JOURNAL TRANSCRIPT
Original Paper Blood Purif 2017;44:184–192 DOI: 10.1159/000476052
Received: February 23, 2017 Accepted: April 24, 2017 Published online: June 14, 2017
Associations of Polyethylenimine-Coated AN69ST Membrane in Continuous Renal Replacement Therapy with the Intensive Care Outcomes: Observations from a Claims Database from Japan Kent Doi b Masao Iwagami a Emiko Yoshida c Mark R. Marshall d a
London School of Hygiene and Tropical Medicine, London, England; b Department of Emergency and Critical Care Medicine, The University of Tokyo, and c Baxter Japan Ltd, Tokyo, Japan; d Baxter Healthcare (Asia) Pte Ltd, Auckland, New Zealand
Keywords Continuous renal replacement therapy · Acute kidney injury · Sepsis · Claims database · Hemofilter
Abstract Background/Aims: Polyethylenimine-coated polyacrylonitrile (AN69ST) membrane is expected to improve the outcomes of critically ill patients treated by continuous renal replacement therapy (CRRT). Methods: Using a Japanese health insurance claim database, we identified adult patients receiving CRRT in intensive care units (ICUs) from April 2014 to October 2015. We used a multivariable logistic regression model to assess in-hospital mortality and Fine and Gray’s proportional subhazards model to assess the ICU length of stay (ICU-LOS) accounting for the competing risks. Results: Of 2,469 ICU patients, 156 were treated by AN69ST membrane. Crude in-hospital mortality was 50.0% in the AN69ST group and 54.0% in the non-AN69ST group. Adjusted odds ratio (OR) of AN69ST membrane use for in-hospital mortality was 0.65 (95% CI 0.45–0.93). The use of AN69ST membrane was also independently associated with shorter ICU-LOS. Conclusion: This retrospective observational study suggested that CRRT with AN69ST membrane might be associated with better in-hospital outcomes. © 2017 The Author(s) Published by S. Karger AG, Basel
© 2017 The Author(s) Published by S. Karger AG, Basel E-Mail
[email protected] www.karger.com/bpu
This article is licensed under the Creative Commons AttributionNonCommercial-NoDerivatives 4.0 International License (CC BYNC-ND) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.
Background
Cytokine removal using the extracorporeal blood purification technique has been expected to improve the outcomes of critically ill patients, especially in those with sepsis. Elevation in cytokine levels is observed in severe conditions, and significantly associated with poor outcomes [1]. The effect of cytokine removal by blood purification has been investigated using the interventions of extremely high volume hemofiltration (HVHF) for enhanced convective clearance, and high cut-off (HCO) membranes for enhanced diffusive clearance. Randomized controlled trials of HVHF show decreases in cytokine levels but no mortality benefit [2, 3]. There is preliminary experience with HCO membranes, with reported improvements of hemodynamic parameters and oxygenation [4]. Adsorption is another blood-purification strategy to remove middle-range molecules, including cytokines. Polymethylmethacrylate (PMMA) and polyacrylonitrile (PAN) membranes are known to have high adsorption capability [5]. Nakada et al. [6] reported that continuous renal replacement therapy (CRRT) with PMMA membrane showed a rapid decline of blood interleukin (IL)-6 levels in 43 septic shock patients together with improvement of hemodynamics and hyperlactemia. PAN membrane such as AN69 can also remove cytokines, mainly by the mechanism of adsorption [7]. The membrane is negMark R. Marshall, FRACP, MPH Baxter Healthcare (Asia) Pte Ltd PO Box 37968, Parnell Auckland 1151 (New Zealand) E-Mail mark_roger_marshall @ baxter.com
atively charged from methallylsulfonate, adsorbing cytokines via ionic bonding between sulfonate groups and amino groups on cytokines. Newly developed polyethylenimine-coated AN69ST has a hydrogel structure, which enables adsorption not only on the membrane surface but also within the bulk layer, thereby exhibiting an increased capacity for cytokine removal. However, like HVHF and HCO membranes, there is only limited evidence that this intervention improves outcomes in critically ill patients. The aim of this study is to investigate whether AN69ST-CRRT is associated with lower hospital mortality and intensive care unit (ICU) length of stay (ICULOS) in critically ill patients. Since 2014, the use of AN69ST membrane has been approved by the National Health Insurance System in Japan for severe sepsis in addition to acute kidney injury (AKI) or end-stage renal disease. We analyzed claims of critically ill patients who were treated by CRRT admitted from April 2014 to October 2015, and evaluated the impact of AN69ST-CRRT on outcomes with adjustment for potential confounders.
