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Background/Aims@#Although the conversion from tacrolimus (TAC) to cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin (CTLA4-Ig) is effective in reducing TAC-induced nephrotoxicity, it remains unclear whether CTLA4-Ig has a direct effect on TAC-induced renal injury. In this study, we evaluated the effects of CTLA4-Ig on TAC-induced renal injury in terms of oxidative stress. @*Methods@#In vitro study was performed to assess the effect of CTLA4-Ig on TAC-induced cell death, reactive oxygen species (ROS), apoptosis, and the protein kinase B (AKT)/forkhead transcription factor (FOXO) 3 pathway in human kidney 2 cells. In the in vivo study, the effect of CTLA4-Ig on TAC-induced renal injury was evaluated using renal function, histopathology, markers of oxidative stress (8-hydroxy-2’-deoxyguanosine) and metabolites (4-hydroxy-2-hexenal, catalase, glutathione S-transferase, and glutathione reductase), and activation of the AKT/FOXO3 pathway with insulin-like growth factor 1 (IGF-1). @*Results@#CTLA4-Ig significantly decreased cell death, ROS, and apoptosis caused by TAC. TAC treatment increased apoptotic cell death and apoptosis-related proteins (increased Bcl-2-associated X protein and caspase-3 and decreased Bcl-2), but it was reversed by CTLA4-Ig treatment. The activation of p-AKT and p-FOXO3 by TAC decreased with CTLA4-Ig treatment. TAC-induced renal dysfunction and oxidative marker levels were significantly improved by CTLA4-Ig in vivo. Concomitant IGF-1 treatment abolished the effects of CTLA4-Ig. @*Conclusions@#CTLA4-Ig has a direct protective effect on TAC-induced renal injury via the inhibition of AKT/FOXO3 pathway.
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Background@#Use of endotracheal tubes (ETTs) with appropriate size and depth can help minimize intubation-related complications in pediatric patients. Existing age-based formulae for selecting the optimal ETT size present several inaccuracies. We developed a machine learning model that predicts the optimal size and depth of ETTs in pediatric patients using demographic data, enabling clinical applications. @*Methods@#Data from 37,057 patients younger than 12 years who underwent general anesthesia with endotracheal intubation were retrospectively analyzed. Gradient boosted regression tree (GBRT) model was developed and compared with traditional age-based formulae. @*Results@#The GBRT model demonstrated the highest macro-averaged F1 scores of 0.502 (95% CI 0.486, 0.568) and 0.669 (95% CI 0.640, 0.694) for predicting the uncuffed and cuffed ETT size (internal diameter [ID]), outperforming the age-based formulae that yielded 0.163 (95% CI 0.140, 0.196, P < 0.001) and 0.392 (95% CI 0.378, 0.406, P < 0.001), respectively. In predicting the ETT depth (distance from tip to lip corner), the GBRT model showed the lowest mean absolute error (MAE) of 0.71 cm (95% CI 0.69, 0.72) and 0.72 cm (95% CI 0.70, 0.74) compared to the age-based formulae that showed an error of 1.18 cm (95% CI 1.16, 1.20, P < 0.001) and 1.34 cm (95% CI 1.31, 1.38, P < 0.001) for uncuffed and cuffed ETT, respectively. @*Conclusions@#The GBRT model using only demographic data accurately predicted the ETT size and depth. If these results are validated, the model may be practical for predicting optimal ETT size and depth for pediatric patients.
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Generally, an induction agent is chosen based on the conditions of the deceased donor and the recipient. Antithymocyte globulin (ATG) is preferred in relatively high-risk conditions. No clear evidence indicates which induction agent is safer or more efficient for deceased donor kidney transplantation (DDKT). This study compares the efficacy and safety of basiliximab (BSX) and ATG according to donor characteristics in DDKT. Methods: A total of 724 kidney transplant recipients from three transplant centers were enrolled, and propensity score matching was performed. Based on a donor age of 60 years, donor kidney with acute kidney injury (AKI), and Kidney Donor Profile Index (KDPI) score of 65%, we investigated how the choice of induction therapy agent affected the posttransplant clinical outcomes of delayed graft function (DGF), acute rejection (AR), infectious complications, and allograft and patient survival. Results: AR and DGF did not differ significantly according to induction agent in elderly/young donor, AKIon-AKI, and high-KDPI/ low-KDPI subgroups. The infection rate did not show meaningful differences. The differences in death-censored allograft survival and patient survival rates between induction agents were not statistically significant. Conclusion: Our study suggests that BSX can produce clinical outcomes similarly favorable to those of ATG even in DDKT cases with relatively poor donor conditions. Nonetheless, the donor and recipient conditions, immunological risk, and infection risk must be all taken into consideration when choosing an induction agent. Therefore, clinicians should carefully select the induction therapy agent for DDKT based on the risks and benefits in each DDKT case.
