Omics-based biomarkers for diagnosis and prediction of kidney allograft rejection

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.

Treatment of rituximab in patients with idiopathic membranous nephropathy: a case series and literature review

Background/Aims@#Membranous nephropathy (MN) is a major cause of nephrotic syndrome in adults. This study aimed to evaluate the effect of rituximab (RTX) in patients with idiopathic MN (iMN) who have a high risk of progression. @*Methods@#We retrospectively analyzed data of 13 patients with iMN, who received RTX treatments from January 2014 to July 2020. RTX was indicated in patients with iMN with severe proteinuria and decreasing estimated glomerular filtration rate (eGFR) in the previous 6 months despite other immunosuppressive therapies. @*Results@#The patients were predominantly males (n = 11) and with a mean age of 55.3 years; median eGFR, 37.0 mL/min/1.73 m2 (interquartile range [IQR], 26.3 to 66.5); serum albumin level, 2.6 g/dL (IQR, 1.9 to 3.1); and spot urine protein-to-creatinine ratio at baseline, 6.6 g/g (IQR, 5.7 to 12.9). In a median follow-up of 22 months, eight patients (61.5%) achieved complete or partial remission. In responder group (n = 8), median eGFR increased from 31.5 to 61.5 mL/min/1.73 m2 (p = 0.049) and serum albumin level increased from 2.3 to 4.2 g/dL (p = 0.017) from RTX initiation to last follow-up. Antiphospholipase A2 receptor antibody (anti-PLA2R-Ab) was positive in six among seven tested patients, which markedly decreased in the responder group. There were no adverse events after RTX. @*Conclusions@#This study suggests that RTX is a safe and effective treatment option for patients with iMN who have a high risk of progression. Individualized therapy based on anti-PLA2R-Ab titer would be needed for better outcomes.

Elderly kidney transplant recipients have favorable outcomes but increased infection-related mortality

The number of elderly patients with end-stage kidney disease has been increasing, but the outcomes of kidney transplants (KT) remain poorly understood in elderly patients. Therefore, we evaluated the clinical outcomes of elderly KT recipients and analyzed the impact of elderly donors. Methods: This retrospective cohort study included patients who underwent KT between 2000 and 2019. KT recipients were divided into four groups according to a combination of recipient and donor age (≥60 or <60 years); elderly recipients: old-to-old (n = 46) and young-to-old (n = 83); young recipients: old-to-young (n = 98) and young-to-young (n = 796). We compared the risks of mortality, graft failure, and acute rejection between groups using Cox regression analysis. Results: The incidence of delayed graft function, graft failure, and acute rejection was not different among groups. Annual mean tacrolimus trough level was not lower in elderly recipients than young recipients during 10-year follow-up. Mortality was significantly higher in elderly recipients (p = 0.001), particularly infection-related mortality (p < 0.001). In multivariable Cox regression analysis, old-toold and young-to-old groups had increased risk of mortality (adjusted hazard ratio [aHR], 2.89; 95% confidence interval [CI], 1.14– 7.32; p = 0.03; aHR, 3.06; 95% CI, 1.51–6.20; p = 0.002). However, graft failure and acute rejection risks were not increased in elderly recipients. Conclusion: In elderly recipients, graft survival and acute rejection-free survival were not inferior to those of young recipients. However, mortality, especially risk of infection-related death, was increased in elderly recipients. Thus, low immunosuppression intensity might help decrease mortality in elderly recipients.

Clinical and Psychological Characteristics of Young Men with Military Adaptation Issues Referred for a Psychiatric Evaluation in South Korea: Latent Profile Analysis of Minnesota Multiphasic Personality Inventory-2 and Temperament and Character Inventory

Objective@#To investigate clinical and psychological characteristics of young men referred for a psychiatric evaluation due to expected unsuitability for military service and identify their heterogeneous subgroups based on the profiles of MMPI-2 and TCI. @*Methods@#We conducted a latent profile analysis of 348 men using MMPI-2 and TCI and then a comparative analysis of four latent classes in relation to sociodemographic, clinical, and IQ variables. @*Results@#We identified four classes with distinct clinical and psychological features: Class 1 (nonclinical: n=68), Class 2 (internalized: n=129), Class 3 (externalized: n=60), Class 4 (confused: n=91). Class 1 showed no significant psychiatric symptoms and relatively adaptive temperament and characteristics. Class 2 showed relatively higher harm avoidance and introverted traits indicating vulnerability to internalizing disorder. Class 3 was related to higher novelty seeking, impulsivity, and bipolarity. Class 4 showed the most severe clinical symptoms including psychotic experiences with extremely unstable temperament and immature personality. In total, 50–70% participants reported clinically significant depression, anxiety, and suicidal idea. Participants showed lower processing speed index (M=85.9, SD=16.6) than the general population. @*Conclusion@#The results suggest that clinical conceptualization and therapeutic intervention considering distinctive features of young men with adaptive problems related to military service are needed.