Materials and Methods Study Design We performed an observational retrospective cohort study comparing AN69ST-CRRT with standard-CRRT, using an “astreated” framework (“did exposure that the patient actually receives affect outcomes?”) [8]. The data were sourced from Medical Data Vision Co., Ltd (https://www.mdv.co.jp), and contains Japanese diagnosis-procedure combination (DPC) codes and health insurance claims data (irrespective of insurer). Data are extracted directly from electronic information systems of hospital participating in the data-sharing networks (177 hospitals, consisting of 21 hospitals with 3–10 fold decrease in risk of death) resulted in the attenuation of the association between type of CRRT and mortality risk. Adjustment for more moderate confounding produced little change in the results. These results suggest that the associations for AN69ST-CRRT versus standard-only-CRRT are unlikely to have been due to confounding only.
Discussion
Severe AKI that requires CRRT, especially complicated with sepsis, shows unacceptably high mortality rates [39]. In our study, the ICU and hospital mortality of our patients were 22.4 and 26.9%, respectively. These mortality rates are somewhat lower than the previous reports from other countries possibly because of region-specific reasons (e.g., proportion of respiratory support in ICU Doi/Iwagami/Yoshida/Marshall
DIC Emergency surgery Invasive abdominal surgery Cardiac surgery Emergency vs. elective admission 1 vasopressor 2 vasopressors Platelet or FFP infusion Albumin infusion
Fig. 4. Fully adjusted main effects from the competing risk model for intensive care unit length of stay (ICU-LOS), accounting for competing risk of ICU death. DIC, disseminated intravascular coagulation; AKI, acute kidney injury; FFP, fresh frozen plasma; DPC, diagnosis procedure combination; CRRT, continuous renal replacement therapy.
Mechanical ventilation Hospital 200 and 500 beds AN69ST-CRRT vs. standard-only-CRRT 0.5
1.0
1.5
2.0
Subhazard ratio for ICU discharge without death
Table 2. Sensitivity of HRs for the association between AN69ST-CRRT and mortality risk (relative to standard-only-CRRT), adjusted
for unmeasured confounding p1
0.65 0.6 0.55 0.5 0.45 0.4 0.35 0.3 0.25 0.2
p0
0.2 0.25 0.3 0.35 0.4 0.45 0.5 0.55 0.6 0.65
HRCD 0.9
0.7
0.5
0.3
0.1
0.81 0.77 0.73 0.70 0.67 0.63 0.60 0.58 0.55 0.52
0.76 0.73 0.71 0.68 0.66 0.64 0.62 0.60 0.58 0.56
0.87 0.81 0.76 0.72 0.67 0.63 0.59 0.55 0.52 0.49
1.03 0.92 0.83 0.76 0.68 0.62 0.56 0.51 0.46 0.41
1.28 1.10 0.94 0.81 0.70 0.60 0.52 0.45 0.39 0.33
HRs are computed as point estimates only. The base model assumes an HR of 0.65, adjusted for known confounders, when unmeasured confounders are present but unaccounted for. When an unmeasured confounder of varying strength and prevalence is introduced into the models, the hazard ratios are only sensitive to strong unmeasured confounding, with an effect that remains after adjustment for only weak-moderate confounding. HRs, hazard ratios; CRRT, continuous renal replacement therapy; HRCD, hazard ratio for the association between unmeasured confounder and mortality risk; p1, prevalence of unmeasured confounder among those on AN69ST-CRRT; p0, prevalence of unmeasured confounder among those on to standard-only-CRRT.
