Sterile kidney tissue injury induces neutrophil swarming in lung alveolar capillaries.

Sterile tissue injury, such as by acute kidney injury, is common in the clinic and frequently associated with respiratory compromise and hypoxemia. We previously described signaling components released by the injured kidney that drive a remote inflammatory response in the lung. How this caused the resultant hypoxemia remained unclear. Here, we report that sterile kidney tissue injury induces rapid intravascular "neutrophil train" formation in lung capillaries, a novel form of neutrophil swarming. Rapid swarming is enhanced by decreased deformability of circulating neutrophils that impedes their lung capillary passage. Classical lung monocytes are required for neutrophil train formation and release CXCL2 to attract and retain stiffened neutrophils in lung capillaries which reduces capillary perfusion. We thus discovered a novel feature of kidney-lung crosstalk after sterile kidney tissue injury, capillary perfusion deficits that lead to reduced oxygenation despite proper alveolar function and ventilation, unlike in infectious inflammatory lung processes, such as bacterial pneumonia.

Serum myostatin at dialysis initiation may predict 1-year mortality and hospitalization.

OBJECTIVE: Myostatin, which is known as a negative skeleton muscle regulator, is associated with mortality in maintenance hemodialysis patients. However, the significance of serum myostatin concentrations at dialysis initiation has not been established. We investigated the relation between serum myostatin concentrations and mortality or hospitalization within one year in incident dialysis patients. METHODS: After a patient initiating hemodialysis or peritoneal dialysis during 2016-2018 was enrolled, the patient's serum myostatin at dialysis initiation was measured. Composite outcomes comprising mortality and hospitalization within 1 year after dialysis initiation were compared between two groups divided according to myostatin levels. The Cox proportional hazards model was used to assess significant relations between myostatin and outcomes. RESULTS: This study examined 104 incident dialysis patients with mean age of 65.5±14.0 (68% male). Kaplan-Meier analyses indicated the 1-year hospitalization-free and survival rate as significantly lower in the lower myostatin group than in the higher myostatin group (p = .0020). Cox proportional hazards regression analyses revealed that the value of myostatin logarithm at dialysis initiation was inversely associated with the occurrence of a composite outcome, independently of age (hazard ratio 0.16, 95% confidence interval 0.05-0.57). Receiver operating characteristic (ROC) analysis showed the area under the curve of serum myostatin for predicting death or hospitalization within 1 year as higher than those of clinical indices of nutritional disturbance and frailty. CONCLUSION: Serum myostatin concentration at dialysis initiation is inversely associated with adverse outcomes in these dialysis-initiated patients.

Interorgan communication networks in the kidney-lung axis.

The homeostasis and health of an organism depend on the coordinated interaction of specialized organs, which is regulated by interorgan communication networks of circulating soluble molecules and neuronal connections. Many diseases that seemingly affect one primary organ are really multiorgan diseases, with substantial secondary remote organ complications that underlie a large part of their morbidity and mortality. Acute kidney injury (AKI) frequently occurs in critically ill patients with multiorgan failure and is associated with high mortality, particularly when it occurs together with respiratory failure. Inflammatory lung lesions in patients with kidney failure that could be distinguished from pulmonary oedema due to volume overload were first reported in the 1930s, but have been largely overlooked in clinical settings. A series of studies over the past two decades have elucidated acute and chronic kidney-lung and lung-kidney interorgan communication networks involving various circulating inflammatory cytokines and chemokines, metabolites, uraemic toxins, immune cells and neuro-immune pathways. Further investigations are warranted to understand these clinical entities of high morbidity and mortality, and to develop effective treatments.

Solute Clearance Evaluation and Filter Clotting Prediction in Continuous Renal Replacement Therapy.

