title: Urinary excretion of monocyte chemoattractant protein-1 in autosomal dominant polycystic kidney disease.
abstract: 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.
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D015153:Blotting, Western; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood / Q000378:metabolism / Q000652:urine*; D054410:Chemokine CCL7; D020420:Cyst Fluid / Q000378:metabolism; D016207:Cytokines; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism / Q000652:urine; D007672:Kidney Cortex / Q000166:cytology; D008297:Male; D008875:Middle Aged; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism / Q000652:urine; D016891:Polycystic Kidney, Autosomal Dominant / Q000097:blood / Q000652:urine*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000652:urine
chemical_list: D015415:Biomarkers; C515450:CCL7 protein, human; C515452:Ccl7 protein, rat; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D016207:Cytokines; D016209:Interleukin-8; D018945:Monocyte Chemoattractant Proteins; D014409:Tumor Necrosis Factor-alpha