This pilot study is proposing a novel approach to directly target intestinal oxalate absorption with the drug Tenapanor, which was recently FDA-approved for treating hyperphosphatemia in patients with chronic kidney disease. Tenapanor works by blocking paracellular phosphate absorption by the intestine, but the underlying mechanisms have not been clearly defined. Since phosphate and oxalate ions are absorbed through the same paracellular pathway, and are of similar size and charge, Tenapanor is hypothesized to also reduce dietary oxalate absorption and consequently lower urinary oxalate excretion.

The proposed proof-of-concept studies will determine whether Tenapanor reduces urine oxalate in normal human subjects receiving a high-oxalate diet in a crossover placebo-controlled short-term metabolic study.

Study Design Screening - One 24-hour urine for analysis of stone-risk profile, one blood sample for comprehensive metabolic panel and cystatin C, one stool sample for fecal calprotectin, physical exam, social and medical history, vital signs, demographic information, personal information.This is a two-phase study, each phase is 5 days in duration.

Phase 1: The subjects will consume a pre-prepared oxalate-rich metabolic diet for 5 days while taking 30 mg Tenapanor or Placebo twice a day just prior to the morning and evening meals. On days 4 and 5 they will collect two 24-hour urines for measurement of urine oxalate and stone-risk profile.

Washout: The subjects will undergo a 9-day washout period. Phase 2: The subjects will consume a pre-prepared oxalate-rich metabolic diet for 5 days while taking 30 mg Tenapanor or Placebo twice a day just prior to the morning and evening meals. On days 4 and 5 they will collect two 24-hour urines for measurement of urine oxalate and stone-risk profile.

Inclusion Criteria:

• Normal, healthy adult volunteers

Exclusion Criteria:

• Personal history of kidney stones
• Pregnant or nursing
• Recurrent urinary tract infections
• Lithogenic urine chemistry at baseline (oxalate > 45 mg/24 h, urine calcium > 300 mg/24 h)
• Chronic kidney disease (eGFR < 90 mL/min/1.73m2)
• Personal history of GI disease, GI obstruction, or GI surgery
• Chronic diarrhea
• Intestinal inflammation (Fecal calprotectin > 120 mcg/g)
• Drugs which are substrates of OATP2B1 (e.g. enalapril)
• Chronic use of sodium polystyrene sulfonate, angiotensin-converting enzyme inhibitors, diuretics, antacids, alkali treatment, or carbonic anhydrase inhibitors.