Unexpected filter clotting is a major problem in continuous renal replacement therapy (CRRT). Reduced solute clearance is observed prior to filter clotting. This single-center, retrospective, observational study aimed to determine whether reduced solute clearance of low- and medium-molecular-weight molecules in CRRT can predict filter clotting. Solute clearances of urea and myoglobin (Mb) were measured at 24 h after initiation of continuous hemodiafiltration (CHDF). Clearance per flow (CL/F) was calculated. The primary outcome was clotting of the filter in the subsequent 24 h, and 775 CHDF treatments conducted on 230 patients for at least 24 consecutive hours in our ICU were analyzed. Filter clotting was observed in 127 treatments involving 39 patients. Urea and Mb CL/F at 24 h were significantly lower in the patients who experienced clotting. Further analysis was limited to the first CHDF treatment of each patient to adjust for confounding factors. Multivariate logistic regression analysis revealed that both urea CL/F < 94% and Mb CL/F < 64% were significant predictors of clotting within the next 24 h. Lower urea and Mb CL/F measured at 24 h after CRRT initiation were associated with filter clotting in the next 24 h. Further study is necessary to ascertain whether measurement of urea and MB CL/F will help with avoiding unexpected filter clotting.

Different Roles of Functional and Structural Renal Markers Measured at Discontinuation of Renal Replacement Therapy for Acute Kidney Injury.

INTRODUCTION: Severe acute kidney injury (AKI) requiring renal replacement therapy (RRT) has been associated with an unacceptably high mortality of 50% or more. Successful discontinuation of RRT is thought to be linked to better outcomes. Although functional and structural renal markers have been evaluated in AKI, little is known about their roles in predicting outcomes at the time of RRT discontinuation. METHODS: In this prospective single-center cohort study, we analyzed patients who received continuous RRT (CRRT) for AKI between August 2016 and March 2018 in the intensive care unit of the University of Tokyo Hospital (Tokyo, Japan). Clinical parameters and urine samples were obtained at CRRT discontinuation. Successful CRRT discontinuation was defined as neither resuming CRRT for 48 h nor receiving intermittent hemodialysis for 7 days from the CRRT termination. Major adverse kidney events (MAKEs) were defined as death, requirement for dialysis, or a decrease in the estimated glomerular filtration rate (eGFR) of more than 25% from the baseline at day 90. RESULTS: Of 73 patients, who received CRRT for AKI, 59 successfully discontinued CRRT and 14 could not. Kinetic eGFR, urine volume, urinary neutrophil gelatinase-associated lipocalin (NGAL), and urinary L-type fatty acid binding protein were predictive for CRRT discontinuation. Of these factors, urine volume had the highest area under the curve (AUC) 0.91 with 95% confidence interval [0.80-0.96] for successful CRRT discontinuation. For predicting MAKEs at day 90, the urinary NGAL showed the highest AUC 0.76 [0.62-0.86], whereas kinetic eGFR and urine volume failed to show statistical significance (AUC 0.49 [0.35-0.63] and AUC 0.59 [0.44-0.73], respectively). CONCLUSIONS: Our prospective study confirmed that urine volume, a functional renal marker, predicted successful discontinuation of RRT and that urinary NGAL, a structural renal marker, predicted long-term renal outcomes. These observations suggest that the functional and structural renal makers play different roles in predicting the outcomes of severe AKI requiring RRT.

Acute Kidney Injury-Induced Circulating TNFR1/2 Elevations Correlate with Persistent Kidney Injury and Progression to Fibrosis.

