The renal metallothionein expression profile is altered in human lupus nephritis

Mikkel Faurschou¹ , Milena Penkowa² , Claus Bøgelund Andersen³ , Henrik Starklint⁴ and Søren Jacobsen¹

¹Department of Rheumatology, The National University Hospital, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark

²Section of Neuroprotection, Faculty of Health Sciences, University of Copenhagen, 3 Blegdamsvej, DK-2200 Copenhagen, Denmark

³Department of Pathology, The National University Hospital, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark

⁴Department of Pathology, Vejle Hospital, 25 Kabbeltoft, DK-7100 Vejle, Denmark

author email corresponding author email

Arthritis Research & Therapy 2008, 10:R76doi:10.1186/ar2450


Published:	6 July 2008

Abstract

Introduction

Metallothionein (MT) isoforms I + II are polypeptides with potent antioxidative and anti-inflammatory properties. In healthy kidneys, MT-I+II have been described as intracellular proteins of proximal tubular cells. The aim of the present study was to investigate whether the renal MT-I+II expression profile is altered during lupus nephritis.

Methods

Immunohistochemistry was performed on renal biopsies from 37 patients with lupus nephritis. Four specimens of healthy renal tissue served as controls. Clinicopathological correlation studies and renal survival analyses were performed by means of standard statistical methods.

Results

Proximal tubules displaying epithelial cell MT-I+II depletion in combination with luminal MT-I+II expression were observed in 31 out of 37 of the lupus nephritis specimens, but not in any of the control sections (P = 0.006). The tubular MT score, defined as the median number of proximal tubules displaying this MT expression pattern per high-power microscope field (40× magnification), was positively correlated to the creatinine clearance in the lupus nephritis cohort (P = 0.01). Furthermore, a tubular MT score below the median value of the cohort emerged as a significant predictor of a poor renal outcome in renal survival analyses. Thus, patients with a tubular MT score < 1.0 had a 6.2-times higher risk of developing end-stage renal disease than patients with a tubular MT score ≥ 1.0 (P = 0.03).

Conclusion

Lupus nephritis is associated with significant alterations in renal MT-I+II expression. Our data indicate that important prognostic information can be deduced from the renal MT-I+II expression profile in systemic lupus erythematosus patients with nephritis.