[Phenotypic characteristics of infiltrated inflammatory cells, renal tubular epithelial cells and interstitial cells and their possible roles in the outcome of human drug-associated interstitial nephritis].
OBJECTIVE
To observe the phenotypic characteristics of infiltrated inflammatory cells, renal tubular epithelial cells (TEC) and interstitial cells in human drug-associated interstitial nephritis (IN) and evaluate their roles in the interstitial inflammation and fibrosis.


METHODS
Immuno-histochemical method was employed to observe the renal biopsy specimens collected from 31 patients with acute or chronic drug -associated IN. Infiltration of T lymphocyte and monocyte/macrophage was observed by the marker CD3(+) and CD68(+). Expressions of PCNA, MCP-1 and alpha-smooth muscle actin (alpha-SMA) were also detected in TEC and interstitial cells. Semi-quantitative data and pathological features together with clinical outcome from these patients were further analyzed.


RESULTS
A great were large amount of CD3(+) and CD68(+) cells was found in the renal interstitium in all patients, with a CD68(+) cells took a higher proportion of in chronic drug-associated IN (CIN), and the ratio of CD3(+)/CD68(+) cells was closely negatively correlated with the level of serum creatinine. PCNA and MCP-1 expression were both increased in TEC in acute drug-associated (AIN), MCP-1 expression in TEC was positively correlated with the number of CD68(+) cells in the renal interstitium. 54.8% of CD68(+) cells in renal interstitium were PCNA positive. There was a high expression of alpha-SMA in the TEC and interstitial cells in AIN and CIN, positively was correlated with the degree of interstitial fibrosis. In AIN, expression of alpha-SMA and positively PCNA in TEC were that of correlated with each other. Much more expression of alpha-SMA was seen in renal interstitial cells in CIN, with its distribution coincided with that of the expression of collagen IV. The degree of interstitial fibrosis was closely correlated with the recovery of renal function.


CONCLUSIONS
During the early stage of human drug-associated interstitial nephritis, TEC is activated and highly expresses chemoattractants, inducing the infiltration of monocyte/macrophage into the interstitium. Monocyte/macrophage may be used as marker for the chronicity of interstitial inflammation and poor outcome of renal function.
Yang
L
L
Renal Division of Department of Medicine, First Hospital and Institute of Nephrology, Peking University, Beijing 100034, China.
Li
X
X
Zheng
X
X
D000199:Actins / Q000032:analysis; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D018932:Chemokine CCL2 / Q000032:analysis; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000737:chemistry; D009395:Nephritis, Interstitial / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D000097382:CD68 Molecule
D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D018932:Chemokine CCL2; D018809:Proliferating Cell Nuclear Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule