Plasma Adrenomedullin and Allelic Variation in the ADM Gene and Kidney Disease in People With Type 2 Diabetes.

Abstract

Production of adrenomedullin (ADM), a vasodilator peptide, increases in response to ischemia and hypoxia in the vascular wall and the kidney. This may be an adaptive response providing protection against organ damage. We investigated the hypothesis that ADM has a nephroprotective effect in two prospective cohorts of patients with type 2 diabetes recruited in France. The highest tertile of plasma MR-proADM (a surrogate for ADM) concentration at baseline was associated with the risk of renal outcomes (doubling of plasma creatinine concentration and/or progression to end-stage renal disease) during follow-up in both cohorts. Four SNPs in the ADM gene region were associated with plasma MR-proADM concentration at baseline and with eGFR during follow-up in both cohorts. The alleles associated with lower eGFR were also associated with lower plasma MR-proADM level. In conclusion, plasma MR-proADM concentration was associated with renal outcome in patients with type 2 diabetes. Our data suggest that the ADM gene modulates the genetic susceptibility to nephropathy progression. Results are consistent with the hypothesis of a reactive rise of ADM in diabetic nephropathy, blunted in risk alleles carriers, and with a nephroprotective effect of ADM. A possible therapeutic effect of ADM receptor agonists in diabetic renal disease would be worth investigating.

• Authors: Gilberto Velho, Stéphanie Ragot, Kamel Mohammedi, Elise Gand, Mathilde Fraty, Frédéric Fumeron, Pierre-Jean Saulnier, Naima Bellili-Munoz, Nadine Bouby, Louis Potier, François Alhenc-Gelas, Michel Marre, Samy Hadjadj, Ronan Roussel
• Journal: Diabetes (Diabetes) Vol. 64 Issue 9 Pg. 3262-72 (Sep 2015) ISSN: 1939-327X [Electronic] United States
• PMID: 25948679 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Chemical References

• ADM protein, human
• Peptide Fragments
• Protein Precursors
• mid-regional pro-adrenomedullin, human
• Adrenomedullin
• Creatinine

Topics

• Adrenomedullin (blood, genetics)
• Aged
• Aged, 80 and over
• Cohort Studies
• Creatinine (blood)
• Diabetes Mellitus, Type 2 (complications, metabolism)
• Diabetic Nephropathies (blood, etiology, genetics)
• Disease Progression
• Female
• Genetic Predisposition to Disease
• Genetic Variation
• Glomerular Filtration Rate
• Humans
• Kidney Failure, Chronic (blood, etiology, genetics)
• Male
• Middle Aged
• Peptide Fragments (blood)
• Prospective Studies
• Protein Precursors (blood)
• Renal Insufficiency, Chronic (blood, etiology, genetics)