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Background: Erythema nodosum and erythema induratum of Bazin are similar inflammatory diseases of the lower extremities. These are clinically distinguishable entities, though overlap can occur. Both diseases are reported to be related to Mycobacterium tuberculosis infection, but it is very difficult to identify Mycobacterium tuberculosis in skin lesions. Aim: This study aimed to develop a new nested polymerase chain reaction targeting the IS6110 insertion sequence of M. tuberculosis to improve the M. tuberculosis detection rate in skin lesions of erythema nodosum or erythema induratum of Bazin. Methods: From May 2016 to Jan 2018, 14 patients with clinically suspicious erythema nodosum or erythema induratum were enrolled in the study. Two cases were classified as erythema nodosum and 12 as erythema induratum. Individual patients were subjected to a 4-mm punch biopsy, and their venous whole blood was sampled immediately after diagnosis. Results: Eight patients were tested for M. tuberculosis using QuantiFERON, of which seven (87.5%) were positive. IS6110-nested polymerase chain reaction on all 14 patients identified 11 (78.6%) positive cases. Four of the eight (50%) individuals tested with QuantiFERON were also positive in the IS6110 nested polymerase chain reaction. The difference between the outcomes of the QuantiFERON and the IS6110-nested polymerase chain reaction tests was not statistically significant. There was also no significant agreement between the results of both assays. Sequencing the IS6110-nested polymerase chain reaction products showed a 97%–100% nucleotide sequence identity with the H37Rv genome. Conclusion: It is important to test for tuberculosis in patients with multiple tender subcutaneous nodules on their lower extremities in high-burden tuberculosis countries like Korea. Limitations: We need to register more suspicious patients to verify the association between erythema nodosum/erythema induratum of Bazin and M. tuberculosis. Furthermore, it is neces
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Purpose@#Oxidative stress plays an important role in the pathogenesis of chronic metabolic diseases. This study investigated the effect of the antioxidant-rich dietary intervention on oxidative stress, metabolic parameters, and arterial stiffness in elderly Koreans with metabolic syndrome (MetS). @*Materials and Methods@#Thirty-one subjects with MetS were enrolled and randomly divided into dietary intervention group and control group. Subjects in the intervention group received three meal boxes prepared with antioxidant-rich ingredients every day for 4 weeks, and subjects in the control group maintained their usual diets. Anthropometric and various biochemical parameters related to oxidative stress, inflammation, and MetS were assessed. Brachial-ankle pulse wave velocity (baPWV) and fat measurement using computed tomography were also conducted before and after 4 weeks. @*Results@#There were significant differences in waist circumference, visceral to subcutaneous fat ratio, lipid peroxidation, oxidized low density lipoprotein (oxLDL), systolic and diastolic blood pressure, lipid parameters, advanced glycation end products, and baPWV between before and after the study in the experimental group (all p<0.05). Significant inter-group differences were observed between the experimental and control group in terms of the differences in body mass index, waist circumference, oxygen radical absorbance capacity, protein carboxylation, lipid peroxidation, oxLDL, blood pressure, lipid parameters, and baPWV between before and after the study (all p<0.05). @*Conclusion@#Antioxidant-rich dietary intervention for a 4-week period ameliorated the state of oxidative stress and improved the components of MetS including central obesity, dyslipidemia, hypertension, and arterial stiffness in elderly Koreans with MetS.
