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.

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.

Progressive Cellular Senescence Mediates Renal Dysfunction in Ischemic Nephropathy.

BACKGROUND: Peripheral vascular diseases may induce chronic ischemia and cellular injury distal to the arterial obstruction. Cellular senescence involves proliferation arrest in response to stress, which can damage neighboring cells. Renal artery stenosis (RAS) induces stenotic-kidney dysfunction and injury, but whether these arise from cellular senescenceand their temporal pattern remain unknown. METHODS: Chronic renal ischemia was induced in transgenic INK-ATTAC and wild type C57BL/6 mice by unilateral RAS, and kidney function (in vivo micro-MRI) and tissue damage were assessed. Mouse healthy and stenotic kidneys were analyzed using unbiased single-cell RNA-sequencing. To demonstrate translational relevance, cellular senescence was studied in human stenotic kidneys. RESULTS: Using intraperitoneal AP20187 injections starting 1, 2, or 4 weeks after RAS, selective clearance of cells highly expressing p16Ink4a attenuated cellular senescence and improved stenotic-kidney function; however, starting treatment immediately after RAS induction was unsuccessful. Broader clearance of senescent cells, using the oral senolytic combination dasatinib and quercetin, in C57BL/6 RAS mice was more effective in clearing cells positive for p21 (Cdkn1a) and alleviating renal dysfunction and damage. Unbiased, single-cell RNA sequencing in freshly dissociated cells from healthy and stenotic mouse kidneys identified stenotic-kidney epithelial cells undergoing both mesenchymal transition and senescence. As in mice, injured human stenotic kidneys exhibited cellular senescence, suggesting this process is conserved. CONCLUSIONS: Maladaptive tubular cell senescence, involving upregulated p16 (Cdkn2a), p19 (Cdkn2d), and p21 (Cdkn1a) expression, is associated with renal dysfunction and injury in chronic ischemia. These findings support development of senolytic strategies to delay chronic ischemic renal 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.

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.

Increased cellular senescence in the murine and human stenotic kidney: Effect of mesenchymal stem cells.

Cell stress may give rise to insuperable growth arrest, which is defined as cellular senescence. Stenotic kidney (STK) ischemia and injury induced by renal artery stenosis (RAS) may be associated with cellular senescence. Mesenchymal stem cells (MSCs) decrease some forms of STK injury, but their ability to reverse senescence in RAS remains unknown. We hypothesized that RAS evokes STK senescence, which would be ameliorated by MSCs. Mice were studied after 4 weeks of RAS, RAS treated with adipose tissue-derived MSCs 2 weeks earlier, or sham. STK senescence-associated ß-galactosidase (SA-ß-Gal) activity was measured. Protein and gene expression was used to assess senescence and the senescence-associated secretory phenotype (SASP), and staining for renal fibrosis, inflammation, and capillary density. In addition, senescence was assessed as p16+ and p21+ urinary exosomes in patients with renovascular hypertension (RVH) without or 3 months after autologous adipose tissue-derived MSC delivery, and in healthy volunteers (HV). In RAS mice, STK SA-ß-Gal activity increased, and senescence and SASP marker expression was markedly elevated. MSCs improved renal function, fibrosis, inflammation, and capillary density, and attenuated SA-ß-Gal activity, but most senescence and SASP levels remained unchanged. Congruently, in human RVH, p21+ urinary exosomes were elevated compared to HV, and only slightly improved by MSC, whereas p16+ exosomes remained unchanged. Therefore, RAS triggers renal senescence in both mice and human subjects. MSCs decrease renal injury, but only partly mitigate renal senescence. These observations support exploration of targeted senolytic therapy in RAS.

Transplanted senescent renal scattered tubular-like cells induce injury in the mouse kidney.

