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Background Continuous renal replacement therapy (CRRT) has become the standard modality of renal replacement therapy (RRT) in critically ill patients. However, consensus is lacking regarding the criteria for discontinuing CRRT. Here we validated the usefulness of the prediction model for successful discontinuation of CRRT in a multicenter retrospective cohort. Methods One temporal cohort and four external cohorts included 1,517 patients with acute kidney injury who underwent CRRT for >2 days from 2018 to 2020. The model was composed of four variables: urine output, blood urea nitrogen, serum potassium, and mean arterial pressure. Successful discontinuation of CRRT was defined as the absence of an RRT requirement for 7 days thereafter. Results The area under the receiver operating characteristic curve (AUROC) was 0.74 (95% confidence interval, 0.71–0.76). The probabilities of successful discontinuation were approximately 17%, 35%, and 70% in the low-score, intermediate-score, and high-score groups, respectively. The model performance was good in four cohorts (AUROC, 0.73–0.75) but poor in one cohort (AUROC, 0.56). In one cohort with poor performance, attending physicians primarily controlled CRRT prescription and discontinuation, while in the other four cohorts, nephrologists determined all important steps in CRRT operation, including screening for CRRT discontinuation. Conclusion The overall performance of our prediction model using four simple variables for successful discontinuation of CRRT was good, except for one cohort where nephrologists did not actively engage in CRRT operation. These results suggest the need for active engagement of nephrologists and protocolized management for CRRT discontinuation.

Heart organoid (HO) technology has successfully overcome the limitations of two-dimensional (2D) disease modeling and drug testing, thereby emerging as a valuable tool in drug discovery for assessing toxicity and efficacy. However, its ability to distinguish drug responses among individuals remain unclear, which is crucial for developing predictive models. We addressed this gap by comparing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with human induced pluripotent stem cell-derived heart organoids (hiPSC-HOs) in the context of doxorubicin-induced cardiotoxicity (DIC). For this study, we utilized hiPSCs generated from breast cancer patients who had previously been treated with doxorubicin. By comparing groups with and without DIC, we examined various parameters, including cell viability, mRNA expression, protein expression and electrophysiological variations. The results of our analysis revealed significant differences between these groups, providing insights into hiPSC-HOs as a potential platform for testing differences in drug responses among patients.

Abstract Anemia is common in critically ill patients undergoing continuous renal replacement therapy (CRRT). We investigated the impact of anemia requiring red blood cell (RBC) transfusion or erythropoiesis-stimulating agents (ESAs) on patient outcomes after hospital discharge in critically ill patients with acute kidney injury (AKI) requiring CRRT. In this retrospective cohort study using the Health Insurance Review and Assessment database of South Korea, 10,923 adult patients who received CRRT for 3 days or more between 2010 and 2019 and discharged alive were included. Anemia was defined as the need for RBC transfusion or ESAs. Outcomes included cardiovascular events (CVEs) and all-cause mortality after discharge. The anemia group showed a tendency to be older with more females and had more comorbidities compared to the control group. Anemia was not associated with an increased risk of CVEs (adjusted hazard ratio [aHR]: 1.05; 95% confidence interval [CI]: 0.85–1.29), but was associated with an increased risk of all-cause mortality (aHR: 1.41; 95% CI 1.30–1.53). For critically ill patients with AKI requiring CRRT, anemia, defined as requirement for RBC transfusion or ESAs, may increase the long-term risk of all-cause mortality.

Background Diastolic dysfunction with left ventricular hypertrophy and myocardial fibrosis is an important characteristic of uremic cardiomyopathy in end-stage kidney disease (ESKD). Few studies explored the relationship between changes in diastolic dysfunction and the risk of mortality or cardiovascular outcome in patients with ESKD. We investigated the clinical impact of diastolic dysfunction and atrial fibrillation (AF) on patients starting hemodialysis (HD).Methods A total of 718 patients who started HD between 2010 and 2020 were included. We classified patients according to the pre- and post-HD diastolic dysfunction grades (DDG) evaluated by echocardiography. Patients with AF were classified separately. The primary outcome was a composite outcome of all-cause mortality and cardiac complication.Results The median age was 63 years, and 61.4% were male. Patients were divided into four groups based on pre-HD echocardiography findings. After initiating HD, the patients were classified according to changes in DDG and AF. Composite outcomes were significantly higher in the pre-HD AF groups. However, after adjusting for age and history of ischemic heart disease, pre-HD AF did not affect the composite outcomes. Patients with normal post-HD diastolic function had better outcomes than those with diastolic dysfunction or AF. Furthermore, the deterioration of diastolic dysfunction after HD was associated with an increased risk of composite outcomes.Conclusions The deterioration of diastolic dysfunction and newly development of AF after initiating HD were identified as risk factors for mortality and cardiac complications, supporting the clinical importance of the appropriate management of diastolic dysfunction and AF in patients with ESKD.

Abstract Excessive activation of poly (ADP-ribose) polymerase (PARP) contributes to ischemic acute kidney injury (AKI). PARP inhibition has been shown to be beneficial in renal ischemia–reperfusion injury (IRI) in the early phase, but its role in the repair process remains unclear. The effects of JPI-289, a novel PARP inhibitor, during the healing phase after renal IRI were investigated. IRI was performed on 9-week-old male C57BL/6 mice. Saline or JPI-289 100 mg/kg was intraperitoneally administered once at 24 h or additionally at 48 h after IRI. Hypoxic HK-2 cells were treated with JPI-289. Renal function and fibrosis extent were comparable between groups. JPI-289 treatment caused more prominent tubular atrophy and proinflammatory intrarenal leukocyte phenotypes and cytokines/chemokines changes at 12 weeks after unilateral IRI. JPI-289 treatment enhanced gene expressions associated with collagen formation, toll-like receptors, and the immune system in proximal tubules and endothelial cells after IRI. JPI-289 treatment at 3 or 6 h after hypoxia facilitated proliferation of hypoxic HK-2 cells, whereas further treatment after 24 h suppressed proliferation. Delayed inhibition of PARP after renal IRI did not facilitate the repair process during the early healing phase but rather may aggravate renal tubular atrophy during the late healing phase in ischemic AKI.

