Objective: Sodium glucose cotransporter 2 inhibitors (SGLT2i) are widely used for diabetes, chronic heart failure, and chronic kidney disease. However, the incidence of volume depletion in patients when pharmacists implement risk-minimization strategies is unknown. Risk factors for volume depletion requiring further treatment have not been investigated in detail. Therefore, we retrospectively investigated the occurrence and risk factors of volume depletion in patients taking SGLT2i. Methods: This study included patients 18 years or older using SGLT2i between November 2014 and December 2021. Patients prescribed an SGLT2i at another hospital who were referred to our clinic where their initial SGLT2i prescription was a continuation prescription, patients who were referred to another medical institution during their 52-week follow-up, patients who discontinued their visits to our clinic or unknown reasons were excluded. The pharmacist provided patients with risk management plan literature at their first provision of an SGLT2 inhibitor. The endpoints were the rate of patients on SGLT2i who experienced volume depletion, rate of hospitalization to treat volume depletion, discontinuation rate, and risk factors. Results: SGLT2i caused volume depletion in 12 patients (0.5 %) and hospitalization in 1 patient (0.04 %), 83.3% of them occurred within 3 months after starting treatment. Risk factors for volume depletion were identified as age ≧ 75 years, renal dysfunction with eGFR less than 60 mL/min/1.73 m2, history of chronic heart failure, and chronic kidney disease. Conclusion: This study revealed risk factors associated with SGLT2i-induced volume depletion, but further investigation is required with an increased number of cases.

Metabolic acidosis is one of the most common complications of chronic kidney disease (CKD). It is associated with the progression of CKD, and many other functional impairments. Until recently, only serum bicarbonate levels have been used to evaluate acid-base changes in patients with reduced kidney function. However, recent emerging evidence suggests that nephrologists should reevaluate the clinical approach for diagnosing metabolic acidosis in patients with CKD based on two perspectives; pH and anion gap. Biochemistry and physiology textbooks clearly indicate that blood pH is the most important acid-base parameter for cellular function. Therefore, it is important to determine if the prognostic impact of hypobicarbonatemia varies according to pH level. A recent cohort study of CKD patients showed that venous pH modified the association between a low bicarbonate level and the progression of CKD. Furthermore, acidosis with a high anion gap has recently been recognized as an important prognostic factor, because veverimer, a nonabsorbable hydrochloride-binding polymer, has been shown to improve kidney function and decrease the anion gap. Acidosis with high anion gap frequently develops in later stages of CKD. Therefore, the anion gap is a time-varying factor and renal function (estimated glomerular filtration rate) is a time-dependent confounder for the anion gap and renal outcomes. Recent analyses using marginal structural models showed that acidosis with a high anion gap was associated with a high risk of CKD. Based on these observations, reconsideration of the clinical approach to diagnosing and treating metabolic acidosis in CKD may be warranted.