Risk Factors for COVID-19 Infection in Adult Patients: A Retrospective Observational Study in Japan.

Purpose: The aim of the study was to identify the characteristics of patients infected with coronavirus disease 2019 (COVID-19) and to determine risk factors for COVID-19 infection in Japanese patients. Patients and Methods: We conducted a single-center retrospective observational study in Japanese adult patients (≥20 years) who visited Kenwakai Hospital (Nagano Japan). We analyzed data of 378 patients (mean age, 75 ± 14 years; men, 54%) from the hospital's electronic information system. COVID-19 was diagnosed by polymerase-chain reaction. Patients were divided into 2 groups based on diagnosis of COVID-19. Results: Patients infected with COVID-19 showed significantly higher rates of men (69.8 vs 51.6%, P = 0.025) than uninfected control patients. After adjustment for possible confounding factors, COVID-19 infection was significantly associated with BUN (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.01-1.03) and serum creatinine (Scr) (OR, 1.14; 95% CI, 1.05-1.24). This association was observed in men (BUN, P = 0.012; Scr, P = 0.012), but not in women (BUN, P = 0.43; Scr, P = 0.54). Conclusion: BUN and Scr are potential risk factors for infection of COVID-19 in Japanese patients, particularly in men. Our results suggest that renal parameters might be important in Japanese male patients for the early detection of COVID-19 infection.

A Pharmacovigilance Study of Drug-Induced Glaucoma Utilizing the Japanese Adverse Event Reporting System.

Purpose: Clinically, glaucoma is a serious problem because it is asymptomatic until a relatively late stage in most cases, which can lead to delays in the diagnosis and treatment of the disease. The purpose of this study was to clarify the rank-order of the association of glaucoma with the causative drugs using a spontaneous reporting system database. Methods: Data were extracted from the Japanese Adverse Drug Event Report database of the Pharmaceuticals and Medical Devices Agency (Japan). Based on reports of glaucoma caused by all drugs, we calculated the reporting odds ratio (ROR) and 95% confidence interval (CI) for glaucoma. Results: Among 609 reports of adverse events corresponding to glaucoma (46%, women), the most frequently implicated drug were steroids (prednisolone, betamethasone sodium phosphate, triamcinolone acetonide, and fluorometholone), pregabalin, ranibizumab, crizotinib, tacrolimus hydrate, darbepoetin alfa, and foscarnet sodium hydrate. Among 207 reports involved in angle-closure glaucoma (86%, women), anticholinergic drug and antidepressants ranked high and showed signals. Signals were also detected in bromazepam (ROR, 69.7; 95% CI, 30.9-157.5), oral brotizolam (ROR, 16.6; 95% CI, 6.18-44.8), and oral milnacipran hydrochloride (ROR, 22.8; 95% CI, 8.46-61.4) for angle-closure glaucoma. Conclusion: A national pharmacovigilance database enabled us to identify the drugs that frequently induce glaucoma. The likelihood of the reporting of glaucoma varied among the drugs, which should be used carefully in clinical practice to avoid it.

Zinc Acetate Hydrate Supplementation versus Polaprezinc Supplementation for Improving Hypozincemia in Hemodialysis Patients: A Randomized Clinical Trial.

Zinc supplementation may ameliorate zinc deficiency in maintenance hemodialysis patients; however, no standard protocol has been established. This study aimed to investigate the effects of zinc acetate hydrate (ZAH) and polaprezinc (PPZ) as zinc supplements in hemodialysis patients. We enrolled 75 hemodialysis patients with serum zinc levels <60 µg/dL for this study and randomly assigned Zinc supplementation to these 75 patients: 37 received ZAH (50 mg/day), and 38 received PPZ (34 mg/day). Serum zinc levels of both groups were compared every 4 weeks for 1 year. In both groups, serum zinc levels significantly increased at 4-52 weeks. Serum zinc levels were significantly higher in the ZAH group at 4-12 weeks; however, no significant differences were observed between the groups at 16-52 weeks. Adverse events requiring a reduction in the zinc dose, including copper deficiency, occurred significantly more frequently in the ZAH group. In conclusion, PPZ can safely maintain serum zinc levels for 1 year. ZAH provides rapid zinc supplementation but can cause adverse events.