Induced pluripotent stem cell (iPSC)-derived cardiac organoids offer a versatile platform for personalized cardiac toxicity assessment, drug screening, disease modeling, and regenerative therapies. While previous image-based contractility analysis techniques allowed the assessment of contractility of two-dimensional cardiac models, they face limitations, including encountering high noise levels when applied to three-dimensional organoid models and requiring expensive equipment. Additionally, they offer fewer functional parameters compared to commercial software. To address these challenges, we developed an open-source, particle image velocimetry-based software (PIV-MyoMonitor) and demonstrated its capacity for accurate contractility analysis in both two- and three-dimensional cardiac models using standard lab equipment. Comparisons with four other open-source software programs highlighted the capability of PIV-MyoMonitor for more comprehensive quantitative analysis, providing 22 functional parameters and enhanced video outputs. We showcased its applicability in drug screening by characterizing the response of cardiac organoids to a known isotropic drug, isoprenaline. In sum, PIV-MyoMonitor enables reliable contractility assessment across various cardiac models without costly equipment or software. We believe this software will benefit a broader scientific community.

AbstractLeft ventricular assist device (LVAD) has been highlighted as a new treatment option in the end-stage heart failure (HF). Kidney outcome after LVAD in severe cardiorenal syndrome (CRS) patients requiring kidney replacement therapy (KRT) is unclear. We investigated the impact of preoperative KRT on kidney function and survival in LVAD patients with severe CRS. A total of 50 patients followed up for at least 1 year after LVAD implantation was analyzed. The primary outcomes were estimated glomerular filtration rate and survival rate. Patients were divided into two groups depending on in-hospital KRT before LVAD implantation: the control group (n = 33) and the KRT group (n = 17). Postoperative KRT was performed for 76.5% of patients in the KRT group, and all of them discontinued KRT before discharge. There were no statistically significant differences in the degree of eGFR decline in survivors according to preoperative KRT. Although there were no statistically significant differences in the degree of eGFR decline in survivors regardless of preoperative KRT, old age (β −0.94, p

Abstract It remains uncertain whether albuminuria can identify elderly patients with diabetes at a high risk of incident end-stage kidney disease (ESKD) or mortality. 3065 patients (aged ≥ 65 years) with type 2 diabetes were included. We examined the association between albuminuria stages (normoalbuminuria, A1; microalbuminuria, A2; and macroalbuminuria, A3) and the risk of incident ESKD and all-cause mortality for each age group (65–69, 70–74, and ≥ 75 years). A2 and A3 were observed in 25.5% and 9.4% of the subjects, respectively. For A1, A2, and A3, the probabilities of ESKD at 8 years were 1.0%, 6.3%, and 29.7% (P

Abstract Common etiologies between age-related macular degeneration (AMD) and kidney disease advocate a close link between AMD and end-stage renal disease (ESRD). However, the risk of ESRD in people with AMD was not reported. Here, we investigated the association between AMD and the risk of ESRD by using a nationwide, population-based cohort data in Korea. 4,206,862 participants aged 50 years or older were categorized by presence of AMD and visual disability. Risk of ESRD was the primary outcome. Cox regression hazard model was used to examine the hazard ratios (HRs) with adjustment for potential confounders. Stratified analyses by age, sex, baseline kidney function, and cardiometabolic comorbidities were performed. During the mean 9.95 years of follow-up, there were 21,759 incident ESRD events (0.52%). AMD was associated with 33% increased risk of ESRD (adjusted HR [aHR] 1.33, 95% confidence interval [CI] 1.24–1.44), and the risk was even higher when accompanied by visual disability (aHR 2.05, 95% CI 1.68–2.50) than when not (aHR 1.26, 95% CI 1.17–1.37). Age, baseline kidney function, and cardiometabolic comorbidities significantly interact between AMD and the risk of ESRD. Our findings have clinical implications on disease prevention and risk factor management of ESRD in patients with AMD.

Background Proteinuria is associated with poor allograft and patient survival in kidney transplant recipients. However, the clinical relevance of spot urine protein-to-creatinine ratio (PCR) or albumin-to-creatinine ratio (ACR) as predictors of renal outcomes during the early postoperative period following kidney transplantation (KT) has not been determined. Methods This single-center retrospective cohort study included 353 kidney transplant recipients who underwent KT between 2014 and 2017 and were followed up for more than 3 years. Among them, 186 and 167 recipients underwent living donor KT and deceased donor KT, respectively. The PCR and ACR were measured during the immediate postoperative period (within 7 days postoperatively), before discharge (2–3 weeks postoperatively), and 3–6 months postoperatively. Results The median age of the patients was 51 years (interquartile range, 43–59 years), and 62.9% were male. An immediate postoperative PCR of ≥1 mg/mg was associated with old age, diabetes mellitus, high systolic blood pressure, delayed graft function, and donor factors (deceased donor KT, old age, and high serum creatinine concentrations). The PCR and ACR 3 to 6 months posttransplant were inversely associated with the estimated glomerular filtration rate at 1 year posttransplant. Deceased donor KT recipients with immediate postoperative PCR of ≥3 mg/mg showed a greater incidence of delayed graft function and lower estimated glomerular filtration rate before discharge than those with immediate postoperative PCR of

