Obesity exacerbates ischemia-reperfusion injury and senescence in murine kidneys and perirenal adipose tissues.

Background: Obesity is a major worldwide health problem and can be related to cellular senescence. Along with the rise in obesity, the comorbidity of renal ischemia-reperfusion (IR) injury is increasing. Whether obesity accelerates the severity of IR injury and whether senescence contributes to these conditions remain unclear. We studied the degree of injury and cellular senescence in the IR kidneys and perirenal adipose tissues of high-fat-diet-induced obese mice. Methods: C57BL/6 mice fed standard chow or a high-fat diet for 16 weeks were randomized to renal IR or sham group (n = 6-10 each). Renal IR was performed by unilateral clamping of the right renal pedicle for 30 minutes. Six weeks after surgery, renal function, perirenal fat/renal senescence, and histology were evaluated ex vivo. Results: Obese mice showed more renal tubular damage and fibrosis in IR injury than control mice, even though the degree of ischemic insult was comparable. Renal expression of senescence and its secretory phenotype was upregulated in either IR injury or with a high-fat diet and was further increased in the IR kidneys of obese mice. Fat senescence and the expression of tumor necrosis factor alpha were also increased, especially in the perirenal depot of the IR kidneys, with a high-fat diet. Conclusion: A high-fat diet aggravates IR injury in murine kidneys, which is associated, at least in part, with perirenal fat senescence and inflammation. These observations support the exploration of therapeutic targets of the adipo-renal axis in injured obese kidneys.

Sarcopenia is independently associated with mortality and recovery from dialysis in critically ill patients with sepsis-induced acute kidney injury receiving continuous renal replacement therapy.

Background: Sarcopenia upon admission to the intensive care unit (ICU) consistently correlates with adverse outcomes, including heightened mortality, in critically ill patients. This study aims to investigate the independent association of sarcopenia with both mortality and recovery from dialysis in critically ill patients with sepsis-induced acute kidney injury (SIAKI) undergoing continuous renal replacement therapy (CRRT). Methods: This retrospective study included 618 patients with SIAKI who underwent CRRT in our ICU. All patients had abdominal computed tomography (CT) scans within 3 days preceding ICU admission. The cross-sectional area of skeletal muscles at the third lumbar vertebra was quantified, and the skeletal muscle index (SMI), a normalized measure of skeletal muscle mass, was computed. Using Korean-specific SMI cutoffs, patients were categorized into sarcopenic and non-sarcopenic groups. Results: Among the 618 patients, 301 expired within 28 days of ICU admission. Multivariable Cox regression analysis revealed that sarcopenia independently predicted 28-day mortality. Among survivors, sarcopenia was independently associated with recovery from dialysis within 28 days after ICU admission. Kaplan-Meier analysis illustrated that sarcopenic patients had a higher mortality rate and a lower rate of recovery from dialysis within 28 days after ICU admission compared to non-sarcopenic patients. Conclusion: This study underscores the independent association of sarcopenia, assessed via CT-derived SMI, with both mortality and recovery from dialysis in critically ill patients with SIAKI undergoing CRRT. The inclusion of sarcopenia assessment could serve as a valuable tool for physicians in effectively stratifying the risk of adverse outcomes in these patients.

Association of 1,25 dihydroxyvitamin D with left ventricular hypertrophy and left ventricular diastolic dysfunction in patients with chronic kidney disease.