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Background@#The relationship between latent tuberculosis and the use of certain biologics is well known, but the relationship between the test for latent tuberculosis results and psoriasis itself or systemic anti-psoriatic treatment (cyclosporine and methotrexate) has not been elucidated to date. @*Objective@#To assess the influence of psoriasis and systemic anti-psoriatic treatment on results of the interferon-gamma release assay. @*Methods@#A retrospective study was conducted on 353 patients who were screened for latent tuberculosis before the use of medicines for moderate to severe psoriasis. The screening was based on results of the interferon-gamma release assay. The control group included 2,025 health care workers who were screened for latent tuberculosis during a general medical examination. @*Results@#Interferon-gamma release assay was positive in 35.4% of the patients and 11.6% of the subjects from the control group. There was a statistically significant correlation between psoriasis and assay positivity (p＜0.05). Among the patients, no statistically-relevant association regarding previous use of cyclosporine or methotrexate was found (cyclosporine: p=0.284, methotrexate: p=0.231). Furthermore, patients were divided into two groups according to treatment duration, i.e., shorter or longer than 6 months. There were no relevant differences in treatment duration cyclosporine: p=0.243, methotrexate: p=0.743). @*Conclusion@#This study revealed a higher prevalence of interferon-gamma release assay positivity in patients with psoriasis. However, conventional anti-psoriatic drugs, such as cyclosporine and methotrexate, showed no significant difference regarding the assay positivity.
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Objective@#The objective of this study was to compare and evaluate the diagnostic value of serum carbohydrate antigen 125 (CA125) and/or human epididymis protein 4 (HE4) and a panel of novel multiple biomarkers in patients with ovarian tumors to identify more accurate and effective markers for screening ovarian cancer. @*Methods@#Candidate ovarian cancer biomarkers were selected based on a literature search. Dozens of candidate biomarkers were examined using 143 serum samples from patients with ovarian cancer and 157 healthy serum samples as noncancer controls. To select the optimal marker panel for an ovarian cancer classification model, a set of biomarker panels was created with the number of possible combinations of eight biomarkers. Using the set of biomarkers as an input variable, the optimal biomarker panel was selected by examining the performance of the biomarker panel set using the Random Forest algorithm as a non-linear classification method and a 10-fold cross-validation technique. @*Results@#The final selected optimal combination of five biomarkers (CA125, HE4, cancer antigen 15-3, apolipoprotein [Apo] A1, and ApoA2) exhibited a sensitivity of 93.71% and specificity of 93.63% for ovarian cancer detection during validation. @*Conclusion@#Combining multiple biomarkers is a valid strategy for ovarian cancer diagnosis and can be used as a minimally invasive screening method for early ovarian cancer. A panel of five optimal biomarkers, including CA125 and HE4, was verified in this study. These can potentially be used as clinical biomarkers for early detection of ovarian cancer.
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Crohn’s disease is usually diagnosed according to intestinal symptoms, but extra-intestinal manifestations are important in approximately one-third of cases. Although several extra-intestinal symptoms associated with various organs have been reported, renal involvement is uncommon in patients with Crohn’s disease. Tubulointerstitial nephritis in a patient with Crohn’s disease is usually caused by infection, sarcoidosis, or medications. However, primary tubulointerstitial nephritis caused by Crohn’s disease alone is extremely rare. A 19-year-old male patient was referred to our hospital because of an increase in serum creatinine level. He underwent a kidney biopsy with renal insufficiency. Renal histological findings revealed granulomatous tubulointerstitial nephritis. Thereafter, a colonoscopy was performed with suspicion of Crohn’s disease. Ultimately, he was diagnosed with granulomatous tubulointerstitial nephritis based on Crohn’s disease. The patient had improved gastrointestinal symptoms after the last treatment. This case report presents a rare case of primary tubulointerstitial nephritis caused by Crohn’s disease.
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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.
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Background/Aims@#Renal ischemia followed by reperfusion (I/R) is a leading cause of acute kidney injury (AKI), which is closely associated with high morbidity and mortality. Studies have shown that induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) exert powerful therapeutic effects in renal ischemia. However, the efficacy of iMSC-derived exosomes (iExo) on I/R injuries remains largely unknown. @*Methods@#Human iPSCs were differentiated into iMSCs using a modified one-step method. Ultrafiltration, combined with purification, was used to isolate iExo from iMSCs. iExo was administered following I/R injury in a mouse model. The effect of iExo on I/R injury was assessed through changes in renal function, histology, and expression of oxidative stress, inflammation, and apoptosis markers. Further, we evaluated its association with the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. @*Results@#Mice subjected to I/R injury exhibited typical AKI patterns; serum creatinine level, tubular necrosis, apoptosis, inflammatory cytokine production, and oxidative stress were markedly increased compared to sham mice. However, treatment with iExo attenuated these changes, significantly improving renal function and tissue damage, similar to the renoprotective effects of iMSCs on I/R injury. Significant induction of activated ERK 1/2 signaling molecules was observed in mice treated with iExo compared to those in the I/R injury group. @*Conclusions@#The present study demonstrates that iExo administration ameliorated renal damage following I/R, suggesting that iMSC-derived exosomes may provide a novel therapeutic approach for AKI treatment.
