Background: Dipeptidyl peptidase-4 (DPP4) inhibitors are frequently prescribed for patients with type 2 diabetes; however, their cost can pose a significant barrier for those with impaired kidney function. This study aimed to estimate the economic benefits of substituting non-renal dose-adjusted (NRDA) DPP4 inhibitors with renal dose-adjusted (RDA) DPP4 inhibitors in patients with both impaired kidney function and type 2 diabetes. Methods: This retrospective cohort study was conducted from January 1, 2012 to December 31, 2018, using data obtained from common data models of five medical centers in Korea. Model 1 applied the prescription pattern of participants with preserved kidney function to those with impaired kidney function. In contrast, model 2 replaced all NRDA DPP4 inhibitors with RDA DPP4 inhibitors, adjusting the doses of RDA DPP4 inhibitors based on individual kidney function. The primary outcome was the cost difference between the two models. Results: In total, 67,964,996 prescription records were analyzed. NRDA DPP4 inhibitors were more frequently prescribed to patients with impaired kidney function than in those with preserved kidney function (25.7%, 51.3%, 64.3%, and 71.6% in patients with estimated glomerular filtration rates [eGFRs] of ≥60, <60, <45, and <30 mL/min/1.73 m2, respectively). When model 1 was applied, the cost savings per year were 7.6% for eGFR <60 mL/min/1.73 m2 and 30.4% for eGFR <30 mL/min/1.73 m2. According to model 2, 15.4% to 51.2% per year could be saved depending on kidney impairment severity. Conclusion Adjusting the doses of RDA DPP4 inhibitors based on individual kidney function could alleviate the economic burden associated with medical expenses.

This retrospective cohort study aimed to compare coronavirus disease 2019 (COVID-19)-related clinical outcomes between patients with and without gout. Electronic health recordbased data from two centers (Seoul National University Hospital [SNUH] and Boramae Medical Center [BMC]), from January 2021 to April 2022, were mapped to a common data model. Patients with and without gout were matched using a large-scale propensityscore algorithm based on population-level estimation methods. At the SNUH, the risk for COVID-19 diagnosis was not significantly different between patients with and without gout (hazard ratio [HR], 1.07; 95% confidence interval [CI], 0.59–1.84). Within 30 days after COVID-19 diagnosis, no significant difference was observed in terms of hospitalization (HR, 0.57; 95% CI, 0.03–3.90), severe outcomes (HR, 2.90; 95% CI, 0.54–13.71), or mortality (HR, 1.35; 95% CI, 0.06–16.24). Similar results were obtained from the BMC database, suggesting that gout does not increase the risk for COVID-19 diagnosis or severe outcomes.

Background: The genetically predicted lipid-lowering effect of HMGCR or PCSK9 variant can be used to assess drug proxy effects on kidney function. Methods: Mendelian randomization (MR) analysis-identified HMGCR and PCSK9 genetic variants were used to predict the low-density lipoprotein (LDL) cholesterol-lowering effects of medications targeting related molecules. Primary summary-level outcome data for log-estimated glomerular filtration rate (eGFR; creatinine) were provided by the CKDGen Consortium (n = 1,004,040 European) from a meta-analysis of CKDGen and UK Biobank data. We also conducted a separate investigation of summary-level data from CKDGen (n = 567,460, log-eGFR [creatinine]) and UK Biobank (n = 436,581, log-eGFR [cystatin C]) samples. Summary-level MRs using an inverse variance weighted method and pleiotropy-robust methods were performed. Results: Summary-level MR analysis indicated that the LDL-lowering effect predicted genetically by HMGCR variants (50-mg/dL decrease) was significantly associated with a decrease in eGFR (–1.67%; 95% confidence interval [CI], –2.20% to –1.13%). Similar significance was found in results from the pleiotropy-robust MR methods when the CKDGen and UK Biobank data were analyzed separately. However, the LDL-lowering effect predicted genetically by PCSK9 variants was significantly associated with an increase in eGFR (+1.17%; 95% CI, 0.10%–2.25%). The results were similarly supported by the weighted median method and in each CKDGen and UK Biobank dataset, but the significance obtained by MR-Egger regression was attenuated. Conclusion Genetically predicted HMG-CoA reductase inhibition was associated with low eGFR, while genetically predicted PCSK9 inhibition was associated with high eGFR. Clinicians should consider that the direct effect of different types of lipid-lowering medication on kidney function can vary.

