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. J. Clin. Apheresis 28:145–284, 2013. © 2013 Wiley Periodicals, Inc.

Guidelines on the use of therapeutic apheresis in clinical practice - Evidence-based approach from the writing committee of the american society for apheresis

Hypertriglyceridemia (HTG) is a well-established but underestimated cause of acute pancreatitis and recurrent acute pancreatitis. The clinical presentation of HTG-induced pancreatitis (HTG pancreatitis) is similar to other causes. Pancreatitis secondary to HTG is typically seen in the presence of on

/pdf/issues-in-hypertriglyceridemic-pancreatitis-an-update-2ek0z0y19j.pdf

Issues in Hypertriglyceridemic Pancreatitis - An Update

The coagulation system has gained much interest again as new anticoagulatory substances have been introduced into clinical practice. Especially patients with renal failure are likely candidates for such a therapy as they often experience significant comorbidity including cardiovascular diseases that require anticoagulation. Patients with renal failure on new anticoagulants have experienced excessive bleeding which can be related to a changed pharmacokinetic profile of the compounds. However, the coagulation system itself, even without any interference with coagulation modifying drugs, is already profoundly changed during renal failure. Coagulation disorders with either episodes of severe bleeding or thrombosis represent an important cause for the morbidity and mortality of such patients. The underlying reasons for these coagulation disorders involve the changed interaction of different components of the coagulation system such as the coagulation cascade, the platelets and the vessel wall in the metabolic conditions of renal failure. Recent work provides evidence that new factors such as microparticles (MPs) can influence the coagulation system in patients with renal insufficiency through their potent procoagulatory effects. Interestingly, MPs may also contain microRNAs thus inhibiting the function of platelets, resulting in bleeding episodes. This review comprises the findings on the complex pathophysiology of coagulation disorders including new factors such as MPs and microRNAs in patients with renal insufficiency.

/pdf/haemostasis-in-chronic-kidney-disease-54sur1yagk.pdf

Haemostasis in chronic kidney disease

Current knowledge of hypertriglyceridemic pancreatitis.

Rhabdomyolysis, a clinical syndrome caused by damage to skeletal muscle and release of its breakdown products into the circulation, can be followed by acute kidney injury (AKI) as a severe complication. The belief that the AKI is triggered by myoglobin as the toxin responsible appears to be oversimplified. Better knowledge of the pathophysiology of rhabdomyolysis and following AKI could widen treatment options, leading to preservation of the kidney: the decision to initiate renal replacement therapy in clinical practice should not be made on the basis of the myoglobin or creatine phosphokinase serum concentrations.

/pdf/acute-kidney-injury-due-to-rhabdomyolysis-and-renal-3yinafh1gy.pdf

Acute kidney injury due to rhabdomyolysis and renal replacement therapy: a critical review

Of the cases of acute pancreatitis, 1-7% are caused by severe hypertriglyceridemia and can be treated with plasma exchange (PE). We report on a large series of patients with acute hyperlipidemic pancreatitis (HLP) treated with PE. In the 1992-2008 period, 50 patients (45 +/- 8 years old, 92% male) with acute HLP were treated with PE, during which 1-2 plasma volumes were exchanged. Heparin was used as anticoagulant in 85% of the procedures, and citrate in the rest. Cholesterol and triglycerides were measured before and after PE. In the 2003-2008 cohort of 40 patients, we retrospectively recorded an Acute Physiology and Chronic Health Evaluation II (APACHE II) score at the first PE session, hospital mortality, and length of hospital stay. A total of 79 PE treatments were done, 1-5 per patient. The volume exchanged was 4890 +/- 1300 mL over a duration of 3.5 +/- 2 h. During the first PE, the triglycerides were lowered from 58.9 +/- 40.8 to 10.8 +/- 10.8 mmol/L, and the total cholesterol was lowered from 20.0 +/- 7.6 to 5.7 +/- 4.3 mmol/L. In 10% of the procedures the plasmafilter was replaced, and in 3% the filter was clotted. Hypotension occurred in 3% of PE and there was one case of gastrointestinal bleeding after PE with heparin anticoagulation. In the 2003-2008 cohort, the median APACHE II score was 5 (range 0-15), the median overall hospital stay was 18 days (range 3-142 days) and the hospital mortality was 15%. To conclude, in acute hyperlipidemic pancreatitis, one to two plasma exchanges effectively reduce the serum triglyceride level. There is a low rate of procedure-related complications. A mortality rate of 15% is considerable.

