Pre-transplant crossmatch-negative donor-specific anti-HLA antibody predicts acute antibody-mediated rejection but not long-term outcomes in kidney transplantation: an analysis of the Korean Organ Transplantation Registry.

Background: Pre-transplant donor-specific anti-human leukocyte antigen antibody (HLA-DSA) is a recognized risk factor for acute antibody-mediated rejection (ABMR) and allograft failure. However, the clinical relevance of pre-transplant crossmatch (XM)-negative HLA-DSA remains unclear. Methods: We investigated the effect of XM-negative HLA-DSA on post-transplant clinical outcomes using data from the Korean Organ Transplantation Registry (KOTRY). This study included 2019 living donor kidney transplant recipients from 40 transplant centers in South Korea: 237 with HLA-DSA and 1782 without HLA-DSA. Results: ABMR developed more frequently in patients with HLA-DSA than in those without (5.5% vs. 1.5%, p<0.0001). Multivariable analysis identified HLA-DSA as a significant risk factor for ABMR (odds ratio = 3.912, 95% confidence interval = 1.831-8.360; p<0.0001). Furthermore, the presence of multiple HLA-DSAs, carrying both class I and II HLA-DSAs, or having strong HLA-DSA were associated with an increased incidence of ABMR. However, HLA-DSA did not affect long-term clinical outcomes, such as allograft function and allograft survival, patient survival, and infection-free survival. Conclusion: Pre-transplant XM-negative HLA-DSA increased the risk of ABMR but did not affect long-term allograft outcomes. HLA-incompatible kidney transplantation in the context of XM-negative HLA-DSA appears to be feasible with careful monitoring and ensuring appropriate management of any occurrence of ABMR. Furthermore, considering the characteristics of pre-transplant XM-negative HLA-DSA, the development of a more detailed and standardized desensitization protocol is warranted.

Association between systemic inflammation biomarkers and mortality in patients with sepsis-associated acute kidney injury receiving intensive care and continuous kidney replacement therapy: results from the RENERGY (REsearches for NEphRology and epidemioloGY) study.

BACKGROUND: Identifying risk factors and improving prognostication for mortality among patients with sepsis-associated acute kidney injury (AKI) undergoing continuous kidney replacement therapy (CKRT) is important in improving the adverse prognosis of this patient population. This study aimed to compare the prognostic value of existing systemic inflammation biomarkers and determine the optimal systemic inflammation biomarker in patients with sepsis-associated AKI receiving CKRT. METHODS: This multi-center, retrospective, observational cohort study included 1,500 patients with sepsis-associated AKI treated with intensive care and CKRT. The main predictor was a panel of 13 different systemic inflammation biomarkers. The primary outcome was 28-day mortality after CKRT initiation. Secondary outcomes included 90-day mortality after CKRT initiation, CKRT duration, kidney replacement therapy dependence at discharge, and lengths of intensive care unit (ICU) and hospital stays. RESULTS: When added to the widely accepted Acute Physiology and Chronic Health Evaluation II score, platelet-to-albumin ratio (PAR) and neutrophil-platelet score (NPS) had the highest improvements in prognostication of 28-day mortality, where the corresponding increases in C-statistic were 0.01 (95% confidence interval [CI], 0.00-0.02) and 0.02 (95% CI, 0.01-0.03). Similar findings were observed for 90-day mortality. The 28- and 90-day mortality rates were significantly lower for the higher PAR and NPS quartiles. These associations remained significant even after adjustment for potential confounding variables in multivariable Cox proportional hazards models. CONCLUSION: Of the available systemic inflammation biomarkers, the addition of PAR or NPS to conventional ICU prediction models improved the prognostication of patients with sepsis-associated AKI receiving intensive care and CKRT.

Phosphate level predicts mortality in acute kidney injury patients undergoing continuous kidney replacement therapy and has a U-shaped association with mortality in patients with high disease severity: a multicenter retrospective study.