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Recent advancements in artificial intelligence (AI) techniques have enabled the development of accurate prediction models using clinical big data. AI models for perioperative risk stratification, intraoperative event prediction, biosignal analyses, and intensive care medicine have been developed in the field of perioperative medicine. Some of these models have been validated using external datasets and randomized controlled trials. Once these models are implemented in electronic health record systems or software medical devices, they could help anesthesiologists improve clinical outcomes by accurately predicting complications and suggesting optimal treatment strategies in real-time. This review provides an overview of the AI techniques used in perioperative medicine and a summary of the studies that have been published using these techniques. Understanding these techniques will aid in their appropriate application in clinical practice.
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Background/Aims@#Coenzyme Q10 (CoQ10), is a promising antioxidant; however, low bioavailability owing to lipid-solubility is a limiting factor. We developed water-soluble CoQ10 (CoQ10-W) and compared its effects with conventional lipid-soluble CoQ10 (CoQ10-L) in an experimental model of chronic tacrolimus (Tac) nephropathy. @*Methods@#CoQ10-W was developed from a glycyrrhizic-carnitine mixed layer CoQ10 micelle based on acyltransferases. Chronic nephropathy was induced in rats with 28-day Tac treatment; they were concomitantly treated with CoQ10-L or CoQ10-W. CoQ10 level in plasma and kidney were measured using liquid chromatography–mass spectrometry. CoQ10-W and CoQ10-L effects on Tac-induced nephropathy were assessed in terms of renal function, histopathology, oxidative stress, and apoptotic cell death. Their effects on cell viability and reactive oxygen species (ROS) production were assessed in cultured proximal tubular cells, human kidney 2 (HK-2) cells. @*Results@#The plasma CoQ10 level was significantly higher in the CoQ10-W group than in the CoQ10-L group. Tac treatment caused renal dysfunction, typical pathologic lesions, and oxidative stress markers. Serum creatinine was restored in the Tac + CoQ10-L or CoQ10-W groups compared with that in the Tac group. CoQ10-W administration reduced oxidative stress and apoptosis markers. Mitochondrial ultrastructure assessment revealed that the addition of CoQ10-L or CoQ10-W with Tac increased mitochondrial size and number than Tac treatment alone. In vitro investigations revealed that both CoQ10-L and CoQ10-W improved cell viability and reduced ROS production in the Tac-induced HK-2 cell injury. @*Conclusions@#CoQ10-W has a better therapeutic effect in Tac-induced renal injury than conventional CoQ10-L, possibly associated with improved CoQ10 bioavailability
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Background@#This study evaluated the impact of acute kidney injury (AKI) on posttransplant clinical outcomes for deceased donor (DD) kidney transplantation (KT) using the Kidney Donor Profile Index (KDPI) system. @*Methods@#Overall, 657 kidney transplant recipients (KTRs) receiving kidneys from 526 DDs from four transplant centers were included. We divided them into the high and low KDPI donor groups by 65%, the KDPI score, and both groups were subdivided into the AKI-DDKT and non-AKI-DDKT subgroups according to AKI in DDs. @*Results@#There was no significant difference in the incidence of delayed graft function (DGF) between the high and low KDPI-KTR groups; however, the AKI-DDKT subgroup showed significantly higher incidence of DGF than the non-AKI-DDKT subgroup in both groups (p = 0.001, p < 0.001, respectively). The death-censored graft survival rate was significantly lower in the high KDPI-KTR group than in the low KDPI-KTR group (p = 0.005). Only in the high KDPI-KTR group, the death-censored graft survival rate was significantly lower in the KT from DDs with AKI stage 3 than KT from DDs with non-AKI or AKI stage 1 or 2 (p = 0.040). The interaction between AKI stage 3 in DDs and high KDPI on the allograft outcome was significant (p = 0.002). @*Conclusion@#KTs from DDs with AKI stage 3 showed an adverse impact on the allograft outcome in the high KDPI-KTR group. Therefore, DDs with a high KDPI score should be managed carefully so that severe AKI does not occur prior to KT.
