It is estimated that in the United States there are approximately 8 million individuals with moderate to severe chronic kidney disease (CKD), not on dialysis. Volume expansion plays an important role in the pathogenesis of hypertension in patients with CKD. For this pilot study, the investigators hypothesize that administration of chlorthalidone among patients with moderate to severe CKD will improve blood pressure (BP).

Inclusion Criteria:

• Age greater than 18 years.
• Estimated glomerular filtration rate (eGFR) ≤ 45 ml/min/1.73m2 but ≥20 mL/min/1.73m2.
• Poorly controlled blood pressure by 24-hour ambulatory blood pressure (BP) monitoring.
• Treated hypertension: use of at least one antihypertensive drug. One of the drugs should be either an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). If these are contraindicated then use of a beta-blocker is required.

Exclusion Criteria:

• Use of thiazide or thiazide-like drugs in the previous 3 months.
• Use of furosemide in a dose >200 mg/d.
• Ambulatory BP of either ≥160 systolic or ≥100 mmHg by 24-hour ambulatory BP monitoring.
• Expected to receive renal replacement therapy within the next 3 months.
• Vascular event such as myocardial infarction, heart failure hospitalization, or stroke within 3 months prior to randomization.
• Pregnant or breastfeeding women or women who are planning to become pregnant or those not using a reliable form of contraception (oral contraceptives. condoms and diaphragms will be considered reliable).
• Known hypersensitivity to thiazide or sulfa drugs.
• Organ transplant recipient or therapy with immunosuppressive agents. Nasal or inhaled corticosteroids will be permitted.

Participants who completed the two-week run-in and enrolled in the study are included in the baseline analysis.

Baseline (week 0) through study completion (week 12)