PMID- 14514736
OWN - NLM
STAT- MEDLINE
DCOM- 20040914
LR  - 20220316
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 14
IP  - 10
DP  - 2003 Oct
TI  - Urinary excretion of monocyte chemoattractant protein-1 in autosomal dominant 
      polycystic kidney disease.
PG  - 2588-95
AB  - Autosomal dominant polycystic kidney disease (ADPKD) progresses to renal 
      insufficiency in >50% of patients and is characterized by interstitial 
      inflammation and fibrosis in the end stage. In a rat model of ADPKD, monocytes 
      accumulate within the renal interstitium in association with increased levels of 
      monocyte chemoattractant protein-1 (MCP-1) in cyst mural cells and increased 
      excretion of this chemokine into the urine. For determining the extent to which 
      this chemokine is abnormally expressed in patients with ADPKD, a cross-section 
      study was performed of MCP-1 in urine, serum, and cyst fluid and MCP-1 production 
      by mural epithelial cells cultured from the cysts of human patients with ADPKD. 
      Upper boundaries for urinary MCP-1 excretion (>263 pg/mg creatinine) and serum 
      creatinine concentration (>1.5 mg/dl) determined in 19 normal individuals were 
      used to sort 55 ADPKD patients into three groups. In group 1 (n = 13), urine 
      MCP-1 excretion (136 +/- 14 pg/mg creatinine) was not different from normal 
      volunteers (152 +/- 16 pg/mg); serum creatinine levels and urine total protein 
      excretion were normal as well. In group 2 (n = 27), urine MCP-1 excretion was 
      increased (525 +/- 39 pg/mg creatinine), but serum creatinine levels and urine 
      protein excretion were not different from normal. In group 3 (n = 15), urine 
      MCP-1 excretion increased further (1221 +/- 171 pg/mg), serum creatinine levels 
      increased to 4.3 +/- 0.8 mg/dl, and urine protein excretion rose to 0.64 +/- 0.28 
      mg/mg creatinine. Serum MCP-1 levels of ADPKD patients (84 +/- 9.9 pg/ml; n = 15) 
      did not differ from normal. Levels of MCP-1 much higher than in serum or urine 
      were found in cyst fluids obtained from nephrectomy specimens (range, 767 to 
      40,860 pg/ml; mean, 6434 +/- 841 pg/ml; n = 73). Polarized, confluent cultures of 
      ADPKD cyst epithelial cells secreted MCP-1 into the apical fluid to levels 
      eightfold greater than in the basolateral medium. Similar results were obtained 
      with tubule epithelial cells cultured from normal human renal cortex. On the 
      basis of these results, it is concluded that urinary excretion of MCP-1 is 
      increased in the majority of adult patients with ADPKD and that the source of 
      some of this chemokine may be the mural epithelium of cysts. Furthermore, it 
      seemed that urinary MCP-1 excretion may have increased in these ADPKD patients 
      before appreciable increases in serum creatinine concentration or urine protein 
      excretion were detected. It is reasonable to include urine MCP-1 excretion among 
      candidate surrogate markers in controlled, longitudinal studies of ADPKD.
FAU - Zheng, Danxia
AU  - Zheng D
AD  - Kidney Institute, Department of Medicine, University of Kansas Medical Center, 
      Kansas City, Kansas 66160, USA.
FAU - Wolfe, Marieka
AU  - Wolfe M
FAU - Cowley, Benjamin D Jr
AU  - Cowley BD Jr
FAU - Wallace, Darren P
AU  - Wallace DP
FAU - Yamaguchi, Tamio
AU  - Yamaguchi T
FAU - Grantham, Jared J
AU  - Grantham JJ
LA  - eng
GR  - P01-DK53763/DK/NIDDK NIH HHS/United States
GR  - P50-DK57301/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Biomarkers)
RN  - 0 (CCL7 protein, human)
RN  - 0 (Ccl7 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL7)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-8)
RN  - 0 (Monocyte Chemoattractant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Chemokine CCL2/blood/metabolism/*urine
MH  - Chemokine CCL7
MH  - Cyst Fluid/metabolism
MH  - *Cytokines
MH  - Epithelial Cells/cytology/metabolism
MH  - Female
MH  - Humans
MH  - Interleukin-8/metabolism/urine
MH  - Kidney Cortex/cytology
MH  - Male
MH  - Middle Aged
MH  - Monocyte Chemoattractant Proteins/metabolism/urine
MH  - Polycystic Kidney, Autosomal Dominant/blood/*urine
MH  - Tumor Necrosis Factor-alpha/metabolism/urine
EDAT- 2003/09/30 05:00
MHDA- 2004/09/15 05:00
CRDT- 2003/09/30 05:00
PHST- 2003/09/30 05:00 [pubmed]
PHST- 2004/09/15 05:00 [medline]
PHST- 2003/09/30 05:00 [entrez]
AID - 10.1097/01.asn.0000088720.61783.19 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2003 Oct;14(10):2588-95. doi: 
      10.1097/01.asn.0000088720.61783.19.