Circulatory endostatin level and risk of cardiovascular events in patients with end-stage renal disease on hemodialysis.

BACKGROUND: Endostatin is released during extracellular matrix remodeling and is involved in the development of vascular pathology and cardiovascular (CV) disease. However, the role of circulating endostatin as a biomarker of vascular calcification and CV events in patients undergoing hemodialysis (HD) remains unclear. METHODS: A total of 372 patients undergoing HD were prospectively recruited. Plasma endostatin levels were measured at baseline, and their associations with circulating mineral bone disease (MBD) biomarkers and abdominal aortic vascular calcification scores were analyzed. The primary endpoint was defined as a composite of CV and cardiac events. RESULTS: Plasma levels of patients in endostatin tertile 3 were significantly associated with low-density lipoprotein cholesterol levels and predialysis systolic blood pressure in multivariate analysis. However, endostatin levels did not correlate with circulating MBD biomarkers or vascular calcification scores. Patients in endostatin tertile 3 had a significantly higher cumulative event rate for the composite of CV events (p = 0.006). Endostatin tertile 3 was also associated with an increased cumulative rate of cardiac events (p = 0.04). In multivariate Cox regression analyses, endostatin tertile 3 was associated with a 4.37-fold risk for composite CV events and a 3.88-fold risk for cardiac events after adjusting for multiple variables. CONCLUSION: Higher circulating endostatin levels were independently associated with atherosclerotic risk factors but did not correlate with MBD markers or vascular calcification. Higher circulating endostatin levels were associated with a greater risk of composite CV events in patients undergoing HD, and endostatin is a biomarker that helps to determine the high risk of CV events.

Clinical significance of urinary inflammatory biomarkers in patients with IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis, although the definitive markers are unknown. We aimed to investigate the clinical significance of urinary cytokines in patients with IgAN. METHODS: From 2009 to 2018, the patients were divided into three groups: IgAN (n = 191), disease control (n = 53), and normal control (n = 76). We used a multiplex enzyme-linked immunosorbent assay to measure 16 selected urinary inflammatory cytokines, evaluated the correlation between clinical and pathological features following regression analysis on progression. RESULTS: The IgAN group exhibited significantly different levels of urinary cytokines compared to the normal control and disease control groups. Urinary levels of B-cell-activating factor, vascular endothelial growth factor receptor-2, monocyte chemoattractant protein-1, C-X-C motif chemokine 10, C-X-C motif ligand 16, epidermal growth factor (EGF), endocan, endostatin, growth/differentiation factor-15 (GDF-15), interleukin-6 (IL-6), mannose-binding lectin, transferrin receptor, and kidney injury molecule-1 were significantly correlated with both the estimated glomerular filtration rate and urine protein-creatinine ratio. In a multivariate Cox regression analysis, urinary EGF (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.17-0.95, P = 0.04), GDF-15 (HR 2.45, 95% CI 1.01-5.94, P = 0.048), and IL-6 (HR 3.02, 95% CI 1.05-8.64, P = 0.04) were associated with progression in IgAN. CONCLUSIONS: Urinary inflammatory biomarkers may serve as alternative predictive biomarkers in patients with IgAN. Further studies are needed to elucidate the physiological mechanisms and confirm the results.

Association of the Intensive Blood Pressure Target and Cardiovascular Outcomes in the Population With Chronic Kidney Disease: A Retrospective Study in Korea.

BACKGROUND: Recently, the target systolic blood pressure (BP) <120 mm Hg was suggested in the population with chronic kidney disease. We aimed to determine the applicability of intensified BP and to assess the incidence of cardiovascular disease (CVD) in the population with chronic kidney disease. METHODS AND RESULTS: Participants who were >20 years old and had estimated glomerular filtration rate 15 to 60 mL/min per 1.73 m2 during 2009 to 2011 were included from the database of Korean National Health Insurance Service and were followed up to 2018. Participants were categorized by BP as <120/80 mm Hg; 120 to 129/<80 mm Hg; 130 to 139/80 to 89 mm Hg; ≥140/90 mm Hg. The primary outcome was CVD risk and the secondary outcomes were all-cause mortality and progression to end-stage renal disease followed by subgroup analysis. Among the 45 263 adults with chronic kidney disease, 5196 CVD events were noted. In Cox regression analysis, higher BP was associated with a higher risk for CVD (hazard ratio [HR], 1.15 [95% CI, 1.12-1.19]; P for trend <0.001), end-stage renal disease (HR, 1.29 [95% CI, 1.22-1.37]; P for trend <0.001), and all-cause mortality (HR, 1.09 [95% CI, 1.06-1.13]; P for trend <0.001) than BP <120/80 mm Hg. In subgroup analysis, the association between BP and CVD showed a different trend in participants taking antihypertensives compared with those not using antihypertensive drugs. When comparing BP-treated individuals to untreated individuals, a significant interaction in the association between BP categories and end-stage renal disease was observed. CONCLUSIONS: The new intensive BP target proposed by 2021 Kidney Disease: Improving Global Outcomes should be applied to patients with chronic kidney disease in a personalized and advisory manner.