Hyperkalemia by eplerenone or esaxerenone in the presence or absence of clarithromycin in hypertensive patients: a retrospective observational cohort study.

OBJECTIVE: Mineralocorticoid receptor antagonists (MRAs), eplerenone and esaxerenone, cause hyperkalemia dose-dependently. We investigated the cytochrome P450 3A4-mediated drug-drug interaction between the MRAs and clarithromycin. METHODS: This retrospective observational study included adult hypertensive patients with MRA plus clarithromycin or MRA alone with a propensity score matching (1:1). The difference in serum potassium level (ΔK, maximum level - baseline level) between groups was compared using the Mann-Whitney U -test. Linear regression analysis was used to detect variables that correlated with ΔK in patients with MRA plus clarithromycin. RESULTS: After propensity score matching (each nine patients), serum potassium level was elevated after treatment with MRA plus clarithromycin [4.3 (3.5 to 5.1) meq/l to 4.9 (4.0 to 5.5) meq/l, P  = 0.0234] and MRA alone [4.3 (4.0 to 4.7) meq/l to 4.6 (4.4 to 5.2) meq/l, P  = 0.0469]. Although there was no significant difference in ΔK between groups [MRA plus clarithromycin: 0.5 (0.1 to 1.1) meq/l vs. MRA alone: 0.3 (0.1 to 1.2) meq/l, P  = 0.7231], ΔK was significantly higher in esaxerenone plus clarithromycin than in esaxerenone alone [0.6 (0.5 to 1.1) meq/l vs. 0.1 (0.1 to 0.2) meq/l, P  = 0.0495]. Conversely, clarithromycin did not show a significant effect on ΔK in patients with eplerenone [0.4 (-0.2 to 1.2) meq/l vs. 0.8 (0.1 to 1.3) meq/l, P  = 0.5745]. A positive correlation was found between ΔK and age in patients with MRA plus clarithromycin ( y  = 0.03 ×  x - 1.38, r  = 0.71, P  = 0.0336). CONCLUSION: The drug-drug interaction between MRAs and clarithromycin was evident, particularly in esaxerenone. Serum potassium levels should be closely monitored in older patients.

Biologic Disease-Modifying and Other Anti-Rheumatic Drugs Use in Patients with Moderate-to-Severe Juvenile Idiopathic Arthritis Based on a Japanese Nationwide Claims Database.

Purpose: Biologic disease-modifying anti-rheumatic drugs (bDMARDs) are highly effective and safe against juvenile idiopathic arthritis (JIA), which is classified into systemic JIA (sJIA) and the other JIA categories (non-sJIA) according to differences in clinical symptoms and pathophysiology. The purpose of the current study was to investigate trends in patterns of prescribing bDMARDs for moderate-to-severe JIA using a relatively large sample size in Japan. Patients and Methods: A descriptive epidemiological study based on a nationwide claims database in Japan was conducted from 2012 to 2018 using the "JMDC Claims Database" to explain annual changes based on the number of patients prescribed bDMARDs. Study drugs were identified based on the Anatomical Therapeutic Chemical codes, such as methotrexate, glucocorticoids, non-steroidal anti-inflammatory drugs, and bDMARDs. Results: From a database of 6,862,244 patients, the following exclusion criteria were applied: aged ≥16 years, without "M08" in their ICD-10 code as disease, and missing the information of prescription date in the database during the study period, resulting in a final number of 111 JIA patients. We found an increasing trend for adalimumab and tocilizumab and a decreasing trend for methotrexate. Differences in medication use between sJIA and non-sJIA patients were also evident, being consistent with national and international guidelines. Conclusion: Although the introduction of bDMARDs has markedly improved the efficacy of JIA therapy, there are still many short- and long-term safety issues to be examined, including the risk of infection and potential risk of associated malignancy. Future studies are needed to clarify these issues.

Current Status of Adverse Event Profile of Cyclosporine in Kidney, Stem Cell, and Heart Transplantations Using the Japanese Pharmacovigilance Database.

