Sodium Bicarbonate and Mitochondrial Energetics in Persons With CKD

Summary

Skeletal muscle metabolic health is critical for mobility and an underrecognized target of metabolic acidosis in chronic kidney disease. Impaired muscle mitochondrial metabolism underlies poor physical endurance increasing the risk of mobility disability. The proposed project will use precise in vivo tools to study the pathophysiology of poor physical endurance in a clinical trial treating metabolic acidosis among persons living with chronic kidney disease.

Eligibility

Inclusion Criteria:

* Moderate-severe CKD determined by eGFR \<50ml/min per 1.73m2 by CKD EPI equation on at least 2 consecutive occasions.
* Metabolic acidosis defined as bicarbonate level\<24 on two consecutive occasions. Bicarbonate level of 24 or less allowed if eGFR\<=45ml/min per 1.73m2
* Age 21 to 85 years old

Exclusion Criteria:

* Type 1 diabetes
* Poorly controlled diabetes (HgbA1c\>10%)
* History of persistent hyperkalemia (K\>5.4)
* History of persistent hypokalemia (K\<3.3)
* Uncontrolled blood pressure (\>170/100)
* Chronic treatment with renal replacement therapy
* History of aortic dissection or severe valvular heart disease
* Exercise induced angina
* Uncontrolled cardiac dysrhythmia
* Oxygen dependent chronic obstructive pulmonary disease (COPD)
* Symptomatic claudication
* End stage liver disease
* Mobility disability defined as inability to walk without human assistance
* Dementia or psychosis
* Patients who cannot consent
* Active use of intraveneous drugs
* Non-english speaking
* History of transplant
* Implants that prohibit MRI measurements or trauma involving metal fragments
* Pacemaker
* Expectation to start dialysis during the course of study.
* Women who are breastfeeding, pregnant, or are wanting to become pregnant
* Any condition which in the judgement of the clinical investigator places the participant at risk from participation in the study.

Exclusion criteria for optional muscle biopsy

* Drugs- anticoagulants or antiplatelets:

  * Anticoagulants, any 1 (coumadin, rivaroxaban, apixaban, dabigatran, edoxaban)
  * Antiplatelets, any 2 (aspirin, cilostazol, clopidogrel, dipyridamole, prasugrel, ticragrelor, ticlopidine, vorapaxar)
* Platelet count \<100,000
* International normalized ratio (INR)\>1.4

Conditions7

Locations2 sites

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