Association between albuminuria and retinal microvascular parameters measured with swept-source optical coherence tomography angiography in patients with diabetic retinopathy.

PURPOSE: To evaluate the relationship between urine albumin excretion (UAE) and retinal microvascular parameters assessed using swept-source optical coherence tomography angiography (SS-OCTA) in patients with diabetic retinopathy (DR). METHODS: This retrospective cross-sectional study included 180 patients with diabetes and 50 age-matched controls. Patients with diabetes were grouped according to the five-stage DR severity, combined with the presence of albuminuria. All subjects underwent 12×12mm2 field SS-OCTA. The foveal avascular zone metrics, vessel density, and capillary nonperfusion area (NPA) were quantified using a semi-automatic software algorithm on three different rectangular fields (3×3 mm2, 6×6 mm2, and 10×10 mm2). The correlations between albuminuria and the four OCTA parameters were analyzed. RESULTS: A total of 105 subjects had normal UAE, and 75 subjects had albuminuria. Of the 102 subjects whose DR severity was higher than mild non-proliferative DR (NPDR), capillary NPA on the 3×3 mm2, 6×6 mm2, and 10×10 mm2 fields was significantly larger in the albuminuria group. None of the OCTA parameters were significantly different between the two groups in subjects with mild NPDR or without DR. Multiple logistic regression analysis showed that an increase in NPA in the 6×6 mm2 and 10×10 mm2 fields was a significant risk factor for the presence of albuminuria (odds ratio = 1.92 and 1.35). CONCLUSION: An increase in capillary NPA was independently associated with albuminuria in patients with clinically significant DR levels. SS-OCTA imaging can be a useful marker for the early detection of diabetic nephropathy.

Association between circulating ECM-associated molecules and cardiovascular outcomes in hemodialysis patients: a multicenter prospective cohort study.

Hemodialysis patients are susceptible to cardiovascular remodeling, which increases the risk of cardiovascular morbidity and mortality. Circulating extracellular matrix (ECM)-associated molecules increase during cardiovascular remodeling and can be potential biomarkers of adverse cardiovascular outcomes. However, their clinical significance in patients undergoing hemodialysis remain unclear. This study aimed to elucidate the association between circulating ECM-associated molecules and cardiovascular outcomes in patients undergoing hemodialysis. To this end, we measured levels of plasma matrix metalloproteinase (MMP)-2, MMP-9, tenascin-C, and thrombospondin-2 in 372 patients with hemodialysis. Plasma MMP-2 levels were significantly higher in patients with future cardiovascular events than in those without future cardiovascular events (P = 0.004). All measured molecules had significant correlations with amino-terminal pro-brain natriuretic peptide levels, but the correlation coefficient was the strongest for plasma MMP-2 (rho = 0.317, P < 0.001). High plasma MMP-2 levels were predictive of left ventricular (LV) diastolic dysfunction (adjusted odds ratio per a standard deviation increase = 1.48, 95% confidence interval [CI] = 1.05-2.08) and were independently associated with an increased risk of composite cardiovascular events (adjusted hazard ratio per a standard deviation increase = 1.30, 95% CI = 1.04-1.63). In conclusion, high plasma MMP-2 levels are associated with LV diastolic dysfunction and an increased risk of adverse cardiovascular outcomes in hemodialysis patients.

Fasting blood glucose and the risk of all-cause mortality in patients with diabetes mellitus undergoing hemodialysis.