Cellular senescence, a permanent arrest of cell proliferation, is characterized by a senescence-associated secretory phenotype (SASP), which reinforces senescence and exerts noxious effects on adjacent cells. Recent studies have suggested that transplanting small numbers of senescent cells suffices to provoke tissue inflammation. We hypothesized that senescent cells can directly augment renal injury. Primary scattered tubular-like cells (STCs) acquired from pig kidneys were irradiated by 10 Gy of cesium radiation, and 3 wk later cells were characterized for levels of senescence and SASP markers. Control or senescent STCs were then prelabeled and injected (5 × 105 cells) into the aorta of C57BL/6J mice. Four weeks later, renal oxygenation was studied in vivo using 16.4-T magnetic resonance imaging and function by plasma creatinine level. Renal markers of SASP, fibrosis, and microvascular density were evaluated ex vivo. Per flow cytometry, irradiation induced senescence in 80-99% of STCs, which showed increased gene expression of senescence and SASP markers, senescence-associated ß-galactosidase staining, and cytokine levels (especially IL-6) secreted in conditioned medium. Four weeks after injection, cells were detected engrafted in the mouse kidneys with no evidence for rejection. Plasma creatinine and renal tissue hypoxia increased in senescent compared with control cells. Senescent kidneys were more fibrotic, with fewer CD31+ endothelial cells, and showed upregulation of IL-6 gene expression. Therefore, exogenously delivered senescent renal STCs directly injure healthy mouse kidneys. Additional studies are needed to determine the role of endogenous cellular senescence in the pathogenesis of kidney injury and evaluate the utility of senolytic therapy.

Mitochondrial Protection Partly Mitigates Kidney Cellular Senescence in Swine Atherosclerotic Renal Artery Stenosis.

BACKGROUND/AIMS: Atherosclerotic renal artery stenosis (ARAS) may cause kidney injury and mitochondrial dysfunction, which is linked to cellular senescence. Elamipretide, a mitochondria-targeted peptide, improves renal function in ARAS, but whether it alleviates senescence is unknown. We hypothesized that elamipretide would reduce senescence stenotic kidney (STK) in ARAS. METHODS: Domestic pigs were randomized to control and unilateral ARAS untreated or treated with subcutaneous elamipretide (5d/wk) for 4 weeks starting after 6 weeks of ARAS or sham (n=6 each). After completion of treatment, STK renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed in-vivo using multi-detector computed-tomography. Renal fibrosis and oxidative stress were analyzed in trichrome- and dihydroethidium-stained slides, respectively. Mitochondrial markers involved in the electrontransport chain (COX4, ATP/ADP ratio), biogenesis (PGC1α, PPARα), dynamics (MFN2, DRP1), and mitophagy (parkin, p62) were measured in the kidney using ELISA, western-blot, and immunohistochemistry. Cellular senescence (senescence-associated ß-galactosidase and heterochromatin foci, phosphorylated-H2AX, and p16/21/53) and senescence-associated secretory phenotype (SASP; PAI-1, MCP-1, TGFß, and TNFα) markers were studied by microscopy, quantitative reverse transcription-polymerase chain reaction, and western-blot. RESULTS: Blood pressure was elevated whereas STK-RBF and GFR were decreased in ARAS pigs, and tissue scarring was increased. ARAS induced STK cellular senescence and accumulated dysfunctional mitochondria, which were associated with cardiolipin loss, upregulated mitochondrial biogenesis, and defective mitophagy. Elamipretide normalized STK-RBF and GFR, alleviated fibrosis and oxidative stress, and restored mitochondrial cardiolipin, biogenesis, and mitophagy in ARAS, but did not change SASP markers, and attenuated only senescenceassociated ß-galactosidase activity and p53 gene expression. CONCLUSION: Mitochondrial protection improved renal function and fibrosis in the ARAS STK, but only partly mitigated cellular senescence. This finding suggests that mitochondrial dysfunction may not be a major determinant of cellular senescence in the early stage of ARAS.

Preserved endothelial progenitor cell angiogenic activity in African American essential hypertensive patients.