Left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD) are highly prevalent predictors of cardiovascular disease in individuals with chronic kidney disease (CKD). Vitamin D, particularly 25-hydroxyvitamin D [25(OH)D], deficiency has been reported to be associated with cardiac structure and function in CKD patients. In the current study, we investigated the association between 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of 25(OH)D, and LVH/LVDD in CKD patients. We enrolled 513 non-dialysis CKD patients. The presence of LVH and LVDD was determined using transthoracic echocardiography. In multivariable analysis, serum 1,25(OH)2D levels, but not serum 25(OH)D, were independently associated with LVH [odds ratio (OR): 0.90, 95% confidential interval (CI): 0.88-0.93, P < 0.001]. Additionally, age, systolic blood pressure, and intact parathyroid hormone levels were independently associated with LVH. Similarly, multivariable analysis demonstrated that serum 1,25(OH)2D levels, but not 25(OH)D levels, were independently associated with LVDD (OR: 0.88, 95% CI: 0.86-0.91, P < 0.001) with systolic blood pressure showing independent association with LVDD. The optimal cut-off values for serum 1,25(OH)2D levels for identifying LVH and LVDD were determined as ≤ 12.7 pg/dl and ≤ 18.1 pg/dl, respectively. Our findings suggest that serum 1,25(OH)2D levels have independent association with LVH and LVDD in CKD patients, underscoring their potential as biomarkers for these conditions in this patient population.

Association between dementia diagnosis at dialysis initiation and mortality in older patients with end-stage kidney disease in South Korea.

Background: The prevalence of dementia is 2- to 7-fold higher among patients with end-stage kidney disease (ESKD) than among the general population; however, its clinical implications in this population remain unclear. Therefore, this study aimed to determine whether comorbid dementia increases mortality among older patients with ESKD undergoing newly initiated hemodialysis. Methods: We analyzed data from the Korean Society of Geriatric Nephrology retrospective cohort, which included 2,736 older ESKD patients (≥70 years old) who started hemodialysis between 2010 and 2017. Kaplan-Meier survival and Cox regression analyses were used to examine all-cause mortality between the patients with and without dementia in this cohort. Results: Of the 2,406 included patients, 8.3% had dementia at the initiation of dialysis; these patients were older (79.6 ± 6.0 years) than patients without dementia (77.7 ± 5.5 years) and included more women (male:female, 89:111). Pre-ESKD diagnosis of dementia was associated with an increased risk of overall mortality (hazard ratio, 1.503; p < 0.001), and this association remained consistent after multivariate adjustment (hazard ratio, 1.268; p = 0.009). In subgroup analysis, prevalent dementia was associated with mortality following dialysis initiation in female patients, those aged <85 years, those with no history of cerebrovascular accidents or severe behavioral disorders, those not residing in nursing facilities, and those with no or short-term hospitalization. Conclusion: A pre-ESKD diagnosis of dementia is associated with mortality following dialysis initiation in older Korean population. In older patients with ESKD, cognitive assessment at dialysis initiation is necessary.

Impact of nonspecific allograft biopsy findings in symptomatic kidney transplant recipients.

A for-cause biopsy is performed to diagnose the cause of allograft dysfunction in kidney transplantation. We occasionally encounter ambiguous biopsy results in symptomatic kidney transplant recipients. Yet, the allograft survival outcome in symptomatic recipients with nonspecific allograft biopsy findings remains unclear. The purpose of this study was to analyze the impact of nonspecific for-cause biopsy findings in symptomatic kidney transplant recipients. We retrospectively collected records from 773 kidney transplant recipients between January 2008 and October 2021. The characteristics of transplant recipients with nonspecific findings in the first for-cause biopsy were analyzed. Nonspecific allograft biopsy findings were defined as other biopsy findings excluding rejection, borderline rejection, calcineurin inhibitor toxicity, infection, glomerulonephritis, and diabetic nephropathy. The graft outcome was compared between recipients who had never undergone a for-cause biopsy and those who had a first for-cause biopsy with nonspecific findings. The graft survival in recipients with nonspecific for-cause biopsy findings was comparable to that in recipients who did not require the for-cause biopsy before and after propensity score matching. Even in symptomatic kidney transplant recipients, nonspecific allograft biopsy findings might not be a poor prognostic factor for allograft survival compared to recipients who did not require the for-cause biopsy.

Pre-treatment with ß-hydroxybutyrate mitigates cisplatin-induced acute kidney injury.