Objectives: The objective of this study was to develop and validate a multicenter-based, multi-model, time-series deep learning model for predicting drug-induced liver injury (DILI) in patients taking angiotensin receptor blockers (ARBs). The study leveraged a national-level multicenter approach, utilizing electronic health records (EHRs) from six hospitals in Korea. Methods: A retrospective cohort analysis was conducted using EHRs from six hospitals in Korea, comprising a total of 10,852 patients whose data were converted to the Common Data Model. The study assessed the incidence rate of DILI among patients taking ARBs and compared it to a control group. Temporal patterns of important variables were analyzed using an interpretable timeseries model. Results: The overall incidence rate of DILI among patients taking ARBs was found to be 1.09%. The incidence rates varied for each specific ARB drug and institution, with valsartan having the highest rate (1.24%) and olmesartan having the lowest rate (0.83%). The DILI prediction models showed varying performance, measured by the average area under the receiver operating characteristic curve, with telmisartan (0.93), losartan (0.92), and irbesartan (0.90) exhibiting higher classification performance. The aggregated attention scores from the models highlighted the importance of variables such as hematocrit, albumin, prothrombin time, and lymphocytes in predicting DILI. Conclusions Implementing a multicenter-based timeseries classification model provided evidence that could be valuable to clinicians regarding temporal patterns associated with DILI in ARB users. This information supports informed decisions regarding appropriate drug use and treatment strategies.

Long-term outcomes of live kidney donors remain controversial, although this information is crucial for selecting potential donors. Thus, this study compared the long-term risk of all-cause mortality between live kidney donors and healthy control. Methods: We performed a retrospective cohort study including donors from seven tertiary hospitals in South Korea. Persons who underwent voluntary health screening were included as controls. We created a matched control group considering age, sex, era, body mass index, baseline hypertension, diabetes, estimated glomerular filtration rate, and dipstick albuminuria. The study outcome was progression to end-stage kidney disease (ESKD), and all-cause mortality as identified in the linked claims database. Results: We screened 1,878 kidney donors and 78,115 health screening examinees from 2003 to 2016. After matching, 1,701 persons remained in each group. The median age of the matched study subjects was 44 years, and 46.6% were male. Among the study subjects, 2.7% and 16.6% had underlying diabetes and hypertension, respectively. There were no ESKD events in the matched donor and control groups. There were 24 (1.4%) and 12 mortality cases (0.7%) in the matched donor and control groups, respectively. In the age-sex adjusted model, the risk for all-cause mortality was significantly higher in the donor group than in the control group. However, the significance was not retained after socioeconomic status was included as a covariate (adjusted hazard ratio, 1.82; 95% confidence interval, 0.87–3.80). Conclusion: All-cause mortality was similar in live kidney donors and matched non-donor healthy controls with similar health status and socioeconomic status in the Korean population.

Appropriate monitoring of intradialytic biosignals is essential to minimize adverse outcomes because intradialytic hypotension and arrhythmia are associated with cardiovascular risk in hemodialysis patients. However, a continuous monitoring system for intradialytic biosignals has not yet been developed. Methods: This study investigated a cloud system that hosted a prospective, open-source registry to monitor and collect intradialytic biosignals, which was named the CONTINUAL (Continuous mOnitoriNg viTal sIgN dUring hemodiALysis) registry. This registry was based on real-time multimodal data acquisition, such as blood pressure, heart rate, electrocardiogram, and photoplethysmogram results. Results: We analyzed session information from this system for the initial 8 months, including data for some cases with hemodynamic complications such as intradialytic hypotension and arrhythmia. Conclusion: This biosignal registry provides valuable data that can be applied to conduct epidemiological surveys on hemodynamic complications during hemodialysis and develop artificial intelligence models that predict biosignal changes which can improve patient outcomes.

