New Approach To Prevention Of Calcium Phosphate Kidney Stones - Project Summary The objective of this study is to test a novel treatment, sodium glucose co-transporter-2 inhibitor medications, for prevention of recurrent idiopathic calcium phosphate (CaP) stones. Kidney stones are common (>10% in the U.S.) and prevalence is rising, leading to higher morbidity and cost. Idiopathic calcium oxalate (CaOx) and CaP stones are the most common types. Both stone types are associated with high recurrence rates, but CaP stones have the highest. High recurrence rates are associated with acute pain and hematuria, and higher risk of chronic kidney disease and end-stage kidney disease. Recurrent events also contribute to the high economic burden to individuals and the healthcare system, including costs from lost workdays and acute care visits. Yet, the only currently available prevention options have not updated in decades and no previous clinical trials have specifically focused on the highest recurring CaP patients. Prevention programs are key to reducing recurrent kidney stone events. Prevention is aimed at lowering supersaturation (SS) of CaOx and CaP as this lowers stone risk. Prevention strategies are limited for both stone types but more limited for CaP. Limited strategies include lowering SS by increasing urine volume with increased fluid intake or reducing urine calcium with low sodium intake or thiazide medications. Supplemental alkali (e.g. potassium citrate) decreases stone risk by increasing urine citrate, an inhibitor of calcium crystals, and is effective in CaOx patients but it is not known if it is effective in CaP patients. Alkali also increases urine pH which increases CaP SS and can potentially worsen CaP stone disease. It is also known that idiopathic CaP patients have an underlying disordered acid-base handling that is not present in CaOx patients. The underlying acid-base disorder and subsequent different response to alkali therapy highlights that CaOx and CaP are distinct patient populations. For this reason, both groups need to be separately studied in prevention trials. Sodium glucose co-transporter inhibitors (SGLT2i) are associated with improved outcomes in many disease states and have also been epidemiologically associated with lower kidney stone risk compared to other diabetes medications. This is likely because, like alkali, SGLT2i increase urine citrate but unlike alkali, SGLT2i decrease urine pH in healthy volunteers. Both CaOx and CaP will benefit from higher urine citrate but SGLT2i may be uniquely beneficial for CaP patients as the lower urine pH reduces CaP SS and therefore stone risk. However, no previous studies of the effect of SGLT2i on urine composition have included stone patients. We will study the effects SGLT2i have on urine citrate, pH and CaP SS in a highly selected population of CaP and CaOx stone patients. We have engaged with the kidney stone community (Kidney Stone Engagement Core) and will work with them throughout study design, implementation, and conduct. This work will lay the foundation for a future larger trial determining the ability of SGLT2i to prevent both stones but particularly CaP stones.