ß-Hydroxybutyrate (ß-HB), the primary circulating ketone body, plays a dual role as both a metabolic fuel and an endogenous signaling molecule, offering diverse systemic benefits. Recent studies have highlighted the renoprotective effects of exogenous ß-HB therapy in various animal models of kidney disease. In this investigation, our goal was to assess whether pre-treatment with exogenous ß-HB could alleviate kidney damage in a mouse model of cisplatin-induced acute kidney injury (AKI). Prior to cisplatin administration, intraperitoneal administration of ß-HB was carried out, and the groups were classified into four: Sham, ß-HB, cisplatin, and ß-HB + cisplatin. The tubular damage score and serum creatinine levels were significantly lower in the ß-HB + cisplatin group compared to the cisplatin group. Furthermore, the expression of phosphorylated NF-κB, inflammatory cytokines, and the quantity of F4/80-positive macrophages in the ß-HB + cisplatin group were reduced compared to those in the cisplatin group. Additionally, oxidative stress markers for DNA, protein, and lipid in the ß-HB + cisplatin group were markedly diminished compared to those in the cisplatin group. The number of TUNEL-positive and cleaved caspase 3-positive tubular cells in the ß-HB + cisplatin group was lower than in the cisplatin group. Pre-treating with exogenous ß-HB effectively mitigated kidney damage by suppressing inflammation, oxidative stress, and tubular apoptosis in cisplatin-induced AKI. Therefore, exogenous ß-HB as a pre-treatment emerges as a promising and novel strategy for preventing cisplatin-induced AKI.

ß-hydroxybutyrate ameliorates sepsis-induced acute kidney injury.

BACKGROUND: Sepsis is a major cause of acute kidney injury (AKI). Recent studies have demonstrated that ß-hydroxybutyrate (ß-HB) alleviates renal ischemia-reperfusion injury and cisplatin-induced renal injury in murine models. This study aimed to investigate whether ß-HB ameliorates sepsis-induced AKI (SIAKI) in a lipopolysaccharide (LPS)-induced mouse sepsis model. METHODS AND RESULTS: SIAKI was induced by intraperitoneally injecting LPS to C57BL/6 male mice. ß-HB was administrated intraperitoneally before LPS injection. The mice were divided into sham, ß-HB, LPS, and ß-HB + LPS groups. The histological damage score and serum creatinine level were significantly increased in the LPS group mice, but attenuated in the ß-HB + LPS group mice. The expression of phosphorylated nuclear factor-κB tumor necrosis factor-α/interleukin-6 and the number of F4/80-positive macrophages in the ß-HB + LPS group mice were lower than those in the LPS group mice. The number of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells, cleaved caspase-3 expression, and Bax/Bcl-2 ratio in the ß-HB + LPS group mice were lower than those in the LPS group mice. CONCLUSION: ß-HB pre-treatment ameliorates SIAKI by reducing tubular apoptosis and inflammatory responses. Thus, ß-HB pre-treatment could be a potential prophylactic strategy against SIAKI.

Errate: Modification of Venous Outflow to Avoid Thrombotic Graft Failure in Pancreas Transplantation.

The authors asked for an errata to correct the affiliation information. The corrected affiliations are as follows:Je Ho Ryu1,2, Jae Ryong Shim1, Tae Beom Lee1, Kwang Ho Yang1, Taeun Kim3, Seo Rin Kim4, Byung Hyun Choi1,21 Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, South Korea2 Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea3 Department of Radiology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea4 Department of Internal medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine,  Yangsan, South KoreaThe change of affiliation does not affect the content or findings of the publication in any way. It is solely an update to the -authors' institutional affiliations.Reference:Je Ho Ryu, Jae Ryong Shim, Tae Beom Lee, Kwangho Yang, Taeun Kim, Seo Rin Kim, Byunghyun Choi. Modification of Venous Outflow to Avoid Thrombotic Graft Failure in Pancreas Transplantation. Ann Transplant. 2022; 27: e937514. DOI: 10.12659/AOT.937514.

