Association of monocyte chemoattractant protein-1 with renal tubular damage in diabetic nephropathy.
Monocyte chemoattractant protein-1 (MCP-1), is a chemokine that mediates renal interstitial inflammation, tubular atrophy, and interstitial fibrosis by recruiting monocytes/macrophages into renal tubulointerstitium. Recent studies have demonstrated that protein overload in renal tubular cells up-regulates MCP-1 gene and its protein expression. Therefore, we hypothesized that increased expression of MCP-1 in renal tubuli, probably triggered by an increase in the leakage of plasma protein from glomerular capillary to tubular fluid, may contribute to renal tubular damage and accelerate the progression of diabetic nephropathy. To test this hypothesis, we examined urinary excretion levels of MCP-1 and N-acetylglucosaminidase (NAG), a sensitive marker of renal tubular damage, in Japanese Type II diabetic patients with normoalbuminuria (n=29), microalbuminuria (n=25), and macroalbuminuria (n=18). The median urinary excretion level of MCP-1 in patients with macroalbuminuria (394.4 ng/g creatinine) was significantly elevated compared to the levels in patients with normoalbuminuria and microalbuminuria (159.6 and 193.9 ng/g creatinine, respectively). Furthermore, the urinary MCP-1 excretion level was positively correlated with urinary excretion levels of albumin (r=.816, P<.001) and NAG (r=.569, P<.001) in all subjects. These results suggest that MCP-1 is produced in renal tubular cells and released into urine in proportion to the degree of proteinuria (albuminuria), and that increased MCP-1 expression in renal tubuli contributes to renal tubular damage. Therefore, we conclude that heavy proteinuria itself may accelerate the progression of diabetic nephropathy by increasing the MCP-1 expression in renal tubuli.
Morii
Tsukasa
T
Department of Geriatric Medicine, Akita University School of Medicine, 1-1-1 Hondo, Japan. morii@med.akita-u.ac.jp
Fujita
Hiroki
H
Narita
Takuma
T
Shimotomai
Takashi
T
Fujishima
Hiromi
H
Yoshioka
Naomi
N
Imai
Hirokazu
H
Kakei
Masafumi
M
Ito
Seiki
S
D000118:Acetylglucosaminidase / Q000652:urine; D000368:Aged; D000419:Albuminuria / Q000378:metabolism; D018932:Chemokine CCL2 / Q000652:urine*; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000652:urine*; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000652:urine*; D005260:Female; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000378:metabolism
D018932:Chemokine CCL2; D003404:Creatinine; D000118:Acetylglucosaminidase