Background: Glycemic control is particularly important in hemodialysis (HD) patients with diabetes mellitus (DM). Although fasting blood glucose (FBG) level is an important indicator of glycemic control, a clear target for reducing mortality in HD patients with DM is lacking. Methods: A total of 26,162 maintenance HD patients with DM were recruited from the National Health Insurance Database of Korea between 2002 and 2018. We analyzed the association of FBG levels at the baseline health examination with the risk of all-cause and cause-specific mortality. Results: Patients with FBG 80100 mg/dL showed a higher survival rate compared with that of other FBG categories (p < 0.001). The risk of all-cause mortality increased with the increase in FBG levels, and adjusted hazard ratios (HRs) were 1.10 (95% confidence interval [CI], 1.04-1.17), 1.21 (95% CI, 1.13-1.29), 1.36 (95% CI, 1.26-1.46), and 1.61 (95% CI, 1.51-1.72) for patients with FBG 100-125, 125-150, 150-180, and ≥180 mg/dL, respectively. The HR for mortality was also significantly increased in patients with FBG < 80 mg/dL (adjusted HR, 1.14; 95% CI, 1.05-1.23). The analysis of cause-specific mortality also revealed a J-shaped curve between FBG levels and the risk of cardiovascular deaths. However, the risk of infection or malignancy-related deaths was not linearly increased as FBG levels increased. Conclusion: A J-shaped association was observed between FBG levels and the risk of all-cause mortality, with the lowest risk at FBG 80100 mg/dL in HD patients with DM.

Comparison of Humoral Response between Third and Fourth Doses of COVID-19 Vaccine in Hemodialysis Patients.

Dialysis patients are more likely to die or become hospitalized from coronavirus disease 2019 (COVID-19). Currently, only a few studies have evaluated the efficacy of a fourth booster vaccination in hemodialysis (HD) patients and there is not enough evidence to recommend for or against a fourth booster vaccination. This study compared the humoral response and disease severity of patients on HD who received either three or four doses of COVID-19 vaccine. A total of 88 patients were enrolled. Humoral response to vaccination was measured by quantifying immunoglobulin G levels against the receptor binding domain of SARS-CoV-2 (anti-RBD IgG) at five different times and plaque reduction neutralization tests (PRNT) at two different times after vaccination over a period of 18 months. Antibody levels were measured at approximately two-month intervals after the first and second dose, then four months after the third dose, and then one to six months after the fourth dose of vaccine. PRNT was performed two months after the second and four months after the third dose of vaccine. We classified patients into four groups according to the number of vaccine doses and presence of COVID-19 infection. Severe infection was defined as hospital admission for greater than or equal to two weeks or death. There was no difference in antibody levels between naïve and infected patients except after a fourth vaccination, which was effective for increasing antibodies in infection-naïve patients. Age, sex, body mass index (BMI), dialysis vintage, and presence of diabetes mellitus (DM) did not show a significant correlation with antibody levels. Four patients who experienced severe COVID-19 disease tended to have lower antibody levels prior to infection. A fourth dose of SARS-CoV-2 vaccine significantly elevated antibodies in infection-naïve HD patients and may be beneficial for HD patients who have not been previously infected with SARS-CoV-2 for protection against severe infection.

Clinical significance of the living kidney donor profile index for predicting long-term posttransplant outcomes: results from the Korean Organ Transplantation Registry.

Background: The usefulness of the living kidney donor profile index (LKDPI) has not been widely demonstrated; therefore, it requires verification before clinical application. We analyzed the LKDPI using data from the Korean Organ Transplantation Registry (KOTRY) to confirm whether the LKDPI can be used to predict the survival of allografts in living donor kidney transplantation (LDKT) patients in Korea. Methods: The study population was obtained from the KOTRY database. A total of 2,598 kidney recipients registered in the KOTRY database were enrolled between May 2014 and December 2020. Donor and recipient information was observed, and the LKDPI was measured. Results: Median LKDPI score was 15.5 with a follow-up duration of 33.7 ± 16.1 months. According to LKDPI scores (group 1, <0; group 2, 0-20; group 3, 20-40; and group 4, >40), LKDPI group 4 had significantly higher death-censored graft loss than LKDPI group 1 (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.06- 3.40; p = 0.03). When divided based on the cutoff value (LKDPI, 36.6), the high LKDPI group had higher graft loss than the low LKDPI group (HR, 2.14; 95% CI, 1.37-3.34; p < 0.001). When follow-up was repeated after transplantation, it was confirmed that the higher the LKDPI value was, the lower the average estimated glomerular filtration rate (p < 0.001). Conclusion: This study confirmed that LKDPI can serve as an independent predictor for assessing the risk of allograft failure and transplant outcomes in Korean LDKT patients.