Recombinant human KAI1/CD82 attenuates M1 macrophage polarization on LPS-stimulated RAW264.7 cells via blocking TLR4/JNK/NF-κB signal pathway.

KAI1/CD82, a membrane tetraspanin protein, can prevent various cancers and retinal disorders through its anti-angiogenic and anti-metastatic capacity. However, little is known about its anti-inflammatory effect and molecular mechanism. Therefore, the present study aimed to inLPSvestigate effect of a recombinant protein of the large extracellular domain of human KAI1 (Gly 111-Leu 228, rhKAI1) on lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage-like cells and mouse bone marrow-derived macrophages (BMDM) and to identify its underlying mechanism. Our data showed that rhKAI1 suppressed expression levels of classically macrophages (M1) phenotyperelated surface markers F4/80+CD86+ in LPS-stimulated BMDM and RAW264.7 cells. In addition, LPS markedly increased mRNA expression and release levels of pro-inflammatory cytokines and mediators such as interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, cyclooxygenase-2, nitric oxide and prostaglandin E2, whereas these increases were substantially down-regulated by rhKAI1. Furthermore, LPS strongly increased expression of NF-κB p65 in the nuclei and phosphorylation of ERK, JNK, and p38 MAPK. However, nuclear translocation of NF-κB p65 and phosphorylation of JNK were greatly reversed in the presence of rhKAI1. Especially, rhKAI1 markedly suppressed expression of toll-like receptor (TLR4) and prevented binding of LPS with TLR4 through molecular docking predict analysis. Importantly, Glu 214 of rhKAI1 residue strongly interacted with Lys 360 of TLR4 residue, with a binding distance of 2.9 Å. Taken together, these findings suggest that rhKAI1 has an anti-inflammatory effect on LPS-polarized macrophages by interacting with TLR4 and down-regulating the JNK/NF-κB signaling pathway. [BMB Reports 2023; 56(6): 359-364].

Effect of fluid overload on survival in patients with sepsis-induced acute kidney injury receiving continuous renal replacement therapy.

The association between fluid overload and survival has not been well elucidated in critically ill patients with sepsis-induced acute kidney injury (SIAKI) receiving continuous renal replacement therapy (CRRT). We investigated the optimal cutoff value of fluid overload for predicting mortality and whether minimizing fluid overload through CRRT is associated with a survival benefit in these patients. We examined 543 patients with SIAKI who received CRRT in our intensive care unit. The degree of cumulative fluid overload in relation to body weight was expressed as the percentage fluid overload (%FO). %FO was further subdivided into %FO from AKI diagnosis to CRRT initiation (%FOpreCRRT) and total fluid overload (%FOtotal). The best cutoff value of fluid overload for predicting the 28-day mortality was %FOpreCRRT > 4.6% and %FOtotal > 9.6%. Multivariable analysis demonstrated that patients with %FOpreCRRT > 4.6% and %FOtotal > 9.6% were 1.9 times and 3.37 times more likely to die than those with %FOpreCRRT ≤ 4.6% and %FOtotal ≤ 9.6%. The 28-day mortality was the highest in patients with %FOpreCRRT > 4.6% and %FOtotal > 9.6% (84.7%), followed by those with %FOpreCRRT ≤ 4.6% and %FOtotal > 9.6% (65.0%), %FOpreCRRT > 4.6% and %FOtotal ≤ 9.6% (43.6%), and %FOpreCRRT ≤ 4.6% and %FOtotal ≤ 9.6% (22%). This study demonstrated that fluid overload was independently associated with the 28-day mortality in critically ill patients with SIAKI. Future prospective studies are needed to determine whether minimizing fluid overload using CRRT improves the survival of these patients.