BACKGROUND: Cyclosporine is widely used to prevent allograft rejection after transplantation. The purpose of this study was to clarify the adverse events profiles associated with cyclosporine in transplant patients using a spontaneous reporting system database. METHODS: Retrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report (JADER) database, with the reporting odds ratio (ROR) and 95% confidence interval (CI) for each adverse event. RESULTS: The database comprised 3,327, 958, and 956 reports associated with cyclosporine in the kidney, stem cell, and heart transplant patients, respectively. Infectious and renal disorders were commonly detected in these transplant patients. The signal scores of cyclosporine for toxic nephropathy were noteworthy in the kidney (ROR: 15.1, 95% CI: 11-20.8) and stem cell (ROR, 216; 95% CI, 29.3-1593) transplantation. Cyclosporine in heart transplantation was strongly associated with gastric cancer (ROR, 39.4; 95% CI, 16.7-93.2), but not kidney or stem cell transplantation. CONCLUSION: It was suggested that there is a diversity in the strength of the association between cyclosporine and adverse events in the kidney, stem cell, and heart transplantation. Our results may provide useful information for treatment with cyclosporine, although further research with more data is needed.

Adverse event profiles of drugs used for treatment of juvenile idiopathic arthritis according to spontaneous reporting system database.

Juvenile idiopathic arthritis (JIA) is a systemic inflammatory disease of childhood onset. The purpose of this study was to clarify the frequency of adverse events caused by drugs used in JIA treatment and characterize their safety profiles using a spontaneous reporting system database. We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. Adverse event reports on drugs used for the treatment of JIA and which were submitted to the Pharmaceuticals and Medical Devices Agency were analyzed, and the reporting odds ratio (ROR) and 95% confidence interval (CI) for reports on each adverse event were calculated. A total of 5,748 reports were identified in the treatment of JIA, in which 35 different drugs were involved. Adverse events by drugs in JIA were frequently reported in females (64.3%) and in those younger than 10 (61.2%). Among the most frequently reported drugs, prednisolone (36.8%) and tocilizumab (36.0%) were predominant. Prednisolone was significantly correlated with hematophagic histiocytosis (ROR, 1.37; 95% CI, 1.18 - 1.61). Tocilizumab was associated with a high ROR for pneumonia (ROR, 8.61: 95% CI, 5.81 - 12.7), a decreased neutrophil count (ROR, 6.1; 95% CI, 4.07 - 9.16), and lymphadenitis (ROR, 8.34; 95% CI, 4.2 - 16.6). Our results revealed the safety profile of drugs for the treatment of JIA patients. It was suggested that there is a diversity in drugs and their strength of association with adverse events in JIA patients. Our results may provide useful information for the treatment of JIA patients, although further research with more data is needed.

Ferroptosis: A Potential Therapeutic Target in Acute Kidney Injury.

Ferroptosis is a recently recognized form of nonapoptotic cell death that is triggered by reactive oxidative species (ROS) due to iron overload, lipid peroxidation accumulation, or the inhibition of phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). Recent studies have reported that ferroptosis plays a vital role in the pathophysiological process of multiple systems such as the nervous, renal, and pulmonary systems. In particular, the kidney has higher rates of O2 consumption in its mitochondria than other organs; therefore, it is susceptible to imbalances between ROS and antioxidants. In ischemia/reperfusion (I/R) injury, which is damage caused by the restoring blood flow to ischemic tissues, the release of ROS and reactive nitrogen species is accelerated and contributes to subsequent inflammation and cell death, such as ferroptosis, as well as apoptosis and necrosis being induced. At the same time, I/R injury is one of the major causes of acute kidney injury (AKI), causing significant morbidity and mortality. This review highlights the current knowledge on the involvement of ferroptosis in AKI via oxidative stress.

Design, synthesis, and evaluation of new vanin-1 inhibitors based on RR6.

Fourteen novel vanin-1 inhibitors coded OMP-# were designed from RR6 and successfully synthesized by a nucleophilic addition-elimination reaction of the pantetheinic acid-derived Weinreb amide as a key step under Barbier conditions. The synthesized OMP compounds exhibited inhibitory activity against human serum vanin-1 in vitro. Among the synthesized compounds, OMP-7, which possesses a trifluoromethoxy group at the para-position on the phenyl ring, exhibited the most potent activity, approximately 20 times that of the mother compound RR6. OMP-7 was further subjected to an in vivo assay using a normal hamster. More potent activity was observed than that of RR6 against both serum and renal vanin-1. The activity lasted for 4 h after injection against serum vanin-1 and 1 h after injection against renal vanin-1, whereas RR6 did not show the desired activity.

