林 宏樹

Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of end-stage kidney disease (ESKD). Vasopressin plays a pivotal role in ADPKD progression; therefore, the selective vasopressin V2 receptor antagonist tolvaptan is used as a key drug in the management of ADPKD. On the other hand, sodium-glucose cotransporter-2 inhibitors (SGLT2i), which may possibly stimulate vasopressin secretion due to the diuretic effect of the drug, have been shown to have both renal and cardioprotective effects in various populations, including those with non-diabetic chronic kidney disease. However, the effect of SGLT2i in patients with ADPKD have not been fully elucidated. Herein, we report the case of a patient with ADPKD on tolvaptan who was administered the SGLT2i dapagliflozin. The patient was a Japanese woman diagnosed with ADPKD at age 30. Despite the treatment with tolvaptan, eGFR was gradually declined from 79.8 to 50 ml/min/1.73 m2 in almost 5 years and 10 mg of dapagliflozin was initiated in the hope of renoprotective effects. Although a small increase in vasopressin levels was observed, eGFR decline rate was moderated after dapagliflozin initiation. This case suggested an additional renoprotective effect of dapagliflozin in patient with ADPKD receiving tolvaptan. Although there is no evidence about the renal protective effect of SGLT2i in patients with ADPKD, we hereby report a case successfully treated with dapagliflozin for approximately 2 years. Further research, including clinical trials, is needed to evaluate whether SGLT2i are effective in patients with ADPKD.

BACKGROUND: Sodium zirconium cyclosilicate, a non-absorbed non-polymer zirconium silicate, is a new potassium binder for hyperkalemia. A previous report showed that administering sodium zirconium cyclosilicate to patients with hyperkalemia allows a higher continuation rate of renin-angiotensin-aldosterone system inhibitors. However, no studies have compared sodium zirconium cyclosilicate with existing potassium binders for renin-angiotensin-aldosterone system inhibitor continuity. The purpose of this study was to evaluate the effect of sodium zirconium cyclosilicate on angiotensin-converting enzyme inhibitor /angiotensin receptor blocker continuation in patients with hyperkalemia compared to that of calcium polystyrene sulfonate. METHODS: Patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers who were newly prescribed sodium zirconium cyclosilicate or calcium polystyrene sulfonate to treat hyperkalemia at a tertiary referral hospital between August 2020 and April 2022 were enrolled in this single-center, retrospective observational study. The primary outcome measure was angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription three months after initiating potassium binders. RESULTS: In total, 174 patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers who were newly administered sodium zirconium cyclosilicate (n = 62) or calcium polystyrene sulfonate (n = 112) were analyzed. The prescription rate of angiotensin-converting enzyme inhibitors /angiotensin receptor blockers at 3 months was significantly higher in the sodium zirconium cyclosilicate group than in the calcium polystyrene sulfonate group (89 vs. 72%). Multivariate logistic regression models showed that sodium zirconium cyclosilicate was independently associated with the primary outcome (odds ratio 2.66, 95% confidence interval 1.05-7.43). The propensity score-matched comparison also showed a significant association between sodium zirconium cyclosilicate and the primary outcome. CONCLUSIONS: Our study suggests that administering sodium zirconium cyclosilicate to patients with hyperkalemia allows for a higher continuation rate of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers than calcium polystyrene sulfonate. These findings suggest that sodium zirconium cyclosilicate has potential benefits for patients with chronic kidney disease receiving renin-angiotensin-aldosterone system inhibitors.

OBJECTIVES: Cardiovascular and renal diseases are closely related. Brain natriuretic peptide (BNP) and urinary albumin are established predictors for cardiac and renal morbidities, respectively. To date, no reports have investigated the combined predictive value of BNP and urinary albumin for long-term cardiovascular-renal events in patients with chronic kidney disease (CKD). The aim of this study was to investigate this theme. METHODS: Four hundred eighty-three patients with CKD were enrolled into this study and followed-up for 10 years. The endpoint was cardiovascular-renal events. RESULTS: During the median follow-up period of 109 months, 221 patients developed cardiovascular-renal events. Log-transformed BNP and urinary albumin were identified as independent predictors for cardiovascular-renal events, with a hazard ratio of 2.59 (95% confidence interval [CI], 1.81-3.72) and 2.27 (95% CI, 1.82-2.84) for BNP and urinary albumin, respectively. For the combined variables, the group with high BNP and urinary albumin had a markedly higher risk (12.41-times; 95% CI 5.23-29.42) of cardiovascular-renal events compared with that of the group with low BNP and urinary albumin. Adding both variables to a predictive model with basic risk factors improved the C-index (0.767, 0.728 to 0.814, p=0.009), net reclassification improvement (0.497, p<0.0001), and integrated discrimination improvement (0.071, p<0.0001) more than each of them alone. CONCLUSIONS: This is the first report to demonstrate that the combination of BNP and urinary albumin can stratify and improve the predictability of long-term cardiovascular-renal events in CKD patients.