Procalcitonin decrease predicts survival and recovery from dialysis at 28 days in patients with sepsis-induced acute kidney injury receiving continuous renal replacement therapy.

Procalcitonin (PCT) is a biomarker for diagnosing infections and guiding antibiotic therapy. In this study, we investigated whether PCT can predict survival and recovery at 28 days in critically ill patients with sepsis-induced acute kidney injury (SIAKI) receiving continuous renal replacement therapy (CRRT). We examined 649 patients with SIAKI who underwent CRRT in our intensive care unit. In a multivariable Cox regression analysis, a single PCT level at CRRT initiation was not associated with survival in all patients. However, the higher % PCT decrease over 72 hours after CRRT initiation was independently associated with the higher chance of 28-day survival (per 10% decrease, hazard ratio [HR] for mortality: 0.87, 95% confidence interval [CI]: 0.85-0.89; P < 0.001). Among the survivors, the % PCT decrease over 72 hours after CRRT initiation, not a single PCT level at CRRT initiation, was independently associated with recovery from dialysis (per 10% decrease, HR for renal recovery: 1.28, 95% CI:1.21-1.36; P < 0.001). This study demonstrated that the higher % PCT decrease was independently associated with the higher chance of survival and recovery from dialysis at 28 days in critically ill patients with SIAKI receiving CRRT. Thus, a decrease in the PCT level, not a single PCT level at CRRT initiation, could be a valuable tool for predicting prognosis in these patients.

Modification of Venous Outflow to Avoid Thrombotic Graft Failure in Pancreas Transplantation.

BACKGROUND Even with recent data, 5-10% of pancreas transplants experience early technical failure. Graft thrombosis is the primary cause of early technical failure, even when only optimal grafts are used, as is the case in Korea. The purpose of this study was to determine whether we can avoid thrombotic graft failure by modifying venous outflow. MATERIAL AND METHODS Between March 2017 and December 2021, a total of 59 pancreas transplantations were performed. Until May 2019, 31 cases of fence-angioplasty with cadaveric vena cava were performed to graft portal veins (the vena cava group). Since then, a total of 28 aortic interposition grafts have been performed to graft portal veins (the aortic group). RESULTS Between the 2 groups, there was no significant difference in baseline characteristics. Each group had 1 instance of technical failure. Early graft failure rates were 3.2% and 3.4%, respectively (P=1.000), while 1-year graft survival rates were 96.8% and 94.4%, respectively (P=0.991). Although a graft-threatening thrombosis occurred in the vena cava group, neither group experienced thrombotic graft failure, despite the decreased (vena cava group) or absence of heparin use (aorta group). CONCLUSIONS When the optimal graft is used, both techniques of modifying venous outflow can significantly reduce thrombotic graft failure.

CD82 attenuates TGF-ß1-mediated epithelial-mesenchymal transition by blocking smad-dependent signaling in ARPE-19 cells.

In retinal pigment epithelial (RPE) cells, transforming growth factor-beta (TGF-ß) plays a critical role in epithelial-mesenchymal transition (EMT), which contributes to various fibrotic retinal disorders. In the present study, we investigated the effect of recombinant human cluster of differentiation 82 (rhCD82), a tumor metastasis suppressor, on TGF-ß-induced EMT in the human RPE cell line APRE-19. The results show that TGF-ß1 significantly enhanced cell migration, invasion and the expression of EMT-mediate factors in ARPE-19 cells. However, rhCD82 markedly inhibited cell mobility and the expression of epithelial marker, zonula occludens-1, as well as increased the expression of mesenchymal markers, such as vimentin and α-smooth muscle actin in TGF-ß1-treated APRE-19 cells. In addition, TGF-ß1 upregulated the phosphorylation of Smad, extracellular signal regulated kinase (ERK) and glycogen synthase kinase-3ß (GSK-3ß), but only phosphorylation of Smad was suppressed by rhCD82. Noteworthy, rhCD82 greatly suppressed the expression of TGF-ß receptor I (TGFRI), TGFRII and integrins in TGF-ß1-treated APRE-19 cells. In particular, the result of molecular docking analysis and structural modeling show that rhCD82 partially interacts with the TGF-ß1 binding sites of TGFRI, TGFRII, integrin ß1 and integrin αv. Taken together, this finding suggested that rhCD82 suppressed TGF-ß1-induced EMT of RPE by blocking of Smad-dependent pathway, which is caused by rhCD82 interaction with TGFRs and integrins, suggesting new insight into CD82 as a potential therapeutic strategy in fibrotic retinal disorders.