BACKGROUND: This study investigated the association between serum phosphate level and mortality in acute kidney injury (AKI) patients undergoing continuous kidney replacement therapy (CKRT) and evaluated whether this association differed according to disease severity. METHODS: Data from eight tertiary hospitals in Korea were retrospectively analyzed. The patients were classified into four groups (low, normal, high, and very high) based on their serum phosphate level at baseline. The association between serum phosphate level and mortality was then analyzed, with further subgroup analysis being conducted according to disease severity. RESULTS: Among the 3,290 patients identified, 166, 955, 1,307, and 862 were in the low, normal, high, and very high phosphate groups, respectively. The 90-day mortality rate was 63.9% and was highest in the very high group (76.3%). Both the high and very high groups showed a significantly higher 90-day mortality rate than did the normal phosphate group (high: hazard ratio [HR], 1.35, 95% confidence interval [CI], 1.21-1.51, p < 0.001; very high: HR, 2.01, 95% CI, 1.78-2.27, p < 0.001). The low group also exhibited a higher 90-day mortality rate than did the normal group among those with high disease severity (HR, 1.47; 95% CI, 1.09-1.99; p = 0.01) but not among those with low disease severity. CONCLUSION: High serum phosphate level predicted increased mortality in AKI patients undergoing CKRT, and low phosphate level was associated with increased mortality in patients with high disease severity. Therefore, serum phosphate levels should be carefully considered in critically ill patients with AKI.

Trends in clinical outcomes of older hemodialysis patients: data from the 2023 Korean Renal Data System (KORDS).

With an increasing aging population, the mean age of patients with end-stage kidney disease (ESKD) is globally increasing. However, the current clinical status of elderly patients undergoing hemodialysis (HD) is rarely reported in Korea. The current study analyzed the clinical features and trends of older patients undergoing HD from the Korean Renal Data System (KORDS) database. The patients were divided into three groups according to age: <65 years (the young group), n = 50,591 (35.9%); 65-74 years (the younger-old group), n = 37,525 (26.6%); and ≥75 years (the older-old group), n = 52,856 (37.5%). The proportion of older-old group undergoing HD significantly increased in incidence and decreased in prevalence from 2013 to 2022. The median levels of hemoglobin, serum creatinine, albumin, calcium, phosphorus, and intact parathyroid hormone significantly decreased in the older-old group. The proportions of arteriovenous fistula creation and left forearm placement showed decreased trends with age. Although the utilization of low surface area dialyzers increased with age, the dialysis adequacy, including urea reduction ratio and Kt/V was within acceptable range in the older-old group on HD. Over the past 20 years, the mortality rate in the older-old group has increased, with cardiovascular diseases decreasing and infectious diseases increasing. The incidence of elderly patients undergoing HD has increased over time, but the high mortality of the older-old group needs to be solved. Therefore, it is imperative to develop holistic strategies based on age and individual needs for patients with ESKD.

Understanding the Korean Dialysis Cohort for Mineral, Vascular Calcification, and Fracture (ORCHESTRA) Study: Design, Method, and Baseline Characteristics.

INTRODUCTION: End-stage renal disease (ESRD) is a growing disease worldwide, including Korea. This is an important condition that affects patient outcome. To provide optimal management for mineral disturbance, vascular calcification, and bone disease in ESRD patients, the Korean dialysis cohort for mineral, vascular calcification, and fracture (ORCHESTRA) study was conducted by enrolling Korean dialysis patients. METHODS: Sixteen university-affiliated hospitals and one Veterans' Health Service Medical Center participated in this study. This prospective cohort study enrolled approximately 900 consecutive patients on dialysis between May 2019 and January 2021. Enrolled subjects were evaluated at baseline for demographic information, laboratory tests, radiologic imaging, and bone mineral densitometry (BMD) scans. After enrollment, regular assessments of the patients were performed, and their biospecimens were collected according to the study protocol. The primary outcomes were the occurrence of major adverse cardiovascular events, invasive treatment for peripheral artery disease, and osteoporotic fractures. The secondary outcomes were hospitalization for cerebrovascular disease or progression of abdominal aortic calcification. Participants will be assessed for up to 3 years to determine whether primary or secondary outcomes occur. RESULTS: Between May 2019 and January 2021, all participating centers recruited 900 consecutive dialysis patients, including 786 undergoing hemodialysis (HD) and 114 undergoing peritoneal dialysis (PD). The mean age of the subjects was 60.4 ± 12.3 years. Males accounted for 57.7% of the total population. The mean dialysis vintage was 6.1 ± 6.0 years. The HD group was significantly older, had a longer dialysis vintage, and more comorbidities. Overall, the severity of vascular calcification was higher and the level of BMD was lower in the HD group than in the PD group. CONCLUSION: This nationwide, multicenter, prospective cohort study focused on chronic kidney disease-mineral and bone disorder and aimed to provide clinical evidence to establish optimal treatment guidelines for Asian dialysis patients.

