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1.
Diabetes Obes Metab ; 26(7): 2588-2597, 2024 Jul.
Article En | MEDLINE | ID: mdl-38618974

AIMS: To explore the effect of renal function on the pharmacokinetic (PK) and pharmacodynamic (PD) profile and safety of enavogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: An open-label, two-part clinical trial was conducted in T2DM patients, stratified by renal function: Group 1, normal renal function; Group 2, mild renal impairment (RI); Group 3, moderate RI; and Group 4, severe RI. In Part A, Groups 2 and 4 received enavogliflozin 0.5 mg once. In Part B, Groups 1 and 3 received enavogliflozin 0.5 mg once daily for 7 days. Serial blood and timed urine samples were collected to analyse the PK and PD characteristics of enavogliflozin. Pearson's correlation coefficients were calculated to assess the correlations between PK or PD parameters and creatinine clearance (CrCL). RESULTS: A total of 21 patients completed the study as planned. The area under the curve (AUC) for enavogliflozin was not significantly correlated with CrCL, although the maximum concentration slightly decreased as renal function decreased. By contrast, daily urinary glucose excretion (UGE) was positively correlated with CrCL after both single- (r = 0.7866, p < 0.0001) and multiple-dose administration (r = 0.6606, p = 0.0438). CONCLUSIONS: Systemic exposure to oral enavogliflozin 0.5 mg was similar among the patients with T2DM regardless of their renal function levels. However, the glucosuric effect of enavogliflozin decreased with RI. Considering the UGE observed and approved therapeutic use of other SGLT2 inhibitors, the efficacy of enavogliflozin with regard to glycaemic control could be explored in patients with mild and moderate RI (estimated glomerular filtration rate ≥30 or ≥45 mL/min/1.73 m2) in a subsequent larger study.


Diabetes Mellitus, Type 2 , Sodium-Glucose Transporter 2 Inhibitors , Humans , Diabetes Mellitus, Type 2/drug therapy , Male , Sodium-Glucose Transporter 2 Inhibitors/pharmacokinetics , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Middle Aged , Female , Aged , Glomerular Filtration Rate/drug effects , Blood Glucose/drug effects , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/therapeutic use , Glucosides/pharmacokinetics , Glucosides/therapeutic use , Glucosides/pharmacology , Glucosides/adverse effects , Kidney/drug effects , Kidney/metabolism , Kidney/physiopathology , Adult , Diabetic Nephropathies/drug therapy , Glycated Hemoglobin/analysis , Glycated Hemoglobin/drug effects , Glycated Hemoglobin/metabolism , Renal Insufficiency/metabolism , Sodium-Glucose Transporter 2 , Glycosuria/chemically induced , Benzofurans
2.
Electrolyte Blood Press ; 21(2): 53-60, 2023 Dec.
Article En | MEDLINE | ID: mdl-38152598

Background: Most hemodialysis (HD) patients suffer from hypertension and have a heightened cardiovascular risk. While blood pressure (BP) control is essential to end-stage kidney disease (ESKD) patients, overly stringent control can lead to intradialytic hypotension (IDH). This study aimed to examine BP variations during and after HD to determine whether these variations correlate with IDH risk. Methods: BP measurements during dialysis were taken from 28 ESKD patients, and ambulatory BP monitoring was applied post-dialysis. Laboratory parameters and risk factors, including diabetes, coronary disease, and LV mass index, were compared between IDH and non-IDH groups using an independent t-test. Results: Of the 28 patients with an average age of 57.4 years, 16 (57.1%) had diabetes, 5 (17.9%) had coronary artery disease, and 1 (3.6%) had cerebrovascular disease. The mean systolic blood pressure (SBP) during and post-HD was 142.26 mmHg and 156.05 mmHg, respectively (p=0.0003). Similarly, the mean diastolic blood pressure (DBP) also demonstrated a significant increase, from 74.59 mmHg during HD to 86.82 mmHg post-HD (p<0.0001). Patients with IDH exhibited a more substantial SBP difference (delta SBP, 36.38 vs. 15.07 mmHg, p=0.0033; age-adjusted OR=1.58, p=0.0168) and a lower post-dialysis BUN level (12.75 vs. 18.77 mg/dL, p=0.0015; age-adjusted OR=0.76, p=0.0242). No significant variations were observed in daytime and nocturnal BP between the IDH and non-IDH groups. Conclusion: Hemodialysis patients exhibited a marked increase in post-dialysis BP and lacked a nocturnal BP dip, suggesting augmented cardiovascular risks. This highlights the importance of more stringent BP control after hemodialysis.

