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.

Long-term risk of all-cause mortality in live kidney donors: a matched cohort study

Long-term outcomes of live kidney donors remain controversial, although this information is crucial for selecting potential donors. Thus, this study compared the long-term risk of all-cause mortality between live kidney donors and healthy control. Methods: We performed a retrospective cohort study including donors from seven tertiary hospitals in South Korea. Persons who underwent voluntary health screening were included as controls. We created a matched control group considering age, sex, era, body mass index, baseline hypertension, diabetes, estimated glomerular filtration rate, and dipstick albuminuria. The study outcome was progression to end-stage kidney disease (ESKD), and all-cause mortality as identified in the linked claims database. Results: We screened 1,878 kidney donors and 78,115 health screening examinees from 2003 to 2016. After matching, 1,701 persons remained in each group. The median age of the matched study subjects was 44 years, and 46.6% were male. Among the study subjects, 2.7% and 16.6% had underlying diabetes and hypertension, respectively. There were no ESKD events in the matched donor and control groups. There were 24 (1.4%) and 12 mortality cases (0.7%) in the matched donor and control groups, respectively. In the age-sex adjusted model, the risk for all-cause mortality was significantly higher in the donor group than in the control group. However, the significance was not retained after socioeconomic status was included as a covariate (adjusted hazard ratio, 1.82; 95% confidence interval, 0.87–3.80). Conclusion: All-cause mortality was similar in live kidney donors and matched non-donor healthy controls with similar health status and socioeconomic status in the Korean population.

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.

Effect of shared decision-making education on physicians’ perceptions and practices of end-of-life care in Korea

Evidence of the ethical appropriateness and clinical benefits of shared decision-making (SDM) are accumulating. This study aimed to not only identify physicians’ perspectives on SDM, and practices related to end-of-life care in particular, but also to gauge the effect of SDM education on physicians in Korea. Methods: A 14-item questionnaire survey using a modified Delphi process was delivered to nephrologists and internal medicine trainees at 17 university hospitals. Results: A total of 309 physicians completed the survey. Although respondents reported that 69.9% of their practical decisions were made using SDM, 59.9% reported that it is not being applied appropriately. Only 12.3% of respondents had received education on SDM as part of their training. The main obstacles to appropriate SDM were identified as lack of time (46.0%), educational materials and tools (29.4%), and education on SDM (24.3%). Although only a few respondents had received training on SDM, the proportion of those who thought they were using SDM appropriately in actual practice was high; the proportion of those who chose lack of time and education as factors that hindered the proper application of SDM was low. Conclusion: The majority of respondents believed that SDM was not being implemented properly in Korea, despite its use in actual practice. To improve the effectiveness of SDM in the Korean medical system, appropriate training programs and supplemental policies that guarantee sufficient application time are required.

Metabolic risks in living kidney donors in South Korea

Background@#Considering the growing prevalence of Western lifestyles and related chronic diseases occurring in South Korea, this study aimed to explore the progression of metabolic risk factors in living kidney donors compared to a control group. @*Methods@#This study enrolled living kidney donors from seven hospitals from 1982 to 2016. The controls were individuals that voluntarily received health check-ups from 1995 to 2016 that were matched with donors according to age, sex, diabetes status, baseline estimated glomerular filtration rate, and date of the medical record. Data on hyperuricemia, hypertension, hypercholesterolemia, and overweight/obesity were collected to determine metabolic risks. The proportion of individuals with three or more metabolic risk factors was evaluated. Logistic regressions with interaction terms between the medical record date and donor status were used to compare the trends in metabolic risks over time in the two groups. @*Results@#A total of 2,018 living kidney donors and matched non-donors were included. The median age was 44.0 years (interquartile range, 34.0–51.0 years) and 54% were women. The living kidney donors showed a lower absolute prevalence for all metabolic risk factors, except for those that were overweight/obese, than the non-donors. The proportion of subjects that were overweight/obese was consistently higher over time in the donor group. The changes over time in the prevalence of each metabolic risk were not significantly different between groups, except for a lower prevalence of metabolic risk factors ≥ 3 in donors. @*Conclusion@#Over time, metabolic risks in living kidney donors are generally the same as in non-donors, except for a lower prevalence of metabolic risk factors ≥ 3 in donors.

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.

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.

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.