IntroductionPost-donation renal outcomes are a crucial issue for living kidney donors considering young donors’ high life expectancy and elderly donors’ comorbidities that affect kidney function. We developed a prediction model for renal adaptation after living kidney donation using interpretable machine learning.MethodsThe study included 823 living kidney donors who underwent nephrectomy in 2009–2020. AutoScore, a machine learning-based score generator, was used to develop a prediction model. Fair and good renal adaptation were defined as post-donation estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73 m2 and ≥ 65% of the pre-donation values, respectively.ResultsThe mean age was 45.2 years; 51.6% were female. The model included pre-donation demographic and laboratory variables, GFR measured by diethylenetriamine pentaacetate scan, and computed tomography kidney volume/body weight of both kidneys and the remaining kidney. The areas under the receiver operating characteristic curve were 0.846 (95% confidence interval, 0.762–0.930) and 0.626 (0.541–0.712), while the areas under the precision-recall curve were 0.965 (0.944–0.978) and 0.709 (0.647–0.788) for fair and good renal adaptation, respectively. An interactive clinical decision support system was developed.1ConclusionThe prediction tool for post-donation renal adaptation showed good predictive capability and may help clinical decisions through an easy-to-use web-based application.

Abstract Low health-related quality of life (HRQOL) is associated with adverse outcomes in diabetic kidney disease (DKD) patients. We examined the modifiable factors associated with low HRQOL in these patients. We enrolled 141 DKD patients. HRQOL was assessed with the Short Form 36 (SF-36) questionnaire. Low HRQOL was defined as a score > one standard deviation below the mean. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS-D and HDAS-A, respectively). The patients’ median age was 65 years, and 73% were men. The prevalence rates of anxiety and depression were 8% (n = 11) and 17% (n = 24), respectively. Forty (28%) patients were identified as poor sleepers, and 40 (28%) had low physical activity levels. Anxiety, depression, and poor sleep quality were negatively correlated with SF-36 scores. Higher levels of physical activity and the estimated glomerular filtration rate (eGFR) were correlated with higher SF-36 scores, which indicated better health status. Higher depression scores (HADS-D scores) were associated with low HRQOL, independent of factors including age, sex, smoking status, comorbidities, eGFR, anemia, sleep quality, anxiety levels, and physical activity levels (odds ratio, 1.43; 95% confidence interval, 1.17–1.75). Among the clinical and psycho-physical factors, depression was a main determinant of low HRQOL in DKD patients.

Abstract Crescentic glomerulonephritis (CrGN) usually requires urgent immunosuppressive treatment. However, aggressive immunosuppressive treatment is often difficult because of the patients’ medical conditions or comorbidities. Prognostic markers including urinary cytokines/chemokines as noninvasive biomarkers were explored in CrGN patients. This prospective cohort study included 82 patients with biopsy-confirmed CrGN from 2002 to 2015 who were followed up for 5 years. Urine and serum cytokines/chemokines on the day of kidney biopsy were analyzed in 36 patients. The median age was 65 years and 47.6% were male. Baseline estimated glomerular filtration rate (eGFR) and interstitial fibrosis and tubular atrophy (IFTA) scores were identified as significant prognostic factors. Among patients with cytokines/chemokines measurement, increased IL-10 level was identified as an independent predictor of good prognosis, and increased levels of urinary MCP-1 and fractalkine tended to be associated with good prognosis after adjusting for baseline eGFR and IFTA score. However, semiquantitative analysis of intrarenal leukocytes did not show prognostic value predicting renal outcome or correlation with urinary cytokines/chemokines. This study supports the clinical importance of baseline eGFR and IFTA scores and suggests potential usefulness of urinary IL-10, MCP-1, and fractalkine as prognostic markers for predicting renal outcomes in patients with CrGN.

Ischemic acute kidney injury (AKI) is a common medical problem with significant mortality and morbidity, affecting a large number of patients globally. Ischemic AKI is associated with intrarenal inflammation as well as systemic inflammation; thus, the innate and adaptive immune systems are implicated in the pathogenesis of ischemic AKI. Among various intrarenal immune cells, T cells play major roles in the injury process and in the repair mechanism affecting AKI to chronic kidney disease transition. Importantly, T cells also participate in distant organ crosstalk during AKI, which affects the overall outcomes. Therefore, targeting T cell-mediated pathways and T cell-based therapies have therapeutic promise for ischemic AKI. Here, we review the major populations of kidney T cells and their roles in ischemic AKI.

Background Hyperthyroidism is associated with an increased glomerular filtration rate (GFR) in the hyperdynamic state, which is reversible after restoring euthyroidism. However, long-term follow-up of renal dysfunction in patients with hyperthyroidism has not been performed. Methods This was a retrospective cohort study using the Korean National Health Insurance database and biannual health checkup data. We included 41,778 Graves’ disease (GD) patients and 41,778 healthy controls, matched by age and sex. The incidences of end-stage renal disease (ESRD) were calculated in GD patients and controls. The cumulative dose and duration of antithyroid drugs (ATDs) were calculated for each patient and categorized into the highest, middle, and lowest tertiles. Results Among 41,778 GD patients, 55 ESRD cases occurred during 268,552 person-years of follow-up. Relative to the controls, regardless of smoking, drinking, or comorbidities, including chronic kidney disease, GD patients had a 47% lower risk of developing ESRD (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37 to 0.76). In particular, GD patients with a higher baseline GFR (≥90 mL/min/1.73 m2; HR, 0.33; 95% CI, 0.11 to 0.99), longer treatment duration (>33 months; HR, 0.31; 95% CI, 0.17 to 0.58) or higher cumulative dose (>16,463 mg; HR, 0.29; 95% CI, 0.15 to 0.57) of ATDs had a significantly reduced risk of ESRD. Conclusion This was the first epidemiological study on the effect of GD on ESRD, and we demonstrated that GD population had a reduced risk for developing ESRD.