Evaluation of Medication Instruction Sheets for Patients Undergoing R-CHOP Therapy in Non-Hodgkin's Lymphoma.

BACKGROUND/AIM: High-dose chemotherapy is frequently administered to patients with hematologic malignancies, thereby causing severe adverse drug reactions (ADRs) at a relatively high frequency. To precisely monitor ADRs, we developed a medication instruction sheet (MIS) for patients who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) combination therapy for non-Hodgkin's lymphoma (NHL). Herein, we evaluated the usefulness of the MIS for managing ADRs in patients who received R-CHOP therapy. PATIENTS AND METHODS: We included patients aged ≥20 years who received R-CHOP therapy as first-line treatment for NHL at the Department of Hematology, Kyushu University Hospital, between August 2014 and December 2018. Medical professionals evaluated the possible occurrence of ADRs according to the present MIS and ADRs were graded according to the Common Toxicity Criteria, version 4.0 (National Cancer Institute, Bethesda, MD, USA). Finally, the accuracy of the MIS in predicting the occurrence of ADRs of different grades and during definite periods was evaluated. RESULTS: Seventy-five patients with NHL were included in the present study. Overall, 359 ADR events were monitored, which were predicted ADR items listed in the MIS. Among these, 254 (71%) events occurred during the same period as those listed in the MIS. The onset timing of any grade of an infusion reaction and peripheral neuropathy precisely matched those listed in the MIS. However, the accuracy of the MIS was reduced in patients with thrombocytopenia (42%). CONCLUSION: The present MIS could be useful for monitoring ADRs in patients with cancer undergoing R-CHOP therapy.

Usefulness of Medication Guidance Sheets for Patients With Non-Hodgkin's Lymphoma Receiving ESHAP±R Therapy.

BACKGROUND/AIM: The occurrence of chemotherapy-related serious adverse events (AEs) is associated with a poor prognosis of hematopoietic malignancies. We have developed a medication guidance sheet (MGS) for monitoring AEs occurring when combining chemotherapy with etoposide, methylprednisolone, cisplatin, cytarabine, and rituximab (ESHAP±R). In this study, the usefulness of MGS was investigated in non-Hodgkin's lymphoma patients. PATIENTS AND METHODS: The MGS was used to monitor AEs in 48 adult patients receiving ESHAP±R. The prediction accuracy of the MGS was estimated before and after modification based on practical data. RESULTS: A total of 246 AEs developed, all of which were predicted by the MGS. Among them, 149 events (61%) occurred during the same period as those predicted by the MGS. After modification of MGS for the onset and duration of AEs, the accuracy increased to 84%. CONCLUSION: The accuracy of the original MGS for ESHAP±R was insufficient but greatly improved after the AEs duration modification.

Drug-induced Neuropsychiatric Adverse Events Using Post-Marketing Surveillance.

BACKGROUND: Several studies reported that abnormal behavior was noted in pediatric patients receiving several drugs, including neuraminidase inhibitors (NIs). However, the information on drugs associated with abnormal behavior in a real-world setting remains limited. The purpose of this study was to clarify the drugs associated with abnormal behavior using a spontaneous reporting system database. METHODS: We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency were analyzed, and the reporting odds ratio at 95% confidence interval were calculated. RESULTS: A total of 1,144 reports of abnormal behavior were identified. The signals were detected through the association of 4 neuraminidase inhibitors (oseltamivir, zanamivir, laninamivir, and peramivir) with the abnormal behaviour. These signals were stronger for oseltamivir than other neuraminidase inhibitors. The signals were also detected for acetaminophen and montelukast. CONCLUSION: Our results should be able to raise physicians' awareness of drugs associated with abnormal behavior, but further investigation of these medications is warranted.

Range of serum transthyretin levels in hemodialysis patients at a high risk of 1-year mortality: A retrospective cohort study.