3.
Int J Mol Sci ; 24(6)2023 Mar 15.
Article En | MEDLINE | ID: mdl-36982713

Enhanced heat shock protein-70 (HSP-70) expression in the lungs is associated with attenuated acute lung injury (ALI) in a sepsis model. Chronic kidney disease (CKD) significantly contributes to the poor prognosis of patients with sepsis. This study examined the relationship between sepsis-induced ALI severity and altered lung HSP-70 expression in CKD. Experimental rats underwent a sham operation (control group) or 5/6 nephrectomy (CKD group). Sepsis was induced with cecal ligation and puncture (CLP). Laboratory tests and lung harvest were performed in the control group (without CLP and after 3, 12, 24, and 72 h of CLP) and in the CKD group (without CLP and after 72 h of CLP). ALI was the most severe after 12 h of sepsis. The mean lung injury score at 72 h after sepsis was significantly higher in the CKD group than in the control group (4.38 versus 3.30, p < 0.01). Nonetheless, enhanced lung HSP-70 expression was not observed in the CKD group. This study shows that altered lung HSP-70 expression is associated with the worsening of sepsis-induced ALI in patients with CKD. Enhancing lung HSP-70 is a novel treatment target for patients with CKD and sepsis-induced ALI.


Acute Lung Injury , Sepsis , Rats , Animals , HSP70 Heat-Shock Proteins/genetics , HSP70 Heat-Shock Proteins/metabolism , Lung/metabolism , Acute Lung Injury/metabolism , Ligation , Sepsis/complications , Sepsis/metabolism , Disease Models, Animal , Cecum/metabolism
4.
J Clin Med ; 11(23)2022 Nov 29.
Article En | MEDLINE | ID: mdl-36498627

Background: The purpose of this study was to investigate the association between responses to intravitreal bevacizumab injection and renal function in diabetic macular edema (DME) patients. Methods: A retrospective study of the medical records of 104 treatment-naïve DME patients who received intravitreal bevacizumab injection (IVBI) was conducted. Based on the estimated glomerular filtration rate (eGFR, mL/min/1.73 m2), the participants were classified into three groups. Intergroup comparisons of the best-corrected visual acuity (BCVA) and central subfield retinal thickness (CST) changes were performed after three-monthly consecutive IVBIs. In the groups with decreased renal function, the response to further treatment with a different drug was investigated. Results: A total of 104 participants were included in the study: 60 participants in the preserved renal function group (eGFR ≥ 60), 25 participants in the moderate chronic kidney disease (CKD) group (30 ≤ eGFR < 60), and 19 participants in the severe CKD group (eGFR < 30). After three-monthly consecutive IVBIs, BCVA (p < 0.001) and CST (p < 0.001) were significantly improved only in the preserved renal function group. Following further treatment of patients with decreased renal function, the treatment results were significantly better in those who were switched to aflibercept or dexamethasone implant than in those who were maintained on IVBI. Conclusions: From this preliminary study, we observed that renal function might affect the response to IVBI treatment in patients with DME. In the case of a poor response to initial IVBI treatment for DME in patients with moderate to severe CKD, our study supports switching to the aflibercept or dexamethasone implant.