Background/Aims The prevalence of simple renal cysts increases with age; however, they are occasionally found in adults aged < 40 years. This cross-sectional study evaluated the clinical significance of simple cysts in young adults, focusing on their associations with hematuria and albuminuria. Methods Adults aged < 40 years who underwent comprehensive medical examination between January 2005 and December 2013 were included. Simple renal cysts were identified by ultrasonography. Results Renal cysts were found in 276 of the 5,832 subjects (4.7%). Subjects with medullary sponge kidney (n = 1) or polycystic kidney disease (n = 5) were excluded. A single cyst and multiple cysts were found in 234 (4.0%) and 42 (0.7%) subjects, respectively. Age, high systolic blood pressure, and history of hypertension were independent risk factors for the presence of simple cysts. Simple cysts were not associated with an increased prevalence of hematuria. However, subjects with cysts showed a higher prevalence of albuminuria than those without (11.3% vs. 4.5%, p < 0.001). Multivariate analysis revealed that the existence of simple renal cysts was associated with a 2.30-fold increased prevalence of albuminuria (95% confidence interval, 1.512 to 3.519; p < 0.001) independent of other risk factors. Conclusions In young adults, the presence of simple renal cysts was independently associated with an increased prevalence of albuminuria. The causal relationship needs to be elucidated in further studies.

Abstract We investigated the clinical relevance of urinary cytokines/chemokines reflecting intrarenal immunologic micromilieu as prognostic markers and the optimal measurement timing after living donor kidney transplantation (LDKT). This prospective cohort study included 77 LDKT patients who were followed for ≥ 5 years. Patients were divided into control (n = 42) or acute rejection (AR, n = 35) group. Early AR was defined as AR occurring within 3 months. Serum and urine cytokines/chemokines were measured serially as follows: intraoperative, 8/24/72 h, 1 week, 3 months, and 1 year after LDKT. Intrarenal total leukocytes, T cells, and B cells were analyzed with immunohistochemistry followed by tissueFAXS. Urinary MCP-1 and fractalkine were also analyzed in a validation cohort. Urinary MCP-1 after one week was higher in the AR group. Urinary MCP-1, fractalkine, TNF-α, RANTES, and IL-6 after one week were significantly higher in the early AR group. Intrarenal total leukocytes and T cells were elevated in the AR group compared with the control group. Urinary fractalkine, MCP-1, and IL-10 showed positive correlation with intrarenal leukocyte infiltration. Post-KT 1 week urinary MCP-1 showed predictive value in the validation cohort. One-week post-KT urinary MCP-1 may be used as a noninvasive diagnostic marker for predicting AR after LDKT.

ObjectiveContinuous renal replacement therapy (CRRT) is the standard treatment for critically ill patients with acute kidney injury (AKI). Electrolyte disturbance such as hypokalemia or hypophosphatemia occurs paradoxically in patients undergoing CRRT due to high clearance. We developed a fluid management protocol for dialysate and replacement fluid that depends on serum electrolytes and focuses on potassium and phosphate levels to prevent electrolyte disturbance during CRRT. The impact of our new fluid protocol on electrolyte stability was evaluated.MethodsAdult patients who received CRRT between 2013 and 2017 were included. Patients treated 2 years before (2013–2014; pre-protocol group) and 2 years following development of the fluid protocol (2016–2017; protocol group) were compared. The primary outcomes were individual coefficient of variation (CV) and abnormal event rates of serum phosphate and potassium. Secondary outcomes were frequency of electrolyte replacement and incidence of cardiac arrhythmias. Individual CV and abnormal event rates for each electrolyte were analyzed using the Wilcoxon rank-sum test and Chi-square test with Yates’ continuity correction.ResultsA total of 1,448 patients was included. Both serum phosphate and potassium were higher in the protocol group. The CVs of serum phosphate (pre-protocol vs. protocol, 0.275 [0.207–0.358] vs. 0.229 [0.169–0.304], p < 0.01) and potassium (0.104 [0.081–0.135] vs. 0.085 [0.064–0.110], p < 0.01) were significantly lower in the protocol group. The abnormal event rates of serum phosphate (rate [95% CI], 0.410 [0.400–0.415] vs. 0.280 [0.273–0.286], p < 0.01) and potassium (0.205 [0.199–0.211] vs. 0.083 [0.079–0.087], p < 0.01) were also significantly lower in the protocol group.ConclusionThe protocolized management of fluid in CRRT effectively prevented hypophosphatemia and hypokalemia by inducing excellent stability of serum phosphate and potassium levels.