Elevated levels of circulating tumor necrosis factor receptors 1 and 2 (cTNFR1/2) predict chronic kidney disease (CKD) progression; however, the mechanisms of their release remain unknown. Whether acute kidney injury (AKI) drives cTNFR1/2 elevations and whether they predict disease outcomes after AKI remain unknown. In this study, we used AKI patient serum and urine samples, mouse models of kidney injury (ischemic, obstructive, and toxic), and progression to fibrosis, nephrectomy, and related single-cell RNA-sequencing datasets to experimentally test the role of kidney injury on cTNFR1/2 levels. We show that TNFR1/2 serum and urine levels are highly elevated in all of the mouse models of kidney injury tested, beginning within one hour post injury, and correlate with its severity. Consistent with this, serum and urine TNFR1/2 levels are increased in AKI patients and correlate with the severity of kidney failure. Kidney tissue expression of TNFR1/2 after AKI is only slightly increased and bilateral nephrectomies lead to strong cTNFR1/2 elevations, suggesting the release of these receptors by extrarenal sources. The injection of the uremic toxin indoxyl sulfate in healthy mice induces moderate cTNFR1/2 elevations. Moreover, TNF neutralization does not affect early cTNFR1/2 elevations after AKI. These data suggest that cTNFR1/2 levels in AKI do not reflect injury-induced TNF activity, but rather a rapid response to loss of kidney function and uremia. In contrast to traditional disease biomarkers, such as serum creatinine or BUN, cTNFR1/2 levels remain elevated for weeks after severe kidney injury. At these later timepoints, cTNFR1/2 levels positively correlate with remaining kidney injury. During the AKI-to-CKD transition, elevations of TNFR1/2 kidney expression and of cTNFR2 levels correlate with kidney fibrosis levels. In conclusion, our data demonstrate that kidney injury drives acute increases in cTNFR1/2 serum levels, which negatively correlate with kidney function. Sustained TNFR1/2 elevations after kidney injury during AKI-to-CKD transition reflect persistent tissue injury and progression to kidney fibrosis.

BENEFIT OF HIGHER BLOOD PRESSURE TARGET IN SEVERE ACUTE KIDNEY INJURY TREATED BY CONTINUOUS RENAL REPLACEMENT THERAPY.

ABSTRACT: Introduction : The optimal target of mean arterial pressure (MAP) during continuous renal replacement therapy (CRRT) is unknown. Method : We retrospectively collected the hourly MAP data in acute kidney injury patients requiring CRRT who admitted to the intensive care unit in the University of Tokyo hospital during 2011-2019. Patients who died within 48 h of CRRT start and whose average value of hourly MAPs during the first 48 h was <65 mm Hg were excluded. When the average value of MAP was ≤75 mm Hg or >75 mm Hg, patients were allocated to the low or high target group. We estimated the effect of MAP on mortality and RRT independence at 90 days, using multivariable the Cox regression model and Fine and Gray model. Result : Of the 275 patients we analyzed, 95 patients were in the low group. There are no differences in sex, baseline kidney function, and disease severity. At 90 days, the low target group had higher mortality with 38 deaths (40.0%) compared with 57 deaths (31.7%) in the high target group ( P < 0.05). The adjusted hazard ratio of the low target group (≤75 mm Hg) for mortality was 1.72 (95% CI, 1.08-2.74). In addition, the low target group had a lower rate of RRT independence, with 60 patients (63.2%) compared with 136 patients (75.6%) in the high target group ( P < 0.05). The multivariable analysis revealed that the adjusted hazard ratio of the low target group for RRT independence was 0.74 (95% CI, 0.54-1.01). Conclusion : This study found the association with low MAP and mortality. The association with low MAP and delayed renal recovery was not revealed.

HMGB1 Is a Prognostic Factor for Mortality in Acute Kidney Injury Requiring Renal Replacement Therapy.

INSTRUCTION: High mobility group box 1 (HMGB1) is a pro-inflammatory cytokine that reportedly causes kidney injury and other organ damage in rodent acute kidney injury (AKI) models. However, it remains unclear whether HMGB1 is associated with clinical AKI and related outcomes. This study aimed to evaluate the association with HMGB1 and prognosis of AKI requiring continuous renal replacement therapy (CRRT). METHODS: AKI patients treated with CRRT in our intensive care unit were enrolled consecutively during 2013-2016. Plasma HMGB1 was measured on initiation. Classic initiation was defined as presenting at least one of the following conventional indications: hyperkalemia (K ≥6.5 mEq/L), severe acidosis (pH <7.15), uremia (UN >100 mg/dL), and diuretics-resistant pulmonary edema. Early initiation was defined as presenting no conventional indications. The primary outcome was defined as 90-day mortality. RESULTS: A total of 177 AKI patients were enrolled in this study. HMGB1 was significantly associated with the primary outcome (hazard ratio, 1.06; 95% CI, 1.04-1.08). When the patients were divided into two-by-two groups by the timing of CRRT initiation and the HMBG1 cutoff value obtained by receiver operating curve (ROC) analysis, the high HMGB1 group (>10 ng/mL) with classic initiation was significantly associated with the primary outcome compared with the others, even after adjusting for other factors including the nonrenal serial organ failure assessment (SOFA) score. CONCLUSION: HMGB1 was associated with 90-day mortality in AKI patients requiring CRRT. Notably, the highest mortality was observed in the high HMGB1 group with classic initiation. These findings suggest that CRRT should be considered for AKI patients with high HMGB1, regardless of the conventional indications.