Status and trends in epidemiologic characteristics of diabetic end-stage renal disease: an analysis of the 2021 Korean Renal Data System.

Korean Renal Data System (KORDS) is a nationwide end-stage renal disease (ESRD) registry database operated by the Korean Society of Nephrology (KSN). Diabetes mellitus is currently the leading cause of ESRD in Korea; this article provides an update on the trends and characteristics of diabetic ESRD patients. The KORDS Committee of KSN collects data on dialysis centers and patients through an online registry program. Here, we analyzed the status and trends in characteristics of diabetic chronic kidney disease stage 5D (CKD 5D) patients using data from 2001 to 2021. In 2021, the dialysis adequacy of hemodialysis (HD) was lower in diabetic CKD 5D patients than in nondiabetic CKD 5D patients, while that of peritoneal dialysis (PD) was similar. Diabetic CKD 5D patients had a higher proportion of cardiac and vascular diseases and were more frequently admitted to hospitals than nondiabetic CKD 5D patients, and the leading cause of death was cardiac disease. From 2001 to 2020, diabetic CKD 5D patients had a higher mortality rate than nondiabetic CKD 5D patients, but in 2021 this trend was reversed. Diabetic PD patients had the highest mortality rate over 20 years. The mortality rate of diabetic HD patients was higher than that of nondiabetic HD patients until 2019 but became lower starting in 2020. There was a decreasing trend in mortality rate in diabetic CKD 5D patients, but cardiac and vascular diseases were still prevalent in diabetic CKD 5D patients with frequent admissions to hospitals. More specialized care is needed to improve the clinical outcomes of diabetic CKD 5D patients.

Phosphodiesterase inhibitor ameliorates senescent changes of renal interstitial pericytes in aging kidney.

Pericytes are mesenchymal cells that surround endothelial cells, playing a crucial role in angiogenesis and vessel maturation. Additionally, they are associated with interstitial fibrosis as a major contributor to renal myofibroblasts. In this study, we aim to investigate whether the phosphodiesterase inhibitor, pentoxifylline (PTX), can ameliorate aging-related functional and histological deterioration in the kidney. We subjected aging C57BL/6 mice, dividing into young, aging, and PTX-treated aging groups. Renal function, albuminuria, and histological changes were assessed. Interstitial pericytes were assessed by immunohistochemistry analysis. We examined changes in pericytes in elderly patients using human kidney tissue obtained from healthy kidney donors for kidney transplantation. In vitro experiments with human pericytes and endothelial cells were performed. Aging mice exhibited declined renal function, increased albuminuria, and aging-related histological changes including mesangial expansion and tubulointerstitial fibrosis. Notably, number of pericytes declined in aging kidneys, and myofibroblasts increased. PTX treatment ameliorated albuminuria, histological alterations, and microvascular rarefaction, as well as modulated angiopoietin expression. In vitro experiments showed PTX reduced cellular senescence and inflammation. Human kidney analysis confirmed similar pericyte changes in aging kidneys. The phosphodiesterase inhibitor, PTX preserved microvascular density and improved renal interstitial fibrosis and inflammation in aging mice kidneys. These protective effects were suggested to be associated with the amelioration of pericytes reduction and the transition to myofibroblasts. Additionally, the upregulation of angiopoietin-1 expression may exert potential impacts. To the best of our knowledge, this is the first report on the changes in renal interstitial pericytes in aging human kidneys.

Salvage treatment of forearm arteriovenous fistula with small caliber inflow distal artery by percutaneous transluminal angioplasty.