5.
Chonnam Med J ; 58(2): 69-74, 2022 May.
Article En | MEDLINE | ID: mdl-35677952

End-stage renal disease (ESRD) patients on hemodialysis have poor nutritional status and associated problems such as inflammation and sarcopenia. Blood urea nitrogen (BUN) is an important measure of uremic toxins, and urea reduction is a marker of hemodialysis efficacy. However, a low protein diet for lower BUN could aggravate malnutrition in patients, and optimal pre-dialysis BUN is not defined. We investigated the association of pre-dialysis BUN with patients' comorbidities and the relationship between pre-dialysis BUN and serum albumin as a nutrient marker. Among the 67 patients, the average pre- and post-dialysis BUN were 59.2 and 15.0 mg/dL, respectively, serum creatinine was 10.1 mg/dL, and the average serum albumin was 4.0 g/dL. Patients' age was negatively correlated with serum creatinine (r=-0.277, p<0.05) and albumin (r=-0.453, p<0.001). Predialysis BUN showed a significant positive correlation with serum albumin (r=0.287, p<0.05) and creatinine (r=0.454, p<0.001). However, the predialysis BUN was not significantly related to diabetes, coronary artery disease, congestive heart failure, or cerebrovascular disease. Hemodialysis patients with high pre-dialysis BUN and high serum creatinine could be regarded as having good nutritional status. The significance of this study lies in the potential utility of pre-dialysis blood urea nitrogen as an indicator of the nutritional status of patients. Liberal protein intake might be recommended to adequately dialyzed patients.

6.
Kidney Res Clin Pract ; 41(2): 253-262, 2022 Mar.
Article En | MEDLINE | ID: mdl-34974655

BACKGROUND: Patients on dialysis have numerous gastrointestinal problems related to uremia, which may represent concealed cholecystitis. We investigated the incidence and risk of acute cholecystitis in dialysis patients and used national health insurance data to identify acute cholecystitis in Korea. METHODS: The Korean National Health Insurance Database was used, with excerpted data from the insurance claim of the International Classification of Diseases code of dialysis and acute cholecystitis treated with cholecystectomy. We included all patients who commenced dialysis between 2004 and 2013 and selected the same number of controls via propensity score matching. RESULTS: A total of 59,999 dialysis and control patients were analyzed; of these, 3,940 dialysis patients (6.6%) and 647 controls (1.1%) developed acute cholecystitis. The overall incidence of acute cholecystitis was 8.04-fold higher in dialysis patients than in controls (95% confidence interval, 7.40-8.76). The acute cholecystitis incidence rate (incidence rate ratio, 23.13) was especially high in the oldest group of dialysis patients (aged ≥80 years) compared with that of controls. Dialysis was a significant risk factor for acute cholecystitis (adjusted hazard ratio, 8.94; 95% confidence interval, 8.19-9.76). Acute cholecystitis developed in 3,558 of 54,103 hemodialysis patients (6.6%) and in 382 of 5,896 patients (6.5%) undergoing peritoneal dialysis. CONCLUSION: Patients undergoing dialysis had a higher incidence and risk of acute cholecystitis than the general population. The possibility of a gallbladder disorder developing in patients with gastrointestinal problems should be considered in the dialysis clinic.

7.
J Clin Pharmacol ; 62(1): 46-54, 2022 01.
Article En | MEDLINE | ID: mdl-34327707

Per the well-known resistance of hepatitis B virus to nucleoside/nucleotide analogs, alternative treatment options with higher resistance barriers have been approved for use in both treatment-naïve and lamivudine-resistant hepatitis B virus infections. This phase I study was conducted in adults with normal and impaired renal function to evaluate the effect of renal impairment on the pharmacokinetics of besifovir, a prodrug of an acyclic nucleotide phosphonate, that is mainly cleared via renal excretion. An open-label, single-dose parallel-group clinical study was conducted in subjects with normal renal function and mild, moderate, and severe renal impairment. Subjects received a single oral dose of besifovir dipivoxil 150 mg, and serial blood and urine samples were collected for up to 72 hours after dosing to assess the pharmacokinetic characteristics of besifovir. The extent of plasma exposure of besifovir, detected as its major and active metabolites, LB80331 and LB80317, respectively, increased with worsening renal function. Compared to the subjects with normal renal function, the mean areas under the concentration-time curves of LB80331 increased by 1.5-, 2.5-, and 4.5-fold in subjects with mild, moderate, and severe impairment, respectively. LB80317 showed a 1.8-, 3.2-, and 6.2-fold increase in subjects with mild, moderate, and severe renal impairment compared to those with normal function. The ratios of LB80331 renal clearance and the average estimated glomerular filtration rate of each renal impairment group with respect to the normal group were similar. The increase in plasma exposure and decrease in renal clearance suggest the need to adjust dosage regimens in patients with moderate to severe renal impairment.