Urinary neutrophil gelatinase-associated lipocalin and plasma IL-6 in discontinuation of continuous venovenous hemodiafiltration for severe acute kidney injury: a multicenter prospective observational study.

BACKGROUND: Patients with severe acute kidney injury (AKI) who require continuous venovenous hemodiafiltration (CVVHDF) in intensive care unit (ICU) are at high mortality risk. Little is known about clinical biomarkers for risk prediction, optimal initiation, and optimal discontinuation of CVVHDF. METHODS: This prospective observational study was conducted in seven university-affiliated ICUs. For urinary neutrophil gelatinase-associated lipocalin (NGAL) and plasma IL-6 measurements, samples were collected at initiation, 24 h, 48 h after, and CVVHDF discontinuation in adult patients with severe AKI. The outcomes were deaths during CVVHDF and CVVHDF dependence. RESULTS: A total number of 133 patients were included. Twenty-eight patients died without CVVHDF discontinuation (CVVHDF nonsurvivors). Urinary NGAL and plasma IL-6 at the CVVHDF initiation were significantly higher in CVVHDF nonsurvivors than in survivors. Among 105 CVVHDF survivors, 70 patients were free from renal replacement therapy (RRT) or death in the next 7 days after discontinuation (success group), whereas 35 patients died or needed RRT again (failure group). Urinary NGAL at CVVHDF discontinuation was significantly lower in the success group (93.8 ng/ml vs. 999 ng/ml, p < 0.01), whereas no significant difference was observed in plasma IL-6 between the groups. Temporal elevations of urinary NGAL levels during the first 48 h since CVVHDF initiation were observed in CVVHDF nonsurvivors and those who failed in CVVHDF discontinuation. CONCLUSIONS: Urinary NGAL at CVVHDF initiation and discontinuation was associated with mortality and RRT dependence, respectively. The serial changes of urinary NGAL might also help predict the prognosis of patients with AKI on CVVHDF.

Application of urinary biomarkers for diagnosing acute kidney injury in critically ill patients without baseline renal function data.

PURPOSE: Estimating the baseline renal function of patients without prior creatinine measurement is crucial for diagnosing acute kidney injury (AKI). This study aimed to incorporate AKI biomarkers into a new AKI diagnosis rule when no premorbid baseline is available. METHODS: This prospective observational study was conducted in an adult intensive care unit (ICU). Urinary neutrophil gelatinase-associated lipocalin (NGAL) and L-type fatty acid-binding protein (L-FABP) were measured at ICU admission. An AKI diagnostic rule was composed by classification and regression tree (CART) analysis. RESULTS: A total of 243 patients were enrolled. In the development cohort, CART analysis composed a decision tree for AKI diagnosis selecting serum creatinine and urinary NGAL at ICU admission as predictors. In the validation cohort, the novel decision rule was superior to the imputation strategy based on Modification of Diet in Renal Disease (MDRD) equation regarding misclassification rate (13.0% vs. 29.6%, p = 0.002). Decision curve analysis demonstrated that the net benefit of the decision rule exceeded the MDRD approach in a threshold probability range of 25% and higher. CONCLUSIONS: The novel diagnostic rule incorporating serum creatinine and urinary NGAL at ICU admission showed superiority to the MDRD approach in AKI diagnosis without baseline renal function data.

TNF or EGFR inhibition equally block AKI-to-CKD transition: opportunities for etanercept treatment.

