The goal of this clinical trial is to test whether potassium citrate improves skeletal health in adults and children with chronic kidney disease. The main questions it aims to answer are:

• To evaluate effects of potassium citrate treatment on bone quality and strength.
• To evaluate mechanism(s) underlying the effects of potassium citrate on skeletal health.

Participants will be asked to:

• provide blood, urine and answer questions about health and diet three times during an 8 months period
• undergo advanced bone imaging with high resolution-peripheral quantitative CT scan twice during 8 months
• take study pills for 4-6 weeks at the beginning of the study to ensure safety
• take either potassium citrate or placebo for 6 months during the blinded portion of the study

As part of the study, there will be a run-in period followed by the placebo-controlled randomized clinical trial. Researchers will compare the bone imaging between the potassium citrate and the placebo groups at the end of the study.

Chronic kidney disease is associated with bone loss and fractures in both children and adults, but bone protective therapies that are both proven and safe to use across the life-course in CKD are lacking. In this study, the investigators will conduct a pilot, double-blinded, randomized, placebo-controlled trial in 15 children and 88 adults evaluating the skeletal effects of potassium alkali therapy. These data will form the basis for a larger U01 proposal to determine the efficacy of potassium citrate on mitigating the effects of CKD on bone.

Inclusion Criteria (Pediatric Inclusion):

• Children 5-17 years old
• Estimated eGFR >30 and <90 ml/min/1.73m2 by CKiD U25 equations
• Females of child-bearing potential must have had a menstrual period in the last month
• Levels of PTH and alkaline phosphatase within 2x normal range and phosphorus within the normal range for age (per local laboratory reference assay)
• 25-hydroxy Vitamin D ≥ 20 ng/mL
• Females of child-bearing potential must be willing to use one form of effective contraception over the course of the study
• Proficiency in English or Spanish
• For participants < 18 years, the participant and/or parent/guardian capable of providing informed consent and assent (assessed by the provider)

Inclusion Criteria (Adult Inclusion):

• Adults ≥ 18 years old
• Estimated eGFR >30 and <90 ml/min/1.73m2 by the new CKD-Epi without race
• Pre-menopausal women of childbearing age must have had a menstrual period in the last month
• Levels of PTH and alkaline phosphatase within 2x normal range and phosphorus up to 5.0 mg/dL (per local laboratory reference assay)
• Levels of 25-hydroxy Vitamin D ≥ 20 ng/mL
• Women of childbearing potential must be willing to use one form of effective contraception over the course of the study
• Proficiency in English or Spanish

Exclusion Criteria (Pediatric and Adult):

• Baseline potassium ≥ 5.5 mEq/L or prior history of hyperkalemia in the last 6 months (potassium > 5.5 mEq/L) or currently taking a potassium lowering agent
• Alkali therapy within the prior 12 months
• Baseline ECG with abnormalities associated with increased risk of arrythmia, excluding left ventricular hypertrophy
• Baseline serum bicarbonate levels < 17 or ≥ 30 mEq/L
• Serum calcium < 8.6 mg/dL, adjusted for serum albumin
• Significant comorbidity causing acid-base imbalance (e.g., active cancer requiring chemotherapy, chronic liver failure, moderate or severe chronic obstructive lung disease, New York Heart Association class 2 or greater congestive heart failure, obstructive sleep apnea requiring nightly continuous positive airway pressure, active glomerular disease requiring immunosuppressive therapy, intestinal malabsorption or celiac disease)
• Plans to relocate out of the area in the next 3 months
• Urine pH > 8 or history of nephrolithiasis
• Lower extremity amputations or non-ambulatory
• Metabolic bone disease not related to CKD (e.g., Paget's disease, primary hyperparathyroidism)
• Endocrinopathy: untreated hyper or hypothyroidism, Cushing's syndrome
• Medical diseases that can affect therapy (severe myocardial damage, acute dehydration, delayed gastric emptying, esophageal compression, or intestinal obstruction or stricture)
• Use of bisphosphonates, denosumab, teriparatide, abaloparatide, romosozumab, raloxifene, estrogen or testosterone replacement therapy, or an unstable dose of glucocorticoids within the 12-months prior to enrollment
• Previous bilateral wrist and tibia fractures
• Solid or liquid organ transplant
• On dialysis or with rapidly deteriorating kidney function or expectation for transplantation or initiation of dialysis in less than 3 months
• Pregnancy or breastfeeding
• Prisoners or institutionalized individuals
• Unwillingness to provide informed consent