How obesity and metabolic syndrome affect cardiovascular events, progression to kidney failure and all-cause mortality in chronic kidney disease.

BACKGROUND: Obesity and metabolic syndrome (MetS) are prevalent among chronic kidney disease (CKD) patients. However, it is unclear whether obesity without MetS is associated with a higher risk of adverse clinical outcomes in CKD patients. METHODS: We searched the National Health Insurance Service database of Korea for patients who underwent national health screenings in 2009-2011 and identified 59 725 CKD patients. Obesity was defined as a body mass index ≥25 kg/m2. MetS was defined as the presence of ≥3 metabolic risks. RESULTS: The cumulative event rate of cardiovascular events, progression to end-stage kidney disease (ESKD), and all-cause mortality was the lowest among obese patients without MetS (all P < 0.001). In multivariable analysis, obese (versus non-obese) patients without MetS were not at increased risks of cardiovascular events (adjusted hazard ratio [HR] 1.02; 95% confidence interval 0.94-1.11) or progression to ESKD (0.92; 0.77-1.09). Their risk of all-cause mortality was significantly decreased (0.82; 0.75-0.90). These findings were consistently observed in overweight, obese, and morbidly obese patients without MetS. Moreover, despite a linear increase in HR for each additional metabolic abnormality in both obese and non-obese patients, the slope of HR increase for cardiovascular events was significantly slower in obese patients (P for interaction = 0.038). CONCLUSIONS: Obesity without MetS did not increase the risk of cardiovascular complications or progression to ESKD. The healthy effect of obesity on all-cause mortality risk and its weakening effect on the association between metabolic hazards and cardiovascular risk should be considered in CKD patients.

Clinical significance of urinary exosomal microRNAs in patients with IgA nephropathy.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. The clinical relevance of 11 urinary exosomal microRNAs (miRNAs) was evaluated in patients with IgAN. From January 2009 to November 2018, IgAN (n = 93), disease control (n = 11), and normal control (n = 19) groups were enrolled. We evaluated the expression levels of urinary exosomal miRNAs at the baseline and their relationship with clinical and pathologic features. This study aimed to discriminate statistically powerful urinary exosomal miRNAs for the prognosis of IgAN. Urinary miRNA levels of miR-16-5p, miR-29a-3p, miR-124-3p, miR-126-3p, miR-199a-3p, miR-199b-5p, and miR-335-3p showed significant correlation with both estimated glomerular filtration rate (eGFR) and urine protein-to-creatinine ratio (uPCR). In univariate regression analysis, age, body mass index, hypertension, eGFR, uPCR, Oxford classification E, and three miRNAs (miR-16-5p, miR-199a-3p, and miR-335-3p) were associated with disease progression in patients with IgAN. The area under the curve (AUC) of miR-199a-3p was high enough (0.749) without any other clinical or pathologic factors, considering that the AUC of the International IgAN Risk Prediction Tool was 0.853. Urinary exosomal miRNAs may serve as alternative prognostic biomarkers of IgAN with further research.

Corrigendum: Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients.

[This corrects the article DOI: 10.3389/fimmu.2023.1190576.].

Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients.

Introduction: Acute rejection (AR) continues to be a significant obstacle for short- and long-term graft survival in kidney transplant recipients. Herein, we aimed to examine urinary exosomal microRNAs with the objective of identifying novel biomarkers of AR. Materials and methods: Candidate microRNAs were selected using NanoString-based urinary exosomal microRNA profiling, meta-analysis of web-based, public microRNA database, and literature review. The expression levels of these selected microRNAs were measured in the urinary exosomes of 108 recipients of the discovery cohort using quantitative real-time polymerase chain reaction (qPCR). Based on the differential microRNA expressions, AR signatures were generated, and their diagnostic powers were determined by assessing the urinary exosomes of 260 recipients in an independent validation cohort. Results: We identified 29 urinary exosomal microRNAs as candidate biomarkers of AR, of which 7 microRNAs were differentially expressed in recipients with AR, as confirmed by qPCR analysis. A three-microRNA AR signature, composed of hsa-miR-21-5p, hsa-miR-31-5p, and hsa-miR-4532, could discriminate recipients with AR from those maintaining stable graft function (area under the curve [AUC] = 0.85). This signature exhibited a fair discriminative power in the identification of AR in the validation cohort (AUC = 0.77). Conclusion: We have successfully demonstrated that urinary exosomal microRNA signatures may form potential biomarkers for the diagnosis of AR in kidney transplantation recipients.