BACKGROUND: Inflammation is a key driver of the transition of acute kidney injury to progressive fibrosis and chronic kidney disease (AKI-to-CKD transition). Blocking a-disintegrin-and-metalloprotease-17 (ADAM17)-dependent ectodomain shedding, in particular of epidermal growth factor receptor (EGFR) ligands and of the type 1 inflammatory cytokine tumor necrosis factor (TNF), reduces pro-inflammatory and pro-fibrotic responses after ischemic AKI or unilateral ureteral obstruction (UUO), a classical fibrosis model. Metalloprotease or EGFR inhibition show significant undesirable side effects in humans. In retrospective studies anti-TNF biologics reduce the incidence and progression of CKD in humans. Whether TNF has a role in AKI-to-CKD transition and how TNF inhibition compares to EGFR inhibition is largely unknown. METHODS: Mice were subjected to bilateral renal ischemia-reperfusion injury or unilateral ureteral obstruction. Kidneys were analyzed by histology, immunohistochemistry, qPCR, western blot, mass cytometry, scRNA sequencing, and cytokine profiling. RESULTS: Here we show that TNF or EGFR inhibition reduce AKI-to-CKD transition and fibrosis equally by about 25%, while combination has no additional effect. EGFR inhibition reduced kidney TNF expression by about 50% largely by reducing accumulation of TNF expressing immune cells in the kidney early after AKI, while TNF inhibition did not affect EGFR activation or immune cell accumulation. Using scRNAseq data we show that TNF is predominantly expressed by immune cells in AKI but not in proximal tubule cells (PTC), and PTC-TNF knockout did not affect AKI-to-CKD transition in UUO. Thus, the anti-inflammatory and anti-fibrotic effects of the anti-TNF biologic etanercept in AKI-to-CKD transition rely on blocking TNF that is released from immune cells recruited or accumulating in response to PTC-EGFR signals. CONCLUSION: Short-term anti-TNF biologics during or after AKI could be helpful in the prevention of AKI-to-CKD transition.

Clinical frailty assessment might be associated with mortality in incident dialysis patients.

Frailty is associated with mortality in maintenance dialysis patients. For incident dialysis patients, we used the clinical frailty scale (CFS) to investigate frailty as related to mortality or hospitalization within 2 years. We retrospectively reviewed the medical records of patients initiating hemodialysis or peritoneal dialysis during 2016-2018. Based on those records, two dialysis nurses independently used a 9-point CFS (1 = "Very fit" to 9 = "Terminally ill") to assess each patient's frailty at dialysis initiation. Patients with a mean CFS value of 5 or higher were classified into the frail group. The 2-year survival rates or hospitalization-free rates after the initiation of dialysis were compared between the frail (mean CFS score ≥ 5) and non-frail (mean CFS score < 5) groups. The analysis included 155 incident dialysis patients with mean age of 66.7 ± 14.1 (71% male). Frailty was inferred for 39 (25%) patients at dialysis initiation. Kaplan-Meier analyses showed that the survival rate and hospitalization-free rate within 2 years were significantly lower in the frail group than in the non-frail group (p < 0.01). Cox proportional hazards regression analyses revealed the CFS score as associated with the occurrence of a composite outcome, independently of age (hazard ratio 1.34, 95% confidence interval 1.04-1.72). Frailty assessment based on clinical judgment using CFS might predict adverse outcomes in dialysis-initiated patients.

Plasma xanthine oxidoreductase is associated with carotid atherosclerosis in stable kidney transplant recipients.