BACKGROUND: Dysfunctional distal arteriovenous fistulas (AVFs) with small caliber distal inflow arteries theoretically require percutaneous transluminal angioplasty (PTA) throughout the entire arterial length. However, in clinical practice, whole distal inflow arterial PTA is not frequently performed due to concerns about possible arterial rupture. Therefore, we investigated the safety and efficacy of this procedure at our center, comparing it with the standard venous PTA. METHODS: From March 2017 to December 2022, 48 cases of distal AVF salvaged by whole distal inflow arterial PTA were assigned into a treatment group and 121 cases of distal AVF salvaged by venous standard PTA not involving the whole inflow artery were assigned into a control group. These two groups were then compared. RESULTS: Those in the treatment group (who received whole distal inflow arterial PTA) were older than those in the control group (mean age, 69 vs 59 years, p < 0.001). Otherwise, differences between the two groups were unremarkable. After the salvage treatment, primary patency seemed to decrease in the treatment group with whole distal inflow arterial PTA compared to the control group with conventional PTA, although such decrease was not significant (p = 0.072). However, primary assisted patency and secondary patency were comparable between the two groups (p = 0.350 and p = 0.590, respectively). And in the treatment group, only one arterial dissection occurred, which was successfully managed with balloon tamponade so that no distal AVF was abandoned due to complications following whole distal inflow arterial PTA. CONCLUSION: Whole distal inflow arterial PTA is an effective and safe option for distal AVF salvage with a narrowed inflow artery, frequently refractory to conventional venous PTA.

The impact of C-reactive protein-to-albumin ratio on mortality in patients with acute kidney injury requiring continuous renal replacement therapy: A multicenter retrospective study.

INTRODUCTION: C-reactive protein-to-albumin ratio (CAR) is a prognostic marker in various diseases that represents patients' inflammation and nutritional status. Here, we aimed to investigate the prognostic value of CAR in critically ill patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). METHODS: We retrospectively collected data from eight tertiary hospitals in Korea from 2006-2021. The patients were divided into quartiles according to CAR levels at the time of CRRT initiation. Cox regression analyses were performed to investigate the effect of CAR on in-hospital mortality. The mortality prediction performance of CAR was evaluated using the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: In total, 3995 patients who underwent CRRT were included, and the in-hospital mortality rate was 67.3% during the follow-up period. The 7-day, 30-day, and in-hospital mortality rates increased toward higher CAR quartiles (all P < 0.001). After adjusting for confounding variables, the higher quartile groups had an increased risk of in-hospital mortality (quartile 3: adjusted hazard ratio [aHR], 1.26, 95% confidence interval [CI], 1.10-1.43, P < 0.001; quartile 4: aHR, 1.22, 95% CI, 1.07-1.40, P = 0.003). CAR combined with APACHE II or SOFA scores significantly increased the predictive power compared to each severity score alone for the AUC, NRI, and IDI (all P < 0.05). CONCLUSIONS: A high CAR is associated with increased in-hospital mortality in critically ill patients requiring CRRT. The combined use of CAR and severity scores provides better predictive performance for mortality than the severity score alone.

Clinical significance of neutrophil-to-lymphocyte ratio on the risk of abdominal aortic calcification and decreased bone mineral density in patients with end-stage kidney disease.

Inflammation plays a major role in the pathogenesis of chronic kidney disease (CKD), but the relationship between systemic inflammation and CKD-mineral bone disease is unclear. We aimed to investigate whether the neutrophil-to-lymphocyte ratio (NLR) is related to abdominal aortic calcification (AAC) and bone mineral density (BMD) in dialysis patients. In this cross-sectional analysis using baseline data of a multicenter cohort, a total of 759 patients were divided into three groups according to NLR level, and the associations between NLR and Kauppila AAC score (AACS) and BMD were assessed. The highest tertile NLR group had more males, alcohol consumers, higher diabetes prevalence, and higher comorbidity index than the lowest tertile NLR group. Fasting glucose and C-reactive protein levels were higher, while serum albumin, serum iron, and lipid profiles except triglycerides were lower in the highest tertile group. AACS was significantly higher in the highest tertile group than in the lowest and middle tertile groups (p = 0.017), but the mean areal BMD and T-score of the lumbar spine and femur were not different between groups. NLR level was positively correlated with AACS in all aortic wall segments except L1 and L3 anterior. In multivariable logistic regression analysis, the highest tertile NLR group was independently associated with AAC (odds ratio 2.876, 95% confidence interval 1.250-6.619, p = 0.013) but was not associated with osteoporosis in the lumbar spine and femur after adjusting for confounding factors. The NLR can be used as a potential indicator of AAC in dialysis patients.

Safety and durable patency of tunneled hemodialysis catheter inserted without fluoroscopy.

