A Novel Approach for Reducing Hyperoxaluria and Kidney Stone Risk.

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.

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.