Urine macrophages reflect kidney macrophage content during acute tubular interstitial and glomerular injury

Clin Immunol. 2019 Aug;205:65-74. doi: 10.1016/j.clim.2019.06.005. Epub 2019 Jun 15.

Abstract

Macrophage polarization is a major contributing factor in acute kidney injury (AKI). We aim to determine its biomarker value in differentiating etiologic causes of various intrinsic renal AKI. A total of 205 patients with renal intrinsic AKI were enrolled. Urinary sCD163 was quantified and macrophage subtypes in urine and in renal biopsy were determined. Compared to healthy controls and AKI due to interstitial or tubular injuries (0 pg/μmol), urinary sCD163 was markedly higher in glomerulopathy, especially in diffuse proliferative glomerulonephritis (275.5 pg/μmol) and significantly correlated with cellular crescent formation. Urine sediment analysis of M1/M2 ratio could differentiate acute tubulointerstitial nephritis (M1/M2 > 2.35) from crescentic glomerulonephritis (M1/M2 < 0.27). Urinary sCD163 levels and M2 subtype positively correlated with infiltrated M2 in the glomeruli, whereas urine M1 positively correlated with infiltrated M1 in the interstitium. Of note, urinary sCD163 showed better diagnositic performance in differentiating disease etiologies compared to tradiational urinary biomarkers of AKI (NGAL and KIM-1) and markers of myeloid cells (CD11b) and pan macrophages (CD68). Thus markers of macrophage polarization could be viewed as the noninvasive "liquid biopsy" in the presence of various intrinsic kidney diseases.

Keywords: Acute kidney injury; Biomarker; Diagnosis; Macrophage; sCD163.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / urine*
  • Adult
  • Cell Count
  • Female
  • Glomerulonephritis / pathology
  • Glomerulonephritis / urine
  • Glomerulonephritis, Membranoproliferative / pathology
  • Glomerulonephritis, Membranoproliferative / urine
  • Humans
  • Kidney / pathology*
  • Kidney Tubular Necrosis, Acute / pathology
  • Kidney Tubular Necrosis, Acute / urine
  • Macrophages*
  • Male
  • Middle Aged
  • Nephritis, Interstitial / pathology
  • Nephritis, Interstitial / urine
  • Thrombotic Microangiopathies / pathology
  • Thrombotic Microangiopathies / urine
  • Urine / cytology*
  • Young Adult

Supplementary concepts

  • Acute Tubulointerstitial Nephritis