Analysis of Risk Factors for Delayed Graft Function After Kidney Transplantation.

BACKGROUND: Delayed graft function (DGF) is a serious complication associated with worsening outcomes in kidney transplantation. To facilitate DGF risk reduction, this study aimed to identify the incidence and modifiable risk factors of this condition in kidney transplant patients. METHODS: This retrospective chart review included 220 patients who underwent kidney transplants between 2012 and 2021 at our kidney transplant center. Delayed graft function was defined as the requirement of hemodialysis within a week of transplantation. Clinical data from patients with DGF and those without this condition were compared to identify risk factors of DGF. RESULTS: Of 205 eligible patients, 20 (9.76%) developed DGF. In the univariate analysis, high hemoglobin level, deceased-donor type, and longer warm and cold ischemic times were significantly associated with DGF (P < .05). In the variable selection in logistic regression analysis, high hemoglobin level, with a cutoff value of 11.35 g/dL, and deceased-donor transplants were associated with higher DGF incidence (P < .05 for both factors). CONCLUSIONS: Our findings newly demonstrated that DGF occurred more frequently in patients with hemoglobin level >11.35 g/dL. As such, improvement in kidney transplantation outcomes could be achieved by reducing this modifiable risk factor.

Graft-Versus-Host Disease Developed After En Bloc Kidney Transplant From a Pediatric Donor: A Case Report.

Graft-versus-host disease is a rare but a potentially fatal complication that can occur after kidney transplant. Furthermore, graft-versus-host disease after kidney transplant has been reported in only a few studies. We present a rare case of graft-versus-host disease in a patient who underwent kidney transplant. A patient who underwent hemodialysis received an en bloc kidney transplantfrom a pediatric donor, and the graft function was excellent. Mild diarrhea started on postoperative day 25. Six days after the onset of diarrhea, pancytopenia worsened and fever persisted. However, there were no test findings indicating infection or adverse medical effects. Graft-versus-host disease was diagnosed after a short tandem repeat evaluation of lymphocytes from the recipient's peripheral blood, which revealed 4.7% donor cells.The findings in this study provide insight into cases where symptoms such as fever and pancytopenia of unknown cause appear after kidney transplant, and we suggest that it is necessary to differentiate these symptoms from graft-versus-host disease.

Maintenance of the critical care system during the pandemic in non-COVID-19 patients requiring continuous renal replacement therapy: a single center experience.

