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We propose to prevent and treat hyperphosphatemia associated with chronic kidney disease (CKD) by harnessing the power of hydrogel encapsulated phosphate-accumulating organisms and chemical agents to remove phosphate from the digestive system via a ‘therapeutic bubble tea’ ingested by a patient. Herein, we will test the efficacy of our innovative phosphate removal approach by utilizing a preclinical CKD mouse model. Hyperphosphatemia is commonly associated with bone and mineral disorders (referred to as CKD-MBD) which is a systemic disorder of mineral and bone metabolism. The high serum phosphate can leach the calcium from bones, contributing to osteoporosis, and cause the deposition of calcium in the heart and arteries increasing the risk of myocardial infarction and stroke. CKD-MBD results in increased risks for fractures, osteoporosis, vascular calcification, and cardiovascular disease. Hyperphosphatemia is considered one of the most critical contributing factors to CKD-MBD and is caused primarily by an inability of kidney excretory function to maintain phosphate homeostasis. CKD-MBD is also associated with hormonal abnormalities, including hyperparathyroidism, diminished calcitriol synthesis, and increased circulating FGF-23 concentrations, each of which can contribute to the observed increased morbidity and mortality risks. Hyperphosphatemia in individuals with CKD is commonly treated with prescribed dietary phosphate binders (such as calcium carbonate, calcium acetate, lanthanum carbonate and sevelamer hydrochloride). However, these agents only bind a modest portion of dietary phosphate, are associated frequently with gastrointestinal side effects, change the human gut microbiome, and require intake of many pills per meal decreasing the quality of life of people with CKD. New phosphate mitigation strategies are urgently needed to prevent and treat hyperphosphatemia. While our strategy is clearly high risk/high reward regarding the benefit to patients, we are aware of the regulatory hurdles for live bacterial therapeutics. As such, we are employing generally regarded as safe (GRAS) phosphate-accumulating organisms and encapsulating them in hydrogels. The bacteria are sequestered within the hydrogels as they transit through the gastrointestinal; tract and exit in the feces intact. We use what we call a double bubble strategy in which the bacteria are encapsulated within hydrogels that are coated in an outer layer that offers protection during post-production transport and consumption.
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