Increased Expression of Mineralocorticoid Effector Mechanisms in Kidney Biopsies of Patients With Heavy Proteinuria

DOI Web Site 被引用文献24件
  • Marcus Quinkler
    From the Division of Medical Sciences (M.Q., S.V.H., M.H., P.M.S.) and Department of Pathology (A.J.H.), University of Birmingham, Birmingham, UK; Department of Nephrology (D.Z., K.L.S.E., J.L., P.C.), Queen Elizabeth Hospital, Birmingham, UK; and Clinical Endocrinology (M.Q.), Centre for Internal Medicine, Gastroenterology, Hepatology and Endocrinology, Charité Campus Mitte, Berlin, Germany.
  • Daniel Zehnder
    From the Division of Medical Sciences (M.Q., S.V.H., M.H., P.M.S.) and Department of Pathology (A.J.H.), University of Birmingham, Birmingham, UK; Department of Nephrology (D.Z., K.L.S.E., J.L., P.C.), Queen Elizabeth Hospital, Birmingham, UK; and Clinical Endocrinology (M.Q.), Centre for Internal Medicine, Gastroenterology, Hepatology and Endocrinology, Charité Campus Mitte, Berlin, Germany.
  • Kevin S. Eardley
    From the Division of Medical Sciences (M.Q., S.V.H., M.H., P.M.S.) and Department of Pathology (A.J.H.), University of Birmingham, Birmingham, UK; Department of Nephrology (D.Z., K.L.S.E., J.L., P.C.), Queen Elizabeth Hospital, Birmingham, UK; and Clinical Endocrinology (M.Q.), Centre for Internal Medicine, Gastroenterology, Hepatology and Endocrinology, Charité Campus Mitte, Berlin, Germany.
  • Julia Lepenies
    From the Division of Medical Sciences (M.Q., S.V.H., M.H., P.M.S.) and Department of Pathology (A.J.H.), University of Birmingham, Birmingham, UK; Department of Nephrology (D.Z., K.L.S.E., J.L., P.C.), Queen Elizabeth Hospital, Birmingham, UK; and Clinical Endocrinology (M.Q.), Centre for Internal Medicine, Gastroenterology, Hepatology and Endocrinology, Charité Campus Mitte, Berlin, Germany.
  • Alexander J. Howie
    From the Division of Medical Sciences (M.Q., S.V.H., M.H., P.M.S.) and Department of Pathology (A.J.H.), University of Birmingham, Birmingham, UK; Department of Nephrology (D.Z., K.L.S.E., J.L., P.C.), Queen Elizabeth Hospital, Birmingham, UK; and Clinical Endocrinology (M.Q.), Centre for Internal Medicine, Gastroenterology, Hepatology and Endocrinology, Charité Campus Mitte, Berlin, Germany.
  • Susan V. Hughes
    From the Division of Medical Sciences (M.Q., S.V.H., M.H., P.M.S.) and Department of Pathology (A.J.H.), University of Birmingham, Birmingham, UK; Department of Nephrology (D.Z., K.L.S.E., J.L., P.C.), Queen Elizabeth Hospital, Birmingham, UK; and Clinical Endocrinology (M.Q.), Centre for Internal Medicine, Gastroenterology, Hepatology and Endocrinology, Charité Campus Mitte, Berlin, Germany.
  • Paul Cockwell
    From the Division of Medical Sciences (M.Q., S.V.H., M.H., P.M.S.) and Department of Pathology (A.J.H.), University of Birmingham, Birmingham, UK; Department of Nephrology (D.Z., K.L.S.E., J.L., P.C.), Queen Elizabeth Hospital, Birmingham, UK; and Clinical Endocrinology (M.Q.), Centre for Internal Medicine, Gastroenterology, Hepatology and Endocrinology, Charité Campus Mitte, Berlin, Germany.
  • Martin Hewison
    From the Division of Medical Sciences (M.Q., S.V.H., M.H., P.M.S.) and Department of Pathology (A.J.H.), University of Birmingham, Birmingham, UK; Department of Nephrology (D.Z., K.L.S.E., J.L., P.C.), Queen Elizabeth Hospital, Birmingham, UK; and Clinical Endocrinology (M.Q.), Centre for Internal Medicine, Gastroenterology, Hepatology and Endocrinology, Charité Campus Mitte, Berlin, Germany.
  • Paul M. Stewart
    From the Division of Medical Sciences (M.Q., S.V.H., M.H., P.M.S.) and Department of Pathology (A.J.H.), University of Birmingham, Birmingham, UK; Department of Nephrology (D.Z., K.L.S.E., J.L., P.C.), Queen Elizabeth Hospital, Birmingham, UK; and Clinical Endocrinology (M.Q.), Centre for Internal Medicine, Gastroenterology, Hepatology and Endocrinology, Charité Campus Mitte, Berlin, Germany.

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<jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> Aldosterone has emerged as a deleterious hormone in the heart, with mineralocorticoid receptor (MR) blockade reducing mortality in patients with severe heart failure. There is also experimental evidence that aldosterone contributes to the development of nephrosclerosis and renal fibrosis in rodent models, but little is known of its role in clinical renal disease. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> We quantified MR, serum- and glucocorticoid-regulated kinase 1 (sgk1), and mRNA expression of inflammatory mediators such as macrophage chemoattractant protein-1 (MCP-1), transforming growth factor-β1, and interleukin-6 in 95 human kidney biopsies in patients with renal failure and mild to marked proteinuria of diverse etiologic origins. We measured renal function, serum aldosterone, urinary MCP-1 protein excretion, and the amount of chronic renal damage. Macrophage invasion was quantified by CD68 and vascularization by CD34 immunostaining. Serum aldosterone correlated negatively with creatinine clearance ( <jats:italic>P</jats:italic> <0.01) and positively with renal scarring ( <jats:italic>P</jats:italic> <0.05) but did not correlate with MR mRNA expression or proteinuria. Patients with heavy albuminuria (>2 g/24 h; n=15) had the most renal scarring and the lowest endothelial CD34 staining. This group showed a significant 5-fold increase in MR, a 2.5-fold increase in sgk1 expression and a significant increase in inflammatory mediators (7-fold increase in MCP-1, 3-fold increase in transforming growth factor-β1, and 2-fold increase in interleukin-6 mRNA). Urinary MCP-1 protein excretion and renal macrophage invasion were significantly increased in patients with heavy albuminuria. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> These studies support animal data linking aldosterone/MR activation to renal inflammation and proteinuria. Further studies are urgently required to assess the potential beneficial effects of MR antagonism in patients with renal disease. </jats:p>

収録刊行物

  • Circulation

    Circulation 112 (10), 1435-1443, 2005-09-06

    Ovid Technologies (Wolters Kluwer Health)

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