Background Current evidence suggests that the initiation of maintenance hemodialysis should not be based on a specific glomerular filtration rate (GFR) but on symptoms or signs attributable to kidney disease. However, it is difficult to predict the time point at which overt uremic syndrome develops in individuals. The estimated GFR is poorly correlated with occurrence of uremic symptoms, and some patients require dialysis at a higher eGFR than others. In this case, patients are more likely to be improperly prepared for dialysis. We investigated the predialysis characteristics of patients who require dialysis at a higher eGFR. Methods A total of 453 incident dialysis patients being monitored by a nephrologist from January 2013 to December 2018 were included. The predialysis characteristics when eGFR decreased to 20 mL/min/1.73 m2 were obtained. Results The mean age was 61 years, and 65.7% were men. Overall, the median eGFR at the first dialysis was 5.8 (interquartile range 4.6–7.3) mL/min/1.73 m2 and initiation of dialysis at the first quintile (≥7.8 mL/min/1.73 m2) was defined as ‘early initiation of dialysis’ Among the predialysis characteristics, heart failure (adjusted odds ratio 3.68; 95% confidence interval, 1.59–8.03), serum albumin 15 mg/mg (1.92, 1.16–3.18), and hyperuricemia (1.84; 1.05–3.23) were independent predictors of early initiation. Diabetes mellitus and the causes of kidney disease were not independent predictors of early initiation. The early initiation group was less likely to initiate dialysis with a permanent vascular access than the late initiation group. Conclusions For patients with heart failure, low serum albumin level, high BUN/Cr ratio, or hyperuricemia, clinicians can provide predialysis counseling in advance and consider early creation of vascular access.

Abstract Background Although urinary angiotensinogen (AGT) and renin reflect intrarenal renin-angiotensin system activity and are enhanced in proteinuric chronic kidney disease, the clinical value of urinary AGT and renin levels during antiproteinuric treatment has yet to be determined. We investigated the clinical usefulness of initial urinary AGT or renin to determine the antiproteinuric effects of angiotensin receptor blockers (ARBs). Methods This multicenter, prospective, single-arm study included 205 patients with overt proteinuria (urinary protein/creatinine ratio [uPCR] ≥ 1 mg/mg) enrolled between April 2009 and December 2011. All patients were treated with valsartan. The urinary AGT/creatinine ratio (uAGT/Cr) was measured at the baseline and 24 weeks, and the renin/creatinine ratio (uR/Cr) was measured at the baseline. Fifty-six patients were followed-up for 5 years. Results The mean age was 47.6 years and 51.2% were male. The mean uPCR was 2.32 mg/mg and the mean eGFR was 63.2 mL/min/1.73m2. Natural logarithms (ln) (uAGT/Cr), ln(uR/Cr), and diabetes mellitus were associated with proteinuria decrement (decrease in uPCR ≥1 mg/mg). Ln(uAGT/Cr) was an independent predictor for proteinuria decrement (OR 1.372, 95% CI, 1.068–1.762, P = 0.013). Among the 56 patients followed-up for 5 years, Δln(uAGT/Cr) at 24 weeks was an independent predictor for uPCR

Background : The diagnosis of latent tuberculosis infection (LTBI) in solid organ transplantation (SOT) patients under lifelong immunosuppression has profound effects on preoperative and postoperative management. Interferon-gamma release assay (IGRA) is widely used to screen LTBI before or after transplantation. Methods : We evaluated the effect of posttransplantation immunosuppression on IGRA and influencing factors by measuring interval change of QuantiFERON-TB Gold Plus (QFT-Plus) between pretransplantation (pre-QFT-Plus) and posttransplantation (post-QFT-Plus) state in 20 patients who previously had reactive IGRA but not taken LTBI treatment. Results : Eleven (55%) out of 20 pre-QFT-Plus reactive patients became nonreactive state in repeated QFT-Plus (post-QFT-Plus) at 194-413 days (median, 257 days) after transplantation (discordant group). Even in persistently reactive group (concordant group), interferon-gamma (IFN-γ) levels after transplantation were decreased about 34% and 36% of their pretransplantation levels for TB1 and TB2, respectively. The only significant factors that affect interval change of QFT-Plus between pre- and post-SOT status were the concentrations of IFN-γ in pre-QFT-Plus (6.93 vs. 0.44 IU/mL in TB1 and 7.33 vs. 0.71 IU/mL in TB2). Conclusions: The reactivity of QFT-Plus is significantly compromised by immunosuppressive therapy, which increase the risk of false negative, particularly in patients with low level of IGRA reactivity. Therefore, interpretation of IGRA under immunosuppressive treatment require a caution and eventually, more sensitive tuberculosis-specific cytokine markers might be needed.

Background : Previous randomized controlled trials of revascularization for atherosclerotic renal artery stenosis (ARAS) were not successful. We investigated the effects of percutaneous transluminal angioplasty with stent insertion (PTA/S) on kidney function and blood pressure (BP) control in patients with ARAS. Methods : From 2000 to 2017, 47 subjects who underwent PTA/S for ARAS were identified. A high-risk group was defined, composed of patients having one or more of the following clinical presentations: pulmonary edema, refractory hypertension, and rapid deterioration of kidney function. Subjects who met the criteria of ‘kidney function improvement’ or ‘hypertension improvement’ after PTA/S were classified as responders. Results : Twenty-one (44.7%) subjects were classified into the high-risk group. Two subjects (8.0%) in the low-risk group (n = 25) and 5 subjects (27.8%) in the high-risk group (n = 18) showed improvement in kidney function after PTA/S (P = 0.110). In patients with rapid decline of kidney function, estimated glomerular filtration rate improved from 28 (interquartile range [IQR], 10-45) mL/min/1.73 m2 to 41 (IQR, 16-67) mL/min/1.73 m2 at 4 months after PTA/S, although the difference was not significant (P = 0.084). Regarding BP control, 9 (36.0%) and 14 (77.8%) subjects showed improvement after PTA/S in the low- (n = 25) and high-risk (n = 18) groups, respectively (P = 0.007). In patients with refractory hypertension, the systolic BP dropped from 157 (IQR, 150-164) mmHg to 140 (IQR, 131-148) mmHg at 4 months after PTA/S (P = 0.005). Twenty-five subjects were defined as responders and comprised a significant proportion of the high-risk group (P = 0.004). Conclusion : PTA/S might improve BP control and kidney function in patients with ARAS presenting with high-risk clinical features. The optimal application of PTA/S should be based on individual assessment of the clinical significance of renal artery stenosis.