patients is lower in Japan than other countries). Of note, the mortality rates in this study are similar to other reports on septic ICU patients treated in Japan [40]. Although CRRT with any currently available membrane can control uremia sufficiently, additive therapeu-
tic effects beyond renal replacement might improve the outcomes of these severely ill patients. Several membranes that have high capability of adsorption including AN69ST are expected to remove the middle-size molecules of inflammatory humoral mediators. In this study,
Polyethylenimine-Coated AN69 in CRRT
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with an anonymized large claim-based database, the use of AN69ST membrane was significantly associated with lower in-hospital mortality (adjusted OR of 0.65, 95% CI 0.45–0.93) and shorter ICU-LOS among patients receiving CRRT in Japanese ICUs. Hypercytokinemia is observed in a variety of serious conditions in ICU patients, including sepsis, trauma, pancreatitis, and burns, and plays a key role in the inflammation cascade [41]. In particular, plasma cytokine levels such as IL-6 and high-mobility group protein B1 are increased with impaired kidney function [42–45]. Therefore, removing cytokines in addition to renal replacement seems a plausible intervention to reduce the maladaptive inflammation cascade in sepsis. AN69ST membrane has been shown to have a high capacity to adsorb cytokines (tumor necrosis factor-α, IL-1β, IL-6, and IL1ra) and HMGM1 in vitro experiments [46, 47]. However, only one clinical study by Shiga et al. [48], which evaluated AN69ST-CRRT has been reported so far. A prospective multicenter study demonstrated that the 28day survival of 34 patients receiving AN69ST-CRRT was 73.5%, which was higher than the predicted 28-day survival of 20.3% based on their severity at ICU admission (Acute Physiology and Chronic Health Evaluation II score 32.7 ± 9.8). Because the study by Shiga et al. [48] was a single-arm study, there was no control group using other CRRT membranes. AN69ST membrane was approved by the National Health Insurance System in Japan since 2014. Therefore, analyzing the claim data for AN69ST use in our study enables us to examine the real-world effectiveness of AN69STCRRT in comparison with other CRRT membranes. The information obtained from the Japanese claim database revealed that the patients in the AN69ST-CRRT group were more likely to receive larger number of vasopressors and mechanical ventilator support than those in the standard-only-CRRT group, suggesting that AN69ST membrane was preferentially used for patients in a more severe condition. After adjusting for differences including severity, the use of AN69ST was significantly associated with a lower in-hospital mortality with adjusted OR of 0.65 (95% CI 0.45–0.93). Although no data regarding blood cytokine concentrations were available in this study, better control of humoral mediators achieved by AN69ST might contribute to the favorable use of this membrane for higher survival rate. We also compared ICU-LOS between the AN69STCRRT and standard-only-CRRT groups, as early discharge from ICU is an indirect marker of patients’ improved conditions. This outcome is also important in terms of cost effectiveness and hospital resource utiliza190
Blood Purif 2017;44:184–192 DOI: 10.1159/000476052
tion. Because crude ICU mortality was lower in the AN69ST-CRRT group than the standard-only-CRRT group (22.4 vs. 26.9%), we took into account the competing risk (i.e., early death leads to early discharge from ICU) in our statistical analysis. As a result, the use of the AN69ST membrane was also independently associated with shorter ICU-LOS. This result may suggest that AN69ST-CRRT not only improved survival rate but also enhanced early recovery from a severe condition. There are several limitations in our study. First, there may be a selection bias of participating hospitals because the Medical Data Vision’s database consists of hospitals voluntarily contributing to the company, and there is no detailed information on how different these hospitals and other Japanese hospitals are in terms of patient characteristics and medical care including CRRT management. However, we acknowledge at least that demographics and crude in-hospital mortality of patients in the current study were similar to those of CRRT-treated patients (median age 72, male 66.0%, and in-hospital mortality of 50.6%) in a Japanese nationwide database consisting of around 1,000 hospitals [39]. Second, although we adjusted for a number of potential confounding factors in