Histopathologic and clinicopathologic classifications of antineutrophil cytoplasmic antibody-associated glomerulonephritis: a validation study in a Korean cohort

Background@#Antineutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AAGN) is a common cause of rapidly progressive glomerulonephritis and requires prompt and proper immunosuppressive therapy to improve renal prognosis. This study aimed to evaluate the predictive value of two different classifications for renal outcomes in Korean AAGN patients. @*Methods@#Ninety-two patients who were diagnosed with AAGN at two tertiary hospitals between 2004 and 2018 were retrospectively analyzed retrospectively. The histopathologic classification according to glomerular pathology and the clinicopathologic classification according to normal glomeruli ratio, degree of interstitial fibrosis/tubular atrophy, and baseline renal function were evaluated using the Cox proportional hazards model. @*Results@#Forty-five patients (48.9%) progressed to end-stage kidney disease (ESKD) during the observation period. The mean age was 61.0 ± 15.3 years, and most patients had myeloperoxidase-ANCA (93.5%). In the histopathologic classification, the best renal survival occurred in the focal class, whereas the sclerotic class had the worst renal survival (sclerotic class vs. focal class; adjusted hazard ratio [aHR], 5.05; 95% confidence interval [CI], 1.32–19.31; p = 0.018). The mixed class had intermediate renal outcomes (mixed class vs. focal class; aHR, 4.23; 95% CI, 1.23–14.58; p = 0.022). In the clinicopathologic classification, the high-risk group had poor renal outcomes compared with the low-risk group (aHR, 6.56; 95% CI, 1.25–34.26; p = 0.026), but renal outcomes did not differ between the low- and medium-risk groups. @*Conclusion@#In Korean AAGN patients, histopathologic and clinicopathologic classifications had predictive value for renal outcomes, especially in the sclerotic class or the high-risk group with higher risk of progression to ESRD despite treatment.

Trends in epidemiologic characteristics of end-stage renal disease from 2019 Korean Renal Data System (KORDS)

Background@#The Korean Society of Nephrology (KSN) has maintained a nationwide end-stage renal disease (ESRD) registry data from Korean Renal Data System (KORDS) since 1985, as the representative registry of ESRD patients in Korea. This review is aimed to update the status of domestic ESRD and to provide evidence on the direction of dialysis therapy. @*Methods@#The KORDS Committee of KSN has collected data on dialysis centers and patients through an online registry program, and the data from 1986 to 2019 were analyzed. @*Results@#The incidence and prevalence of ESRD patients in Korea are increasing. The ESRD population numbered more than 100,000 in 2019, doubling during the 10 years since 2010. The proportion of diabetes mellitus as a major cause of ESRD seems to have reached a plateau. The increasing number of elderly dialysis patients is a constant trend, with more than half for the proportion of patients older than 65 years old in 2019. All-cause mortality decreased for the last approximately 20 years, regardless of sex, age, and cause of ESRD. The 5-year patient survival rate in both hemodialysis and peritoneal dialysis increased from 2001 to 2013. Since 2013, the patient survival rates in peritoneal dialysis were similar to those in hemodialysis. Cardiovascular complications were the leading cause of death in ESRD patients. @*Conclusions@#The incidence and prevalence of Korean ESRD patients have increased over time, although patient survival has also steadily increased. The establishment of a surveillance method to address the major cause of mortality in ESRD patients will help improve outcomes.

New-onset Nephrotic Syndrome after Janssen COVID-19 Vaccination: a Case Report and Literature Review

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.