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Background/Aims@#Coenzyme Q10 (CoQ10), is a promising antioxidant; however, low bioavailability owing to lipid-solubility is a limiting factor. We developed water-soluble CoQ10 (CoQ10-W) and compared its effects with conventional lipid-soluble CoQ10 (CoQ10-L) in an experimental model of chronic tacrolimus (Tac) nephropathy. @*Methods@#CoQ10-W was developed from a glycyrrhizic-carnitine mixed layer CoQ10 micelle based on acyltransferases. Chronic nephropathy was induced in rats with 28-day Tac treatment; they were concomitantly treated with CoQ10-L or CoQ10-W. CoQ10 level in plasma and kidney were measured using liquid chromatography–mass spectrometry. CoQ10-W and CoQ10-L effects on Tac-induced nephropathy were assessed in terms of renal function, histopathology, oxidative stress, and apoptotic cell death. Their effects on cell viability and reactive oxygen species (ROS) production were assessed in cultured proximal tubular cells, human kidney 2 (HK-2) cells. @*Results@#The plasma CoQ10 level was significantly higher in the CoQ10-W group than in the CoQ10-L group. Tac treatment caused renal dysfunction, typical pathologic lesions, and oxidative stress markers. Serum creatinine was restored in the Tac + CoQ10-L or CoQ10-W groups compared with that in the Tac group. CoQ10-W administration reduced oxidative stress and apoptosis markers. Mitochondrial ultrastructure assessment revealed that the addition of CoQ10-L or CoQ10-W with Tac increased mitochondrial size and number than Tac treatment alone. In vitro investigations revealed that both CoQ10-L and CoQ10-W improved cell viability and reduced ROS production in the Tac-induced HK-2 cell injury. @*Conclusions@#CoQ10-W has a better therapeutic effect in Tac-induced renal injury than conventional CoQ10-L, possibly associated with improved CoQ10 bioavailability
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Background@#This study evaluated the impact of acute kidney injury (AKI) on posttransplant clinical outcomes for deceased donor (DD) kidney transplantation (KT) using the Kidney Donor Profile Index (KDPI) system. @*Methods@#Overall, 657 kidney transplant recipients (KTRs) receiving kidneys from 526 DDs from four transplant centers were included. We divided them into the high and low KDPI donor groups by 65%, the KDPI score, and both groups were subdivided into the AKI-DDKT and non-AKI-DDKT subgroups according to AKI in DDs. @*Results@#There was no significant difference in the incidence of delayed graft function (DGF) between the high and low KDPI-KTR groups; however, the AKI-DDKT subgroup showed significantly higher incidence of DGF than the non-AKI-DDKT subgroup in both groups (p = 0.001, p < 0.001, respectively). The death-censored graft survival rate was significantly lower in the high KDPI-KTR group than in the low KDPI-KTR group (p = 0.005). Only in the high KDPI-KTR group, the death-censored graft survival rate was significantly lower in the KT from DDs with AKI stage 3 than KT from DDs with non-AKI or AKI stage 1 or 2 (p = 0.040). The interaction between AKI stage 3 in DDs and high KDPI on the allograft outcome was significant (p = 0.002). @*Conclusion@#KTs from DDs with AKI stage 3 showed an adverse impact on the allograft outcome in the high KDPI-KTR group. Therefore, DDs with a high KDPI score should be managed carefully so that severe AKI does not occur prior to KT.
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Purpose@#To report a case of preseptal cellulitis after strabismus surgery in a patient with no previous history of ocular surgery.Case summary: A 33-year-old male visited the ophthalmology clinic with a 4-day history of left eye pain and lid swelling after strabismus surgery. He was a healthy patient with a history of polio resulting in left hemiparalysis and difficulty walking. He was followed up with left medial rectus and lateral rectus muscle resection surgery for secondary sensory esotropia. His best corrected visual acuity was 0.6 in his left eye and physical examination revealed pain, eyelid edema, chemosis, and purulent discharge from the left conjunctival fornix. Computed tomography scanning with contrast enhancement revealed diffuse preseptal periorbital soft tissue swelling and enhanced fat stranding suggesting left preseptal cellulitis. The patient was hospitalized with intravenous broad spectrum antibiotics. Left eye swelling was improved and purulent discharge had decreased after 3 days; he was discharged after a 5-day course of intravenous antibiotic treatment. Oral antibiotics were administrated for 1 week. The patient had no recurrent symptoms during the 3-month follow-up. @*Conclusions@#Although rare, preseptal cellulitis after strabismus surgery must be promptly recognized to prevent secondary complications related to infection.
