Sarcopenia, or loss of muscle and strength is common in patients with poor kidney function. Although a high protein diet is generally recommended for sarcopenia, patients with poor kidney function are advised to follow a low-protein diet. In this study, we will evaluate the practicality and potential benefits of two different amino acids (molecules that form proteins) in improving sarcopenia in patients with advanced kidney disease.

The study aims to improve muscle mass and strength. All study procedures are free of cost and do not require significant time commitment. You will have time to ask questions and discuss the study with your family, primary care physician, and your kidney doctor to make the decision if this is right study for you to participate in.

The overall objective of this study is to evaluate the feasibility, tolerability, metabolic effects, and potential therapeutic potential of isolated valine or EAA in patients with CKD stage 5.

• Primary Objective: To evaluate the feasibility, tolerability, and potential therapeutic benefits of isolated valine or EAA for the management of sarcopenia in patients with stage 5 CKD not on dialysis.
• Secondary Objectives: To assess the effects of valine and EAA on measures of kidney function and anorexia in patients with stage 5 CKD not on dialysis.

Inclusion Criteria:

1. Ability of participant to understand and the willingness to sign a written informed consent document.
2. Males and females of age 45-75 yrs
3. Hand grip strength of <26 kg for male and <16 kg for female
4. Documented diagnosis of estimated glomerular filtration rate (eGFR) of ≤15 mL/min/1.73 m2, based on CKD-EPI serum-creatinine based formula in the past ≥3 months in absence of acute kidney injury.
5. Not on dialysis and is not expected to initiate dialysis or any kidney replacement therapy in next 4 months
6. Receiving standard of care including dietary recommendation for diabetes, hypertension, CKD, and other comorbidities
7. Patients who are on an SGLT2-i or GLP-1 agonist should be on a stable dose for at least 3 months prior randomization, with no dose adjustments expected in the next 4 months
8. Serum HCO3 concentration 20-29 mmol/L based on two consecutive recent routine labs
9. HbA1c 7-9% based on most recent routine lab
10. Serum albumin ≥3.8 g/dL based on most recent routine lab
11. Blood hemoglobin ≥10 g/dL based on most recent routine lab
12. Willingness to adhere to lifestyle management, including diet and exercise as recommended by care providers, and to the study intervention, procedures, and regimen.

Exclusion Criteria:

1. Any known history of hypersensitivity/intolerance to valine or specific amino acids
2. Any condition that may indicate the individual is not "metabolically stable" which may include active infection, currently on systemic antibiotic, hospitalization within 2 weeks on consenting, active malignancy, on immunosuppressive agents, and unexplained significant weight loss during the past 3 months
3. With a cardiac pacemaker and/or an implantable cardioverter-defibrillator
4. Significant arthritis prohibiting strength test and walk gait speed test
5. Significant comorbidities including heart failure (NY Class III or IV), neurological disorders, HIV AIDS, etiology of CKD other than diabetes and hypertension, or any condition that could compromise the subject's ability to study procedures as judged by study clinician
6. Currently taking any protein supplements
7. Pregnant, lactating, childbearing women
8. History of Maple syrup urine disease (MSUD)
9. Scheduled for kidney transplantation or dialysis in next 4 months
10. Current participation in another interventional trial
11. Documented noncompliance with regard to clinic visits, medications, and lifestyle management.
12. Documentation of current or history of substance abuse.

This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals.

Data may be available beginning 1 year after the end of the trial and publication of the primary outcomes, and will be available for 24 months.

Data may be available to researchers who provide a methodologically sound proposals. Proposals should be directed to the principal investigator. To gain access, data requestors will need to sign a data access agreement.