Histopathologic and clinicopathologic classifications of antineutrophil cytoplasmic antibody-associated glomerulonephritis: a validation study in a Korean cohort

Background@#Antineutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AAGN) is a common cause of rapidly progressive glomerulonephritis and requires prompt and proper immunosuppressive therapy to improve renal prognosis. This study aimed to evaluate the predictive value of two different classifications for renal outcomes in Korean AAGN patients. @*Methods@#Ninety-two patients who were diagnosed with AAGN at two tertiary hospitals between 2004 and 2018 were retrospectively analyzed retrospectively. The histopathologic classification according to glomerular pathology and the clinicopathologic classification according to normal glomeruli ratio, degree of interstitial fibrosis/tubular atrophy, and baseline renal function were evaluated using the Cox proportional hazards model. @*Results@#Forty-five patients (48.9%) progressed to end-stage kidney disease (ESKD) during the observation period. The mean age was 61.0 ± 15.3 years, and most patients had myeloperoxidase-ANCA (93.5%). In the histopathologic classification, the best renal survival occurred in the focal class, whereas the sclerotic class had the worst renal survival (sclerotic class vs. focal class; adjusted hazard ratio [aHR], 5.05; 95% confidence interval [CI], 1.32–19.31; p = 0.018). The mixed class had intermediate renal outcomes (mixed class vs. focal class; aHR, 4.23; 95% CI, 1.23–14.58; p = 0.022). In the clinicopathologic classification, the high-risk group had poor renal outcomes compared with the low-risk group (aHR, 6.56; 95% CI, 1.25–34.26; p = 0.026), but renal outcomes did not differ between the low- and medium-risk groups. @*Conclusion@#In Korean AAGN patients, histopathologic and clinicopathologic classifications had predictive value for renal outcomes, especially in the sclerotic class or the high-risk group with higher risk of progression to ESRD despite treatment.

Trends in epidemiologic characteristics of end-stage renal disease from 2019 Korean Renal Data System (KORDS)

Background@#The Korean Society of Nephrology (KSN) has maintained a nationwide end-stage renal disease (ESRD) registry data from Korean Renal Data System (KORDS) since 1985, as the representative registry of ESRD patients in Korea. This review is aimed to update the status of domestic ESRD and to provide evidence on the direction of dialysis therapy. @*Methods@#The KORDS Committee of KSN has collected data on dialysis centers and patients through an online registry program, and the data from 1986 to 2019 were analyzed. @*Results@#The incidence and prevalence of ESRD patients in Korea are increasing. The ESRD population numbered more than 100,000 in 2019, doubling during the 10 years since 2010. The proportion of diabetes mellitus as a major cause of ESRD seems to have reached a plateau. The increasing number of elderly dialysis patients is a constant trend, with more than half for the proportion of patients older than 65 years old in 2019. All-cause mortality decreased for the last approximately 20 years, regardless of sex, age, and cause of ESRD. The 5-year patient survival rate in both hemodialysis and peritoneal dialysis increased from 2001 to 2013. Since 2013, the patient survival rates in peritoneal dialysis were similar to those in hemodialysis. Cardiovascular complications were the leading cause of death in ESRD patients. @*Conclusions@#The incidence and prevalence of Korean ESRD patients have increased over time, although patient survival has also steadily increased. The establishment of a surveillance method to address the major cause of mortality in ESRD patients will help improve outcomes.

New-onset Nephrotic Syndrome after Janssen COVID-19 Vaccination: a Case Report and Literature Review

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.

Patterns in renal diseases diagnosed by kidney biopsy: A single-center experience

Background@#The worldwide incidence of renal disease diagnosed by a kidney biopsy varies with age, race, sex, and region. Owing to a lack of studies and limited research resources for this disease in Korea, we investigated renal disease patterns by analyzing data from kidney biopsies performed over 13 years in a university-based teaching hospital in Korea. @*Methods@#Among 2,053 kidney biopsies performed from 2001 to 2013 at Kyungpook National University Hospital, 1,924 were retrospectively analyzed for histopathologic, demographic, and clinical data as well as laboratory results. @*Results@#Among the 1,924 studied kidney biopsies, 1,078 were males (56.0%) and the mean age was 37.7 ± 16.5 years. Asymptomatic urinary abnormalities were the most common clinical manifestation (62.5%). Immunoglobulin A nephropathy (IgAN) was the most common primary glomerular disease (37.4%), followed by minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulonephritis and crescentic glomerulonephritis. Secondary glomerular diseases accounted for 10.3% of the total biopsies, with lupus nephritis being the most common (4.6%) followed by Henoch-Schönlein purpura nephritis and diabetic nephropathy. The most common cause of nephrotic syndrome was MCD (42.1%) followed by MN. Among patients seropositive for hepatitis B or C, IgAN (28.3% and 21.4%, respectively) was the most common cause. @*Conclusion@#IgAN and lupus nephritis were the most common primary and secondary glomerular diseases, respectively. Race, region, and practice patterns may affect renal disease patterns in different cohorts.