Antiviral Agents/pharmacokinetics , Guanine/analogs & derivatives , Organophosphonates/pharmacokinetics , Renal Insufficiency/epidemiology , Renal Insufficiency/metabolism , Adult , Antiviral Agents/blood , Antiviral Agents/therapeutic use , Antiviral Agents/urine , Area Under Curve , Female , Glomerular Filtration Rate , Guanine/blood , Guanine/pharmacokinetics , Guanine/therapeutic use , Guanine/urine , Hepatitis B/drug therapy , Hepatitis B/epidemiology , Humans , Kidney/metabolism , Kidney Function Tests , Male , Middle Aged , Models, Biological , Organophosphonates/blood , Organophosphonates/therapeutic use , Organophosphonates/urine , Patient Acuity , Young Adult
8.
J Korean Med Sci ; 36(30): e201, 2021 Aug 02.
Article En | MEDLINE | ID: mdl-34342186

BACKGROUND: We investigated the incidence and risk of retinal vein occlusion (RVO) in end-stage renal disease (ESRD) patients on dialysis in Korea. METHODS: In this nationwide cohort study, we used Korean National Health Insurance Service data between 2004 and 2013 for analysis. ESRD patients who started dialysis from 2004 to 2013 and an equal number of controls were selected through propensity score matching. RVO incidence in both cohorts were calculated for 2004-2013 using washout data from 2003. The multivariable Cox proportional hazards model was used to assess the risk of RVO in dialysis cohort. The Kaplan-Meier method was used to generate the cumulative RVO incidence curve. Whether the dialysis modality affects the development of RVO was also evaluated. RESULTS: In this study, 74,551 ESRD patients on dialysis and the same number of controls were included. The incidence of RVO was significantly higher in the dialysis cohort than in the control cohort (dialysis = 7.3/1,000 person-years [PY]; control = 1.9/1,000 PY; P < 0.001). The cumulative-incidence of RVO was also significantly higher in the dialysis cohort than in the control cohort (P < 0.001; log-rank test). However, there was no significant difference in the incidence of RVO between the two dialysis methods (P = 0.550; log-rank test). CONCLUSION: This study provided epidemiological evidence that receiving dialysis for ESRD could increase the risk of developing RVO. We also found a rapid increase in the incidence of RVO with a longer dialysis period. These results strengthen the relationship between retinal vascular disease and renal function.


Kidney Failure, Chronic/therapy , Renal Dialysis/adverse effects , Retinal Vein Occlusion/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Child , Child, Preschool , Cohort Studies , Female , Humans , Incidence , Infant , Infant, Newborn , Kaplan-Meier Estimate , Kidney Failure, Chronic/complications , Male , Middle Aged , Republic of Korea/epidemiology , Retinal Vein Occlusion/etiology , Retrospective Studies , Risk Factors
9.
Retina ; 41(10): 2140-2147, 2021 Oct 01.
Article En | MEDLINE | ID: mdl-34029028

PURPOSE: To examine the incidence and risk of retinal artery occlusion (RAO) in patients who have undergone dialysis in Korea. METHODS: A nationwide, population-based study using South Korean national health insurance data from 2004 to 2013 was used for analysis. All patients who began dialysis between 2004 and 2013 and the same number of control subjects were selected via propensity score matching. The incidence of RAO in the dialysis and control cohorts was calculated for 2004 to 2013 using washout data from 2003. The multivariable Cox proportional hazards model was used to evaluate the risk of developing RAO in dialysis patients. Cumulative RAO incidence curves were generated using the Kaplan-Meier method. Whether dialysis modalities influenced the incidence of RAO was also evaluated. RESULTS: Seventy-six thousand seven hundred and eighty-two end-stage renal disease patients on dialysis were included in the dialysis cohort, and 76,782 individuals were included in the control cohort. During the study period, 293 patients in the dialysis cohort and 99 patients in the control cohort developed RAO. The person-years incidence of RAO was significantly higher in the dialysis cohort than in the control cohort (dialysis = 1.1/1,000 person-years; control = 0.3/1,000 person-years; P < 0.001). The incidence of RAO was not significantly different between the two methods of dialysis (hemodialysis vs. peritoneal dialysis; P = 0.25, log-rank test). CONCLUSION: The current study provided epidemiological evidence that undergoing dialysis for end-stage renal disease was associated with an increased risk of developing RAO. The incidence of RAO rapidly increased as the duration of dialysis increased. These results strengthen the significant role of the renal function in retinal vascular disease.