Treatment of Hyperlipidemic Acute Pancreatitis With Plasma Exchange: A Single‐Center Experience

Serum creatine kinase (CK) is routinely used as a marker in the assessment of rhabdomyolysis and acute myoglobinuric kidney injury (Mb-AKI), while the use of myoglobin is much less explored in this respect. We retrospectively analyzed the incidence of Mb-AKI (creatinine [Cr] > 200 μmol/L) and the need for hemodialysis (HD) in 484 patients (70.5% males) with suspected rhabdomyolysis, grouped according to peak serum myoglobin (A: 1-5 mg/L, B: 5-15 mg/L, C: >15 mg/L). The median peak myoglobin was 7163 μg/L. Both peak Cr and peak CK were significantly higher in group C. The incidence of Mb-AKI was 24.6% in group A, 38.6% in group B (P 20 mg/L. Creatine kinase correlated with the severity of rhabdomyolysis, but less so with Mb-AKI. The peak Cr levels were not significantly different between patients divided by CK 60 μkat/L, or grouped into CK tertiles or quartiles. A significant proportion of patients with rhabdomyolysis experienced Mb-AKI, whose frequency increased in parallel with myoglobin levels. Myoglobin levels above 15 mg/L were most significantly related to the development of AKI and the need for HD. Blood myoglobin could serve as a valuable early predictor and marker of rhabdomyolysis and Mb-AKI.

Use of myoglobin as a marker and predictor in myoglobinuric acute kidney injury

Acute renal failure is a major complication of rhabdomyolysis. New membranes for hemodialysis have been developed with a high cut-off pore size allowing efficient removal of myoglobin. We report on six patients treated by hemodiafiltration with a high cut-off membrane (HCO-HDF) for myoglobinuric acute renal failure. Rhabdomyolysis was caused by infection in two patients, by a statin in one patient and a non-traumatic crush in another, and followed cardiovascular surgery in two others. Ten HCO-HDF procedures were performed. A high cut-off hemofilter was used, with citrate anticoagulation and postdilutional fluid substitution of 2-3 L/h, dialysate flow 500 mL/min, and blood flow within 250-300 mL/min. Albumin losses were replaced by infusion of human albumin solution, and the mean myoglobin reduction ratio was 77% (range, 62-89%). An excellent clearance of 81 mL/min (range 42-131 mL/min) was achieved. Nearly 5 g of myoglobin was removed into the dialysate collected in one of the procedures. A high rebound in serum myoglobin, on average to 244% of the post-procedure myoglobin level, was observed. The four patients alive at the time remained anuric for a week. Slow myoglobin elimination with a mean half-time of 39 h (range 19-59 h) was observed in that period. Highly efficient myoglobin removal by high cut-off membrane hemodiafiltration was demonstrated in our patients. Rapid redistribution from the extracellular fluid and sustained myoglobin release were suggested by the high rebound observed. Elimination of myoglobin within the body was shown in our study to occur slowly during the period of anuria.

High Cut‐Off Membrane Hemodiafiltration in Myoglobinuric Acute Renal Failure: A Case Series