Mycophenolic Acid Trough Concentration and Dose Are Associated with Hematologic Abnormalities but Not Rejection in Kidney Transplant Recipients

Background@#Little is known regarding the safe fixed dose of mycophenolic acid (MPA) for preventing biopsy-proven acute rejection (BPAR) in kidney transplant recipients (KTRs). We investigated the correlation of MPA trough concentration (MPA C0) and dose with renal transplant outcomes and adverse events. @*Methods@#This study included 79 consecutive KTRs who received MPA with tacrolimus (TAC) and corticosteroids. The MPA C0 of all the enrolled KTRs was measured, which was determined monthly by using particle-enhanced turbidimetric inhibition immunoassay for 12 months, and clinical data were collected at each time point. The clinical endpoints included BPAR, any cytopenia, and BK or cytomegalovirus infections. @*Results@#No differences in MPA C0 and dose were observed between KTRs with or without BPAR or viral infections under statistically comparable TAC concentrations. MPA C0 was significantly higher in patients with leukopenia (P = 0.021) and anemia (P = 0.002) compared with those without cytopenia. The MPA dose was significantly higher in patients with thrombocytopenia (P = 0.002) compared with those without thrombocytopenia. MPA C0 ≥ 3.5 μg/mL was an independent risk factor for leukopenia (adjusted odds ratio [AOR], 3.80; 95% confidence interval [CI], 1.24–11.64; P = 0.019) and anemia (AOR, 5.90; 95% CI, 1.27–27.51; P = 0.024). An MPA dose greater than the mean value of 1,188.8 mg/day was an independent risk factor for thrombocytopenia (AOR, 3.83; 95% CI, 1.15–12.78; P = 0.029). However, an MPA dose less than the mean value of 1,137.3 mg/day did not increase the risk of BPAR. @*Conclusion@#Either a higher MPA C0 or dose is associated with an increased risk of cytopenia, but neither a lower MPA C0 nor dose is associated with BPAR within the first year of transplantation. Hence, a reduced MPA dose with TAC and corticosteroids might be safe in terms of reducing hematologic abnormalities without causing rejection.

Clinical Characteristics and Long-Term Prognosis of Alport Syndrome: A Retrospective Single-Center Study

Purpose@#Alport syndrome (AS) is one of the most common inherited renal diseases caused due to mutations of genes encoding specific proteins of the type IV collagen family, and its major clinical manifestations include progressive renal failure, sensorineural deafness, and ocular abnormalities. We investigated the clinical characteristics and long-term prognosis of AS in Korean pediatric and adult populations. @*Methods@#We conducted a retrospective review of medical records of 33 children and adults who had been diagnosed or treated with AS from 1985 to 2019. @*Results@#The mean age of the 33 patients diagnosed with AS was 16.2±13.6 years, and the male-to-female ratio was 2:1. At the first visit, recurrent gross hematuria was the most common initial symptom. In 10 of 33 patients (30.3%), sensorineural hearing loss (SNHL) was diagnosed, but none had ophthalmic problems. Moreover, 11 of 33 patients (33.3%) had advanced to end-stage renal disease (ESRD), and a significant difference was observed in the age of the patients who progressed to ESRD based on the presence or absence of SNHL (P =0.035). @*Conclusion@#SNHL in AS can be an important prognostic factor for long-term deterioration of renal function. Further investigation is required to confirm the clinical course and the genetic characteristics of AS in Korea through prospective national cohort studies.

Hypertension and Electrolyte Disorders in Patients with COVID-19

The worldwide coronavirus disease 2019 (COVID-19) pandemic is still in progress, but much remains unknown about the disease. In this article, we review the association of hypertension or the renin-angiotensin system (RAS) with COVID-19 and the correlation between electrolyte disorders and disease severity. Underlying hypertension is likely to be associated with severe or critical COVID-19, but the relationship is not clear owing to confounding factors. Angiotensin-converting enzyme 2 (ACE2) plays an important role in the non-classical RAS pathway and binds to a receptor binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The RAS blockade is known to increase ACE2 levels, but controversy remains regarding the effect of RAS blockade therapy in the course of COVID-19. Some reports have indicated a protective effect of RAS blockade on COVID-19, whereas others have reported an association of RAS blockade therapy with the occurrence of severe complications such as acute kidney injury and admission to the intensive care unit. Electrolyte disorders are not uncommon in patients with COVID-19, and severe COVID-19 has frequently shown hypokalemia, hyponatremia, and hypocalcemia. Electrolyte imbalances are caused by alteration of RAS, gastrointestinal loss, effects of proinflammatory cytokines, and renal tubular dysfunction by the invasion of SARS-CoV-2.