National trends in the prevalence of chronic kidney disease among Korean adults, 2007-2020.

Little is known about the prevalence of chronic kidney disease (CKD) during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to investigate the long-term trends in CKD prevalence from South Korea including the early pandemic. We used data from 108,152 Korean adults from 2007 to 2020 obtained from a representative longitudinal serial study. We defined CKD as a condition when the participant's estimated glomerular filtration rate was < 60 mL/min/1.73 m2, or one-time spot proteinuria was ≥ 1 +, and then examined the overall trends in the prevalence of CKD. Among the included adults (n = 80,010), the overall national prevalence of CKD was 6.2%. The trend slope gradually increased from 2007 to 2019, however, there was a sudden decrease in 2020 (2007-2010, 5.1% [95% confidence interval (CI) 4.7-5.5]; 2017-2019, 7.1% [95% CI 6.6-7.6]; pandemic period, 6.5% [95% CI 5.7-7.3]; and ßdiff, - 0.19; 95% CI - 0.24 to - 0.13). The prevalence of CKD among younger adults and those with poor medical utilization significantly decreased during the early pandemic. This study was the first large-scale study to investigate the longitudinal prevalence of CKD from 2007 to 2020. Further research is needed to fully understand the exact causes for this decline and to identify healthcare policy strategies for preventing and managing CKD.

Clinical implications of circulating follistatin-like protein-1 in hemodialysis patients.

Follistatin-like protein-1 (FSTL-1) is secreted glycoprotein, which regulates cardiovascular, immune and skeletal system. However, the clinical significance of circulating FSTL-1 levels remains unclear in hemodialysis patients. A total 376 hemodialysis patients were enrolled from June 2016 to March 2020. Plasma FSTL-1 level, inflammatory biomarkers, physical performance, and echocardiographic findings at baseline were examined. Plasma FSTL-1 levels were positively correlated with TNF-α and MCP-1. Handgrip strength showed weak positive correlation in male patients only, and gait speed showed no correlation with FSTL-1 levels. In multivariate linear regression analysis, FSTL-1 level was negatively associated with left ventricular ejection fraction (ß = - 0.36; p = 0.011). The cumulative event rate of the composite of CV event and death, and cumulative event rate of CV events was significantly greater in FSTL-1 tertile 3. In multivariate Cox-regression analysis, FSTL-1 tertile 3 was associated with a 1.80-fold risk for the composite of CV events and death(95% confidence interval (CI) 1.06-3.08), and a 2.28-fold risk for CV events (95% CI 1.15-4.51) after adjustment for multiple variables. In conclusion, high circulating FSTL-1 levels independently predict the composite of CV events and death, and FSTL-1 level was independently associated with left ventricular systolic dysfunction.

Plasma Interleukin-6 Level Predicts the Risk of Arteriovenous Fistula Dysfunction in Patients Undergoing Maintenance Hemodialysis.

Systemic inflammation has been proposed as a relevant factor of vascular remodeling and dysfunction. We aimed to identify circulating inflammatory biomarkers that could predict future arteriovenous fistula (AVF) dysfunction in patients undergoing hemodialysis. A total of 282 hemodialysis patients were enrolled in this prospective multicenter cohort study. Plasma cytokine levels were measured at the time of data collection. The primary outcome was the occurrence of AVF stenosis and/or thrombosis requiring percutaneous transluminal angioplasty or surgery within the first year of enrollment. AVF dysfunction occurred in 38 (13.5%) patients during the study period. Plasma interleukin-6 (IL-6) levels were significantly higher in patients with AVF dysfunction than those without. Diabetes mellitus, low systolic blood pressure, and statin use were also associated with AVF dysfunction. The cumulative event rate of AVF dysfunction was the highest in IL-6 tertile 3 (p = 0.05), and patients in tertile 3 were independently associated with an increased risk of AVF dysfunction after multivariable adjustments (adjusted hazard ratio = 3.06, p = 0.015). In conclusion, circulating IL-6 levels are positively associated with the occurrence of incident AVF dysfunction in hemodialysis patients. Our data suggest that IL-6 may help clinicians identify those at high risk of impending AVF failure.

