The renal metallothionein expression profile is altered in human lupus nephritis.
BACKGROUND
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 (40x 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 >or= 1.0 (P = 0.03).


CONCLUSIONS
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.
Faurschou
Mikkel
M
Department of Rheumatology, The National University Hospital, Rigshospitalet, Copenhagen, Denmark. mfaurschou@dadlnet.dk
Penkowa
Milena
M
Andersen
Claus Bøgelund
CB
Starklint
Henrik
H
Jacobsen
Søren
S
D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D005921:Glomerulonephritis / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology; D008137:Longitudinal Studies; D008181:Lupus Nephritis / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors
D008668:Metallothionein