NDT Advance Access published online on May 21, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn270
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Glomerular expression of monocyte chemoattractant protein-1 is predictive of poor renal prognosis in paediatric lupus nephritis
1 Nephro–Urology Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH 2 Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London WC1N 3JH, UK 3 Department of Paediatric Pathology, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London WC1N 3JH, UK
Correspondence and offprint requests to: Stephen D. Marks, Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London WC1N 3JH, UK. Tel: +44-20-7405-9200 extension 0292; Fax: +44-20-7829-8841; E-mail: s.marks{at}ich.ucl.ac.uk
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Abstract |
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Background. Monocyte chemoattractant protein-1 (MCP-1) is upregulated and it recruits and activates inflammatory cells in murine lupus nephritis (LN).
Methods. Clinical outcomes of children with LN were examined in relation to glomerular expression of MCP-1 and macrophage infiltration, as determined by immunohistochemical staining of renal biopsy sections with MCP-1 and CD68. Sections were analysed using a modified histological score (H-score; maximum of 300) based on both percentage of positively stained cells and intensity of staining.
Results. Renal biopsies were examined from 34 children [27 (79%) female] aged 7.7–17.3 (median 13.7) years with 50% ISN/RPS Class IV LN. Renal dysfunction and proteinuria at follow-up of 2.2–15.4 (median 6.5) years were analysed with estimated glomerular filtration rates (eGFR) of 11.2–124.1 (median 93.6) ml/min/1.73 m2 and urine albumin:creatinine ratios of 1–535 (median 63) mg/mmol. There was a correlation between glomerular expression of MCP-1 and CD68 (r = 0.98, P = 0.04; median modified H-score of 219.7 and 230.8, respectively). Patients with Class III and IV LN had increased glomerular expression of both MCP-1 and PGM1 compared to the other classes (P = 0.01) with Class IV-G LN patients having the most glomerular expression of MCP-1 (median of 227.3) and PGM1 (median of 237.5) and the worst renal prognosis (with proteinuria and reduced eGFR).
Conclusions. There is a correlation between glomerular expression of MCP-1 and PGM1 and worsening renal prognosis in paediatric LN. Larger prospective studies of paediatric LN are required to further evaluate MCP-1 and other markers of disease progression.
Keywords: histopathology; lupus nephritis; MCP-1 (monocyte chemoattractant protein-1); outcomes; paediatric
Received for publication: 17. 7.07
Accepted in revised form: 17. 4.08