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.

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.

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.

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.

Paralytic Ileus during Treatment of Pulmonary and Renal Tuberculosis in a Non-Human Immunodeficiency Virus Patient: An Unusual Presentation of Tuberculosis-immune Reconstitution Inflammatory Syndrome.

Paralytic ileus as tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) is extremely rare. We herein report a 44-year-old man with pulmonary and renal tuberculosis who developed paralytic ileus 14 days after starting antituberculosis therapy (ATT) despite an initial favorable response to ATT. Paralytic ileus was successfully managed with conservative care. He initially required hemodialysis because of obstructive uropathy due to renal tuberculosis, but he was able to withdraw from dialysis after placement of ureteral stents. TB-IRIS can affect organs other than the original sites of tuberculosis, and the combined use of steroids may be effective for its prevention and treatment.

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.

Decrease in Glycosaminoglycan with Aging in Normal Rat Articular Cartilage Is Greater in Females than in Males.

OBJECTIVE: Osteoarthritis (OA) is more prevalent in females. We hypothesized that changes in articular cartilage (AC) constituents with aging may cause differences. Herein, we aimed to compare the changes in AC constituents with aging in male and female normal rats. DESIGN: The glycosaminoglycan (GAG) and collagen (COL) contents of the AC in knee, hip, and shoulder joints of male and female rats were quantified and compared between age groups and sexes. RESULTS: The amount of GAG was decreased in multiple joints in both males and females with aging. In females, it had a significant decrease in all joints measured. The decrease in GAG with aging was more severe in females than in males. Even in young rats, the amount of knee joint GAG was significantly less in females than in males. The amount of COL in the AC was unchanged with aging in both sexes. CONCLUSIONS: The drastic GAG decrease with aging in female normal rats may explain the higher prevalence and more severe OA in females.

Postoperative outcomes of cancer surgery in patients with and without kidney failure with dialysis therapy: a matched-pair cohort study.

Background: The difference in outcomes of cancer surgery between patients with and without kidney failure with dialysis therapy (KFDT) remains uncertain. Methods: Using 2010-18 data in a national inpatient database in Japan, we identified patients who had undergone resection of colorectal, lung, gastric or breast cancer. We matched selected patient characteristics, type of cancer, surgical procedure and hospital of up to four patients without KFDT to each patient with KFDT. We assessed 30-day mortality and postoperative complications. Results: Through matching, we identified 2248 patients with KFDT (807 with colorectal, 579 with lung, 500 with gastric and 362 with breast cancer) and 8210 patients without KFDT (2851 with colorectal, 2216 with lung, 1756 with gastric and 1387 with breast cancer). Postoperative complications occurred in a higher proportion of patients with KFDT than of those without KFDT after colorectal {20.3% versus 14.6%; risk difference (RD): 5.7% [95% confidence interval (95% CI) 2.6%-8.8%]}, lung [18.0% versus 12.9%; RD: 5.1% (95% CI 1.6%-8.4%)], gastric [25.0% versus 13.2%; RD: 11.8% (95% CI 7.6%-16.2%)] and breast cancer surgery [7.5% versus 3.5%; RD: 3.9% (95% CI 1.1%-6.9%)]. Patients with KFDT had a higher 30-day mortality than those without KFDT after gastric cancer surgery [1.6% versus 0.3%; RD: 1.3% (95% CI 0.1%-2.3%)]. Heart failure and ischemic heart disease occurred more frequently in patients with KFDT. Conclusions: Patients with KFDT had higher rates of postoperative complications and 30-day mortality; however, RDs varied between cancer types. The higher rates of postoperative complications in patients with KFDT were mainly attributable to cardiovascular complications.

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.

Preexisting heart failure with reduced ejection fraction attenuates renal fibrosis after ischemia reperfusion via sympathetic activation.

Although chronic heart failure is clinically associated with acute kidney injury (AKI), the precise mechanism that connects kidney and heart remains unknown. Here, we elucidate the effect of pre-existing heart failure with reduced ejection fraction (HFrEF) on kidney via sympathetic activity, using the combining models of transverse aortic constriction (TAC) and unilateral renal ischemia reperfusion (IR). The evaluation of acute (24 h) and chronic (2 weeks) phases of renal injury following IR 8 weeks after TAC in C57BL/6 mice revealed that the development of renal fibrosis in chronic phase was significantly attenuated in TAC mice, but not in non-TAC mice, whereas no impact of pre-existing heart failure was observed in acute phase of renal IR. Expression of transforming growth factor-ß, monocyte chemoattractant protein-1, and macrophage infiltration were significantly reduced in TAC mice. Lastly, to investigate the effect of sympathetic nerve activity, we performed renal sympathetic denervation two days prior to renal IR, which abrogated attenuation of renal fibrosis in TAC mice. Collectively, we demonstrate the protective effect of pre-existing HFrEF on long-term renal ischemic injury. Renal sympathetic nerve may contribute to this protection; however, further studies are needed to fully clarify the comprehensive mechanisms associated with attenuated renal fibrosis and pre-existing HFrEF.

Peritoneal Dialysis-Related Peritonitis Caused by Streptococcus oralis.

A 77-year-old man developed peritoneal dialysis-related peritonitis caused by Streptococcus oralis, a rare pathogen causing the disease. The infection, which was not controlled by one-week intraperitoneal administration of cefazolin and ceftazidime, was cured only after switching to two-week intravenous administration of cefazolin and ceftazidime. The patient had no major dental disease or recent history of dental intervention. This case suggests that S. oralis might cause peritoneal dialysis-related peritonitis with persistent systemic inflammation via an extra-oral infection route. The clinical course is discussed along with a review of the literature.

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.

Evaluation of the performance, operability, and safety of Plasauto µ, a new type of machine for cell-free and concentrated ascites reinfusion therapy, in a postmarketing clinical study.

Cell-free and concentrated ascites reinfusion therapy (CART) is performed by collecting the ascites from the patient, followed by filtration and concentration. Thereafter, concentrated cell-free ascites is reinfused into the patient intravenously. The new type of machine, Plasauto µ, for managing the process of CART was launched onto the market. We have evaluated the machine through postmarketing clinical study in 17 patients with malignant ascites. The amounts of original and concentrated ascites were 3673 ± 1920 g and 439 ± 228 g, respectively. Recovery rates were acceptable regarding values of total protein, albumin, and IgG that were 55.6% ± 17.3%, 60.2% ± 20.8%, and 58.2% ± 20.5%, respectively. Recovery rates were positively associated with amounts of original ascites and negatively associated with total protein concentration. No adverse events related to the machine were observed. The new type of machine showed preferable performance in processing malignant ascites.

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.

Ultrafiltration volume by once-weekly hemodialysis is a predictor of technique survival of combination therapy with peritoneal dialysis and hemodialysis.

Overhydration is a major cause of technique failure of peritoneal dialysis (PD). Hence, we investigated the impact of ultrafiltration (UF) volume by once-weekly hemodialysis (HD), excess volume beyond their dry weight, on technique survival of PD and HD combination therapy (PD+HD). Forty-six anuric PD+HD patients were divided into three groups according to baseline UF volume by HD: low-UF (