Urine Exosomal bkv-miR-B1-5p and BK Virus Nephropathy in Kidney Transplant Recipients.

BACKGROUND: Urine exosomal bkv-miR-B1-5p is associated with BK virus (BKV) nephropathy (BKVN); however, its posttransplantation changes and predictability for BKVN have not been determined in kidney transplant recipients (KTRs). METHODS: Urine exosomal bkv-miR-B1-5p and urine and plasma BKV DNA were measured at 2 weeks and 3, 6, and 12 months posttransplant in 83 KTRs stratified into biopsy-proven or presumptive BKVN, BKV viruria, and no evidence of BKV reactivation. Joint model, multivariable Cox model and receiver operating characteristic curve (ROC) were used to investigate the association of each assay with the following events: a composite of biopsy-proven or presumptive BKVN, and biopsy-proven BKVN. RESULTS: Urine exosomal bkv-miR-B1-5p and urine and plasma BKV DNA showed similar posttransplant time-course changes. Joint models incorporating serial values demonstrated significant associations of all assays with the events, and Cox analyses using single time point values at 2 weeks posttransplant showed that only urine exosomal bkv-miR-B1-5p was significantly associated with the events, although it did not outperform urine BKV DNA in ROC analyses. CONCLUSIONS: Urine exosomal bkv-miR-B1-5p was associated with BKVN as were urine and plasma BKV DNA loads on serial follow-up, and might have potential as a predictive marker for BKVN during the early posttransplant period. CLINICAL TRIALS REGISTRATION: Clinical Research Information Service (https://cris.nih.go.kr/cris/), KCT0001010.

Impact of donor hypertension on graft survival and function in living and deceased donor kidney transplantation: a nationwide prospective cohort study.

OBJECTIVES: Hypertensive living donors are potential candidates to expand the kidney donor pool. However, the impact of donor hypertension on graft survival and function remains to be clarified. METHODS: We analyzed 3907 kidney transplant recipients registered in a nationwide prospective cohort from 2014 to 2018. Patients were divided by donor types and the presence of donor hypertension. The primary and secondary outcome was the occurrence of death-censored graft failure and renal allograft function, respectively. RESULTS: The prevalence of hypertension was 9.4% (258/2740) and 19.9% (232/1167) in living and deceased donors, respectively. During a median follow-up of 21.8 months, death-censored graft survival rate was significantly worse in recipients of hypertensive living donors than in those of normotensive living donors ( P  = 0.008). In multivariable analysis, recipients of hypertensive living donors had a significantly increased risk of graft loss (adjusted hazard ratio 2.91; P  = 0.009). The risk of allograft loss was not different between recipients of hypertensive living and normotensive deceased donors. Propensity score-matched analyses had consistent worse graft survival rate in recipients of hypertensive living donors compared to those of normotensive living donors ( P  = 0.027), while it was not different between recipients of hypertensive living and normotensive deceased donors. Hypertension in living donors had a significant negative impact on one-year graft function (adjusted unstandardized ß -3.64; P  = 0.011). CONCLUSIONS: Hypertensive living donor recipients have significantly higher risks of renal allograft loss than normotensive living donor recipients, and showed similar outcomes compared to recipients of normotensive deceased donors.

Hydrophilic Versus Lipophilic Statin Treatments in Patients With Renal Impairment After Acute Myocardial Infarction.

