We propose to study the effects of sodium bicarbonate treatment in subjects with chronic kidney disease (CKD). The proposal is based on the broad hypothesis that: Alkali supplementation will benefit patients with chronic kidney disease. Four specific domains of disabilities suffered by CKD patients will be examined for the effects of sodium bicarbonate treatment: 1) Muscle weakness, 2) Insulin resistance, 3) Renal injury, and 4) Bone disease. The study design is a randomized, prospective, blinded and parallel comparison of sodium bicarbonate and placebo. In the domains of effects on muscle and bone and insulin sensitivity, standard clinically relevant endpoints should be reached. In the domain of renal injury a formal trial of progression is not attempted as it would be beyond the scope of a single center RO1. However, meaningful biomarkers and tubular functions reflecting renal injury will be measured. Also the effects of alkali therapy on standard markers of renal functional will be defined. Such definition would be critical to any larger trial. Despite the well recognized coincidence of acidosis and CKD and the accumulated evidence of deleterious effects of acidosis, treatment of acidosis has been very little tested especially with standard clinical outcomes. Indeed, compared to commercially driven studies of other metabolic disabilities of CKD, e.g. anemia, phosphate retention and vitamin D deficiency, treatment of acidosis has been neglected. Yet based on fundamental research, alkali supplementation has a strikingly broad array of potential benefits.

Public Health Relevance

Chronic kidney disease is common in the US with about 10 million people having depressed kidney function. They are at high risk for progressing to kidney failure and are also at high risk for premature death from cardiovascular disease. They suffer a large number of associated debilities including progressive weakness and bone disease. We have a very limited set of treatments for these people. We are proposing to test the benefits of a simple therapy - sodium bicarbonate. This compound is the same as baking soda and will be administered to combat the acid accumulation known to occur with chronic kidney disease. We hypothesize that by reducing acid retention we will improve muscle weakness, enhance the response to insulin, reduce bone breakdown and lessen kidney damage.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK087783-03
Application #
8140528
Study Section
Pathobiology of Kidney Disease Study Section (PBKD)
Program Officer
Kimmel, Paul
Project Start
2010-09-15
Project End
2016-08-31
Budget Start
2012-04-01
Budget End
2013-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$314,000
Indirect Cost
$114,000
Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Crowley, Steven D (2014) The cooperative roles of inflammation and oxidative stress in the pathogenesis of hypertension. Antioxid Redox Signal 20:102-20
Atkinson, Meredith A; Melamed, Michal L; Kumar, Juhi et al. (2014) Vitamin D, race, and risk for anemia in children. J Pediatr 164:153-158.e1
Zhang, Jiandong; Crowley, Steven D (2013) The role of type 1 angiotensin receptors on T lymphocytes in cardiovascular and renal diseases. Curr Hypertens Rep 15:39-46
Abramowitz, Matthew K; Melamed, Michal L; Bauer, Carolyn et al. (2013) Effects of oral sodium bicarbonate in patients with CKD. Clin J Am Soc Nephrol 8:714-20
Essien, Utibe; Goel, Narender; Melamed, Michal L (2013) Role of vitamin D receptor activation in racial disparities in kidney disease outcomes. Semin Nephrol 33:416-24
Melamed, Michal L; Thadhani, Ravi I (2012) Vitamin D therapy in chronic kidney disease and end stage renal disease. Clin J Am Soc Nephrol 7:358-65
Abramowitz, Matthew K; Hostetter, Thomas H; Melamed, Michal L (2012) Lower serum bicarbonate and a higher anion gap are associated with lower cardiorespiratory fitness in young adults. Kidney Int 81:1033-42
Skversky, Amy L; Kumar, Juhi; Abramowitz, Matthew K et al. (2011) Association of glucocorticoid use and low 25-hydroxyvitamin D levels: results from the National Health and Nutrition Examination Survey (NHANES): 2001-2006. J Clin Endocrinol Metab 96:3838-45