Background: African American (AA) subjects with essential hypertension (EH) have greater inflammation and cardiovascular complications than Caucasian EH. An impaired endogenous cellular repair system may exacerbate vascular injury in hypertension, yet whether these differ between AA EH and Caucasian EH remains unknown. Vascular repair by circulating endothelial progenitor cells (EPCs) is controlled by regulators of EPC mobilization, homing, adhesion and new vessel formation, but can be hindered by various cytokines. We hypothesized that EPC levels and function would be impaired in AA EH compared with Caucasian EH, in association with increased levels of inflammatory mediators and EPC regulators. Methods: CD34+/KDR+ EPCs were isolated from inferior vena cava and renal vein blood samples of AA EH and Caucasian EH patients (n = 18 each) and from peripheral veins of 17 healthy volunteers (HVs) and enumerated using fluorescence-activated cell sorting. Angiogenic function of late-outgrowth endothelial cells expanded from these samples for 3 weeks was tested in vitro. Levels of inflammatory mediators, angiogenic factors and EPC regulators were measured by Luminex. Results: EPC levels were decreased in both AA and Caucasian EH compared with HVs, whereas their late-outgrowth endothelial cell angiogenic function was comparable. Levels of several inflammatory mediators were elevated in AA EH compared with Caucasian EH and HVs. Contrarily, vascular endothelial growth factor and its receptor-2 were lower. EPC levels inversely correlated with blood pressure in all hypertensive patients and estimated glomerular filtration rate with inflammatory mediators only in AA EH. Conclusions: Despite lower EPC numbers, decreased vascular endothelial growth factor signaling and inflammation, EPC function is preserved in AA EH compared with Caucasian EH and HVs, suggesting compensatory mechanisms for vascular repair.

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.

Time-restricted feeding protects against cisplatin-induced acute kidney injury in mice.

Background: Time-restricted feeding (TRF), devoid of calorie restriction, is acknowledged for promoting metabolic health and mitigating various chronic metabolic diseases. While TRF exhibits widespread benefits across multiple tissues, there is limited exploration into its impact on kidney function. In this study, our aim was to investigate the potential ameliorative effects of TRF on kidney damage in a mouse model of cisplatin-induced acute kidney injury (AKI). Methods: Cisplatin-induced AKI was induced through intraperitoneal injection of cisplatin into C57BL/6 male mice. Mice undergoing TRF were provided unrestricted access to standard chow daily but were confined to an 8-hour feeding window during the dark cycle for 2 weeks before cisplatin injection. The mice were categorized into four groups: control, TRF, cisplatin, and TRF + cisplatin. Results: The tubular damage score and serum creatinine levels were significantly lower in the TRF + cisplatin group compared to the cisplatin group. The TRF + cisplatin group exhibited reduced expression of phosphorylated nuclear factor kappa B, inflammatory cytokines, and F4/80-positive macrophages compared to the cisplatin group. Furthermore, oxidative stress markers for DNA, protein, and lipid were markedly decreased in the TRF + cisplatin group compared to the cisplatin group. TUNEL-positive tubular cells, cleaved caspase-3 expression, and the Bax/Bcl-2 ratio in the TRF + cisplatin group were lower than those in the cisplatin group. Conclusion: TRF, without calorie restriction, effectively mitigated kidney damage by suppressing inflammatory reactions, oxidative stress, and tubular apoptosis in a mouse model of cisplatin-induced AKI. TRF holds promise as a novel dietary intervention for preventing cisplatin-induced AKI.

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.

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.

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.

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.

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.

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].

Relapse of minimal change disease following infection with the 2009 pandemic influenza (H1N1) virus.

We report a case of relapse of minimal change disease following infection with the influenza A (H1N1) virus responsible for the 2009 pandemic. A 22-year-old man who had been diagnosed with minimal change disease presented with systemic edema. He had achieved complete remission with an oral steroid (prednisolone 1 mg/kg/day) by the 17th day of administration. On the 27th day of prednisolone administration, he presented with a new onset of generalized edema after several days of productive coughing. His urine showed proteinuria (4+) with a protein/creatinine ratio (PCR) of 2852.1 mg/g. His nasal swab sample was positive for the 2009 pandemic influenza (H1N1) virus by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). He received oseltamivir (150 mg/day) for 5 days. A day after completing the oseltamivir therapy, his proteinuria returned to a normal range; urinalysis was negative for protein with PCR 79.2 mg/g. One month later, the patient remained normal with no proteinuria.