Hypertension and Electrolyte Disorders in Patients with COVID-19

The worldwide coronavirus disease 2019 (COVID-19) pandemic is still in progress, but much remains unknown about the disease. In this article, we review the association of hypertension or the renin-angiotensin system (RAS) with COVID-19 and the correlation between electrolyte disorders and disease severity. Underlying hypertension is likely to be associated with severe or critical COVID-19, but the relationship is not clear owing to confounding factors. Angiotensin-converting enzyme 2 (ACE2) plays an important role in the non-classical RAS pathway and binds to a receptor binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The RAS blockade is known to increase ACE2 levels, but controversy remains regarding the effect of RAS blockade therapy in the course of COVID-19. Some reports have indicated a protective effect of RAS blockade on COVID-19, whereas others have reported an association of RAS blockade therapy with the occurrence of severe complications such as acute kidney injury and admission to the intensive care unit. Electrolyte disorders are not uncommon in patients with COVID-19, and severe COVID-19 has frequently shown hypokalemia, hyponatremia, and hypocalcemia. Electrolyte imbalances are caused by alteration of RAS, gastrointestinal loss, effects of proinflammatory cytokines, and renal tubular dysfunction by the invasion of SARS-CoV-2.

Dialysis modality-related disparities in sudden cardiac death: hemodialysis versus peritoneal dialysis

BACKGROUND: Patients require risk stratification and preventive strategies for sudden cardiac death (SCD) based on the dialysis modality because the process of dialysis is a risk factor for SCD. This study aimed to compare the risk of SCD in patients undergoing hemodialysis (HD) versus peritoneal dialysis (PD).METHODS: Patients on HD and PD were included in the end-stage renal disease registry of the Korean Society of Nephrology between 1985 and 2017. The incidence and associated factors of SCD were analyzed based on the dialysis modalityRESULTS: Of 132,083 patients, 34,632 (26.2%) died during 94.8 ± 73.6 months of follow-up. In patients on HD and PD, 22.2% and 19.6% of total deaths were SCDs. In the propensity score-matched population, SCD accounted for 21.7% and 19.6% of total deaths in patients on HD and PD, respectively. HD was independently associated with SCD even after adjusting for age and significant comorbidities. Hypertension, coronary artery disease, and congestive heart failure, and age at the time of death < 65 years were independent risk factors for SCD in patients on HD but not in those on PD. Diabetes was significantly associated with SCD regardless of the dialysis modality.CONCLUSION: Compared with patients on PD, Korean patients on HD have a higher risk of SCD, which is attributable to cardiac comorbidities.

Comparison of Transplant Outcomes for Low-level and Standard-level Tacrolimus at Different Time Points after Kidney Transplantation

BACKGROUND: Optimal tacrolimus (TAC) trough levels for different periods after kidney transplantation (KT) has not been definitely established. This study aimed to investigate transplant outcomes of low-level (LL) and standard-level (SL) TAC according to post-transplant period. METHODS: A total of 278 consecutive kidney transplant recipients (KTRs) receiving TAC-based immunosuppression were divided into LL and SL-TAC groups (4–7 and 7–12 ng/mL for 0–2 months, 3–6 and 6–10 ng/mL for 3–6 months, 2–5 and 5–8 ng/mL for 7–12 months, respectively) according to TAC trough level at each period. We compared estimated glomerular filtration rate (eGFR), biopsy-proven acute rejection (BPAR), de novo donor-specific antibody (dnDSA), calcineurin inhibitor (CNI) toxicity, opportunistic infection, and allograft survival. RESULTS: SL-TAC group showed significantly higher mean eGFR at 0–2 months than LL-TAC group (72.1 ± 20.3 vs. 64.2 ± 22.7 mL/min/1.73m2; P = 0.003). Incidence of BPAR at 7–12 months was significantly lower in SL-TAC group than in LL-TAC group (0.0% vs. 3.9%; P = 0.039). Patients with persistent SL-TAC lasting 12 months showed higher eGFR at 7–12 months than those with persistent LL-TAC (65.5 ± 13.0 vs. 57.9 ± 13.9 mL/min/1.73m2; P = 0.007). No significant differences in dnDSA, CNI toxicity, serious infections, or allograft survival were observed. CONCLUSIONS: Maintenance of proper TAC trough level after 6 months could reduce BPAR without adverse drug toxicities in KTRs. Moreover, persistent SL-TAC during the first year after KT might have a beneficial effect on a trend for a lower incidence of dnDSA and better renal allograft function.