Kidney Failure, Chronic/therapy , Renal Dialysis/adverse effects , Retinal Artery Occlusion/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Child , Child, Preschool , Databases, Factual , Female , Humans , Incidence , Infant , Infant, Newborn , Kidney Failure, Chronic/physiopathology , Male , Middle Aged , National Health Programs/statistics & numerical data , Proportional Hazards Models , Republic of Korea/epidemiology , Retinal Artery Occlusion/physiopathology , Retrospective Studies , Risk Factors
10.
Diagnostics (Basel) ; 10(6)2020 Jun 18.
Article En | MEDLINE | ID: mdl-32570782

This study aims to compare the classification performance of statistical models on highly imbalanced kidney data. The health examination cohort database provided by the National Health Insurance Service in Korea is utilized to build models with various machine learning methods. The glomerular filtration rate (GFR) is used to diagnose chronic kidney disease (CKD). It is calculated using the Modification of Diet in Renal Disease method and classified into five stages (1, 2, 3A and 3B, 4, and 5). Different CKD stages based on the estimated GFR are considered as six classes of the response variable. This study utilizes two representative generalized linear models for classification, namely, multinomial logistic regression (multinomial LR) and ordinal logistic regression (ordinal LR), as well as two machine learning models, namely, random forest (RF) and autoencoder (AE). The classification performance of the four models is compared in terms of accuracy, sensitivity, specificity, precision, and F1-Measure. To find the best model that classifies CKD stages correctly, the data are divided into a 10-fold dataset with the same rate for each CKD stage. Results indicate that RF and AE show better performance in accuracy than the multinomial and ordinal LR models when classifying the response variable. However, when a highly imbalanced dataset is modeled, the accuracy of the model performance can distort the actual performance. This occurs because accuracy is high even if a statistical model classifies a minority class into a majority class. To solve this problem in performance interpretation, we not only consider accuracy from the confusion matrix but also sensitivity, specificity, precision, and F-1 measure for each class. To present classification performance with a single value for each model, we calculate the macro-average and micro-weighted values for each model. We conclude that AE is the best model classifying CKD stages correctly for all performance indices.

11.
Int J Mol Sci ; 20(23)2019 Nov 29.
Article En | MEDLINE | ID: mdl-31795376

Acute kidney injury (AKI) is common in patients with sepsis and causes renal ischemia. Glucagon-like peptide-1 (GLP-1) protects the vascular system and the kidney, and GLP-1 receptor (GLP-1R) is expressed in the kidney. Renal GLP-1R activity is decreased in chronic kidney disease (CKD), but is increased by the inflammatory response; however, the effect of AKI on GLP-1R expression is unknown. We investigated the role of GLP-1 by assessing GLP-1R expression in the renal cortex in animals with AKI-related sepsis, CKD, and CKD-with-sepsis. We generated a model of CKD by 5/6 nephrectomy, and sepsis induced by cecal perforation, in male Sprague-Dawley rats. We compared renal GLP-1R expression at 3, 6, 12, 24, and 72 h after cecal perforation, and in CKD and CKD-with-sepsis. We performed blood and urine tests, western blotting (WB), and immunohistochemistry (IHC) to assay GLP-1R expression in renal tubules. The CKD-with-sepsis group showed the lowest kidney function, urine volume, and serum glucose and albumin levels. GLP-1R expression in renal tubules was decreased at 3 h, increased at 24 h, and decreased at 72 h after sepsis induction. GLP-1R expression was decreased at 8 weeks after CKD and was lowest in the CKD-with-sepsis group. The WB results were verified against those obtained by IHC. GLP-1R expression in renal tubules is increased in early sepsis, which may explain the protective effect of endogenous GLP-1 against sepsis-related inflammation.