BACKGROUND: During the COVID-19 pandemic, maintenance of essential healthcare systems became very challenging. We describe the triage system of our institute, and assess the quality of care provided to critically ill non-COVID-19 patients requiring continuous renal replacement therapy (CRRT) during the pandemic. METHODS: We introduced an emergency triage pathway early in the pandemic. We retrospectively reviewed the medical records of patients who received CRRT in our hospital from January 2016 to March 2021. We excluded end-stage kidney disease patients on maintenance dialysis. Patients were stratified as medical and surgical patients. The time from hospital arrival to intensive care unit (ICU) admission, the time from hospital arrival to intervention/operation, and the in-hospital mortality rate were compared before (January 2016 to December 2019) and during (January 2021 to March 2021) the pandemic. RESULTS: The mean number of critically ill patients who received CRRT annually in the surgical department significantly decreased during the pandemic in (2016-2019: 76.5 ± 3.1; 2020: 56; p < 0.010). Age, sex, and the severity of disease at admission did not change, whereas the proportions of medical patients with diabetes (before: 44.4%; after: 56.5; p < 0.005) and cancer (before: 19.4%; after: 32.3%; p < 0.001) increased during the pandemic. The time from hospital arrival to ICU admission and the time from hospital arrival to intervention/operation did not change. During the pandemic, 59.6% of surgical patients received interventions/operations within 6 hours of hospital arrival. In Cox's proportional hazard modeling, the hazard ratio associated with the pandemic was 1.002 (0.778-1.292) for medical patients and 1.178 (0.783-1.772) for surgical patients. CONCLUSION: Our triage system maintained the care required by critically ill non-COVID-19 patients undergoing CRRT at our institution.

Worsening or improving hypoalbuminemia during continuous renal replacement therapy is predictive of patient outcome: a single-center retrospective study.

BACKGROUND: Hypoalbuminemia at the initiation of continuous renal replacement therapy (CRRT) is a risk factor for poor patient outcomes. However, it is unknown whether the patterns of changes in serum albumin levels during CRRT can be used to predict patient outcomes. METHODS: This retrospective study analyzed data that had been consecutively collected from January 2016 to December 2020 at the Third Affiliated Hospital. We included patients with acute kidney injury who received CRRT for ≥ 72 h. We divided the patients into four groups based on their serum albumin levels (albumin ≥ 3.0 g/dL or < 3.0 g/dL) at the initiation and termination of CRRT. RESULTS: The 793 patients in this study were categorized into the following albumin groups: persistently low, 299 patients (37.7%); increasing, 85 patients (10.4%); decreasing, 195 patients (24.6%); and persistently high, 214 patients (27.1%). In-hospital mortality rates were highest in the persistently low and decreasing groups, followed by the increasing and persistently high groups. The hazard ratio for in-hospital mortality was 0.481 (0.340-0.680) in the increasing group compared to the persistently low group; it was 1.911 (1.394-2.620) in the decreasing group compared to the persistently high group. The length of ICU stay was 3.55 days longer in the persistently low group than in the persistently high group. CONCLUSIONS: Serum albumin levels changed during CRRT, and monitoring of patterns of change in serum albumin levels is useful for predicting in-hospital mortality and the length of ICU stay.

Microvascular remodeling and altered angiogenic signaling in human kidneys distal to occlusive atherosclerotic renal artery stenosis.

BACKGROUND: Renal artery stenosis (RAS) is an important cause of chronic kidney disease and secondary hypertension. In animal models, renal ischemia leads to downregulation of growth factor expression and loss of intrarenal microcirculation. However, little is known about the sequelae of large-vessel occlusive disease on the microcirculation within human kidneys. METHOD: This study included five patients who underwent nephrectomy due to renovascular occlusion and seven nonstenotic discarded donor kidneys (four deceased donors). Micro-computed tomography was performed to assess microvascular spatial densities and tortuosity, an index of microvascular immaturity. Renal protein expression, gene expression and histology were studied in vitro using immunoblotting, polymerase chain reaction and staining. RESULTS: RAS demonstrated a loss of medium-sized vessels (0.2-0.3 mm) compared with donor kidneys (P = 0.037) and increased microvascular tortuosity. RAS kidneys had greater protein expression of angiopoietin-1, hypoxia-inducible factor-1α and thrombospondin-1 but lower protein expression of vascular endothelial growth factor (VEGF) than donor kidneys. Renal fibrosis, loss of peritubular capillaries (PTCs) and pericyte detachment were greater in RAS, yet they had more newly formed PTCs than donor kidneys. Therefore, our study quantified significant microvascular remodeling in the poststenotic human kidney. RAS induced renal microvascular loss, vascular remodeling and fibrosis. Despite downregulated VEGF, stenotic kidneys upregulated compensatory angiogenic pathways related to angiopoietin-1. CONCLUSIONS: These observations underscore the nature of human RAS as a microvascular disease distal to main vessel stenosis and support therapeutic strategies directly targeting the poststenotic kidney microcirculation in patients with RAS.