BACKGROUND: A tunneled hemodialysis (HD) catheter is preferred due to its lower incidence of infection and malfunction than non-tunneled ones. For safer insertion, fluoroscopic guidance is desirable. However, if the patient is unstable, transfer to the fluoroscopy may be impossible or inappropriate. METHODS: From June 2019 to September 2022, 81 tunneled HD catheter insertion cases performed under ultrasound guidance without fluoroscopy and 474 cases with fluoroscopy in our institutional HD catheter cohort were retrospectively compared. RESULTS: Immediate complications, later catheter-associated problems, including infections and catheter dysfunction, were comparable between the two groups (p = 0.20 and p = 0.37, respectively). The patency of tunneled catheters inserted without fluoroscopy was comparable to the patency of tunneled catheters inserted with fluoroscopic guidance (p = 0.90). CONCLUSION: Tunneled HD catheter insertion without fluoroscopy can be performed safely and has durable patency compared to the insertion with fluoroscopy. Therefore, this method can be considered for the selected unstable patients (e.g., ventilator care) in the intensive care unit.

The effects of muscle mass and quality on mortality of patients with acute kidney injury requiring continuous renal replacement therapy.

This study examined the effects of muscle mass on mortality in patients with acute kidney injury requiring continuous renal replacement therapy. It was conducted in eight medical centers between 2006 and 2021. The data of 2200 patients over the age of 18 years with acute kidney injury who required continuous renal replacement therapy were retrospectively collected. Skeletal muscle areas, categorized into normal and low attenuation muscle areas, were obtained from computed tomography images at the level of the third lumbar vertebra. Cox proportional hazards models were used to investigate the association between mortality within 1, 3, and 30 days and skeletal muscle index. Sixty percent of patients were male, and the 30-day mortality rate was 52%. Increased skeletal muscle areas/body mass index was associated with decreased mortality risk. We also identified a 26% decreased risk of low attenuation muscle area/body mass index on mortality. We established that muscle mass had protective effects on the mortality of patients with acute kidney injury requiring continuous renal replacement therapy. This study showed that muscle mass is a significant determinant of mortality, even if the density is low.

Dynamic nature and prognostic value of the neutrophil-to-lymphocyte ratio in critically ill patients with acute kidney injury on continuous renal replacement therapy: A multicenter cohort study.

Introduction: Patients with acute kidney injury (AKI) receiving renal replacement therapy constitute the subgroup of AKI with the highest risk of mortality. Despite recent promising findings on the neutrophil-to-lymphocyte ratio (NLR) in AKI, studies have not yet addressed the clinical implication of the NLR in this population. Therefore, we aimed to examine the prognostic value of NLR in critically ill patients requiring continuous renal replacement therapy (CRRT), especially focusing on temporal changes in NLR. Methods: We enrolled 1,494 patients with AKI who received CRRT in five university hospitals in Korea between 2006 and 2021. NLR fold changes were calculated as the NLR on each day divided by the NLR value on the first day. We performed a multivariable Cox proportional hazard analysis to assess the association between the NLR fold change and 30-day mortality. Results: The NLR on day 1 did not differ between survivors and non-survivors; however, the NLR fold change on day 5 was significantly different. The highest quartile of NLR fold change during the first 5 days after CRRT initiation showed a significantly increased risk of death (hazard ratio [HR], 1.65; 95% confidence intervals (CI), 1.27-2.15) compared to the lowest quartile. NLR fold change as a continuous variable was an independent predictor of 30-day mortality (HR, 1.14; 95% CI, 1.05-1.23). Conclusion: In this study, we demonstrated an independent association between changes in NLR and mortality during the initial phase of CRRT in AKI patients receiving CRRT. Our findings provide evidence for the predictive role of changes in the NLR in this high-risk subgroup of AKI.

Evaluation of outcomes with permanent vascular access in an elderly Korean population based on the National Health Insurance Service database.

INTRODUCTION: As nearly half of patients with end-stage kidney disease (ESKD) who initiate hemodialysis (HD) are over 65 years old (commonly defined as elderly), the fistula first strategy is controversial even in HD patients ≥65 years. METHODS: In Korea's National Health Insurance Service database from 2008 to 2019, 41,989 elderly (≥ 65 years) HD patients were retrospectively reviewed to identify their clinical characteristics and outcomes. Vascular access (VA) patencies, risk factors associated with patencies and patient survival between arteriovenous fistula (AVF) and arteriovenous graft (AVG) were compared. RESULTS: Elderly AVF group (n = 28,467) had superior primary, primary assisted, and secondary patencies than elderly AVG group (n = 13,522) (all p values are <0.001). Patient survival was also better in the elderly AVF group than in the elderly AVG (p < 0.001). In multivariate Cox regression analyses for diverse outcomes, AVG (vs. AVF) was identified as a risk factor for all-cause mortality (adjusted hazard ratio [HR]: 1.307; 95% confidence interval [CI]: 1.272-1.343; p < 0.001), primary patency (adjusted HR: 1.745; 95% CI: 1.701-1.790; p < 0.001), primary-assisted patency (adjusted HR: 2.163; 95% CI: 2.095-2.233; p < 0.001), and secondary patency (adjusted HR: 3.718; 95% CI: 3.533-3.913; p < 0.001). CONCLUSION: Our study demonstrated that as a permanent VA for HD, AVF should be strongly considered in elderly (≥ 65 years) ESKD Korean patients. The age limit for AVF creation in ESKD patients should be adjusted more upward.

