Therapeutic Plasma Exchange in the Critically Ill Patient: Technology and Indications.

Therapeutic plasma exchange (TPE) is frequently the most common Apheresis Medicine technique used for extracorporeal therapy of a wide variety of renal, neurological, hematological, and other clinical indications. Many of these clinical indications require intensive care during critical illness. Conventional TPE uses one of two main technical methods to achieve the goal of removing known disease mediators from the plasma: using centrifugal forces to separate and remove components of blood, or a membrane filtration method that separates plasma from the cellular components of blood. The following review discusses the basic principles of TPE, the technological aspects, and relevant clinical scenarios encountered in the intensive care unit, including relevant guidelines and recommendations from the American Society for Apheresis.

Association of Race with In-Hospital and Post-Hospitalization Mortality in Patients with Acute Kidney Injury.

INTRODUCTION: Acute kidney injury (AKI) is known to be associated with increased mortality, and racial differences in hospital mortality exist in patients with AKI. However, it remains to be seen whether racial differences exist in post-hospitalization mortality among AKI patients. METHODS: We analyzed data of adult AKI patients admitted to the University of Virginia Medical Center between January 1, 2001, and December 31, 2015, to compare in-hospital and post-hospitalization mortality among hospitalized black and white patients with AKI. Multivariable logistic regression analysis was used to analyze the association between race and in-hospital mortality, and 90-day post-hospitalization mortality among AKI patients that were discharged. Kaplan-Meier survival curve was used to evaluate long-term survival between black and white patients. RESULTS: Black patients had lower in-hospital mortality than white patients after adjusting for age, sex, estimated glomerular filtration rate, hospital length of stay, severity of AKI, comorbidities, and the need for dialysis and mechanical ventilation (odds ratio: 0.82; 95% confidence interval, 0.70-0.96, p = 0.0015). Similarly, at 90-day post-hospitalization, black patients had significantly lower adjusted odds of death than white patients (odds ratio: 0.64; 95% confidence interval, 0.46-0.93; p = 0.008). The median length of follow-up was 11.9 months (0.6-46.7 months). Kaplan-Meier survival curve showed that long-term survival was significantly better in black patients compared to white patients (median duration of survival; 39.7 vs. 24.8 months; p ≤ 0.001). CONCLUSIONS: Black patients with AKI had lower in-hospital mortality, 90-day post-hospitalization mortality, and better long-term survival rates compared to white patients with AKI.

Association between Palliative Care Consultation and Advance Palliative Care Rates: A Descriptive Cohort Study in Patients at Various Stages in the Continuum of Chronic Kidney Disease.

Background: Despite evidence that advance care planning (ACP) benefits patients with serious illnesses, there is a dearth of information about "who" is referred for palliative care (PC) consultation, the rate of PC consultation, and the outcomes of referrals in patients with advanced chronic kidney disease/end-stage kidney disease (aCKD/ESKD). Objectives: (1) To describe patient characteristics associated with PC consultations and (2) to determine the frequency and outcome of PC consultation on documented ACP discussions for patients with aCKD/ESKD. Methodology/Design: This is retrospective observational electronic health record cohort review. Settings: University of Virginia (UVA) hospital, clinics, and dialysis units. Participants: Patients were studied along two time intervals. Time period January 1, 2015 to June 30, 2017 included all patients admitted to UVA during that time period with estimated glomerular filtration rate (eGFR) <60 mL/minute. Time period January 1, 2018 to March 31, 2019 included two cohorts: patients with eGFR <15 mL/minute who had died during study period excluding those who withdrew from dialysis and those who were dialysis dependent and withdrew from dialysis. Results: Aside from higher rates of PC consultation in patients with heart failure, none of the demographic and comorbidity data studied affected whether or not a patient is referred to PC in patients with aCKD/ESKD. PC consultation rates were low among all patients studied: 14.7% in patients with eGFR <60 mL/minute, 28.9% in dialysis patients withdrawing from dialysis, and 57.1% in terminally ill patients with eGFR <15 mL/minute. In all cohorts, PC consultations were associated with improved ACP. Conclusion: PC consultation is significantly associated with better end-of-life outcomes with more completion of ACP and hospice referral in patients with aCKD/ESKD. PC consultation rates remain low. Even in terminally ill patients with more aCKD, >40% were never seen by PC. Until policies and curricula better prepare nephrologists to independently address ACP, collaboration between nephrologists and PC specialists is recommended.