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Background@#While microscopy (MS) evaluation of skin scrapings has a 100% positive predictive value and specificity by definition for scabies diagnosis, it has low sensitivity. Dermoscopy (DS) has not yet been widely accepted for diagnosis, and long-term clinician training is required. @*Objective@#To evaluate the diagnostic validity of cytochrome c oxidase subunit 1 (cox1) gene nested polymerase chain reaction (PCR) as an adjunctive method for diagnosing scabies. @*Methods@#This was a prospective, single institution study, conducted on a total of 302 skin lesions from 50 patients suspected of scabies at Kangdong Sacred Heart Hospital in Seoul, Korea. DS, MS, and cox1 nested PCR were performed on all patients. @*Results@#Of the 302 lesions, 145 (48.0%) were obtained at first visit and 157 (52.0%) were identified in the course of follow-up visits after treatment. For all lesions, DS and MS sensitivity levels were 55.9% (73/136) and 55.2% (75/136), respectively, with cox1 gene nested PCR considered as 100%. The results of DS and MS identification showed no difference between each other and showed significant difference from that of cox1 gene nested PCR. @*Conclusion@#Nested PCR detecting cox1 may be prospectively used to comprehensively diagnose lesions of scabies in clinical practice.
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Background/Aims@#Tacrolimus has been used as an immunosuppressive agent in organ transplantation. Despite the therapeutic benefits, tacrolimus’s use is limited due to its nephrotoxicity. To reduce tacrolimus nephrotoxicity, effective humanized experimental models may be helpful. Here, we modeled tacrolimus nephrotoxicity using kidney organoids derived from human inducible pluripotent stem cells (iPSCs) in vitro. @*Methods@#Kidney organoids were differentiated from the CMC11 iPSC cell line, re-seeded in 96-well plates, and treated with tacrolimus at doses of 0, 30, or 60 μM for 24 hours. This in vitro model was compared to a mouse model of tacrolimus nephrotoxicity and the associated mechanisms were investigated. @*Results@#The size of the kidney organoids and cell viability decreased in dose-dependent manners after treatment with tacrolimus. The number of tubular cells decreased with a loss of polarity, similar to the effects seen in mouse tacrolimus nephrotoxicity. Ultrastructural analysis showed numerous vacuoles in the proximal tubular cells of the kidney organoids treated with tacrolimus. Tacrolimus treatment induced oxidative stress and mitochondrial dysfunction, and autophagic activity was enhanced in the kidney organoids. Rapamycin, an autophagy inducer, accelerated cell death in the kidney organoid model of tacrolimus nephrotoxicity, which was attenuated by treatment with 3-methyladenine, an autophagy inhibitor. These findings indicate that the augmentation of autophagy by rapamycin treatment accelerated tacrolimus nephrotoxicity. @*Conclusions@#Our data suggest that human kidney organoids are an effective in vitro model of tacrolimus nephrotoxicity and that autophagy plays a critical role in tacrolimus nephrotoxicity.
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Background/Aims@#Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. @*Methods@#Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). @*Results@#Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. @*Conclusions@#Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.
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In kidney transplantation (KT), overcoming donor shortage is particularly challenging in patients with preexisting donor-specific antibodies (DSAs) against human leukocyte antigen (HLA), called HLA-incompatible KT (HLAi KT), carrying the risk of rejection and allograft loss. Thus, it is necessary to accurately evaluate the degree of sensitization before HLAi KT, and undertake appropriate pretreatment strategies. To determine the degree of sensitization, complement-dependent cytotoxicity has been the only method employed; the development of a method using flow cytometry further improved the test sensitivity. However, these tests present disadvantages, including the need for living cells, with a solid-phase assay developed to resolve this problem. Currently, the method using Luminex (Luminex Corp.) is widely used in clinical practice. As this method measures DSAs using single antigen beads, it is possible to classify immunological risks by measuring the type and amount of DSAs. Furthermore, there have been major advances in methods that involve DSA removal before HLAi KT. In the early stages of desensitization, plasmapheresis and intravenous immunoglobulins were the main treatment methods employed; however, the introduction of CD20 monoclonal antibody and proteasome inhibitors further increased the success rate of desensitization. Currently, HLAi KT has been established as an important transplant method, but an understanding of DSAs and a novel desensitization treatment are warranted.