Background/Aims: This study analyzed the risk factors for technique survival in dialysis patients and compared technique survival rates between hemodialysis (HD) and peritoneal dialysis (PD) in a prospective cohort of Korean patients. Methods: A total of 1,042 patients undergoing dialysis from September 2008 to June 2011 were analyzed. The dialysis modality was defined as that used 90 days after commencing dialysis. Technique survival was compared between the two dialysis modalities, and the predictive risk factors were evaluated. Results: The dialysis modality was an independent risk factor predictive of technique survival. PD had a higher risk for technique failure than HD (hazard ratio [HR], 10.8; 95% confidence interval [CI], 1.9 to 62.0; p = 0.008) during a median follow-up of 11.0 months. In the PD group, a high body mass index (BMI) was an independent risk factor for technique failure (HR, 1.3; 95% CI, 1.0 to 1.8; p = 0.036). Peritonitis was the most common cause of PD technique failure. The difference in technique survival between PD and HD was more prominent in diabetic patients with a good nutritional status and in non-diabetic patients with a poor nutritional status. Conclusions: In a prospective cohort of Korean patients with end-stage renal disease, PD was associated with a higher risk of technique failure than HD. Diabetic patients with a good nutritional status and non-diabetic patients with a poor nutritional status, as well as patients with a higher BMI, had an inferior technique survival rate with PD compared to HD.
Abstract Epithelial-to-mesenchymal transition (EMT) is one of the main causes of peritoneal fibrosis. However, the pathophysiological mechanisms of EMT, specifically its relationship with autophagy, are still unknown. This study aimed to evaluate the role of autophagy in transforming growth factor-beta 1 (TGF-β1)-induced EMT in human peritoneal mesothelial cells (HPMCs). Primary cultured HPMCs were treated with TGF-β1 (2 and 5 ng/mL) and changes in autophagy markers and the relationship between autophagy and EMT were evaluated. We also identified changes in EMT- and autophagy-related signaling pathways after autophagy and NADPH oxidase 4 (NOX4) inhibition. TGF-β1 increased the generation of NOX4 and reactive oxygen species (ROS) in HPMCs, resulting in mitochondrial damage. Treatment with GKT137831 (20 μM), a NOX1/4 inhibitor, reduced ROS in the mitochondria of HPMC cells and reduced TGF-β1-induced mitochondrial damage. Additionally, the indirect inhibition of autophagy by GKT137831 (20 μM) downregulated TGF-β1-induced EMT, whereas direct inhibition of autophagy using 3-methyladenine (3-MA) (2 mM) or autophagy-related gene 5 ( ATG5 ) gene silencing decreased the TGF-β1-induced EMT in HPMCs. The suppressor of mothers against decapentaplegic 2/3 (Smad2/3), autophagy-related phosphoinositide 3-kinase (PI3K) class III, and protein kinase B (Akt) pathways, and mitogen-activated protein kinase (MAPK) signaling pathways, such as extracellular signal-regulated kinase (ERK) and P38, were involved in TGF-β1-induced EMT. Autophagy and NOX4 inhibition suppressed the activation of these signaling pathways. Direct inhibition of autophagy and its indirect inhibition through the reduction of mitochondrial damage by upstream NOX4 inhibition reduced EMT in HPMCs. These results suggest that autophagy could serve as a therapeutic target for the prevention of peritoneal fibrosis in patients undergoing peritoneal dialysis.
Seong Wook Lee, Young-Hwan Lee, You Hyun Jeon, Jeong-Hoon Lim, Hee-Yeon Jung, Sun-Hee Park, Chan-Duck Kim, Yong-Lim Kim, Jang-Hee Cho. Korean J Transplant 2023;37:110. https://doi.org/10.4285/ATW2023.F-6899
Introduction To investigate the correlation between serum anti-ABO immunoglobulin G (IgG) and IgG subtypes, anti-ABO IgG subclasses were measured by flow cytometry (FCM) in ABO-incompatible (ABO-i) kidney transplant recipients (KTRs). We also evaluated baseline anti-ABO C1q antibody of KTRs. Method Baseline anti-ABO IgG titers were measured with both FCM and column agglutination technique (CAT) methods in 18 ABO-i KTRs. The mean florescence intensity (MFI) ratios of baseline Anti-ABO IgG subclasses were obtained by FCM method and followed up after rituximab (RTX), each plasmapheresis (PP) session and kidney transplantation. Correlation between the values of IgG subclass and total IgG titer were analyzed. Baseline anti-ABO C1q antibody was measured by FCM methods. Result The baseline MFI ratios of total IgG, IgG1, IgG2, IgG3 and IgG4 were 202.46, 62.41, 30.01, 1.04 and 1.13, respectively. The MFI ratios of IgG1, IgG2, and total IgG measured at baseline and pre-PP were positively correlated with the baseline ABO titer measured by CAT (rho, baseline; 0.641, 0.638, 0.663, PP; 0.662, 0.581, 0.662). However, Spearman correlation analysis revealed that baseline ABO titer did not show any correlation with the values after final PP and transplantation. IgG1 and IgG2 as well as total IgG were removed effectively after serial PP. However, anti-ABO C1q antibody was not detected and neither correlated with total IgG and any IgG subclasses. Conclusion Our findings suggest that IgG1 and IgG2 are dominant IgG subtypes in ABO-i KTRs. The mean baseline levels of IgG1 and IgG2 were correlated with baseline total IgG titer. However, anti-ABO C1q antibody was not detected in the present study. Further study is warranted to evaluate the function of each IgG subtype to activate complement pathway.