Abstract Background Although no specific treatment facilitates renal tubular regeneration in acute kidney injury (AKI), the rapid increase in aging populations with more comorbidities and advances in critical care management are expected to change the epidemiology of AKI. However, few recent studies dissected the current epidemiologic characteristics of critically ill patients with AKI. We investigated recent epidemiologic changes in severe AKI in critically ill patients. Methods All adult admissions to intensive care units (ICUs) in Korea from 2008 to 2015 were screened using the national health insurance review and assessment database, and 1,744,235 patients were included. Clinical characteristics and changes in AKI incidence and mortality rate were analyzed. Results The incidence of AKI increased from 7.4% in 2008 to 8.3% in 2015 (p for trend

Abstract Background Many studies have evaluated the usefulness of creatinine- (eGFRcr) and cystatin C-based estimated glomerular filtration rate (eGFRcys) at specific time points in predicting renal outcome. This study compared the performance of both eGFR changing slopes in identifying patients at high risk of end-stage renal disease (ESRD). Methods From 2012 to 2017, patients with more than three simultaneous measurements of serum creatinine and cystatin C for 1 year were identified. Rapid progression was defined as eGFR slope

Summary: The relationship between diabetes and endothelial dysfunction remains unclear, particularly the association with pathological activation of calpain, an intracellular cysteine protease. Here, we used human induced pluripotent stem cells-derived endothelial cells (iPSC-ECs) to investigate the effects of diabetes on vascular health. Our results indicate that iPSC-ECs exposed to hyperglycemia had impaired autophagy, increased mitochondria fragmentation, and was associated with increased calpain activity. In addition, hyperglycemic iPSC-ECs had increased susceptibility to cell death when subjected to a secondary insult—simulated ischemia-reperfusion injury (sIRI). Importantly, calpain inhibition restored autophagy and reduced mitochondrial fragmentation, concurrent with maintenance of ATP production, normalized reactive oxygen species levels and reduced susceptibility to sIRI. Using a human iPSC model of diabetic endotheliopathy, we demonstrated that restoration of autophagy and prevention of mitochondrial fragmentation via calpain inhibition improves vascular integrity. Our human iPSC-EC model thus represents a valuable platform to explore biological mechanisms and new treatments for diabetes-induced endothelial dysfunction. : In this article, Ong and colleagues used human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) as a novel disease modeling platform to study the effects of diabetes on vascular dysfunction and provided the cause for calpain inhibitors as an anti-diabetic and cardioprotective drug. Keywords: diabetes, endothelial dysfunction, iPSC, iPSC-ECs, calpain, autophagy, mitochondrial morphology, ischemia-reperfusion injury

Abstract Background The introduction of a continuous renal replacement therapy (CRRT) device into the extracorporeal membrane oxygenation (ECMO) circuit is widely used. However, excessive pressure transmitted to the CRRT device is a major disadvantage. We investigated the effects of using additional pressure control lines on the pressure and the lifespan of the CRRT circuit connected to the ECMO. Methods This is an observational study using prospectively collected data from consecutive patients receiving CRRT connected into the ECMO circuit at a university-affiliated, tertiary hospital from January 2013 to December 2016. The CRRT circuit was connected into the ECMO circuit through the Luer Lock connection without an additional pressure control line in 16 patients (9%, no line group), an additional pressure control line on the inlet line in 36 patients (23%, single line group), and additional pressure control lines on both the inlet and outlet lines in 118 patients (77%, double line group). The outcome measures of interest were compared among the three groups. Results The median access pressure was higher in the no line group compared to the groups. However, median filter pressure, effluent pressure, and return pressure were higher in the double line group compared to the other groups. There were no significant differences in platelets, lactate dehydrogenase, and plasma hemoglobin among the 3 groups over the time period studied. Median lifespan of the CRRT circuits in the double line group was 45.0 (29.0–63.7) hours, which was higher compared to 21.8 (11.6–31.8) hours in the no line group and 23.0 (15.0–34.6) hours in the single line group, respectively. In addition, in-hospital mortality was lower in the double line group (48.3%) compared to the no line group (68.8%) and the single line group (75.0%). Conclusions Additional tubing can be considered a simple and safe method for pressure control and lengthening circuit survival when connecting the CRRT device to the ECMO circuit.

The versatility of the intrarenal immunologic micromilieu through dietary modification and the subsequent effects on susceptibility to ischemic acute kidney injury (AKI) are unclear. We investigated the effects of high-salt (HS) or high-fat (HF) diet on intrarenal immunologic micromilieu and development of ischemic AKI using murine ischemic AKI and human kidney-2 (HK-2) cell hypoxia models. Four different diet regimens [control, HF, HS, and high-fat diet with high-salt (HF+HS)] were provided individually to groups of 9-week-old male C57BL/6 mice for 1 or 6 weeks. After a bilateral ischemia-reperfusion injury (BIRI) operation, mice were sacrificed on day 2 and renal injury was assessed with intrarenal leukocyte infiltration. Human kidney-2 cells were treated with NaCl or lipids. The HF diet increased body weight and total cholesterol, whereas the HF+HS did not. Although the HF or HS diet did not change total leukocyte infiltration at 6 weeks, the HF diet and HF+HS diet increased intrarenal CD8 T cells. Plasma cells increased in the HF and HS diet groups. The expression of proinflammatory cytokines including TNF-α, IFN-γ, MCP-1, and RANTES was increased by the HF or HS diet, and intrarenal VEGF decreased in the HS and HF+HS diet groups at 6 weeks. Deterioration of renal function following BIRI tended to be aggravated by the HF or HS diet. High NaCl concentration suppressed proliferation and enhanced expression of TLR-2 in hypoxic HK-2 cells. The HF or HS diet can enhance susceptibility to ischemic AKI by inducing proinflammatory changes to the intrarenal immunologic micromilieu.