Prognostic value of chronicity grading on renal outcomes in patients with IgA nephropathy.

Many studies have shown that chronic changes are strong predictors of renal outcomes in various kidney diseases, including IgA nephropathy. The Mayo Clinic/Renal Pathology Society suggested a glomerulonephritis reporting system with a proposal for standardized grading of chronic changes. The purpose of this study was to predict renal outcomes in patients with IgA nephropathy using chronicity grading in comparison to the Oxford classification which did not include global sclerosis. A total of 4,151 patients with IgA nephropathy were enrolled from the Korean GlomeruloNephritis Study Group registry. Chronicity grading was categorized into minimal, mild, moderate, and severe according to the extent of chronic changes. The Oxford T and S scores were considered as chronic lesions. Three prediction models were constructed: the Oxford classification model (Oxford S plus T), chronicity grading model A (chronicity grading), and chronicity grading model B (chronicity grading plus Oxford S). Using these three prediction models, the primary renal outcome (end-stage renal disease) was evaluated using Cox regression analysis and prediction performance. During the median follow-up of 6.1 (2.7-9.9) years, 304 (7.3%) patients progressed to end-stage renal disease with a cumulative incidence rate of 1.02 events per 100 person-years. In a fully adjusted multivariable model, chronicity grading was independently associated with the primary renal outcome in both models A and B. Compared to the Oxford model, both models A and B showed improvements in model fit, but not in discrimination (ΔC 0.001; 95% CI, -0.010 to 0.013 and ΔC 0.002; 95% CI, -0.005 to 0.008, respectively). Model B demonstrated improvements in integrated discrimination improvement (0.01; 95% CI, 0-0.03) and continuous net reclassification improvement (0.49; 95% CI, 0.02-0.72). The severity of chronicity grading is closely related to adverse renal outcomes in patients with IgA nephropathy, and chronicity grading could provide additional information in clinical practice alongside the Oxford classification.

Relationships between monocyte count to high-density lipoprotein cholesterol ratio and cardiovascular outcomes in patients commencing dialysis.

OBJECTIVE: High monocyte to high-density lipoprotein cholesterol ratio (MHR) is known to be a risk factor for cardiovascular (CV) complications. We aimed to evaluate the relationship between MHR and CV outcomes in patients commencing dialysis. METHODS: The medical records of patients who started maintenance dialysis between January 2006 and July 2017 were reviewed. The primary outcomes were all-cause mortality and overall CV mortality and the secondary outcomes were CV event-free survival and the incidence of CV complications. RESULTS: Five hundred ninety-seven patients were enrolled and allocated to low- or high-MHR groups. All-cause mortality did not differ between the groups during a mean follow-up period of 3.9 years. In addition, overall CV mortality did not differ between the groups. However, CV event-free survival was significantly lower in the high-MHR group than in the low-MHR group (47.5% vs. 59.0%). Multivariate Cox regression analysis showed that high MHR was an independent predictor of CV events (HR 1.886, 95% CI 1.015-3.505). CONCLUSION: High MHR at the time of initiation of dialysis may represent a useful predictor of CV complications.

Role of Aberrantly Activated Lysophosphatidic Acid Receptor 1 Signaling Mediated Inflammation in Renal Aging.

