Byung Chul Shin

Background: Efepoetin alfa (GC1113, GX-E2) is a long-acting recombinant human erythropoietin fused to a hybrid fragment crystallizable (hyFc) that prolongs systemic exposure via neonatal Fc receptor-mediated recycling. This active-controlled phase 2 trial evaluated efepoetin alfa and informed phase 3 starting dose selection for chronic kidney disease-related anemia in dialysis patients. Methods: In this multicenter, open-label, active-controlled trial, adults on hemodialysis (HD) or peritoneal dialysis (PD) with hemoglobin (Hb) levels <10 g/dL were randomized after erythropoiesis-stimulating agent discontinuation. Over 12 weeks, HD patients received intravenous efepoetin alfa (5 or 8 µg/kg once weekly [Q1W], 8 µg/kg every 2 weeks [Q2W]) or darbepoetin alfa (30 µg Q1W). PD patients received subcutaneous efepoetin alfa (5 or 8 µg/kg Q2W) or methoxy polyethylene glycol-epoetin beta (0.6 µg/kg Q2W). The primary endpoint was the mean Hb change from baseline after 12 weeks of treatment, and an exploratory dose-conversion ratio (DCR) analysis was performed in the PD cohort to inform phase 3 dosing.Results: Efepoetin alfa showed dose-dependent Hb increases. In the HD cohort, mean Hb increases were 3.19 g/dL for efepoetin alfa 5 and 8 µg/kg Q1W and 2.52 g/dL for darbepoetin alfa. In the PD cohort, mean Hb increases were 2.69 g/dL and 3.48 g/dL for efepoetin alfa 5 and 8 µg/kg Q2W, respectively, and 2.01 g/dL for the control group. Exploratory DCR analysis supported 4 µg/kg Q2W efepoetin alfa as the phase 3 starting dose.Conclusion: Efepoetin alfa demonstrated dose-dependent erythropoietic efficacy and an acceptable safety profile in dialysis patients, supporting dose-range characterization and phase 3 starting dose selection.

Diabetes mellitus (DM) is a major global health concern, associated with both microvascular and macrovascular complications. Early identification of individuals at risk of hyperglycemia and diabetes progression is crucial for preventing long-term complications and improving patient outcomes. We investigated the association between neck circumference (NC) and hyperglycemia in non-diabetic individuals and in patients with uncontrolled DM, using data from the nationally representative Korea National Health and Nutrition Examination Survey (KNHANES) 2019–2021. Uncontrolled DM was defined as hemoglobin A1c (HbA1c) ≥ 7.0%, while hyperglycemia in non-diabetic individuals was defined as fasting blood glucose ≥ 126 mg/dL or HbA1c ≥ 6.5%. Logistic regression analyses were conducted to evaluate the association between NC and glycemic outcomes. NC was independently associated with hyperglycemia in non-diabetic individuals (Model 1: odds ratio (OR): 1.09; 95% confidence interval (CI): 1.05–1.13; Model 2: OR: 1.09; 95% CI: 1.05–1.13) and patients with uncontrolled DM (Model 1: OR: 1.10; 95% CI: 1.03–1.17; Model 2: OR: 1.11; 95% CI: 1.04–1.18) after adjusting for potential confounders. This study demonstrates that NC is a significant risk factor for hyperglycemia in the general population and for individuals with uncontrolled DM. NC may serve as a simple, non-invasive anthropometric marker to help identify individuals at elevated risk for poor glycemic control.

Kiyoung Choi, Youngmin Yoon, Ran Hong, Hyun Lee Kim, Jong Hoon Chung, Byung Chul Shin. Clin Transplant Res 2024;38:150-3. https://doi.org/10.4285/ctr.24.0011

Although tacrolimus (TAC) significantly reduces allograft rejection incidence in solid-organ transplantation, its long-term use is associated with an increased risk of TAC-induced nephrotoxicity. In this study, we investigated the renoprotective effects of green tea extract (GTE) with or without the dipeptidyl peptidase 4 inhibitor, gemigliptin, by assessing serum creatinine levels, the amount of proteinuria, and histopathology in TAC-induced nephrotoxicity. TAC-induced nephrotoxicity was induced by intraperitoneal TAC injection, GTE was administered via subcutaneous injection, and gemigliptin was administered orally. Mice with TAC-induced nephrotoxicity exhibited a significant increase in both serum creatinine levels and 24-hour urine protein. However, when treated with GTE via subcutaneous injection, mice showed a decrease in serum creatinine levels and the amount of proteinuria. When GTE was combined with gemigliptin, further renoprotective effects were observed in biochemical assessments, consistent with the attenuation of TAC-induced nephrotoxicity in histopathology. The expression of p53 protein was lower in the mice treated with the combination of GTE and gemigliptin compared to mice with TAC-induced nephrotoxicity. Our results demonstrate that the combination of GTE and gemigliptin treatment reveals synergistic renoprotective effects by decreasing the expression of p53 protein. These findings suggest that the combination of GTE and gemigliptin could potentially be used as a prophylactic or therapeutic strategy for TAC-induced nephrotoxicity.

Chronic kidney disease (CKD) is a major public health problem and a leading cause of cardiovascular disease and death. Early recognition and management of CKD risk factors are necessary to prevent its onset and progression. Neck circumference (NC) is a non-invasive and easily accessible anthropometric measure associated with central obesity and subcutaneous fat accumulation in the upper body. Our study aimed to explore the relationship between NC and the prevalence of CKD using data from the nationally representative Korea National Health and Nutrition Examination Survey (2019–2021). We analyzed data from 10,219 subjects (age > 19 years, no missing values). CKD was defined as an estimated glomerular filtration rate (eGFR) 2. Logistic regression analysis was performed, which revealed a significant association between NC and CKD prevalence even after adjusting for confounding factors, both when NC was considered a continuous variable (OR [95% CI], 1.11 [1.03–1.19]) and in quartiles (Q1 as reference; Q2 OR [95% CI], 1.23 [0.91–1.67]; Q3 OR [95% CI], 1.59 [1.16–2.18]; Q4 OR [95% CI], 1.70 [1.16–2.50]). Our findings suggest that NC could be a simple and effective anthropometric measurement for identifying individuals at risk for CKD.

Hyun Lee Kim, Young Min Yoon, Jong Hoon Chung, Byung Chul Shin. Med Biol Sci Eng 2023;6:110-3. https://doi.org/10.30579/mbse.2023.6.2.110

Byung Chul Shin, Hyun Lee Kim, Jong Hoon Chung. Korean J Transplant 2021;35:69. https://doi.org/10.4285/ATW2021.PO-1154

Kidney transplantation is the treatment of choice for end-stage renal disease. A successful kidney transplant improves the quality of life and reduces the mortality risk of patients, as compared to maintenance dialysis. The number of patients awaiting kidney transplantation has steadily increased, and the gap between allograft supply and demand continues to widen despite initiatives to expand the use of nonstandard deceased-donor allografts. The use of organs from living donors is one strategy to address the need for transplants. A medical, surgical, and psychosocial evaluation is mandatory prior to living kidney donation to ensure that the donor candidate is in good health and has normal kidney function, is not a risk to the recipient with respect to transmission of infections and malignancy, and will not face unacceptable risks after donation.

Han SA, et al. Electrolyte Blood Press. 2019 Dec;17(2):62-65. https://doi.org/10.5049/EBP.2019.17.2.62