AIM: Xanthine oxidoreductase (XOR) is known as an enzyme related to purine metabolism, catalysing the oxidation of hypoxanthine to xanthine and of xanthine to uric acid. We investigated the relationship between plasma XOR activity in stable kidney transplantation (KT) recipients and carotid artery lesions. METHODS: A total of 42 KT patients visiting our outpatient clinic on regular basis were recruited. Associations between plasma XOR activity and the existence of plaque in the common carotid artery (CCA) or internal carotid artery (ICA) and maximum intima-medial thickness (IMT) of CCA (max-CIMT) > 0.9 mm were examined using univariate and multivariate analyses. RESULTS: At blood sampling, the mean and SD patient age was 52.7 ± 13.8 years old. Plasma XOR(pmol/h/ml) activity was significantly higher in patients with CCA/ICA plaque or max-CIMT >0.9 mm than those without. [23.9 (11.8, 38.3) vs. 8.29 (6.67, 17.5), p < .01, 23.9 (16.9, 71.2) vs. 9.16 (6.67, 28.2), p = .01] Univariate and multivariate logistic regression analyses revealed age and plasma XOR activity as independent predictors of CCA/ICA plaque or max-CIMT >0.9 mm. Receiver operator characteristic curve analyses revealed that the cutoff value of plasma XOR activity for the diagnosis of CCA/ICA plaque or CCA-IMT > 0.9 mm was 16.3 pmol/h/ml. CONCLUSION: Plasma XOR activity is associated independently with atherosclerotic changes in the carotid artery of stable post-KT patients.

Prognostic significance of concentric left ventricular hypertrophy at peritoneal dialysis initiation.

BACKGROUND: Concentric left ventricular hypertrophy (cLVH) is a common left ventricular geometric pattern in patients undergoing maintenance dialysis, including peritoneal dialysis (PD). The relationship between cLVH at PD initiation and the prognosis of patients remains unclear, however. This study aimed to investigate the impact of cLVH at PD initiation on patient survival and major adverse cardiovascular events (MACE). METHODS: The retrospective cohort study included 131 patients who underwent echocardiography during the PD initiation period. Based on echocardiographic measurements, cLVH was defined as a condition with increased LV mass index and increased relative wall thickness. The relationship between cLVH and the prognosis was assessed. RESULTS: Concentric LVH was identified in 29 patients (22%) at PD initiation, and patient survival, MACE-free survival and PD continuation were significantly reduced in the cLVH group compared with the non-cLVH group. In the Cox regression analysis, cLVH was demonstrated as an independent risk factor of mortality (HR [95%CI]: 3.32 [1.13-9.70]) for all patients. For patients over 65 years old, cLVH was significantly associated with mortality and MACE (HR [95%CI]: 3.51 [1.06-11.58] and 2.97 [1.26-7.01], respectively). Serum albumin at PD initiation was independently correlated with cLVH. CONCLUSIONS: In our study, cLVH at PD initiation was independently associated with survival in all patients and with both survival and MACE in elderly patients. Evaluation of LV geometry at PD initiation might therefore help identify high-risk patients. Further studies involving larger numbers of patients are needed to confirm the findings from this study and clarify whether treatment interventions for factors such as nutrition status could ameliorate cLVH and improve patient outcomes.

Time until treatment initiation is associated with catheter survival in peritoneal dialysis-related peritonitis.

For peritonitis, a serious complication of peritoneal dialysis (PD), we investigated the relation between duration from the sign (PD effluent abnormalities) to treatment with appropriate antibiotics (ST time) and catheter removal. For 62 PD hospital patients, data of PD-related peritonitis (n = 109) were collected retrospectively. We examined ST time and PD catheter removal times using univariate and multivariate analyses. The catheter removal rate in the delayed ST time group (≥ 24 h) was higher than that in early ST time group (< 24 h) (38 vs. 16%, p = 0.02). Concomitant tunnel infection and delayed ST time were associated with catheter removal (OR [95% CI] 32.3 [3.15-329] and 3.52 [1.11-11.1]). Rates of catheter removal and re-development of peritonitis within 1 month after starting treatment were higher in the delayed ST time group (p = 0.02). PD duration at peritonitis and the first peritonitis episode were associated with delayed ST time (1.02 [1.00-1.04] and 3.42 [1.09-10.7]). Significant association was found between PD catheter removal and the start of treatment more than 24 h after appearance of abnormal effluent. Education for patients about prompt visitation at the onset of peritonitis with long PD duration might improve outcomes.

Catheter Diversion Procedure With Exit-Site Renewal Promotes Peritoneal Dialysis Catheter Survival.