Update to the ASFA guidelines on the use of therapeutic apheresis in ANCA-associated vasculitis.

Since 1986, the American Society for Apheresis (ASFA) has published practice guidelines on the use of therapeutic apheresis in the Journal of Clinical Apheresis (JCA) Special Issue. Since 2007, updated guidelines have been published every 3 years to reflect current evidence based apheresis practice with the most recent edition (8th) published in 2019. With each edition, the guidelines are reviewed and updated based on any newly published literature since the last review. The PEXIVAS study, an international, randomized controlled trial comparing therapeutic plasma exchange (TPE) vs no TPE and standard vs reduced dose steroid regimen on the primary composite outcome of end stage renal disease or death in patients with ANCA-associated vasculitis (AAV), was published in February 2020. This study represents the largest study on the role of therapeutic apheresis in AAV published to date and prompted the JCA Special Issue Writing Committee to reassess the current AAV fact sheet for updates based on this newly available evidence. This interim fact sheet summarizes current ASFA recommendations for the evidence-based use of therapeutic apheresis in AAV and supersedes the recommendations published in the 2019 guidelines.

Burden and etiopathogenesis of acute kidney injury in the tropics.

Acute kidney injury (AKI) is prevalent and is associated with high morbidity and mortality globally. The epidemiology differs remarkably between developing and developed economies. Infections, diarrheal illnesses, obstetric causes and nephrotoxins are very rampant in the tropics. Even though the etiologies are different, the final common pathway in the pathogenesis is similar - tubular damage or necrosis, tubular blockage, and back leak of glomerular filtrate. The mechanism of AKI in infections could be through ischemic insult consequent to hypovolemia and/or hemoglobinuria, as seen in malaria and viral hemorrhagic fevers, interstitial inflammation, or nephrotoxicity. On the contrary, the mechanism of nephrotoxin-induced AKI includes direct toxic effect on the renal tubules, intratubular precipitation of substances like djenkolic and oxalic acids (crystalluria) as well as intratubular obstruction and AKI. Toxicity could also be indirect by interacting with the pharmacokinetic profile of other coadministered medications. Bites and envenomation as well as obstetric complications also induce AKI through hypovolemia, interstitial nephritis, and other unclear mechanisms in eclampsia and preeclampsia. Outcome is variable and dependent on etiology. Prognosis appears to be significantly better in hypovolemic or prerenal and/or obstructive AKI compared to intrarenal or intrinsic AKI.

Burden of end-stage renal disease in sub-Saharan Africa.

Chronic kidney disease (CKD) particularly in its most severe form, end-stage renal disease (ESRD), is highly prevalent globally. Although both the incidence and prevalence appears to be increasing, the rate of increase is far higher in developing countries, probably as a result of underdevelopment, high incidence of communicable and noncommunicable diseases, poverty as well as inaccessible, unavailable, or unaffordable treatment modalities. The epidemiology differs remarkably between developing and developed economies - it afflicts the young and middle-aged in the former and older individuals in the latter. The etiologies also differ significantly, and the outcome is mainly determined by accessibility and availability of renal replacement therapies. While the three modalities of treatment namely hemodialysis, peritoneal dialysis, and kidney transplantation are available in sub-Saharan Africa, affordability of care remains a major challenge due to nonavailability of healthcare insurance in many of the countries, and where state support is available, dialysis and transplant rationing based on certain criteria remains a major limitation. Data on CKD and ESRD are largely unreliable because of a lack of renal registries in most countries, but the reactivation of the South African Renal Registry and its extension to cover other African countries may improve data quality.
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Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue.

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating and categorizing indications for the evidence-based use of therapeutic apheresis (TA) in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Eighth Edition of the JCA Special Issue continues to maintain this methodology and rigor in order to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Eighth Edition, like its predecessor, continues to apply the category and grading system definitions in fact sheets. The general layout and concept of a fact sheet that was introduced in the Fourth Edition, has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of TA in a specific disease entity or medical condition. The Eighth Edition comprises 84 fact sheets for relevant diseases and medical conditions, with 157 graded and categorized indications and/or TA modalities. The Eighth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.

Dialysis Requirement and Long-Term Major Adverse Cardiovascular Events in Patients with Chronic Kidney Disease and Superimposed Acute Kidney Injury.

