Role of renal expression of CD68 in the long-term prognosis of proliferative lupus nephritis

J Nephrol. 2017 Feb;30(1):87-94. doi: 10.1007/s40620-015-0252-7. Epub 2015 Nov 30.

Abstract

Introduction: Renal histology of proliferative lupus nephritis (LN) shows increased macrophage infiltration, but its association with renal outcome is a matter of debate. Here, we investigate the potential relationship that macrophage expression has with renal prognosis in patients with proliferative LN.

Methods: Fifty patients newly diagnosed with proliferative LN were followed for a median of 8 years. Laboratory testing was conducted at diagnosis, after induction therapy and at the final follow-up evaluation. Renal biopsies were obtained at diagnosis and underwent immunohistochemical analysis with anti-CD68 and monocyte chemoattractant protein 1 monoclonal antibodies. Patients were stratified at final follow-up evaluation into glomerular filtration rate (GFR) >60 ml/min/1.73 m2 (non-progressor group; n = 24) and GFR ≤60 ml/min/1.73 m2 (progressor group; n = 26). All patients were treated with prednisone and six pulses of cyclophosphamide on induction therapy. Conventional maintenance therapy was administered in both groups.

Results: Compared to progressors, the non-progressor group showed a lower chronicity index (p = 0.01) and fewer CD68-positive cells in the renal tubules (p = 0.01) and particularly in the renal interstitium (p = 0.0003). Baseline and final serum creatinine correlated positively with the chronicity index (r = 0.3, p = 0.01 and r = 0.3, p = 0.04, respectively), and final serum creatinine correlated positively with interstitial expression of CD68 (r = 0.4, p = 0.0006).

Conclusion: Renal expression of CD68 and the chronicity index are associated with progression to chronic kidney disease in patients with proliferative LN.

Keywords: Lupus nephritis; Macrophage inflammatory proteins; Prognosis; Tissue macrophage.

MeSH terms

  • Adult
  • Antigens, CD / physiology*
  • Antigens, Differentiation, Myelomonocytic / physiology*
  • Chemokine CCL2 / physiology
  • Creatinine / blood
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kidney / physiology*
  • Lupus Nephritis / complications*
  • Macrophages / physiology
  • Male
  • Prognosis
  • Renal Insufficiency, Chronic / etiology*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CCL2 protein, human
  • CD68 antigen, human
  • Chemokine CCL2
  • Creatinine