Acute Kidney Injury/pathology , Glucagon-Like Peptide-1 Receptor/analysis , Kidney Tubules/pathology , Renal Insufficiency, Chronic/pathology , Sepsis/pathology , Acute Kidney Injury/etiology , Animals , Male , Rats, Sprague-Dawley , Sepsis/complications
12.
J Korean Med Sci ; 34(25): e176, 2019 Jul 01.
Article En | MEDLINE | ID: mdl-31243935

BACKGROUND: The numbers of patients on dialysis and their life expectancies are increasing. Reduced renal function is associated with an increased risk of cancer, but the cancer incidence and sites in dialysis patients compared with those of the general population require further investigation. We investigated the incidences of various cancers in dialysis patients in Korea and used national health insurance data to identify cancers that should be screened in dialysis clinics. METHODS: We accessed the Korean National Health Insurance Database and excerpted data using the International Classification of Disease codes for dialysis and malignancies. We included all patients who commenced dialysis between 2004 and 2013 and selected the same number of controls via propensity score matching. RESULTS: A total of 48,315 dialysis patients and controls were evaluated; of these, 2,504 (5.2%) dialysis patients and 2,201 (4.6%) controls developed cancer. The overall cancer risk was 1.54-fold higher in dialysis patients than in controls (adjusted hazard ratio, 1.71; 95% confidence interval, 1.61-1.81). The cancer incidence rate (incidence rate ratio [IRR], 3.27) was especially high in younger dialysis patients (aged 0-29 years). The most common malignancy of end-stage renal disease patients and controls was colorectal cancer. The major primary cancer sites in dialysis patients were liver and stomach, followed by the lung, kidney, and urinary tract. Kidney cancer exhibited the highest IRR (6.75), followed by upper urinary tract (4.00) and skin cancer (3.38). The rates of prostate cancer (0.54) and oropharyngeal cancer (0.72) were lower than those in the general population. CONCLUSION: Dialysis patients exhibited a higher incidence of malignancy than controls. Dialysis patients should be screened in terms of colorectal, liver, lung, kidney and urinary tract malignancies in dialysis clinics.


Kidney Failure, Chronic/therapy , Neoplasms/diagnosis , Renal Dialysis/adverse effects , Adolescent , Adult , Aged , Child , Child, Preschool , Databases, Factual , Female , Humans , Incidence , Infant , Infant, Newborn , Kidney Neoplasms/diagnosis , Kidney Neoplasms/epidemiology , Kidney Neoplasms/etiology , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/etiology , Proportional Hazards Models , Republic of Korea/epidemiology , Young Adult
14.
BMC Nephrol ; 20(1): 75, 2019 03 01.
Article En | MEDLINE | ID: mdl-30823876

BACKGROUND: Chronic kidney disease (CKD) is strongly associated with cardiovascular disease and is a significant risk factor for increased morbidity and mortality. In contrast, GLP-1 receptor (GLP-1R) activation has been shown to confer both renal and cardiovascular protection, though its relationship with CKD and CKD with myocardial ischemia/reperfusion (MI/R) remains poorly understood. Here, we investigated changes in renal and myocardial GLP-1R expression in the CKD rat model with MI/R. METHODS: Male Sprague Dawley rats with 5/6 nephrectomy were used as a rat model of CKD and CKD with MI/R. For myocardial ischemia, the left coronary artery was ligated and released for 30 min 1 week after 5/6 nephrectomy. Dipeptidyl-peptidase 4 (DPP-4) inhibitors were administered orally with linagliptin once daily for 8 weeks. Renal cortical and myocardial GLP-1R expression were measured via immunohistochemistry and western blot analysis. RESULTS: DPP-4 activity was increased in CKD. Western blot density of GLP-1R in renal cortex extracts revealed increased abundance 2 weeks after 5/6 nephrectomy, followed by a decrease at 8 weeks. In contrast, CKD and CKD with MI/R rats showed decreases in renal and cardiac expression of GLP-1R; these effects were attenuated in rats treated with linagliptin. CONCLUSIONS: In CKD with MI/R, linagliptin attenuated renal injury and increased renal and myocardial GLP-1R expression. These data suggest that activation of renal and myocardial GLP-1R expression may provide both cardio- and renoprotective effects.


Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Glucagon-Like Peptide-1 Receptor/metabolism , Kidney Tubules , Myocardial Infarction , Myocardium/metabolism , Renal Insufficiency, Chronic , Reperfusion Injury , Animals , Immunohistochemistry , Kidney Tubules/drug effects , Kidney Tubules/metabolism , Linagliptin/pharmacology , Male , Myocardial Infarction/complications , Myocardial Infarction/metabolism , Rats , Rats, Sprague-Dawley , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/metabolism , Reperfusion Injury/etiology , Reperfusion Injury/metabolism , Reperfusion Injury/prevention & control
15.
J Allergy Clin Immunol Pract ; 7(4): 1271-1276, 2019 04.
Article En | MEDLINE | ID: mdl-30580048

BACKGROUND: Thus far, human leukocyte antigen (HLA)-B∗58:01 has been recognized as the most important risk factor for allopurinol induced severe cutaneous adverse reactions (SCARs). OBJECTIVE: To determine the usefulness of prospective screening for the HLA-B∗58:01 allele to identify Korean individuals at risk for SCARs induced by allopurinol treatment. METHODS: We prospectively enrolled 542 patients with chronic renal insufficiency (CRI) from 10 hospitals nationwide and performed DNA genotyping to determine whether they carried the HLA-B∗58:01 allele. Of these, 503 HLA-B∗58:01-negative patients (92.8% of total) were treated with allopurinol, and 39 HLA-B∗58:01-positive patients (7.2%) were treated with febuxostat, an alternative drug. The patients then were followed up biweekly for 90 days using a telephone survey to monitor symptoms of adverse drug reactions, including SCARs. As a control, we used the historical incidence rate of allopurinol-induced SCARs in 4002 patients with CRI from the same hospitals who were enrolled retrospectively. RESULTS: Nineteen patients in the prospective cohort developed mild and transient adverse reactions but none showed allopurinol-induced SCARs. By contrast, we identified 38 patients with allopurinol-induced SCARs (0.95%) in the historical control. The difference in the incidence of allopurinol-induced SCARs between the prospective cohort and historical control was statistically significant (0% vs 0.95%, respectively; P = .029). CONCLUSIONS: The present study demonstrated the clinical usefulness of the HLA-B∗58:01 screening test before allopurinol administration to prevent allopurinol-induced SCARs in patients with CRI.


Allopurinol/adverse effects , Drug Hypersensitivity/diagnosis , Genotype , HLA-B Antigens/genetics , Renal Insufficiency, Chronic/diagnosis , Skin/pathology , Aged , Allergens/immunology , Allopurinol/immunology , Allopurinol/therapeutic use , Drug Hypersensitivity/epidemiology , Febuxostat/therapeutic use , Female , Histocompatibility Testing , Humans , Korea/epidemiology , Male , Mass Screening , Middle Aged , Prospective Studies , Renal Insufficiency, Chronic/epidemiology , Risk
17.
Electrolyte Blood Press ; 16(1): 15-17, 2018 Jun.
Article En | MEDLINE | ID: mdl-30046330

Severe eating disorders characterized by repetitive episodes of purging and vomiting can occasionally trigger acute kidney injury. However, interstitial nephritis induced by episodes of repeated vomiting has rarely been reported, and the pathophysiology of this entity remains unknown. A 26-year-old man was admitted to our hospital because of known hypokalemia. His serum electrolyte profile showed: sodium 133 mEq/L, potassium 2.6 mEq/L, chloride 72 mEq/L, total carbon dioxide 50 mEq/L, blood urea nitrogen/creatinine ratio (BUN/Cr) 21.9/1.98 mg/dL, and magnesium 2.0 mg/dL. Arterial blood gas analysis showed: pH 7.557, partial pressure of carbon dioxide 65.8 mmHg, and bicarbonate 58.5 mEq/L. His urinary potassium concentration was 73.2 mEq/L, and Cr was 111 mg/dL. Renal biopsy revealed acute tubular necrosis and tubulointerstitial nephritis with a few shrunken glomeruli. Repeated psychogenic vomiting may precipitate acute kidney injury and interstitial nephritis secondary to volume depletion and hypokalemia. Serum electrolyte levels and renal function should be carefully monitored in patients diagnosed with eating disorders to prevent tubular ischemia and interstitial nephritis.