Background: Cardiovascular complications are the leading cause of mortality in patients with chronic kidney disease (CKD). Uremic vasculopathy plays a crucial role in facilitating the progression of cardiovascular complications in advanced CKD. However, the improvement of conventional research methods could provide further insights into CKD.Objectives: In this study, we aimed to develop a novel model of uremic vasculopathy as a potential drug screening system.Methods and Results: The effects of uremic serum and different combinations of uremic toxins on induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) of a normal control and a CKD patient were investigated using several functional assays. We found that a mixture of uremic toxins composed of high urea, creatinine, uric acid, and indoxyl sulfate exerted deleterious effects on normal control iPSC-ECs that were comparable to uremic serum by increasing reactive oxygen species and apoptosis, as well as suppression of tube formation. Additional characterization revealed a potential involvement of dysregulated TGF-β signaling as treatment with either losartan or TGF-β inhibitors led to the attenuation of adverse effects induced by uremic toxins. Importantly, impaired wound healing potential seen in CKD patient-specific iPSC-ECs was rescued by treatment with losartan and TGF-β inhibitors.Conclusion: Our study demonstrated that simplified uremic toxin mixtures can simulate the uremic micromilieu reproducibly and CKD patient-specific iPSC-ECs can potentially recapitulate susceptibility to uremic vasculopathy. This novel model of uremic vasculopathy may provide a new research tool as a drug screening system.

Intrarenal robust inflammatory response following ischemia-reperfusion injury (IRI) is a major factor in the pathogenesis of renal injury in ischemic acute kidney injury (AKI). Although numerous studies have investigated various agents of immune modulation or suppression for ischemic AKI, few showed reproducible effects. We hypothesized that poly (ADP-ribose) polymerase (PARP) inhibitor may favorably change post-ischemic intrarenal immunologic micromilieu by reducing damage-associated molecular pattern (DAMP) signals and improve renal outcome in ischemic AKI. The effects of JPI-289 (a PARP inhibitor) on early renal injury in a murine IRI model and hypoxic HK-2 cell model were investigated. Bilateral IRI surgery was performed in three groups of 9-week-old male C57BL/6 mice (control, JPI-289 50 mg/kg, and JPI-289 100 mg/kg; n = 9–10 in each group). Saline or JPI-289 was intraperitoneally injected. Renal function deterioration was significantly attenuated in the JPI-289 treatment groups in a dose-dependent manner. Inflammatory cell infiltration and proinflammatory cytokine/chemokine expressions in the post-ischemic kidneys were also attenuated by JPI-289 treatment. JPI-289 treatment at 0.5 and 0.75 μg/ml facilitated the proliferation of hypoxic HK-2 cells. PARP inhibition with JPI-289 treatment showed favorable effects in ischemic AKI by attenuating intrarenal inflammatory cascade in a murine model and facilitating proliferation of hypoxic HK-2 cells.

Abstract Background Despite aggressive application of continuous renal replacement therapy (CRRT) in critically ill patients with acute kidney injury (AKI), there is no consensus on diuretic therapy when discontinuation of CRRT is attempted. The effect of diuretics on discontinuation of CRRT in critically ill patients was evaluated. Methods This retrospective cohort study enrolled 1176 adult patients who survived for more than 3 days after discontinuing CRRT between 2009 and 2014. Patients were categorized depending on the re-initiation of renal replacement therapy within 3 days after discontinuing CRRT or use of diuretics. Changes in urine output (UO) and renal function after discontinuing CRRT were outcomes. Predictive factors for successful discontinuation of CRRT were also analyzed. Results The CRRT discontinuation group had a shorter duration of CRRT, more frequent use of diuretics after discontinuing CRRT, and greater UO on the day before CRRT discontinuation [day minus 1 (day − 1)]. The diuretics group had greater increases in UO and serum creatinine elevation after discontinuing CRRT. In the CRRT discontinuation group, continuous infusion of furosemide tended to increase UO more effectively. Multivariable regression analysis identified high day − 1 UO and use of diuretics as significant predictors of successful discontinuation of CRRT. Day − 1 UO of 125 mL/day was the cutoff value for predicting successful discontinuation of CRRT in oliguric patients treated with diuretics following CRRT. Conclusions Day − 1 UO and aggressive diuretic therapy were associated with successful CRRT discontinuation. Diuretic therapy may be helpful when attempting CRRT discontinuation in critically ill patients with AKI, by inducing a favorable fluid balance, especially in oliguric patients.