BACKGROUND: Chronic kidney disease (CKD) patients who experience superimposed acute kidney injury (AKI) have been shown to be at higher risk of long-term sequelae of AKI when compared to those who do not experience AKI. It remains unclear whether the need for temporary dialysis intervention following superimposed AKI in patients with CKD has any effect on the long-term major adverse cardiovascular events (MACE). This study examines the relationship between temporary dialysis therapy following AKI and long-term major cardiovascular events in patients with background CKD. METHODS: The study population consists of adults who developed AKI while on admission at the University of Virginia Medical Center between January 1, 2002 and December 31, 2012, and who had preadmission estimated glomerular filtration rate (eGFR) between 20 and 60 mL/min/1.73 m2 and survived beyond 30 days of AKI. Demographic and baseline clinical variables were used to generate propensity score. Survivors who had temporary dialysis were matched to those managed conservatively according to the propensity score in a ratio of 1:3. RESULTS: Overall, 6,634 (n = 381 and 6,253 in the temporary dialysis-requiring AKI and non-dialysis AKI groups respectively) met entry criteria for the full cohort. Of these, 381 (5.7%) received temporary dialysis. There were 3,147 (47.4% of all patients) MACE events during the study period. The crude incidence for MACE after 30 days of AKI was similar in both dialyzed and non-dialyzed patients. After the propensity score matching, the adjusted hazard ratio for MACE in dialyzed versus non dialyzed patients was 1.162 (95% CI 0.978-1.381). CONCLUSIONS: Treatment of AKI with temporary dialysis in hospitalized patients with baseline eGFR between 20 and 60 mL/min/1.73 m2 was not associated with an increased risk for subsequent admission for MACE. If confirmed by prospective studies, clinicians may not need to worry that the dialysis procedure may contribute to additional risk for long-term MACE in CKD patients with superimposed AKI.

Major Depression and Long-Term Outcomes of Acute Kidney Injury.

BACKGROUND: The prevalence of depression and its relationship to poor outcomes in chronic kidney disease are established facts. Such prognostic impact in acute kidney injury (AKI) is not known. This study determines the prognostic implication of a diagnosis of depression on renal recovery and major adverse cardiovascular events (MACE), a new diagnosis of myocardial infarction, cerebrovascular disease (CVD, stroke or transient ischemic attack) or congestive heart failure (CHF) after hospitalization with AKI. METHODS: The study population comprises adults admitted to the University of Virginia Medical Center between January 1, 2002 and December 31, 2012 who suffered AKI during admission. Long-term outcomes, MACE and all-cause mortality, were compared between 2 groups; patients with preexisting diagnosis of major depression and those without. Risk adjusted multivariable Cox proportional hazards regression examined the association between major depression and these outcomes. RESULTS: Patients with AKI numbering 11,425 survived beyond 90 days and had data available. Of these patients, 2,519 (22%) were majorly affected by depression; more often, younger patients, females, African Americans, and those with more comorbid conditions, especially CHF, CVD, diabetes, peptic ulcer disease, chronic pulmonary disease and liver disease were found to be affected with depression. Crude hazard ratio for MACE was 1.245, 95% CI 1.150-1.348 and for all-cause mortality 1.186, 95% CI 1.091-1.290; p < 0.001, that is, the cohort with major depression had a long-term risk for MACE and all-cause mortality increased by 24 and 18%, respectively. CONCLUSION: Patients who develop AKI in hospital and have preexisting major depression are at greater long-term risk of MACE and all-cause mortality.

Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Seventh Special Issue.

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc.

Dialysis requirement, long-term major adverse cardiovascular events (MACE) and all-cause mortality in hospital acquired acute kidney injury (AKI): a propensity-matched cohort study.