Background: An inverse observational association between alcohol use and the risk of chronic kidney disease (CKD) or end-stage kidney disease (ESKD) has been reported. The causal effect of alcohol use on the risk of ESKD warrants additional investigation. Methods: The study was an observational cohort study investigating the UK Biobank and performed Mendelian randomization (MR) analysis. Amounts of alcohol use were collected using a touchscreen questionnaire. In the observational analysis, 212,133 participants without prevalent ESKD were studied, and the association between alcohol use and the risk of prevalent CKD or incident ESKD was investigated. The genetic analysis included 337,138 participants of white British ancestry. For one-sample MR, an analysis based on a polygenic risk score (PRS) was conducted with genetically predicted alcohol intake. The MR analysis investigated ESKD outcome and related comorbidities. Results: Lower alcohol use was observationally associated with a higher risk of prevalent CKD or incident ESKD. However, the genetic risk of CKD was significantly associated with lower alcohol use, suggesting reverse causation. A higher PRS for alcohol use was significantly associated with a higher risk of ESKD (per units of one phenotypical alcohol drink; adjusted odds ratio of 1.16 [95% confidence interval, 1.02–1.31]) and related comorbidities, including hypertension, diabetes mellitus, obesity, and central obesity. Conclusion The inverse observational association between alcohol use and the risk of CKD or ESKD may have been affected by reverse causation. Our study supports a causal effect of alcohol use on a higher risk of ESKD and related predisposing comorbidities.

Background: An inverse observational association between alcohol use and the risk of chronic kidney disease (CKD) or end-stage kidney disease (ESKD) has been reported. The causal effect of alcohol use on the risk of ESKD warrants additional investigation. Methods: The study was an observational cohort study investigating the UK Biobank and performed Mendelian randomization (MR) analysis. Amounts of alcohol use were collected using a touchscreen questionnaire. In the observational analysis, 212,133 participants without prevalent ESKD were studied, and the association between alcohol use and the risk of prevalent CKD or incident ESKD was investigated. The genetic analysis included 337,138 participants of white British ancestry. For one-sample MR, an analysis based on a polygenic risk score (PRS) was conducted with genetically predicted alcohol intake. The MR analysis investigated ESKD outcome and related comorbidities. Results: Lower alcohol use was observationally associated with a higher risk of prevalent CKD or incident ESKD. However, the genetic risk of CKD was significantly associated with lower alcohol use, suggesting reverse causation. A higher PRS for alcohol use was significantly associated with a higher risk of ESKD (per units of one phenotypical alcohol drink; adjusted odds ratio of 1.16 [95% confidence interval, 1.02–1.31]) and related comorbidities, including hypertension, diabetes mellitus, obesity, and central obesity. Conclusion The inverse observational association between alcohol use and the risk of CKD or ESKD may have been affected by reverse causation. Our study supports a causal effect of alcohol use on a higher risk of ESKD and related predisposing comorbidities.

Background: An activating mutation (c.617A>C/p.Lys206Arg, L206R) in protein kinase cAMP-activated catalytic subunit alpha (PRKACA) has been reported in 35% to 65% of cases of cortisol-producing adenomas (CPAs). We aimed to compare the clinical characteristics and transcriptome analysis between PRKACA L206R mutants and wild-type CPAs in Korea. Methods: We included 57 subjects with CPAs who underwent adrenalectomy at Seoul National University Hospital. Sanger sequencing for PRKACA was conducted in 57 CPA tumor tissues. RNA sequencing was performed in 13 fresh-frozen tumor tissues. Results: The prevalence of the PRKACA L206R mutation was 51% (29/57). The mean age of the study subjects was 42±12 years, and 87.7% (50/57) of the patients were female. Subjects with PRKACA L206R mutant CPAs showed smaller adenoma size (3.3±0.7 cm vs. 3.8±1.2 cm, P=0.059) and lower dehydroepiandrosterone sulfate levels (218±180 ng/mL vs. 1,511±3,307 ng/mL, P=0.001) than those with PRKACA wild-type CPAs. Transcriptome profiling identified 244 differentially expressed genes (DEGs) between PRKACA L206R mutant (n=8) and wild-type CPAs (n=5), including five upregulated and 239 downregulated genes in PRKACA L206R mutant CPAs (|fold change| ≥2, P<0.05). Among the upstream regulators of DEGs, CTNNB1 was the most significant transcription regulator. In several pathway analyses, the Wnt signaling pathway was downregulated and the steroid biosynthesis pathway was upregulated in PRKACA mutants. Protein-protein interaction analysis also showed that PRKACA downregulates Wnt signaling and upregulates steroid biosynthesis. Conclusion The PRKACA L206R mutation in CPAs causes high hormonal activity with a limited proliferative capacity, as supported by transcriptome profiling.