Giacomo Garibotto1, Alice Bonanni, Daniela Verzola. 1. Department of Internal Medicine, University of Genoa, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy. gari@unige.it
Abstract
PURPOSE OF REVIEW: Despite technological innovations in renal replacement therapy, mortality is still high in patients with end-stage renal disease. This increase in mortality is not only limited to dialysis patients, but also includes all stages of chronic kidney disease (CKD) and is mainly because of cardiovascular disease. Protein-energy wasting becomes clinically manifest at an advanced CKD stage, early before or during the dialytic stage, and increases the morbidity and mortality in this patients' population. The purpose of this article is to review the recent observations on alterations of amino acid and protein metabolism which cause wasting and increase cardiovascular risk. RECENT FINDINGS: Recent studies have consistently increased our understanding of mechanisms causing wasting and vascular disease in CKD patients. These include changes in amino acid and lipoprotein metabolism potentially leading to alterations of biology and function of the vascular wall, anorexia and endocrine dysfunction, altered muscle intracellular signaling through the insulin receptor substrate/phosphatidylinositol 3-kinase/Akt pathway, and defective myocyte regeneration. These mechanisms may trigger wasting through an increase in protein degradation and/or acceleration of apoptotic processes in skeletal muscle and may be accelerated by hemodialysis, leading to progression of vascular disease and wasting. SUMMARY: The new understanding holds promise for new treatments which can prevent/treat vascular diseases and wasting in CKD patients.
PURPOSE OF REVIEW: Despite technological innovations in renal replacement therapy, mortality is still high in patients with end-stage renal disease. This increase in mortality is not only limited to dialysis patients, but also includes all stages of chronic kidney disease (CKD) and is mainly because of cardiovascular disease. Protein-energy wasting becomes clinically manifest at an advanced CKD stage, early before or during the dialytic stage, and increases the morbidity and mortality in this patients' population. The purpose of this article is to review the recent observations on alterations of amino acid and protein metabolism which cause wasting and increase cardiovascular risk. RECENT FINDINGS: Recent studies have consistently increased our understanding of mechanisms causing wasting and vascular disease in CKDpatients. These include changes in amino acid and lipoprotein metabolism potentially leading to alterations of biology and function of the vascular wall, anorexia and endocrine dysfunction, altered muscle intracellular signaling through the insulin receptor substrate/phosphatidylinositol 3-kinase/Akt pathway, and defective myocyte regeneration. These mechanisms may trigger wasting through an increase in protein degradation and/or acceleration of apoptotic processes in skeletal muscle and may be accelerated by hemodialysis, leading to progression of vascular disease and wasting. SUMMARY: The new understanding holds promise for new treatments which can prevent/treat vascular diseases and wasting in CKDpatients.
Authors: Michael Holzer; Gernot Schilcher; Sanja Curcic; Markus Trieb; Senka Ljubojevic; Tatjana Stojakovic; Hubert Scharnagl; Chantal M Kopecky; Alexander R Rosenkranz; Akos Heinemann; Gunther Marsche Journal: J Am Soc Nephrol Date: 2015-03-05 Impact factor: 10.121