Acid retention because of chronic kidney disease (CKD) increases tissue acidity and accelerates progression of CKD, whereas reduction in acid retention slows progression of CKD. Herein, we describe the mechanisms through which increased tissue acidity worsens CKD, modalities for countering acid retention and their impact on progression of CKD, and current recommendations for therapy.
Studies in animals and humans show that increased tissue acidity raises the renal levels of endothelin, angiotensin II, aldosterone, and ammoniagenesis, thereby worsening renal fibrosis and causing progression of CKD. Measures that counter acid retention, such as providing alkali or modifying the quantity or type of dietary protein, reduce the levels of endothelin, angiotensin II, aldosterone, and ammoniagenesis, slowing progression of CKD. Alkali can be provided as NaHCO3, sodium citrate, or base in fruits and vegetables. A serum [HCO3−] of 24–26 mEq/l is targeted, because higher values can be associated with adverse consequences.
Insights into the mechanisms through which increased tissue acidity mediates progression of CKD and the beneficial impact of ameliorating positive acid balance underlie our recommendation for modalities that counter acid retention in CKD.
aMedical and Research Services, VHAGLA Healthcare System
bUCLA Membrane Biology Laboratory
cDivision of Nephrology, VHAGLA Healthcare System
dDavid Geffen School of Medicine, Los Angeles, California
eDivision of Nephrology, Department of Medicine, St. Elizabeth's Medical Center
fDepartment of Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA
Correspondence to Nicolaos E. Madias, MD, Division of Nephrology, St. Elizabeth's Medical Center, 736 Cambridge St., Boston, MA 02135, USA. E-mail: firstname.lastname@example.org