Decreased synthesis of glomerular adrenomedullin in patients with IgA nephropathy.
Adrenomedullin (AM) immunostaining and gene expression have seldom been measured in human kidneys. Because previous studies have shown that AM exerts antiproliferative effects on rat mesangial cells in vitro and that urine AM levels are decreased in patients with chronic glomerulonephritis, we measured glomerular AM and its gene expression in patients with primary IgA nephropathy (IgAN). Glomerular AM was measured by immunohistochemical staining, and glomerular AM mRNA was measured by in situ hybridization. Plasma and urine AM were measured by radioimmunoassay. The results showed that both the intensity of immunostaining for glomerular AM and the glomerular expression of AM mRNA were significantly decreased in IgAN patients compared with normal controls (both P < .05). Similar results were not observed in patients with non-IgA MsPGN. Glomerular AM immunostaining and glomerular AM mRNA expression were significantly correlated ( P < .001), and both were negatively correlated with the number of glomerular cells ( P < .05 and < .01, respectively). Both glomerular AM immunostaining and glomerular AM mRNA expression were correlated with urine AM levels (both P < .001), but not with plasma AM levels. The urine AM level was significantly lower in IgAN patients than in normal controls ( P < .01), whereas the plasma level was not different between the 2 groups. Our findings indicate that glomerular production of AM was decreased in patients with IgA nephropathy and that this lack of glomerular AM may be related to the pathogenesis of this mesangial disease.
Kuo
Mei-Chuan
MC
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University, Taiwan, Republic of China.
Kuo
Hung-Tien
HT
Chiu
Yi-Wen
YW
Chang
Jer-Ming
JM
Guh
Jinn-Yuh
JY
Lai
Yung-Hsiung
YH
Chen
Hung-Chun
HC
D053607:Adrenomedullin; D000328:Adult; D005260:Female; D015870:Gene Expression; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000378:metabolism* / Q000652:urine; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007672:Kidney Cortex / Q000737:chemistry; D007678:Kidney Glomerulus / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay
D010455:Peptides; D012333:RNA, Messenger; D053607:Adrenomedullin