Changes in estimated glomerular filtration rate in patients administered proton pump inhibitors: a single-center cohort study.

Proton pump inhibitor (PPI) use may be associated with renal dysfunction. Renal dysfunction in PPI users requires evaluation of development and progression risks simultaneously, using estimated glomerular filtration rate (eGFR) slope, which indicates changes in eGFR per year. To the best of our knowledge, no studies have evaluated eGFR slope in PPI users. This study investigated the association between PPI use and renal dysfunction using eGFR slope. A single-center cohort study was conducted using the health records data at Hamamatsu University Hospital in Japan. Participants were defined as first users of acid-suppressing drugs (PPIs or Histamine H2 receptor antagonists (H2RAs)) from 2010 to 2021 and continuously prescribed for ≥ 90 days. The H2RA group was used for the propensity-score matching (PSM) to the PPI group to minimize the effects of confounders. The eGFR slope was estimated using a linear mixed effects model. Participants were stratified by baseline eGFR and age, respectively, as subgroup analyses. A total of 4,649 acid-suppressing drug users met the inclusion criteria, including 950 taking H2RAs and 3,699 PPIs. After PSM, 911 patients were assigned to each group. The eGFR slopes of the PPI and H2RA users were -4.75 (95% CI: -6.29, -3.20) and -3.40 (-4.38, -2.42), respectively. The difference between the groups was not significant. Significant declines in eGFR were observed with PPIs with baseline eGFR ≥ 90 and age < 65. PPI use for ≥ 90 days may hasten eGFR decline compared to H2RA use, especially in patients with eGFR ≥ 90 or age < 65.

Influence of Genetic Polymorphisms and Concomitant Anxiolytic Doses on Antidepressant Maintenance Doses in Japanese Patients with Depression.

To prevent recurrent depression, patients should ideally continue treatment for >6 months with the antidepressant dose that effectively suppressed acute depressive symptoms. However, there are inter-individual differences in the antidepressant doses required to achieve response and maintenance. Therefore, this study was conducted to examine the role of clinical features, including genetic polymorphisms, on the antidepressant dose required for maintenance therapy in 82 Japanese patients with depression. We calculated the antidepressant dose using the imipramine equivalent scale and the dose of concomitant anxiolytics and hypnotics using the diazepam equivalent scale. The 82 participants were classified into two groups based on the median imipramine equivalent dose, and we examined the influence of patient characteristics and the presence of genetic polymorphisms of brain-derived neurotropic factor (BDNF; rs6265) and cyclic adenosine monophosphate responsive element-binding protein 1 (CREB1; rs2253306, rs4675690, rs769963) on the antidepressant maintenance dose. Using a multivariate logistic regression analysis, we found that the concomitant diazepam equivalent dose and presence of the CREB1 rs4675690 polymorphism were significantly associated with the antidepressant maintenance dose. We concluded that these factors influenced the antidepressant dose in maintenance therapy among Japanese patients with depression. However, further research is required in large cohorts.