regression analyses, residual confounding cannot be fully removed in observational studies. Unmeasured confounding factors mainly include vital signs and laboratory results. However, we were able to adjust for the use of vasopressors, mechanical ventilation, blood products and albumin, which are expected to reflect patients’ severity. Moreover, our sensitivity analysis suggested that current findings are unlikely to be explained only by confounding, unless the level of confounding is very strong (Table 2). Third, we used recorded diagnoses (ICD-10 and DPC codes) of sepsis, DIC, and AKI for confounding adjustment and test for interaction (effect modification). However, recorded diagnoses of sepsis and DIC are known to have high specificity but low sensitivity in the Japanese claims system [49]. This was similar in a US validation study of AKI diagnosis [50], although there has been no validation study of AKI diagnosis in Japan. Misclassification of disease diagnoses may make the interpretation of our interaction test difficult. More accurate classification of sepsis, DIC, and AKI status based on vital signs and laboratory results would be necessary for identifying the best target group of this treatment in future studies. Finally, we were dependent on the classification of filters in the Japanese claims data, which distinguish only AN69ST membranes from other filters by virtue of a different reimbursement code. Our standard group included patients treated with polysulfone, cellulose, and PMMA membranes. AlDoi/Iwagami/Yoshida/Marshall
though evidence suggests that AN69ST might have slightly greater adsorption of HMGB-1 [47], AN69ST and PMMA are both classified as adsorptive membranes. Unfortunately, we cannot differentiate PMMA from other membranes in the standard group, since the reimbursement is the same for all membranes other than AN6ST, and our study is based on claim records. We cannot estimate the proportion of patients treated with PMMA in the standard group, although the inclusion of PMMA membranes in this group would potentially reduce the observed and modeled benefit of AN69ST in our study, if adsorption were truly effective. Therefore, the benefit of AN69ST observed in this study might be underestimated. In conclusion, this retrospective observational study suggests that the use of AN69ST membrane might be associated with improved outcomes including in-hospital mortality and ICU-LOS among patients receiving CRRT in ICU. Further prospective studies including random-
ized control trials are warranted to confirm this finding and to better elucidate the clinical significance of cytokine removal in patients admitted to ICUs.
Disclosure Statement M.R.M. is a Director of Medical Affairs, Therapeutic Area, Baxter Healthcare (Asia) Pte. Ltd, and E.Y. was an employee of Baxter Japan Ltd at the time of her contribution to the study. The remaining authors declare that they have no competing interests.
Acknowledgment Dr. Masao Iwagami is funded by the Honjo International Scholarship Foundation. The funders had no role in the execution of this study or interpretation of results.
References 1 Doi K, Rabb H: Impact of acute kidney injury on distant organ function: recent findings and potential therapeutic targets. Kidney Int 2016; 89:555–564. 2 Clark E, Molnar AO, Joannes-Boyau O, Honoré PM, Sikora L, Bagshaw SM: High-volume hemofiltration for septic acute kidney injury: a systematic review and meta-analysis. Crit Care 2014;18:R7. 3 Park JT, Lee H, Kee YK, Park S, Oh HJ, Han SH, Joo KW, Lim CS, Kim YS, Kang SW, Yoo TH, Kim DK: High-dose versus conventional-dose continuous venovenous hemodiafiltration and patient and kidney survival and cytokine removal in sepsis-associated acute kidney injury: a randomized controlled trial. Am J Kidney Dis 2016; 68: 599–608. 4 Villa G, Zaragoza JJ, Sharma A, Neri M, De Gaudio AR, Ronco C: Cytokine removal with high cut-off membrane: review of literature. Blood Purif 2014;38:167–173. 5 Fujimori A, Naito H, Miyazaki T: Adsorption of complement, cytokines, and proteins by different dialysis membrane materials: evaluation by confocal laser scanning fluorescence microscopy. Artif Organs 1998; 22: 1014– 1017. 6 Nakada TA, Oda S, Matsuda K, Sadahiro T, Nakamura M, Abe R, Hirasawa H: Continuous hemodiafiltration with PMMA hemofilter in the treatment of patients with septic shock. Mol Med 2008;14:257–263. 7 Cole L, Bellomo R, Davenport P, Tipping P, Ronco C: Cytokine removal during continuous renal replacement therapy: an ex vivo comparison of convection and diffusion. Int J Artif Organs 2004;27:388–397.