Background Hydrophilic and lipophilic statins have similar efficacies in treating coronary artery disease. However, specific factors relevant to renal impairment and different arterial pathogeneses could modify the clinical effects of statin lipophilicity, and create differences in protective effects between statin types in patients with renal impairment. Methods and Results A total of 2062 patients with acute myocardial infarction with an estimated glomerular filtration rate <60 mL/min per 1.73 m2 were enrolled from the Korea Acute Myocardial Infarction Registry between November 2011 and December 2015. The primary end point was a composite of 2-year major adverse cardiac and cerebrovascular events (MACEs) after acute myocardial infarction occurrence. MACEs were defined as all-cause death, recurrent myocardial infarction, revascularization, and stroke. Propensity-score matching and Cox proportional hazards regression were performed. A total of 529 patients treated with hydrophilic statins were matched to 529 patients treated with lipophilic statins. There was no difference in the statin equivalent dose between the 2 statin groups. The cumulative event rate of MACEs, all-cause mortality, and recurrent myocardial infarction were significantly lower in patients treated with hydrophilic statins in the propensity-score matched population (all P<0.05). In the multivariable Cox regression analysis, patients treated with hydrophilic statins had a lower risk for composite MACEs (hazard ratio [HR], 0.70 [95% CI, 0.55-0.90]), all-cause mortality (HR, 0.67 [95% CI, 0.49-0.93]), and recurrent myocardial infarction (HR, 0.40 [95% CI, 0.21-0.73]), but not for revascularization and ischemic stroke. Conclusions Hydrophilic statin treatment was associated with lower risk of MACEs and all-cause mortality than lipophilic statin in a propensity-score matched observational cohort of patients with renal impairment following acute myocardial infarction.

Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Response After Heterologous Immunizations With ChAdOx1/BNT162b2 in End-Stage Renal Disease Patients on Hemodialysis.

The Korean government decided to schedule heterologous vaccinations on dialysis patients for early achievement of immunization against Coronavirus disease 2019(COVID-19). However, the effects of heterologous immunizations in hemodialysis (HD) patients are unclear. One hundred (HD) patients from Gangdong Kyung Hee University Hospital and Kyung Hee Medical Center and 100 hospital workers from Gangdong Kyung Hee University Hospital were enrolled in this study. The HD patients received the mixing schedule of ChAdOx1/BNT162b2 vaccinations at 10-week intervals, while hospital workers received two doses of ChAdOx1 vaccines at 12-week intervals. Serum IgG to a receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2 was measured 1 month after the first dose, 2 months and 4 months after the second dose. The median [interquartile range] anti-RBD IgG was 82.1[34.5, 176.6] AU/ml in HD patients and 197.1[124.0, 346.0] AU/ml in hospital workers (P < 0.001) after the first dose. The percentage of positive responses (IgG > 50 AU/ml) was 65.0% and 96.0% among the both group, respectively (P < 0.001). The anti-RBD IgG levels increased significantly by 2528.8 [1327.6, 5795.1] AU/ml with a 100.0% positive response rate in HD patients 2 months after the second dose, which was higher than those in hospital workers 981.4[581.5, 1891.4] AU/ml (P < 0.001). Moreover, anti-RBD IgG remains constantly high, and positive response remains 100% in HD patients 4 months after the second dose. This study suggests that heterologous vaccinations with ChAdOx1/BNT162b2 can be an alternative solution on HD patients for early and strong induction of humoral response.

Galactose-Deficient IgA1 as a Candidate Urinary Marker of IgA Nephropathy.

In patients with IgA nephropathy (IgAN), circulatory IgA1 and IgA1 in the mesangial deposits contain galactose-deficient IgA1 (Gd-IgA1). Some of the Gd-IgA1 from the glomerular deposits is excreted in the urine and thus urinary Gd-IgA1 may represent a disease-specific marker. We recruited 338 Japanese biopsy-proven IgAN patients and 120 patients with other renal diseases (disease controls). Urine samples collected at the time of renal biopsy were used to measure Gd-IgA1 levels using a specific monoclonal antibody (KM55 mAb). Urinary Gd-IgA1 levels were significantly higher in patients with IgAN than in disease controls. Moreover, urinary Gd-IgA1 was significantly correlated with the severity of the histopathological parameters in IgAN patients. Next, we validated the use of urinary Gd-IgA1 levels in the other Asian cohorts. In the Korean cohort, urinary Gd-IgA1 levels were also higher in patients with IgAN than in disease controls. Even in Japanese patients with IgAN and trace proteinuria (less than 0.3 g/gCr), urinary Gd-IgA1 was detected. Thus, urinary Gd-IgA1 may be an early disease-specific biomarker useful for determining the disease activity of IgAN.