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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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.

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.

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.

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.

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.

Risk assessment for hypocalcemia in therapeutic apheresis for kidney transplantation.

INTRODUCTION: The increase in the number of kidney transplants performed in the United States has been paralleled with an increase in the utilization of therapeutic apheresis (TA) for kidney transplant indications. Hypocalcemia remains a significant contributor to the adverse event in TA. The magnitude of hypocalcemia and its risk factors are scarcely discussed in literature. METHODS: This is a retrospective cohort review of adults from 18 years and above who received TA for kidney transplant-related indications from January 1, 2017 to December 31, 2022. Data extracted included basic demographics, indication for apheresis, procedure characteristics, serum ionized calcium at the mid and end of procedure and serum creatinine at the beginning of apheresis, and so forth. RESULTS: Data from 131 patients and 860 sessions of TA were analyzed. Antibody-mediated rejection (69%) and recurrent FSGS (15%) were the leading indications for TA. There were 60 (7%) TA sessions complicated by hypocalcemia. Of these, 53 (88%) occurred in the first session, 5 (8%) occurred in second session while 2 (4%) occurred in the third and subsequent sessions. Female sex, elevated serum creatinine and use of fresh frozen plasma- are the risk factors for hypocalcemia with odd's ratio of 2.34, 7.42, and 5.01, respectively. Binary logistic regression showed that elevated serum creatinine at the commencement of therapy is an independent predictor of hypocalcemia (adjusted odd's ratio = 3.31, p = 0.001). CONCLUSION: Hypocalcemia is prevalent in this study. Clinical vigilance and tailored procedure will avert adverse consequences.

A multicenter evaluation of a new therapeutic plasma exchange procedure.

BACKGROUND: The AMICUS (Fenwal, Inc.) was cleared in the United States for platelet (PLT) and plasma collection in 1996 with subsequent clearances for the collection of other blood products. Although not previously used for therapeutic plasma exchange (TPE), new disposables, software, and hardware were developed to enable TPE on the AMICUS. STUDY DESIGN AND METHODS: A multicenter, randomized, nonblinded, crossover paired treatment protocol was performed. Thirty patients with orders for at least two TPE procedures were randomly assigned to the AMICUS or the COBE Spectra (TerumoBCT) for the first treatment. Each patient was crossed over to the other device using the same procedure settings from the first procedure. The primary objective compared efficiency of plasma removal (EPR) with secondary objectives of comparing PLT and hemoglobin (Hb) waste plasma content, coagulation factor and complement activation, fluid balance tracking accuracy, procedure length, and adverse events. RESULTS: The EPR for the AMICUS (81.9 ± 7.62%) was superior to that of the COBE Spectra (75.2 ± 6.29%; p = 0.00001). The AMICUS also demonstrated statistically higher fluid balance accuracy (99.84%) compared to that of the COBE Spectra (98.83%; p < 0.0001) and a statistically shorter procedure time (103.9 ± 30.8 vs. 110.5 ± 27.1 min, p < 0.001). No significant differences with regard to PLT and Hb content in the waste plasma, change in patient PLT count, or changes in markers of coagulation and complement cascade activation were seen. Frequency and severity of adverse reactions were similar. CONCLUSION: The AMICUS separator can effectively perform TPE. The AMICUS demonstrated superior plasma removal efficiency compared to the COBE Spectra with no evidence of significant differences in PLT removal, hemolysis, and coagulation or complement activation.

Therapeutic apheresis in kidney transplantation: a review of renal transplant immunobiology and current interventions with apheresis medicine.

Transplantation is the treatment of choice for end stage renal disease. Kidney transplants convey both a significant survival advantage to the individual recipient as well as cost savings to the medical system. Circulating alloantibodies directed against donor human leukocyte antigens and blood group antigens are fairly common among potential recipients. They are known to injure allografts, shorten allograft survival, and limit access to kidney transplantation. Hence, screening for pretransplant alloantibodies using complement dependent cytotoxic cross-matching and more sensitive techniques such as the solid phase assays, have become routine in an attempt to avoid incompatible donor-recipient pairs and risk stratify those with donor specific antibodies (DSA). By removing harmful antibodies, therapeutic apheresis (TA) has become a critical tool for improving access to transplantation in cases where the immunologic risk had previously been considered unacceptable. It has also allowed us to transplant across the barrier of ABO blood group incompatibility and expand the pool of donors with reasonable success. Furthermore, it is an important tool in the treatment of antibody-mediated rejection. Advanced apheresis technologies, such as immunoadsorption, and the use of TA in combination with innovative paired-donor exchange programs, offer the potential to further improve access and outcomes, minimizing the short comings of one single form of therapy alone.

Therapeutic apheresis in the elderly: an update.

Therapeutic apheresis medicine comprises many procedures, the most common being therapeutic plasma exchange (TPE). There is wide acceptance and use of TPE in the treatment of disease conditions that cut across several organ systems in the body and affect patients of various age groups. Patients that are 65 years or older form a significant cohort with increasing need for TPE. This brief report addresses special considerations in this cohort with useful comparisons made with younger cohorts as presented in the Therapeutic Apheresis Academy at the University of Virginia in September 2012.