Polyethylenimine-Coated AN69 in CRRT
8 Vonesh E, Schaubel D, Hao W, Collins A: Statistical methods for comparing mortality among ESRD pateints: examples of regional/ international variations. Kidney Int 2000; 57:S19–S27. 9 Urushihara H, Taketsuna M, Liu Y, Oda E, Nakamura M, Nishiuma S, Maeda R: Increased risk of acute pancreatitis in patients with type 2 diabetes: an observational study using a Japanese hospital database. PLoS One 2012;7:e53224. 10 Hashikata H, Harada KH, Kagimura T, Nakamura M, Koizumi A: Usefulness of a large automated health records database in pharmacoepidemiology. Environ Health Prev Med 2011;16:313–319. 11 Chang CH, Kusama M, Ono S, Sugiyama Y, Orii T, Akazawa M: Assessment of statin-associated muscle toxicity in Japan: a cohort study conducted using claims database and laboratory information. BMJ Open 2013; 3:pii:e002040. 12 Hanatani T, Sai K, Tohkin M, Segawa K, Saito Y: Impact of Japanese regulatory action on metformin-associated lactic acidosis in type II diabetes patients. Int J Clin Pharm 2015; 37: 537–545. 13 Hori K, Kobayashi N, Atsumi H, Nagayama A, Kondoh M, Noge I, Kimura M, Utsugi H, Iwasaki T, Nakamura M, Kimura T: Changes in compliance with Japanese antiemetic guideline for chemotherapy-induced nausea and vomiting: a nationwide survey using a distributed research network. Support Care Cancer 2014;22:969–977. 14 Ueyama H, Hinotsu S, Tanaka S, Urushihara H, Nakamura M, Nakamura Y, Kawakami K: Application of a self-controlled case series
15
16
17
18
19
Blood Purif 2017;44:184–192 DOI: 10.1159/000476052
study to a database study in children. Drug Saf 2014;37:259–268. Kamae I, Hashimoto Y, Koretsune Y, Tanahashi N, Murata T, Phatak H, Liu LZ, Tang AC, Feng Wang P, Okumura K: Cost-effectiveness analysis of apixaban against warfarin for stroke prevention in patients with nonvalvular atrial fibrillation in Japan. Clin Ther 2015;37:2837–2851. Tanaka K, Hamada K, Nakayama T, Matsuda S, Atsumi A, Shimura T, Nemoto M: Risk for cardiovascular disease in Japanese patients with rheumatoid arthritis: a large-scale epidemiological study using a healthcare database. Springerplus 2016;5:1111. Tanabe M, Motonaga R, Terawaki Y, Nomiyama T, Yanase T: Prescription of oral hypoglycemic agents for patients with type 2 diabetes mellitus: a retrospective cohort study using a Japanese hospital database. J Diabetes Investig 2016;8:227–234. Teramoto T, Uno K, Miyoshi I, Khan I, Gorcyca K, Sanchez RJ, Yoshida S, Mawatari K, Masaki T, Arai H, Yamashita S: Low-density lipoprotein cholesterol levels and lipidmodifying therapy prescription patterns in the real world: an analysis of more than 33,000 high cardiovascular risk patients in Japan. Atherosclerosis 2016; 251: 248–254. Hanatani T, Sai K, Tohkin M, Segawa K, Kimura M, Hori K, Kawakami J, Saito Y: A detection algorithm for drug-induced liver injury in medical information databases using the Japanese diagnostic scale and its comparison with the Council for International Organizations of Medical Sciences/the Roussel Uclaf Causality Assessment Method scale. Pharmacoepidemiol Drug Saf 2014;23:984–988.