INTRODUCTION: Transthyretin (TTR) is a sensitive marker of nutritional status and independent risk factor for mortality in hemodialysis patients. However, its range associated with prognosis in Japanese hemodialysis patients is unknown. METHODS: Maintenance hemodialysis Patients (n = 664) were enrolled, and their TTR levels were measured to assess 1-year mortality. Patients were assigned to four groups based on TTR levels: <20, 20 to <30 (control), 30 to <40, and ≥40 mg/dl. One-year mortality at each TTR range was analyzed using a Cox proportional hazards model after adjustment for prognostic factors. RESULTS: Seventy-seven (11.6%) deaths were recorded during follow-up. The hazard ratio (HR) of TTR <20 mg/dl was significantly higher compared with the control group in terms of all-causes (HR: 3.14) and non-cardiovascular mortality (HR: 6.986). CONCLUSION: TTR levels were independent and sensitive predictors of mortality in hemodialysis patients. TTR <20 mg/dl is a risk factor for 1-year mortality in Japanese hemodialysis patients.

Clinical predictors of nephrotoxicity associated with teicoplanin: Meta-analysis and meta-regression.

Teicoplanin is a glycopeptide antibiotic against methicillin-resistant Staphylococcus aureus infections. However, the impact of clinical characteristics on nephrotoxicity associated with teicoplanin has not been determined. This meta-analysis aimed to investigate the relationship between clinical characteristics and nephrotoxicity associated with teicoplanin. We identified clinical research published from January 1975 to June 2021 using PubMed, Cochrane Library, and Scopus, which described the nephrotoxicity associated with teicoplanin. Meta-analysis determined the incidence of nephrotoxicity. Using meta-regression analysis, we evaluated the impact of clinical characteristics on outcomes. Of the 567 articles, eight articles including 634 patients were analysed. The overall incidence of nephrotoxicity associated with teicoplanin was 11.0% (95% confidence interval: 8.0-13.0) for the fixed-effect model. Additionally, patients with >65 years had a high trend for the risk of nephrotoxicity compared to those with ≤65 years (>65 years; 12.0% [95% confidence interval: 9.0-15.0] vs. ≤65 years; 7.0% [95% confidence interval: 3.0-12.0], p = 0.09) for the fixed-effect model. Meta-regression analysis demonstrated that only serum albumin level negatively correlated with the risk of nephrotoxicity (y = -17.0 x + 56.7, r = 0.74, p = 0.01). This meta-analysis ascertained that hypoalbuminemia leads to nephrotoxicity associated with teicoplanin.

In Vivo and In Vitro Evaluation of Urinary Biomarkers in Ischemia/Reperfusion-Induced Kidney Injury.

Oxidative stress plays an important role in the pathophysiology of acute kidney injury (AKI). Previously, we reported that vanin-1, which is involved in oxidative stress, is associated with renal tubular injury. This study was aimed to determine whether urinary vanin-1 is a biomarker for the early diagnosis of AKI in two experimental models: in vivo and in vitro. In a rat model of AKI, ischemic AKI was induced in uninephrectomized rats by clamping the left renal artery for 45 min and then reperfusing the kidney. On Day 1 after renal ischemia/reperfusion (I/R), serum creatinine (SCr) in I/R rats was higher than in sham-operated rats, but this did not reach significance. Urinary N-acetyl-ß-D-glucosaminidase (NAG) exhibited a significant increase but decreased on Day 2 in I/R rats. In contrast, urinary vanin-1 significantly increased on Day 1 and remained at a significant high level on Day 2 in I/R rats. Renal vanin-1 protein decreased on Days 1 and 3. In line with these findings, immunofluorescence staining demonstrated that vanin-1 was attenuated in the renal proximal tubules of I/R rats. Our in vitro results confirmed that the supernatant from HK-2 cells under hypoxia/reoxygenation included significantly higher levels of vanin-1 as well as KIM-1 and NGAL. In conclusion, our results suggest that urinary vanin-1 might be a potential novel biomarker of AKI induced by I/R.

Biomarkers of high salt intake.

High salt intake is associated with hypertension, which is a leading modifiable risk factor for cardiovascular disease (CVD) and chronic kidney disease (CKD). International Guidelines recommend a large reduction in the consumption of sodium to reduce blood pressure, organ damage, and mortality. In its early stages, the symptoms of CKD are generally not apparent. CKD proceeds in a "silent" manner, necessitating the need for urinary biomarkers to detect kidney damage at an early stage. Since traditional renal biomarkers, such as serum creatinine, are not sufficiently sensitive, difficulties are associated with detecting kidney damage induced by a high salt intake, particularly in normotensive individuals. Several new biomarkers for renal tubular damage, such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), vanin-1, liver-type fatty acid-binding protein (L-FABP), and monocyte chemotactic protein-1 (MCP-1), have recently been identified. However, few studies have investigated early biomarkers for CKD progression associated with a high salt diet. This chapter provides insights into novel biomarkers for CKD in normo- and hypertensive individuals with a high salt intake. Recent studies using spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) fed a high salt diet identified urinary vanin-1 and NGAL as early biomarkers for renal tubular damage in SHR and WKY, whereas urinary KIM-1 was a useful biomarker for salt-induced renal injury in SHR only. Clinical studies are needed to confirm these findings.