INTRODUCTION: Catheter-related infections such as exit site infection (ESI) and tunnel infection (TI) are major causes of peritoneal dialysis (PD) discontinuation. For ESI/TI treatment, catheter diversion procedure (CDP) with exit-site renewal for catheter salvage presents an alternative to catheter removal. Nevertheless, CDP capability of improving PD catheter survival remains unclear. METHODS: We retrospectively reviewed our hospital patients who started PD during 2001-2019 (n=148): 33 treated for ESI/TI by CDP (CDP group) and 115 treated for ESI/TI using conservative therapy or none (non-CDP group). A "virtual discontinuation group" was designated for patients in the CDP group who had received PD catheter removal instead of CDP and who had stopped PD. Kaplan-Meier analysis and log-rank test PD were used for intergroup catheter survival comparison. Associations between clinical factors and PD discontinuation or death were examined using Cox proportional hazards regression analyses. RESULTS: For patients (76% male, mean age of 61.7±13.0 years), 40 CDP were performed for 33 CDP group patients. Infection-free rates at 30 and 90 days after CDP were, respectively, 90% and 67%. The CDP group PD catheter survival rate was significantly higher than that of virtual discontinuation group (P < .01) and higher than that of the non-CDP group (P = .03). Multivariate analysis revealed independent association of serum albumin concentration (hazard ratio 0.33, 95% confidence interval 0.17-0.67), PD+HD combination therapy (hazard ratio 0.29, 95% confidence interval 0.17-0.49), and CDP (hazard ratio 0.44, 95% confidence interval 0.24-0.80) with PD discontinuation or death. CONCLUSION: Results show that CDP may improve PD catheter survival as an effective and less-invasive surgical treatment for ESI/TI to avoid withdrawal of PD.

Acute Kidney Injury in Sepsis: Evidence From Asia.

Acute kidney injury (AKI) is one of the most frequent complications of sepsis. Because sepsis and AKI synergistically worsen the outcomes of critically ill patients, better therapeutics against septic AKI urgently are required. In addition to the complexity of disease mechanisms of both sepsis and AKI, there is substantial regional variation in clinical practice, which further hampers the development of new treatments for septic AKI. To overcome this problem, evidence accumulation is necessary for building the foundation for developing novel septic AKI treatments. This review provides a summary of updated evidence regarding septic AKI from Asian regions.

Hierarchical Clustering Analysis for Predicting 1-Year Mortality After Starting Hemodialysis.

INTRODUCTION: For patients with end-stage renal disease (ESRD), due to the heterogeneity of the population, appropriate risk assessment approaches and strategies for further follow-up remain scarce. We aimed to conduct a pilot study for better risk stratification, applying machine learning-based classification to patients with ESRD who newly started maintenance hemodialysis. METHODS: We prospectively studied 101 patients with ESRD, who were new to maintenance hemodialysis therapy, between August 2016 and March 2018. Baseline values of variables such as blood and urine tests were obtained before the initiation of hemodialysis. Agglomerative hierarchical clustering was conducted with the collected continuous data. The resulting clusters were followed up for the primary outcome of 1-year mortality, as analyzed by the Kaplan-Meier survival curve with log-rank test and the Cox proportional hazard model. RESULTS: The participants were divided into 3 clusters (cluster 1, n = 62; cluster 2, n = 15; cluster 3, n = 24) by hierarchical clustering, using 46 clinical variables. Patients in cluster 3 showed lower systolic blood pressures, and lower serum creatinine and urinary liver-type fatty acid-binding protein levels, before the initiation of hemodialysis. Consequently, cluster 3 was associated with the highest 1-year mortality in the study cohort (P < 0.001), and the difference was significant after adjustment for age and sex (hazard ratio: 10.2; 95% confidence interval: 2.94-46.8, cluster 1 as reference). CONCLUSION: In this proof-of-concept study, hierarchical clustering discovered a subgroup with a higher 1-year mortality at the initiation of hemodialysis. Applying machine learning-derived classification to patients with ESRD may contribute to better risk stratification.