Diabetes insipidus (DI) is characterized by excessive urination and thirst. This disease results from inadequate output of antidiuretic hormone (ADH) from the pituitary gland or the absence of the normal response to ADH in the kidney. We present a case of transient central DI in a patient who underwent a cardiopulmonary bypass (CPB) for coronary artery bypass grafting (CABG). A 44-yr-old male underwent a CABG operation. An hour after the operation, the patient developed polyuria and was diagnosed with central DI. The patient responded to desmopressin and completely recovered five days after surgery. It is probable that transient cerebral ischemia resulted in the dysfunction of osmotic receptors in the hypothalamus or hypothalamus-pituitary axis during CPB. It is also possible that cardiac standstill altered the left atrial non-osmotic receptor function and suppressed ADH release. Therefore, we suggest that central DI is a possible cause of polyuria after CPB.
Kidney transplantation is the preferred treatment for patients with end-stage kidney disease, because it prolongs survival and improves quality of life. Allograft biopsy is the gold standard for diagnosing allograft rejection. However, it is invasive and reactive, and continuous monitoring is unrealistic. Various biomarkers for diagnosing allograft rejection have been developed over the last two decades based on omics technologies to overcome these limitations. Omics technologies are based on a holistic view of the molecules that constitute an individual. They include genomics, transcriptomics, proteomics, and metabolomics. The omics approach has dramatically accelerated biomarker discovery and enhanced our understanding of multifactorial biological processes in the field of transplantation. However, clinical application of omics-based biomarkers is limited by several issues. First, no large-scale prospective randomized controlled trial has been conducted to compare omics-based biomarkers with traditional biomarkers for rejection. Second, given the variety and complexity of injuries that a kidney allograft may experience, it is likely that no single omics approach will suffice to predict rejection or outcome. Therefore, integrated methods using multiomics technologies are needed. Herein, we introduce omics technologies and review the latest literature on omics biomarkers predictive of allograft rejection in kidney transplant recipients.
Various coronavirus disease 2019 (COVID-19) vaccines are being developed, which show practical preventive effects. Here, we report a 51-year-old healthy man with nephrotic syndrome secondary to minimal change disease (MCD) after Ad26.COV.2 (Janssen) vaccination. He had no comorbid disease and received Ad26.COV.2 on April 13, 2021. Seven days after vaccination, he developed edema and foamy urine. Edema rapidly aggravated with decreased urine volume. He was admitted to the hospital 28 days after vaccination, and his body weight increased by 21 kg after vaccination. His serum creatinine level was 1.54 mg/dL, and 24-h urinary protein excretion was 8.6 g/day. Kidney biopsy revealed no abnormality in the glomeruli and interstitium of the cortex and medulla under the light microscope. Electron microscopy revealed diffuse effacement of the podocyte foot processes, thus, he was diagnosed with MCD. High-dose steroid therapy was applied, and his kidney function improved three days after steroid therapy. Three weeks after steroid use, his serum creatinine decreased to 0.95 mg/dL, and spot urine protein-to-creatine decreased to 0.2 g/g. This case highlights the risk of new-onset nephrotic syndrome secondary to MCD after vectored COVID-19 vaccination. Although the pathogenesis is uncertain, clinicians need to be careful about adverse renal effects of COVID-19 vaccines.
The role of infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in terms of survival among dialysis patients remains incompletely understood. In the present multicenter prospective cohort study, we investigated the prevalences of HBV and HCV infection among 3,321 patients receiving maintenance dialysis in Korea, and assessed the impacts of these infections on survival. All included patients underwent hepatitis B antigen (HBsAg) and HCV antibody (Ab) testing, which revealed that 236 patients (7.1%) were HBsAg-positive, and 123 patients (3.7%) were HCV Ab-positive. HBsAg-positive and HCV Ab-positive patients were matched to hepatitis virus-negative patients using a propensity score at a ratio of 1:2. The prevalences of HBV and HCV infection did not significantly differ according to dialysis modality. Linear-by-linear association analysis revealed that hepatitis B prevalence significantly increased with increasing dialysis vintage (p = 0.001), and hepatitis C prevalence tended to be higher with increasing dialysis vintage (p = 0.074). We compared the survival of HBsAg-positive and HCV Ab-positive patients to that of hepatitis virus-negative patients. After propensity score matching, cumulative survival did not differ between HBsAg-positive and HBsAg-negative patients (p = 0.37), while HCV Ab-positive patients showed significantly lower survival than HCV Ab-negative patients (p = 0.03). The main conclusions of the present study are that HBV infection prevalence increased with longer dialysis vintage, and that both HBV and HCV infections were most prevalent among patients with the longest dialysis vintage. Additionally, HCV infection among maintenance dialysis patients is associated with an increased risk of mortality.
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