191
20 Bennett D, Davé S, Sakaguchi M, Chang CH, Dolin P: Association between therapy with dipeptidyl peptidase-4 (DPP-4) inhibitors and risk of ileus: a cohort study. Diabet Int 2016; 7:375–383. 21 Sugitani Y, Udagawa Y, Matsuda S, Yamada K, Miyawaki N, Konishi I: Postmarketing benefit-risk assessment for erythropoiesisstimulating agents using a health care database. Ther Innov Regul Sci 2016;50:823–832. 22 Verburg IW, de Keizer NF, de Jonge E, Peek N: Comparison of regression methods for modeling intensive care length of stay. PLoS One 2014;9:e109684. 23 Zimmerman JE, Kramer AA, McNair DS, Malila FM, Shaffer VL: Intensive care unit length of stay: benchmarking based on acute physiology and chronic health evaluation (APACHE) IV. Crit Care Med 2006;34:2517–2529. 24 Charlson ME, Pompei P, Ales KL, MacKenzie CR: A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: 373–383. 25 Deyo RA, Cherkin DC, Ciol MA: Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 1992;45:613–619. 26 Quan H, Parsons GA, Ghali WA: Validity of information on comorbidity derived rom ICD-9-CCM administrative data. Med Care 2002;40:675–685. 27 Hosmer DW, Lemeshow S: Applied Logistic Regression (2nd ed). New Jersey, Wiley-Interscience, USA, 2000. 28 Verburg IW, de Keizer NF, de Jonge E, Peek N: Comparison of regression methods for modeling intensive care length of stay. PLoS One 2014;9:e109684. 29 Straney L, Clements A, Alexander J, Slater A; ANZICS Paediatric Study Group: A twocompartment mixed-effects gamma regression model for quantifying between-unit variability in length of stay among children admitted to intensive care. Health Serv Res 2012; 47:2190–2203. 30 Moran JL, Solomon PJ: A review of statistical estimators for risk-adjusted length of stay: analysis of the Australian and New Zealand intensive care adult patient data-base, 2008– 2009. BMC Med Res Methodol 2012;12:68. 31 Fine JP, Gray RJ: A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999;94:496–509. 32 Grunkemeier GL, Jin R, Eijkemans MJ, Takkenberg JJ: Actual and actuarial probabilities
192
33
34
35
36 37
38
39
40
41
Blood Purif 2017;44:184–192 DOI: 10.1159/000476052
of competing risks: apples and lemons. Ann Thorac Surg 2007;83:1586–1592. Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Oudemansvan Straaten HM, Ronco C, Kellum JA; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators: Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol 2007;2:431–439. Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Doig GS, Oudemans van Straaten H, Ronco C, Kellum JA; Beginning and Ending Supportive Therapy for the Kidney (B.E.S.T. Kidney) Investigators: External validation of severity scoring systems for acute renal failure using a multinational database. Crit Care Med 2005;33:1961–1967. Arah OA, Chiba Y, Greenland S: Bias formulas for external adjustment and sensitivity analysis of unmeasured confounders. Ann Epidemiol 2008;18:637–646. Lash TL, Fox CS, Fink AK: Applying Quantitative Bias Analysis to Epidemiologic Data. New York, Springer, 2009. Sudan M, Kheifets L, Arah OA, Olsen J: Cell phone exposures and hearing loss in children in the Danish National Birth Cohort. Paediatr Perinat Epidemiol 2013;27:247–257. Vanderweele TJ, Arah OA: Bias formulas for sensitivity analysis of