The increasing load of senescent cells is a source of aging, and chronic inflammation plays a pivotal role in cellular senescence. In addition, senescent renal tubular epithelial cells are closely associated with renal aging. Lysophosphatidic acid (LPA) is a bioactive lipid mainly produced by the catalytic action of autotaxin (ATX), and its ligation to LPA receptor-1 (LPAR1) is associated with chronic inflammation and renal fibrosis; however, its role in renal aging is unclear. Male 2-, 12-, and 24-month-old C57BL/6 mice and Human renal proximal tubular epithelial cells (HRPTEpiC) were used in the present study. DNA damage and oxidative stress-induced senescence were simulated using doxorubicin (DOXO) and H2O2, respectively. The aged kidney showed decreased renal function, increased fractional mesangial area, and tubulointerstitial fibrosis. Both aged kidney and senescent cells showed increased levels of LPAR1, Nuclear factor κB (NF-κB), and inflammatory cytokines. In addition, LPAR1-knockdown reduced NF-κB and subsequent inflammatory cytokine induction, and NF-κB-knockdown resulted in decreased LPAR1 expression. Our study revealed a positive feedback loop between LPAR1 and NF-κB, which reinforces the role of inflammatory response, suggesting that blocking of aberrantly activated LPAR1 may reduce excessive inflammation, thereby providing a new possible therapeutic strategy to attenuate renal aging.

Hypertriglyceridemia Is Associated with More Severe Histological Glomerulosclerosis in IgA Nephropathy.

IgA nephropathy (IgAN) is a globally well-known primary glomerular nephropathy. Hypertriglyceridemia (HTG) is one factor contributing to atherosclerosis and is a common complication of renal failure. HTG is a significant risk factor for decreased renal function in patients with IgAN. We evaluated the association of HTG with the histopathological features of IgAN patients. A total of 480 patients diagnosed with IgAN via kidney biopsy from eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea were included in the final cohort. Pathological features were evaluated by eight expert pathologists with hospital consensus. HTG was defined as a serum triglyceride (TG) level of ≥150 mg/dL. In the study population analysis, the HTG group was older, with more males; higher body mass index (BMI), low-density lipoprotein cholesterol (LDL-C) and spot urine protein ratio; and lower estimated glomerular filtration rate (eGFR). In the lipid profile analysis, eGFR was negatively correlated with TGs/ high-density lipoprotein cholesterol (HDL) and triglyceride-glucose index (TyG). Proteinuria positively correlated with TGs/HDL, non-HDL/HDL, LDL/HDL, TyG, TGs and LDL. The percentages of global sclerosis (GS), segmental sclerosis (SS) and capsular adhesion (CA), and the scores for mesangial matrix expansion (MME) and mesangial cell proliferation (MCP), were more elevated in the HTG group compared to the normal TG group. Multivariable linear regression analysis showed that the percentages of global sclerosis, segmental sclerosis and capsular adhesion, as well as the scores for mesangial matrix expansion and mesangial cell proliferation, were positively associated with TG level. In binary logistic regression, the HTG group showed a higher risk for global sclerosis and segmental sclerosis. In conclusion, HTG is a significant risk factor for glomerulosclerosis in IgAN.

Synergistic impact of pre-sensitization and delayed graft function on allograft rejection in deceased donor kidney transplantation.

The aim of this study is to investigate whether or not delayed graft function (DGF) and pre-transplant sensitization have synergistic adverse effects on allograft outcome after deceased donor kidney transplantation (DDKT) using the Korean Organ Transplantation Registry (KOTRY) database, the nationwide prospective cohort. The study included 1359 cases between May 2014 and June 2019. The cases were divided into 4 subgroups according to pre-sensitization and the development of DGF post-transplant [non-pre-sensitized-DGF(-) (n = 1097), non-pre-sensitized-DGF(+) (n = 127), pre-sensitized-DGF(-) (n = 116), and pre-sensitized-DGF(+) (n = 19)]. We compared the incidence of biopsy-proven allograft rejection (BPAR), time-related change in allograft function, allograft or patient survival, and post-transplant complications across 4 subgroups. The incidence of acute antibody-mediated rejection (ABMR) was significantly higher in the pre-sensitized-DGF(+) subgroup than in other 3 subgroups. In addition, multivariable cox regression analysis demonstrated that pre-sensitization combined with DGF is an independent risk factor for the development of acute ABMR (hazard ratio 4.855, 95% confidence interval 1.499-15.727). Moreover, DGF and pre-sensitization showed significant interaction (p-value for interaction = 0.008). Pre-sensitization combined with DGF did not show significant impact on allograft function, and allograft or patient survival. In conclusion, the combination of pre-sensitization and DGF showed significant synergistic interaction on the development of allograft rejection after DDKT.