Background Antibody-mediated rejection (AMR) of a kidney graft has been increasingly recognized as an important cause of graft failure. Our historic cohort study sought to analyze its treatment and outcomes at our center. Methods All patients with AMR between 2005 and 2011 were treated with plasma exchange (PE), intravenous low-dose cytomegalovirus (CMV) hyperimmune globulin, and adjustment of basal immunosuppression. We analyzed data regarding baseline characteristics, rejection treatment with focus on PE, complications, and 1-year outcomes. Results Twenty-three AMRs occurred in 23 patients (10 male, 13 female) of mean age 41 ± 16 years, all recipients of deceased-donor kidneys with a median of 3 HLA mismatches. The subjects had a median peak panel-reactive antibodies (PRA) of 7% (interquartile range [IQR] 1%–10%). Basal serum creatinine was 174 ± 84 μmol/L estimated glomerular filtration rate (eGFR) (eGFR 42 ± 22 mL/min/1.73 m2), while 3 patients were dialysis- dependent. Median period between transplantation and rejection was 38 months (IQR 1.5–88.5). Concomitant T-cell–mediated rejection was treated in 78% of cases. Median number of PE procedures per patient was 10 (range, 5–17). Treatment was estimated to be successful in 83%. Donor-specific antibodies documented in 12 patients (52%) disappeared or showed reduced titers in 7/10 patients with repeated measurements. An infection was present during treatment in 7 (30%) patients. Among 237 PE, there was 1 (0.4%) mild allergic reaction to fresh frozen plasma and significant metabolic alkalosis occurred after 7 (3%) procedures. One year after rejection the mean serum creatinine level was 144 ± 52 μmol/L and Kaplan-Meier estimated graft and patient survival rates were 62% and 95%, respectively. Conclusions Intensive treatment with PE, intravenous immunoglobulin, and adjustment of basal immunosuppression were safe and effective to reverse AMR with improved graft function in the majority of patients. However, AMR was associated with markedly decreased 1-year graft survival and the optimal treatment remains uncertain.

Plasma exchange and intravenous immunoglobulin in the treatment of antibody-mediated rejection after kidney transplantation: a single-center historic cohort study.

Introduction An elevated serum concentration of soluble the form of CD30 (sCD30), an activation marker of mainly T H 2-type cytokines producing T lymphocytes, has been reported as a predictive factor for acute cellular rejection episodes and poor graft outcomes in kidney transplantation. This historic cohort study investigated the association of a pretransplant sCD30 serum concentrations with kidney graft function and graft survival 3 years posttransplantation in adult recipients of deceased donor kidney grafts, treated with monoclonal anti-CD25 antibodies as an induction treatment combined with a cyclosporine (CsA)-based maintenance triple therapy. Materials and Methods The pretransplant sera of 296 recipients were tested for sCD30 content using a microsphere flow-cytometry assay. The estimated glomerular filtration rate (eGFR) was determined by the 4-variable Modification of Diet in Renal Disease equation. The incidences of graft loss were calculated with the use of Kaplan-Meier survival analysis and compared using the log-rank test. Results According to the distribution of the pretransplant sCD30 levels concentration ≥2700 pg/mL was defined as high ( n = 146) and concentration n = 150). Three years posttransplantation, the eGFR was not significantly different in the recipients in high and low sCD30 groups (65 ± 24 vs 67 ± 21 mL/min/1.73 m 2 ; P = .43); there was no association between the eGFR 3 years after transplantation and the pretransplant sCD30 levels ( r 2 = 0.002; P = .49). Graft survival 3 years after transplantation was also not different in the recipients in high and low sCD30 groups ( P = .52). Conclusion In our adult deceased-donor kidney graft recipients, the pretransplant sCD30 serum concentration was not a predictive factor of immunologic risk associated with the kidney graft function 3 years posttransplantation; neither did it affect graft survival 3 years after transplantation. The immunosuppression with anti-CD25 antibodies as an induction treatment combined with the CsA-based maintenance triple therapy could possibly be decisive for our findings.

Janko Kovač

Papers

Treatment of Hyperlipidemic Acute Pancreatitis With Plasma Exchange: A Single‐Center Experience

Use of myoglobin as a marker and predictor in myoglobinuric acute kidney injury

High Cut‐Off Membrane Hemodiafiltration in Myoglobinuric Acute Renal Failure: A Case Series

Plasma exchange and intravenous immunoglobulin in the treatment of antibody-mediated rejection after kidney transplantation: a single-center historic cohort study.

Pretransplant soluble CD30 serum concentration does not affect kidney graft outcomes 3 years after transplantation.