unmeasured confounding for general outcomes, treatments, and confounders. Epidemiology 2011;22:42–52. Iwagami M, Yasunaga H, Noiri E, Horiguchi H, Fushimi K, Matsubara T, Yahagi N, Nangaku M, Doi K: Current state of continuous renal replacement therapy for acute kidney injury in Japanese intensive care units in 2011: analysis of a national administrative database. Nephrol Dial Transplant 2015;30:988–995. Fujishima S, Gando S, Saitoh D, Mayumi T, Kushimoto S, Shiraishi S, Ogura H, Takuma K, Kotani J, Ikeda H, Yamashita N, Suzuki K, Tsuruta R, Takeyama N, Araki T, Suzuki Y, Miki Y, Yamaguchi Y, Aikawa N; Japanese Association for Acute Medicine Sepsis Registry (JAAM SR) Study Group: A multicenter, prospective evaluation of quality of care and mortality in Japan based on the Surviving Sepsis Campaign guidelines. J Infect Chemother 2014;20:115–120. Hirasawa H, Oda S, Nakamura M, Watanabe E, Shiga H, Matsuda K: Continuous hemodiafiltration with a cytokine-adsorbing he-
42
43
44
45
46
47
48
49
50
mofilter for sepsis. Blood Purif 2012; 34: 164– 170. Hoke TS, Douglas IS, Klein CL, He Z, Fang W, Thurman JM, Tao Y, Dursun B, Voelkel NF, Edelstein CL, Faubel S: Acute renal failure after bilateral nephrectomy is associated with cytokine-mediated pulmonary injury. J Am Soc Nephrol 2007;18:155–164. Klein CL, Hoke TS, Fang WF, Altmann CJ, Douglas IS, Faubel S: Interleukin-6 mediates lung injury following ischemic acute kidney injury or bilateral nephrectomy. Kidney Int 2008;74:901–909. Andres-Hernando A, Dursun B, Altmann C, Ahuja N, He Z, Bhargava R, Edelstein CE, Jani A, Hoke TS, Klein C, Faubel S: Cytokine production increases and cytokine clearance decreases in mice with bilateral nephrectomy. Nephrol Dial Transplant 2012;27:4339–4347. Doi K, Ishizu T, Tsukamoto-Sumida M, Hiruma T, Yamashita T, Ogasawara E, Hamasaki Y, Yahagi N, Nangaku M, Noiri E: The high-mobility group protein B1-Toll-like receptor 4 pathway contributes to the acute lung injury induced by bilateral nephrectomy. Kidney Int 2014;86:316–326. Rimmelé T, Assadi A, Cattenoz M, Desebbe O, Lambert C, Boselli E, Goudable J, Etienne J, Chassard D, Bricca G, Allaouchiche B: High-volume haemofiltration with a new haemofiltration membrane having enhanced adsorption properties in septic pigs. Nephrol Dial Transplant 2009;24:421–427. Yumoto M, Nishida O, Moriyama K, Shimomura Y, Nakamura T, Kuriyama N, Hara Y, Yamada S: In vitro evaluation of high mobility group box 1 protein removal with various membranes for continuous hemofiltration. Ther Apher Dial 2011;15:385–393. Shiga H, Hirasawa H, Nishida O, Oda S, Nakamura M, Mashiko K, Matsuda K, Kitamura N, Kikuchi Y, Fuke N: Continuous hemodiafiltration with a cytokine-adsorbing hemofilter in patients with septic shock: a preliminary report. Blood Purif 2014; 38: 211–218. Yamana H, Horiguchi H, Fushimi K, Yasunaga H: Comparison of procedure-based and diagnosis-based identifications of severe sepsis and disseminated intravascular coagulation in administrative data. J Epidemiol 2016; 26:530–537. Grams ME, Waikar SS, MacMahon B, Whelton S, Ballew SH, Coresh J: Performance and limitations of administrative data in the identification of AKI. Clin J Am Soc Nephrol 2014; 9:682–689.
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