Abstract This study aimed to investigate the association of nonalcoholic fatty liver disease (NAFLD) and its severity with the decline in kidney function in patients with chronic kidney disease (CKD). We conducted a cohort study of 1,525 CKD patients who underwent repeated health check-up examinations from January 2003 through December 2013. NAFLD was diagnosed by ultrasonography and its severity was assessed by the NAFLD fibrosis score. At baseline, the prevalence of NAFLD was 40.9%, and the mean estimated glomerular filtration rate (eGFR) was 59.1 ml/min/1.73 m2. The average follow-up was 6.5 years. The age- and sex-adjusted decline in eGFR was greater in patients with NAFLD (−0.79% per year, 95% CI −1.31%, −0.27%) compared to those without it (0.30%, 95% CI −0.14%, 0.76%; p = 0.002). In multivariable adjusted models, the average difference in annual percent change in decline in eGFR comparing patients with NAFLD to those without NAFLD was −1.06% (−1.73%, −0.38%; p = 0.002). The decline in eGFR associated with NAFLD was greater in patients with higher NAFLD fibrosis score, in those with proteinuria or with low eGFR at baseline (

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Renal artery stenosis (RAS) is commonly presented with hypertension and chronic kidney disease. We report a rare case of RAS occurring in a 78-year-old man who presented with nephrotic-range proteinuria. Renal biopsy on the left side was performed, and results showed mesangiopathic glomerulonephritis, which was not compatible with the cause of nephrotic-range proteinuria. Proteinuria was decreased by angiotensin receptor blocker, but azotemia was aggravated. Therefore, angiotensin receptor blocker was discontinued inevitably and thorough evaluation for the possibility of RAS was performed. Computed tomography angiography revealed significant RAS on the left side and a renal artery stent was inserted. After stenting, aortic dissection developed and progressed despite tight control of blood pressure. After inserting another stent graft through the true lumen of the left renal artery, the patient's renal function and proteinuria improved markedly.

Warfarin skin necrosis (WSN) is an infrequent complication of warfarin treatment and is characterized by painful ulcerative skin lesions that appear a few days after the start of warfarin treatment. Calciphylaxis also appears as painful skin lesions caused by tissue injury resulting from localized ischemia caused by calcification of small- to medium-sized vessels in patients with end-stage renal disease. We report on a patient who presented with painful skin ulcers on the lower extremities after the administration of warfarin after a valve operation. Calciphylaxis was considered first because of the host factors; eventually, the skin lesions were diagnosed as WSN by biopsy. The skin lesions improved after warfarin discontinuation and short-term steroid therapy. Most patients with end-stage renal disease have some form of cardiovascular disease and some require temporary or continual warfarin treatment. It is important to differentiate between WSN and calciphylaxis in patients with painful skin lesions.

Background: Advances in immunosuppression after kidney transplantation have decreased the influence of early acute rejection (EAR) on graft survival. Several studies have suggested that late acute rejection (LAR) has a poorer effect on long-term graft survival than EAR. We investigated whether the timing of acute rejection (AR) influences graft survival, and analyzed the risk factors for EAR and LAR. Methods: We performed a retrospective cohort study involving 709 patients who underwent kidney transplantation between 2000 and 2009 at the Samsung Medical Center, Seoul, Korea. Patients were divided into three groups: no AR, EAR, and LAR. EAR and LAR were defined as rejection before 1 year and after 1 year, respectively. Differences in graft survival between the three groups and risk factors of graft failure were analyzed. Results: Of the 709 patients, 198 (30%) had biopsy-proven AR [EAR=152 patients (77%); LAR=46 patients (23%)]. A total of 65 transplants were lost. The 5-year graft survival rates were 97%, 89%, and 85% for patients with no AR, EAR, and LAR, respectively. These differences were significant (P

Idiopathic membranous nephropathy is a common cause of nephrotic syndrome, and has been reported as a cause of idiopathic primary glomerulonephropathy in up to 90% of patients. However, the treatment options remain controversial. We report two cases of idiopathic membranous nephropathy that were treated with rituximab. A 54-year-old man and a 64-year old man were admitted for rituximab therapy. They had previously been treated with combinations of immunosuppressive agents including cyclophosphamide, cyclosporine, mycophenolate, and steroids. However, the patients' heavy proteinuria was not resolved. Both patients received rituximab therapy, 2 weeks apart. After several months of follow-up and a second round of rituximab treatment for each patient, their proteinuria decreased and partial remission of disease was achieved in both patients.

Colchicine is a relatively safe medication that is widely used for both prevention and treatment of gout attack. However, serious adverse events, including myoneuropathy and multiorgan failure, have been reported. We report a case of colchicine-induced myoneuropathy in a female kidney transplant recipient who had been taking cyclosporine. She developed gastrointestinal discomfort and paresthesia 5 days after the initiation of colchicine. She showed signs of myoneuropathy, and hepatic and renal injury. Colchicine toxicity was suspected, and colchicine was discontinued. Her symptoms and laboratory findings improved gradually. Literature was reviewed for previous reports of colchicine-induced myoneuropathy in solid organ transplant recipients.

A 48-year-old man presented with acute right flank pain. A computed tomography scan revealed right renal infarction. Because he had no thrombosis in the renal vessels and no clear embolic source, a further examination was performed to find the cause of the renal infarction. On transesophageal echocardiography, a right-to-left shunt during the Valsalva maneuver established a diagnosis of patent foramen ovale. This is a case of paradoxical embolism through a PFO leading to renal infarction.

Background: The purpose of this study was to evaluate the incidence of contrast-induced nephropathy (CIN), and the effect of intravenous albumin for prophylaxis of CIN in patients with liver cirrhosis (LC) and chronic kidney disease (CKD). Methods: We conducted a retrospective study of 81 subjects with LC and CKD (estimated glomerular filtration rate (eGFR)

The manifestation of infective endocarditis often resembles vasculitis. Approximately one in five infective endocarditis cases are referred initially to a nephrologist because of abnormal renal function or abnormal urinalysis; therefore, infection should be ruled out before diagnosing vasculitis.