18.
J Korean Med Sci ; 33(53): e341, 2018 Dec 31.
Article En | MEDLINE | ID: mdl-30595682

BACKGROUND: The converging epidemics of tuberculosis (TB) and end-stage renal disease (ESRD) have generated a significant public health burden, however, previous studies have been limited to a small number of patients. This nationwide cohort study aimed to assess the rate of developing active TB among patients receiving dialysis for ESRD. METHODS: The Korean national health insurance database was used to identify patients receiving dialysis for new-onset ESRD during 2004-2013, who were propensity score matched to an equivalent number of non-dialysis subjects from the general population. The incidences of active TB in the ESRD and control cohorts were calculated for 2004-2013, and multivariable Cox proportional hazards model was used to evaluate the ESRD-related risk of active TB. RESULTS: During 2004-2013, 59,584 patients received dialysis for newly diagnosed ESRD. In the dialysis and control cohorts, 457 (0.8%) and 125 (0.2%) cases of active TB were detected, respectively. Patients with ESRD were associated with a significantly higher risk of active TB compared to the controls (incidence rate ratio, 4.80). The ESRD cohort had an independently elevated risk of active TB (adjusted hazard ratio, 4.39; 95% confidence interval, 3.60-5.37). CONCLUSION: We found that patients receiving dialysis for ESRD had an elevated risk of active TB. These results highlight the need for detailed and well-organised guidelines for active TB screening among patients with ESRD.


Kidney Failure, Chronic/diagnosis , Tuberculosis/diagnosis , Adult , Aged , Cohort Studies , Databases, Factual , Female , Humans , Incidence , Kidney Failure, Chronic/complications , Male , Middle Aged , Proportional Hazards Models , Renal Dialysis , Risk Factors , Tuberculosis/epidemiology , Tuberculosis/etiology
20.
Article En | MEDLINE | ID: mdl-27801876

(1) Background: Oxidative stress and inflammation are associated with higher risk of chronic kidney disease (CKD). Serum ferritin concentrations correlate with total iron levels and systemic inflammation. (2) Methods: This study was cross-sectionally designed, based on the 2010-2012 Korean National Health and Nutrition Examination Survey (KNHANES). According to ferritin values, 13,462 participants (6082 men and 7380 women) were categorized into the normal- and high-ferritin groups (cut-off points: 200 ng/mL in men, 150 ng/mL in women). (3) Results: The mean ages of men and women were 44.5 and 48.4 years, respectively. The percentage of participants categorized into the high-ferritin group was 15.1% for men and 3.6% for women. The estimated glomerular filtration rate levels in the normal- and high-ferritin groups were 93.2 and 93.8 mL/min/1.73 m² for men and 97.1 and 87.7 mL/min/1.73 m² for women, respectively. The prevalence of CKD in the normal- and high-ferritin groups was 2.6% and 3.9% for men and 3.2% and 8.1% for women, respectively. Compared with the normal-ferritin group, the odds ratios (95% confidence intervals) for CKD of the high-ferritin group were 1.573 (1.014-2.441) in men and 1.061 (0.381-2.955) in women, after adjustments for age and other covariates. (4) Conclusions: High ferritin levels were associated with a higher risk of CKD in men but not in women.


Ferritins/blood , Inflammation/blood , Nutrition Surveys , Renal Insufficiency, Chronic/blood , Adult , Cross-Sectional Studies , Female , Humans , Inflammation/complications , Male , Middle Aged , Odds Ratio , Oxidative Stress , Prevalence , Renal Insufficiency, Chronic/epidemiology , Republic of Korea/epidemiology
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