BACKGROUND: Dialysis-requiring acute kidney injury (D-AKI) is common in hospitalized patients. Many patients survive the immediate post AKI period, thus at risk of suffering long-term sequelae of AKI. Prior studies examining long term outcomes lack non-dialyzed AKI control groups. Without non-dialyzed AKI control group, these studies cannot provide relevant information on long-term risks or benefits associated with dialysis intervention following AKI. METHODS: The study cohort comprises of adults admitted to the University of Virginia Medical Center between January 1, 2002 and December 31, 2012 with baseline eGFR ≥60 ml/min per 1.73 m2, who developed AKI during hospitalization and survived beyond 30 days of the AKI event. Follow up was done until MACE, death or through Dec 31, 2013 (n = 11,779). AKI was defined according to KDIGO definition. MACE was defined as subsequent admission for Myocardial Infarction (MI), cerebrovascular disease (CVD) and heart failure using ICD 9-CM codes. The date of MACE was defined as the date of the first qualifying event. Demographic and premorbid clinical variables were used to generate propensity score. Patients who had temporary dialysis were matched with those managed conservatively according to propensity score in a ratio of 1:3. RESULTS: After the propensity score match, the adjusted hazard ratio for MACE, all-cause mortality and composite end point "all-cause mortality or MACE" in dialyzed versus non dialyzed patients were 1.081 (95 % CI 0.848-1.378), 1.107 (95 % CI 0.869-1.410) and 1.107 (95 % CI 0.880-1.307), respectively. CONCLUSION: Management of AKI with temporary dialysis in hospitalized patients with baseline eGFR of ≥60 ml/min per 1.73 m2 was NOT associated with an increased risk for subsequent admission for MACE or all-cause mortality. Clinicians may not need to worry that the dialysis procedure itself may confer additional risk for long-term MACE and all-cause mortality in AKI patients with normal pre-hospitalization GFR.

Acute kidney injury (AKI) outcome, a predictor of long-term major adverse cardiovascular events (MACE).

BACKGROUND AND OBJECTIVES: The incidence of acute kidney injury (AKI) in hospitalized patients is increasing. Many of these patients survive the immediate post-AKI period and may be prone to developing long-term complications of AKI. This study aimed to determine whether complete recovery following an episode of AKI is associated with a lower risk of long-term major adverse cardiovascular events (MACE). DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Adults admitted to the University of Virginia Medical Center between January 1, 2002 and December 31, 2012 who developed hospital-acquired AKI. PREDICTOR: AKI was defined as an increase in serum creatinine (SCr) by ≥ 0.3 mg/dL from the baseline and or requirement for acute dialysis during index hospitalization. Complete recovery was defined as a return of SCr to less than 1.25 times the baseline value and not dialysis dependent. Outcome and measurement: MACE was defined as subsequent admission for myocardial infarction, stroke or transient ischemic attach and heart failure using ICD- 9-CM codes. RESULTS: Overall, 11,538 patients survived beyond 90 days of AKI and had data available for analysis. Of the 9,673 survivors of AKI in whom recovery could be assessed, 7170 (74.12%) had complete renal recovery. MACE occurred in 27.28% of our study population over a median follow-up period of 399 days. 28.19% of patients who completely recovered renal function developed MACE, while only 32.48% did in those who did not recover completely. Patients who had complete recovery had a lower risk of long-term MACE when compared with those without complete recovery (adjusted hazard ratio 95% confidence interval (CI): 0.774 (0.713, 0.842)). LIMITATION: Measurement of albuminuria was not available. CONCLUSION: Complete renal recovery after an episode of AKI in patients with normal baseline kidney function is associated with a lower risk of long-term MACE when compared with those who did not fully recover.

Crescentic glomerulonephritis with dual positive anti-GBM and C-ANCA/PR3 antibodies.

Antiglomerular basement membrane (anti-GBM) antibodies are more often accompanied by myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) than by proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA). Both disease processes can affect the kidneys and/or the lungs. Patients with dual positive disease may have an atypical presentation which may delay diagnosis and treatment. Here we report a case of crescentic glomerulonephritis associated with positive PR3-ANCA and anti-GBM antibodies who underwent both lung and kidney biopsies.

