Background/Purpose: Lupus nephritis (LN) is one of the common manifestations of systemic lupus erythematosus (SLE), and the occurrence of LN is considered to be a very important factor influencing the course of the disease. Although kidney biopsy is the gold standard for defining the histopathologic class of LN, it is invasive and sometimes associated with a risk of bleeding; furthermore, repeated biopsies are not always applicable in clinical practice. For this reason, some form of novel non-invasive examination would be useful for detecting renal flare-up in LN patients. We have already reported that, in patients with glomerulonephritis, T cells and macrophages appear in the urine when there are accompanying signs of active cellular infiltration such as cellular crescent formation and diffuse interstitial cell infiltration, but not when active inflammatory lesions are absent. In the present study, we assessed the utility of urinary immune cell analysis in patients with SLE by examining the correlation between the numbers of urinary inflammatory cells and disease activity, kidney function, and histopathological classification of lupus nephritis.

Methods: Sixty-four samples from 56 patients with SLE, who had been referred to Niigata University Hospital between 2004 and 2013, were recruited for this study. Flow-cytometric analysis of urinary inflammatory cells was performed for each sample. Numbers of urinary T cells or macrophages were determined by multiplying the number of viable cells in the gated mononuclear cell region in each sample by the percentage of urinary CD3-positive or CD14-positive cells in the population, respectively. The numbers of urinary CD3-positive cells (T cells) and CD14-positive cells (macrophages), laboratory markers, kidney function, and SLE disease activity index (SLEDAI) were examined in each subject and compared with reference to their urinalysis data. The data were also analyzed by Spearman’s rank correlation coefficient and stepwise multiple regression analysis to determine the relationship with urinary T cells and macrophages. In 15 patients who underwent kidney biopsy simultaneously, the relationship between histopathologic classification and the number of urinary inflammatory cells was examined.

Results: The number of urinary CD3-positive cells was significantly elevated in patients with both proteinuria and abnormal urinary sedimentation, relative to patients with proteinuria alone or normal urinalysis data. The number of CD3-positive cells was positively correlated with serum Cr, abnormal urinary sedimentation, and SLEDAI, and negatively correlated with serum CH50, while the number of urinary CD14-positive cells was positively correlated with serum Cr, abnormal urinary sedimentation, 24-hour urinary protein excretion, and SLEDAI. Among the 15 patients who underwent kidney biopsy, 8 showing a significant increase in the total number of CD3-positive cells and CD14-positive cells (≥120/ml urine) were diagnosed as ISN/RPS class III or IV, while the remaining 7 were diagnosed as ISN/RPS class V.

Conclusion: These results indicate the usefulness of urinary immune cell analysis for assessment of patients with SLE.