Current status of adverse event profile of tacrolimus in patients with solid organ transplantation from a pharmacovigilance study.

OBJECTIVE: The calcineurin inhibitor tacrolimus has been widely used to prevent allograft rejection after transplantation. The purpose of this study was to clarify the adverse events associated with tacrolimus in solid organ transplantation using a spontaneous reporting system database. MATERIALS AND METHODS: We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency were analyzed, and the reporting odds ratio (ROR) and 95% confidence interval (CI) for each adverse event were calculated. RESULTS: The database comprised 26,620 reports associated with tacrolimus, of which 2,014, 1,988, and 725 reports involved heart, kidney, and liver transplantation, respectively. Infectious disorder was commonly detected in these transplant patients. There was a significant association between tacrolimus use and colon cancer in patients undergoing heart transplantation (ROR: 3.33, 95% CI: 2.18 - 5.08), but not kidney or liver transplantation. Tacrolimus use in those undergoing kidney transplantation is strongly associated with bronchitis (ROR, 8.95; 95% CI, 6.34 - 12.6). A signal for seizure was detected in liver transplant patients with tacrolimus (ROR, 4.12; 95% CI, 1.77 - 9.59). CONCLUSION: It was suggested that there is a diversity in the strength of the association between tacrolimus and adverse events in patients receiving heart, kidney, and liver transplantation. Our results may provide useful information for treatment with tacrolimus, although further research with more data is needed to clarify this.

Association of urinary vanin-1 with kidney function decline in hypertensive patients.

Previously, the authors reported the utility of urinary vanin-1 as an early biomarker of kidney injury in spontaneously hypertensive rats and in humans. However, little is known about whether urinary vanin-1 can be used to predict the clinical outcome. This study aimed to evaluate the predictive power of urinary vanin-1 based on kidney function decline in hypertensive patients. The authors measured urinary vanin-1 in 147 patients at the baseline and examined its association with the incidence of ≥20% decline in the estimated glomerular filtration rate (eGFR) using the Cox regression analysis. The mean age of the patients averaged 72.9 ± 8.2 years, and 39% were women. Median (interquartile range) urinary vanin-1 was 0.33 (0-2.6) ng/mg Cr During a median follow-up of 12 months, 14 patients showed kidney function decline. A higher urinary vanin-1 level was associated with an increased risk of kidney function decline (hazard ratio, 9.87; 95% CI, 1.11-87.5) (p = .04) in the fully adjusted model. In conclusion, urinary vanin-1 is an independent risk factor for kidney function decline in hypertensive patients and it could be useful in clinical settings. The underlying pathophysiologic mechanisms warrant additional investigation.

Association between a low dose of proton pump inhibitors and kidney function decline in elderly hypertensive patients: a retrospective observational study.

OBJECTIVES: Proton pump inhibitors (PPIs) are widely used for acid suppression therapy. Recently, PPI use was reported to be associated with chronic kidney disease (CKD); however, whether a low dose of PPIs is associated with CKD remains unknown. METHODS: This retrospective observational study included hypertensive patients who visited Kenwakai Hospital between 2017 and 2019. Renal parameters, such as the estimated glomerular filtration rate (eGFR) and serum creatinine (Scr), were extracted from medical records and compared between three years before treatment and the baseline. PPI use was assessed as cumulative exposure for three years. RESULTS: The study population included 152 patients (57.9% men; mean age, 74.5 years). Of those, 35.5% were PPI users (low dose, 17.1%; high dose, 18.4%). A significant decrease in eGFR and an increase in Scr were observed between three years before treatment and the baseline in the high-dose PPI group but not the non-use or low-dose PPI groups. CONCLUSIONS: Our results suggest that a low dose of PPIs may be safe in clinical settings, but further prospective studies are needed to clarify our findings.