MeSH terms

  • Biomarkers / blood
  • Biomarkers / urine*
  • Case-Control Studies
  • Complement Activation*
  • Complement C3a / urine*
  • Complement C5a / urine*
  • Complement Membrane Attack Complex / urine*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / pathology*
  • Diabetic Nephropathies / urine
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Kidney Tubules / injuries
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology*
  • Male
  • Middle Aged
  • Prognosis

Substances

  • Biomarkers
  • Complement Membrane Attack Complex
  • Complement C3a
  • Complement C5a