Filter membrane-based automated therapeutic plasma exchange: a report of two cases from Nigeria.

These case reports demonstrated the diagnostic dilemma encountered in patients with systemic lupus erythematosus and thrombotic thrombocytopenic purpura particularly in settings with limited diagnostic facilities and laboratory support. The similarities in the diagnostic criteria for both conditions make clear distinction as well as management decisions difficult. We present the difficulties encountered with both the diagnosis and the management of these two patients that were managed in our facility.

Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the Writing Committee of the American Society for Apheresis: the sixth special issue.

The American Society for Apheresis (ASFA) JCA Special Issue Writing Committee is charged with reviewing, updating and categorizating indications for therapeutic apheresis. Beginning with the 2007 ASFA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence-based approach in the grading and categorization of indications. This Sixth Edition of the ASFA Special Issue has further improved the process of using evidence-based medicine in the recommendations by consistently applying the category and GRADE system definitions, but eliminating the "level of evidence" criteria (from the University HealthCare Consortium) utilized in prior editions given redundancy between GRADE and University HealthCare Consortium systems. The general layout and concept of a fact sheet that was utilized in the Fourth and Fifth Editions, has been largely maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. This article consists of 78 fact sheets (increased from 2010) for therapeutic indications in ASFA categories I through IV, with many diseases categorized having multiple clinical presentations/situations which are individually graded and categorized.

Association of echocardiographic abnormalities with mortality in men with non-dialysis-dependent chronic kidney disease.

BACKGROUND: The interrelationship of left ventricular hypertrophy (LVH) with ejection fraction (EF) and their impact on mortality in non-dialysis-dependent chronic kidney disease (NDD-CKD) is unclear. METHODS: We examined the associations of EF and LVH with all-cause mortality in a historic cohort of 650 male US veterans with moderate-to-advanced NDD-CKD. EF and LVH were examined both separately and after categorizing patients according to their concomitant EF and presence/absence of LVH. Associations with mortality were examined in Cox models with adjustments for demographics, blood pressure, comorbidities, smoking status, medication use and biochemical characteristics. RESULTS: EF <30 and 30-50% were associated with higher all-cause mortality compared to EF >50% even after multivariable adjustments [multivariable adjusted hazard ratio, 95% confidence interval (CI): 2.83 (1.86-4.30) and 1.38 (1.06-1.78), P < 0.001 for linear trend]. LVH in itself was not associated with mortality [multivariable adjusted hazard ratio, 95% CI: 0.83 (0.66-1.05), P = 0.12], but the presence of LVH combined with an EF <50% was associated with the highest mortality [multivariable adjusted hazard ratios, 95% CI in patients with EF >50% + LVH, EF ≤ 50%-LVH and EF ≤ 50% + LVH, compared to EF >50%-LVH: 0.84 (0.63-1.13), 1.36 (1.00-1.83) and 1.62 (1.07-2.46)]. CONCLUSIONS: Low EF is associated with higher mortality in patients with NDD-CKD. In the presence of a low EF, LVH is also associated with higher mortality. Clinical trials are needed to determine if interventions targeting patients with low EF and LVH can lower mortality in NDD-CKD.

Septic shock with multiorgan failure: from conventional apheresis to adsorption therapies.

Septic shock is often associated with multiorgan failure, a life threatening clinical condition during which there is an imbalance in the proinflammatory and anti-inflammatory cytokines, chemokines, antigens, endotoxins, procoagulant, and anticoagulant factors and also resultant effects of therapeutic intervention like volume overload. Various extracorporeal therapies have shown some positive results as adjunctive therapeutic intervention to traditional antimicrobials in an effort to bring the inflammatory mediators to a homeostatic balance and to improve poor organ perfusion caused by hypotension and thrombosis in the microcirculation. This review focuses on current information on the use of therapeutic apheresis procedures as adjunctive therapy in such clinical situations as well as the exciting prospects for the near future. The sometimes disappointing results of early phase clinical studies may, in some cases, be related to the well known barriers to successful clinical trials in critically ill patients rather than to failure of the novel concept of adjunctive extracorporeal treatment of septic shock. It should be noted that some of the specialized apheresis technologies reviewed in this article are not yet available for clinical use in the United States as they are not yet approved for use by the US Food and Drug Administration.

Medications in patients treated with therapeutic plasma exchange: prescription dosage, timing, and drug overdose.

Therapeutic plasma exchange (TPE) is an extracorporeal process commonly used in clinical medicine for the treatment of a variety of neurological, renal, hematological, dermatological, and other diseases. Inherent to the procedure, patients' plasma removal may lead to the extraction of drugs they are concurrently receiving. This review discusses the published literature assessing TPE's influence on different drug classes' disposition and, when applicable, sets forth management recommendations in cases where the drugs are used at the usual doses and in cases of drug overdose.