Long-Term Changes in Self-Report Auditory Verbal Hallucinations in Patients with Schizophrenia Using Clozapine

This study explored long-term changes in self-report auditory verbal hallucinations (AVHs) among patients with schizophrenia taking clozapine. Forty-four patients who were evaluated more than twice and were above the mild severity category on the Hamilton Program for Schizophrenia Voices Questionnaire (HPSVQ) were enrolled. The mean observation period was 492.5±350.1 days (median, 452 days). The mean total, physical, and emotional factor scores on the HPSVQ were significantly reduced from baseline to the final observations except for one item “interference with life,” which was not significantly reduced. Regarding the time-dependent longitudinal changes modeled using linear mixed-effect regression, the total and physical factor scores showed significant changes during the first year, but the emotional factor score did not satisfy a more stringent level of significance. Female gender was negatively associated with the reduction in total and physical factor scores. The duration of treatment with clozapine also had a negative relationship with the reductions in all three scores.

Transgenerational Transmission of Trauma: Psychiatric Evaluation of Offspring of Former “Comfort Women,” Survivors of the Japanese Military Sexual Slavery during World War II

“Comfort women” are survivors of sexual slavery by the Imperial Japanese Army during World War II, who endured extensive trauma including massive rape and physical torture. While previous studies have been focused on the trauma of the survivors themselves, the effects of the trauma on the offspring has never been evaluated before. In this article, we reviewed the first study on the offspring of former “comfort women” and aimed to detect the evidence of transgenerational transmission of trauma. In-depth psychiatric interviews and the Structured Clinical Interview for DSM-5 Axis I Disorders were conducted with six offspring of former “comfort women.” Among the six participants, five suffered from at least one psychiatric disorder including major depressive disorder, panic disorder, posttraumatic stress disorder, adjustment disorder, insomnia disorder, somatic symptom disorder, and alcohol use disorder. Participants showed similar shame and hyperarousal symptoms as their mothers regarding stimuli related to the “comfort woman” issue. Increased irritability, problems with aggression control, negative worldview, and low self-esteem were evident in the children of mothers with posttraumatic stress disorder. Finding evidence of transgenerational transmission of trauma in offspring of “comfort women” is important. Future studies should include more samples and adopt a more objective method.

Outcomes of open heart surgery in patients with end-stage renal disease

BACKGROUND: Cardiovascular diseases of chronic dialysis patients are often undertreated because of their higher surgical risk. This study aimed to assess mortality and morbidity after open heart surgery in chronic dialysis patients compared to those with normal renal function and identify risk factors for postoperative outcomes. METHODS: We retrospectively analyzed 2,432 patients who underwent open heart surgery from 2002 to 2017 and collected data from 116 patients (38 patients on dialysis and 78 age-, sex-, and diabetes mellitus status-matched control patients with normal kidney function). We assessed comorbidities, New York Heart Association (NYHA) class, laboratory data, surgical methods, and postoperative outcomes. RESULTS: The dialysis group had more comorbidities, higher NYHA classes, and greater need for urgent surgeries compared to the control group. They exhibited significantly higher postoperative mortality (18.4% vs. 2.6%, P = 0.005) and more overall complications (65.8% vs. 25.6%, P < 0.001). Dialysis itself significantly increased relative risk for in-hospital mortality after adjustment. EuroSCORE II was not as useful as in the general population. Multivariate logistic regression analysis demonstrated that total (adjusted odds ratio [AOR], 10.7; P = 0.029) and in-hospital death risk (AOR, 14.7; P = 0.033), the durations of postoperative hospitalization (AOR, 4.6; P = 0.034), CRRT (AOR 36.8; P = 0.004), and ventilator use (AOR, 7.6; P = 0.022) were significantly increased in the dialysis group. CONCLUSION: The dialysis group exhibited a higher risk for mortality and overcall complications after open heart surgery compared to the patients with normal renal function. Therefore, the benefit of surgical treatment must be balanced against potential risks.