Advertisement
Research Article

The Relationship between Proteinuria and Coronary Risk: A Systematic Review and Meta-Analysis

  • Vlado Perkovic mail,

    To whom correspondence should be addressed. E-mail: vperkovic@george.org.au

    Affiliations: The George Institute for International Health, Sydney, New South Wales, Australia, University of Sydney, Sydney, New South Wales, Australia

    X
  • Christine Verdon,

    Affiliation: University of Sydney, Sydney, New South Wales, Australia

    X
  • Toshiharu Ninomiya,

    Affiliation: The George Institute for International Health, Sydney, New South Wales, Australia

    X
  • Federica Barzi,

    Affiliations: The George Institute for International Health, Sydney, New South Wales, Australia, University of Sydney, Sydney, New South Wales, Australia

    X
  • Alan Cass,

    Affiliations: The George Institute for International Health, Sydney, New South Wales, Australia, University of Sydney, Sydney, New South Wales, Australia

    X
  • Anushka Patel,

    Affiliations: The George Institute for International Health, Sydney, New South Wales, Australia, University of Sydney, Sydney, New South Wales, Australia

    X
  • Meg Jardine,

    Affiliation: The George Institute for International Health, Sydney, New South Wales, Australia

    X
  • Martin Gallagher,

    Affiliations: The George Institute for International Health, Sydney, New South Wales, Australia, University of Sydney, Sydney, New South Wales, Australia

    X
  • Fiona Turnbull,

    Affiliations: The George Institute for International Health, Sydney, New South Wales, Australia, University of Sydney, Sydney, New South Wales, Australia

    X
  • John Chalmers,

    Affiliations: The George Institute for International Health, Sydney, New South Wales, Australia, University of Sydney, Sydney, New South Wales, Australia

    X
  • Jonathan Craig,

    Affiliation: University of Sydney, Sydney, New South Wales, Australia

    X
  • Rachel Huxley

    Affiliations: The George Institute for International Health, Sydney, New South Wales, Australia, University of Sydney, Sydney, New South Wales, Australia

    X
  • Published: October 21, 2008
  • DOI: 10.1371/journal.pmed.0050207

Reader Comments (1)

Post a new comment on this article

Is ACE the missing link?

Posted by plosmedicine on 31 Mar 2009 at 00:31 GMT

Author: David Moskowitz MD FACP
Position: CEO, Chief Medical Officer
Institution: GenoMed, Inc.
E-mail: dwmoskowitz@genomed.com
Submitted Date: October 28, 2008
Published Date: October 29, 2008
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

This is only the most recent of many articles showing a tight link between kidney and heart disease. For example, heart disease is the major cause of the atrocious mortality among dialysis patients.

Proteinuria results from cytokine (especially TNF-alpha) release by mesangial cells, the resident macrophage of the glomerulus (1). Macrophages express CD143 during autocrine and paracrine activation. CD143 is just another name for the angiotensin I-converting enzyme, or ACE.

Overactivity of ACE (the deletion/deletion, or D/D, genotype) has long been linked to both heart and kidney diseases (2 and refs. therein). Angiotensin II, the product of ACE, stimulates macrophage protein kinase C and macrophage production of cytokines like TNF-alpha. TNF-alpha has a TPA response element in its promoter.

Could ACE therefore be the key missing link between renal and heart disease? Intensive inhibition of, presumably, tissue ACE has been shown to be sufficient for reversing early diabetic and hypertensive nephropathy (3). Perhaps it can reverse heart disease as well (2).

If so, the #1 killer of the developed world will have been finally hobbled.

1. Lai KN, Leung JC, Chan LY, Saleem MA, Mathieson PW, Tam KY, Xiao J, Lai FM, Tang SC. Podocyte injury induced by mesangial-derived cytokines in IgA nephropathy. Nephrol Dial Transplant. 2008 Aug 6. [Epub ahead of print] PMID: 18685143

2. Moskowitz DW. Is angiotensin I-converting enzyme a "master" disease gene? Diabetes Technol Ther. 2002;4(5):683-711. PMID: 12458570

3. Moskowitz DW. From pharmacogenomics to improved patient outcomes: angiotensin I-converting enzyme as an example. Diabetes Technol Ther. 2002;4(4):519-32. PMID: 12396747

Competing interests declared: I am the CEO of GenoMed, which owns a pending patent on the use of high-dose ACE inhibitors to reverse early diabetic and hypertensive nephropathy.