Predictors and Outcomes of Post-Hospitalization Dialysis Dependent Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication of hospitalized patients and is associated with poor outcomes. Hospitalized patients with AKI may need prolonged dialysis, necessitating post-hospitalization dialysis (PHD-AKI). Scarce information is available to stratify the risks and predict outcomes. This study aims to assess outcomes and identify predictors of outcomes of PHD-AKI within 90 days. METHODS: All adult AKI patients initiating hemodialysis (HD) at the University of Virginia (UVA) between June 1, 2012, and September 30, 2013 were retrospectively studied. PHD-AKI patients continued treatment at a specifically designated unit. They were followed until an outcome (end-stage renal disease [ESRD], death or dialysis-independence) was achieved. RESULTS: During the study period, 108 patients required outpatient dialysis out of 365 AKI patients initiating in-patient HD at UVA. An additional 11 patients who developed dialysis-requiring AKI at referring hospitals but underwent HD at our unit were included for a total of 119 patients studied. ESRD was declared in 48.7%, while 9.2% expired and 42.0% achieved dialysis independence. Congestive heart failure, baseline renal function and a prior episode of AKI within the preceding 6 months were statistically significant predictors of renal outcomes. CONCLUSION: Dialysis independence of PHD-AKI patients is not uncommon. Certain clinical parameters may help predict renal outcome. Identifying predictors of renal recovery will guide further interventions, especially with the Centers for Medicare and Medicaid Services soon to allow AKI patients to be dialyzed at outpatient ESRD facilities. Ongoing biomarkers research may add further knowledge for optimum diagnosis and prognosis of AKI.

Therapeutic plasma exchange in antisynthetase syndrome with severe interstitial lung disease.

Antisynthetase syndrome (ASS) is a rare condition characterized by interstitial lung disease (ILD), inflammatory myositis, fever, Raynaud phenomenon, mechanic's hand, and inflammatory polyarthritis in the setting of antibodies to amino acyl-transfer RNA synthetases, with anti-Jo-1 antibody being the most common. Prognosis is very poor especially when there is associated ILD. To date, there is no standardized treatment for ILD associated ASS. Therapy is based on the use of steroids alone or in combination with other immunosuppressive agents, especially in severe or refractory cases. The role of therapeutic plasma exchange (TPE) in the management of this rare condition has not been established. Here, we report a case of severe ILD associated ASS in a 41-year-old woman who did not show clinical or laboratory response after six doses of high dose steroids and a dose of IV cyclophosphamide. Because of the aggressive nature of her disease and poor prognostic indices present, a decision was made to add TPE to her treatment. She underwent five sessions of TPE. At the end of the 5th session, the anti-Jo-1 antibody levels dropped to 3.6 AI (antibody index) and her creatinine kinase (CK) level from 875 to 399 U L(-1) (Units per liter) with overall improvement in her respiratory status. This case suggests TPE may be a promising treatment option in patients with ILD associated ASS refractory to steroids and other immunosuppressive therapy, particularly those with severe disease.

Neurologic indications for therapeutic plasma exchange: 2013 update.

Neurologists commonly use therapeutic plasma exchange (TPE) to treat a number of conditions. This concise review considers the most common neurologic indications for TPE. It focuses on Guillain-Barré syndrome and myasthenia gravis and also the role of TPE in chronic inflammatory demyelinating polyneuropathy, Lambert-Eaton syndrome, multiple sclerosis, neuromyelitis optica, paraproteinemic polyneuropathy, Sydenham's chorea, and natalizumab-associated progressive multifocal leukoencephalopathy. As with any treatment, the proven efficacy, cost, side effects, and availability must be considered before initiation of therapy.

Benefits and challenges of starting a new therapeutic apheresis service in a resource-constrained setting.

Therapeutic apheresis (TA) refers to a group of extracorporeal blood treatment modalities with clinical indications for which the clinicians' knowledge, availability and applicability vary widely worldwide. Therapeutic plasma exchange (TPE), the most common TA technique, is neither readily available nor affordable in many parts of Africa. This article focuses on the challenges of starting a TPE program in a resource-constrained economy and the result of a survey of Nigerian nephrology professionals on TPE. A critical appraisal of published manuscripts from Nigeria on TA was undertaken to assess uses, methods, and challenges encountered followed by a survey of the perceptions of Nigerian nephrology professionals on TPE. Survey results: 56.7% of respondents had very little or no knowledge of TPE; 40.5% moderate and only 2.7% admitting to having a good knowledge. Only 18.9% of respondents have ever participated or observed a TPE procedure with the remaining 81.1% not having any exposure to the procedure. A vast majority of the respondents 97.3% felt they needed better exposure and training in TPE and its applications. Among consultants, 56% had little knowledge, 88% had never participated or observed the TPE procedure, and 94% felt they needed better exposure and training. There is significant limitation in accessibility, availability, and use of TPE in Nigeria; knowledge of TPE and its applications is minimal among nephrology professionals. Efforts should be concentrated on improving the knowledge and availability of TPE in resource-constrained economy like Nigeria. Centers that would be able to manage cases requiring TA should be developed.