Estimation of kidney injury molecule-1 (Kim-1) in patients with lupus nephritis

Abstract

Biomarkers of disease activity in lupus nephritis (LN) are needed. Ideally, such biomarkers would be capable of detecting early sub-clinical disease and could be used to gauge response to therapy, thus obviating the need for serial renal biopsies. Much of the focus in the search for LN biomarkers has been on the measurement of urinary chemokines and cytokines in LN patients. However, these have yet to be widely implemented in clinical practice. Kidney injury molecule-1 (Kim-1) is expressed in damaged tubules, but whether urinary (u) and tubular (t)-Kim-1 could serve as a biomarker of active LN is unknown. To investigate the disease activity and histological findings in LN, we evaluated u-Kim-1 levels and t-Kim-1 cells in patients with systemic lupus erythematosus (SLE). We measured u-Kim-1 levels and stained t-Kim-1 expression in 57 patients with LN using an ELISA and immunohistochemistry staining. Patients were classified into two groups (active LN, n = 37; inactive LN, n = 20) based on the presence of active renal disease according to the renal SLE disease activity index. correlations of clinical, laboratory data, and histological findings with urinary and t-Kim-1 expression were assessed. The u-Kim-1 levels were significantly correlated with the expression of t-Kim-1 (R = 0.64; P = 0.004) in the SLE patients. The active LN patients exhibited elevated u-Kim-1 levels compared to the inactive LN patients. The number of t-Kim-1 cells was also correlated with histological findings (both glomerular and interstitial inflammation). The u-Kim-1 levels were also correlated with proteinuria and tubular damage in the active LN group. The number of t-Kim-1 cells at baseline was significantly correlated with the estimated glomerular filtration rate (R = 0.72; P = 0.005) and serum creatinine (R = 0.53; P = 0.005) after 6-8 months of treatment. These data suggest the potential use of the u-Kim-1 levels to screen for active LN and for the estimation of t-Kim-1 expression in renal biopsies to predict renal damage, ongoing glomerular nephritis and tubulointerstitial inflammation, and tubular atrophy.