The differential effects of anemia on mortality in young and elderly end-stage renal disease patients

Background@#The aim of this study was to compare the effect of anemia on clinical outcomes according to age in patients with end-stage renal disease (ESRD). @*Methods@#A total of 3,409 patients from the Clinical Research Center for ESRD were included and divided into three groups by age: age < 40 (n = 488), 40 ≤ age < 60 (n = 1,650), and age ≥ 60 (n = 1,271). We compared overall and cardiovascular mortality, and all-cause and cardiovascular hospitalization according to mean hemoglobin (Hb) concentration. @*Results@#Among participants ≥ 60 years of age, the Hb < 10 g/dL group had greater all-cause mortality (adjusted hazard ratio [HR], 2.098; 95% confidence interval [CI], 1.567-2.808; P < 0.001) than the 10 ≤ Hb < 12 g/dL group, whereas among participants < 40 years of age, the Hb ≥ 12 g/dL group had greater mortality than the 10 ≤ Hb < 12 g/dL group. Moreover, in participants ≥ 60 years of age, the HR for all-cause hospitalization for the Hb < 10 g/dL group was significantly greater than that of the 10 ≤ Hb < 12 g/dL group (HR, 1.472; 95% CI, 1.057-2.051; P = 0.022), whereas it was significantly lower in the Hb ≥ 12 g/dL group (HR, 0.544; 95% CI, 0.362-0.820; P = 0.004) However, among participants < 40 years of age, the incidence of all-cause hospitalization did not differ according to the Hb concentration (HR, 1.273; 95% CI, 0.814-1.991; P = 0.290 for the Hb < 10 g/dL group; reference, 10 ≤ Hb < 12 g/dL; HR, 0.787; 95% CI, 0.439-1.410; P = 0.265 for Hb ≥ 12 g/dL group). @*Conclusion@#The impact of anemia on mortality was more significant in elderly ESRD patients. Strict monitoring and management of anemia should be required for elderly ESRD patients.

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.

Impact of health-related quality of life on survival after dialysis initiation: a prospective cohort study in Korea

Background@#The effect of each health-related quality of life (HRQOL) component on hemodialysis prognosis has not been well studied. We aimed to investigate the clinical factors associated with HRQOL and the effect of HRQOL after dialysis initiation on long-term survival in an Asian population. @*Methods@#A total of 568 hemodialysis patients were included from a nationwide prospective cohort study. HRQOL was evaluated using the Kidney Disease Quality of Life (KDQOL) Short FormTM 1.3 at 3 months after dialysis initiation. The effect of each KDQOL item score on mortality was analyzed. Multivariable Cox analysis was performed after adjusting for age, sex, modified Charlson comorbidity index, and causes of primary kidney disease. @*Results@#Old age, diabetes mellitus, high comorbidities, and low serum albumin levels were associated with poor physical health status. Decreased urine output was associated with both poor physical and mental health status.The scores of 3 indices in the kidney disease domain (effect of kidney disease, social support, and dialysis staff encouragement) showed significant associations with mortality, as did the 3 indices (physical function, physical role limitation, and body pain) in the physical health domain. Neither the 4 indices in the mental health domain nor the mental composite score showed a significant association with mortality. However, a high physical composite score was associated with decreased overall patient mortality (P = 0.003). The effect of physical composite score on survival was prominent among young or middle-aged groups. @*Conclusion@#Poor physical health status 3 months after hemodialysis start correlates significantly with overall mortality.

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.

Impact of health-related quality of life on survival after dialysis initiation: a prospective cohort study in Korea

Background@#The effect of each health-related quality of life (HRQOL) component on hemodialysis prognosis has not been well studied. We aimed to investigate the clinical factors associated with HRQOL and the effect of HRQOL after dialysis initiation on long-term survival in an Asian population. @*Methods@#A total of 568 hemodialysis patients were included from a nationwide prospective cohort study. HRQOL was evaluated using the Kidney Disease Quality of Life (KDQOL) Short FormTM 1.3 at 3 months after dialysis initiation. The effect of each KDQOL item score on mortality was analyzed. Multivariable Cox analysis was performed after adjusting for age, sex, modified Charlson comorbidity index, and causes of primary kidney disease. @*Results@#Old age, diabetes mellitus, high comorbidities, and low serum albumin levels were associated with poor physical health status. Decreased urine output was associated with both poor physical and mental health status.The scores of 3 indices in the kidney disease domain (effect of kidney disease, social support, and dialysis staff encouragement) showed significant associations with mortality, as did the 3 indices (physical function, physical role limitation, and body pain) in the physical health domain. Neither the 4 indices in the mental health domain nor the mental composite score showed a significant association with mortality. However, a high physical composite score was associated with decreased overall patient mortality (P = 0.003). The effect of physical composite score on survival was prominent among young or middle-aged groups. @*Conclusion@#Poor physical health status 3 months after hemodialysis start correlates significantly with overall mortality.

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.