Selective kidney targeting increases the efficacy of mesenchymal stromal/stem cells for alleviation of murine stenotic-kidney senescence and damage.

Chronic ischemia triggers senescence in renal tubules and at least partly mediates kidney dysfunction and damage through a p16Ink4a -related mechanism. We previously showed that mesenchymal stromal/stem cells (MSCs) delivered systemically do not effectively decrease cellular senescence in stenotic murine kidneys. We hypothesized that selective MSC targeting to injured kidneys using an anti-KIM1 antibody (KIM-MSC) coating would enhance their ability to abrogate cellular senescence in murine renal artery stenosis (RAS). KIM-MSC were injected into transgenic INK-ATTAC mice, which are amenable for selective eradication of p16Ink4a+ cells, 4 weeks after induction of unilateral RAS. To determine whether KIM-MSC abolish p16Ink4a -dependent cellular senescence, selective clearance of p16Ink4a+ cells was induced in a subgroup of RAS mice using AP20187 over 3 weeks prior to KIM-MSC injection. Two weeks after KIM-MSC aortic injection, renal senescence, function, and tissue damage were assessed. KIM-MSC delivery decreased gene expression of senescence and senescence-associated secretory phenotype factors, and improved micro-MRI-derived stenotic-kidney glomerular filtration rate and perfusion. Renal fibrosis and tubular injury also improved after KIM-MSC treatment. Yet, their efficacy was slightly augmented by prior elimination of p16Ink4a+ senescent cells. Therefore, selective targeting of MSC to the injured kidney markedly improves their senolytic potency in murine RAS, despite incomplete eradication of p16+ cells. KIM-MSC may constitute a useful therapeutic strategy in chronic renal ischemic injury.

Virtual conference participant's perceptions of its effectiveness and future projections.

BACKGROUND: The virtual conference format has become an essential tool for professional development of researchers around the world since the outbreak of the COVID-19 pandemic. This study aims to identify empirical evidence of the benefits and challenges of virtual conferences by investigating participants' experiences with them. METHODS: The study participants were delegates to the 40th annual meeting of the Korean Society of Nephrology, which was held virtually in September, 2020. A questionnaire was developed and implemented among the conference attendees. The 44-item questionnaire included five sub-scales related to participant perceptions of the virtual conference, which were (a) convenience and accessibility, (b) planning and organization, (c) technology use, (d) social exchanges, and (e) overall satisfaction, their preferences of conference formats, and their views of future projections for a virtual conference. RESULTS: A total of 279 delegates completed and returned the questionnaires (18.8% response rate). Participants varied in gender, age, profession, work location, and prior experience with conferences. On a four-point Likert scale (1 = "strongly disagree" and 4 = "strongly agree"), participants showed positive perceptions of the virtual conference in general, where the total mean (M) was 3.03 and less positive perceptions on social exchanges (M = 2.72). Participant perceptions of the virtual conference differed across age groups, professions, and prior experience with conferences (p < .05). Approximately half of the participants (n = 139) preferred the virtual format, and 33% (n = 92) preferred the conventional format. Participant preferences for the virtual format were somewhat evenly distributed between asynchronous (32.9%) and synchronous (29.1%) modes. Participants predicted a virtual conference would continue to be a popular delivery format after the end of the COVID-19. CONCLUSIONS: Although participants had positive perceptions of the virtual conference, more support needs to be offered to those who may be less comfortable with using technology or with online interactions, and there is a need for improvement in supporting social exchange among attendees. Also, it is suggested that a blend of asynchronous and synchronous delivery methods should be considered to meet the varied needs of attendees.