To the Editor: Bosch and colleagues (July 2 issue)1 observethat although conventional hemodialysis filters do not removemyoglobin (molecular weight, 17.8 kD), hemodiafiltration withsuper-high-flux dialyzers may be effective.2 We used a hemodialysisprescription with a super-high-flux dialyzer (HCO-1100, Gambro)that efficiently removed molecules of up to 60 kD. In two patientswith rhabdomyolysis and acute kidney injury, the mean serummyoglobin clearance with a single dialysis treatment was 59%.3A 4-hour dialysis treatment cleared myoglobin from the equivalentof 9 liters of extravascular fluid (twice the intravascularvolume). The kinetics of myoglobin that we observed were similarto the kinetics of free light chains (25 to 50 kD).4
The experience gained in the use of super-high-flux dialysisto remove free light chains in myeloma kidney (or cast nephropathy)should expedite the development of a randomized trial of theremoval of myoglobin. A randomized, controlled trial of theuse of super-high-flux dialysis to remove free light chainsis under way.5
Kolitha Basnayake, M.B., B.S. Paul Cockwell, Ph.D. Colin A. Hutchison, Ph.D. University of Birmingham Birmingham, United Kingdom k.basnayake{at}bham.ac.uk
References
Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med 2009;361:62-72. [Free Full Text]
Ronco C. Extracorporeal therapies in acute rhabdomyolysis and myoglobin clearance. Crit Care 2005;9:141-142. [CrossRef][Web of Science][Medline]
Hutchison CA, Harding S, Basnayake K, Bradwell AR, Cockwell P. Myoglobin removal by high cut-off hemodialysis: in-vivo studies. J Am Soc Nephrol 2007;18:250A-250A.
Hutchison CA, Cockwell P, Reid S, et al. Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: in vitro and in vivo studies. J Am Soc Nephrol 2007;18:886-895. [Free Full Text]
Hutchison CA, Cook M, Heyne N, et al. European trial of free light chain removal by extended haemodialysis in cast nephropathy (EuLITE): a randomised control trial. Trials 2008;9:55-55. [CrossRef][Medline]
To the Editor: In their review article on rhabdomyolysis andacute kidney injury, Bosch et al. summarize the limited efficacyand prognostic impact of extracorporeal myoglobin removal bystandard blood-purification techniques. New options are nowpossible given the availability of protein-permeable, high-cutofffilters in Europe (filing for approval by the U.S. Food andDrug Administration is in preparation). These filters are currentlyunder investigation for elimination of nephrotoxic free lightchains in cast nephropathy associated with multiple myeloma.1With an in vivo molecular cutoff at 45 kD, high-cutoff filtersare effective in eliminating the 17-kD molecule myoglobin.2We have used high-cutoff hemodialysis for myoglobin removalin severe rhabdomyolysis. Myoglobin clearance with high-cutofffilters, corrected for membrane-surface area, is up to 20 timesas high as myoglobin clearance with standard high-flux hemodialysisin intraindividual comparison. With the use of full-size, high-cutofffilters for 2.1 m2 of membrane-surface area (Theralite, Gambro),myoglobin clearances in excess of 70 ml per minute can be obtained,resulting in a rapid and highly effective reduction of the plasmamyoglobin concentration.
Nils Heyne, M.D. Martina Guthoff, M.D. Katja C. Weisel, M.D. University of Tübingen Tübingen, Germany nils.heyne{at}med.uni-tuebingen.de
Dr. Heyne reports receiving lecture fees from Gambro. No otherpotential conflict of interest relevant to this letter was reported.
References
Hutchison CA, Cook M, Heyne N, et al. European trial of free light chain removal by extended haemodialysis in cast nephropathy (EuLITE): a randomised control trial. Trials 2008;9:55-55. [CrossRef][Medline]
Naka T, Jones D, Baldwin I, et al. Myoglobin clearance by super high-flux hemofiltration in a case of severe rhabdomyolysis: a case report. Crit Care 2005;9:R90-R95. [CrossRef][Web of Science][Medline]
The authors reply: Basnayake and colleagues comment on the potentialuse of extracorporeal removal of myoglobin with the use of super-high-fluxdialysis membranes, and Heyne and colleagues suggest the useof high-cutoff membranes for this purpose. Although the experiencewith super-high-flux membranes or high-cutoff membranes maybe encouraging, it is still limited. A number of questions aboutmyoglobin metabolism, kinetics, and body distribution have notbeen answered, and these issues may complicate the applicationof the appropriate extracorporeal treatment in terms of frequency,duration, and intensity.1 In addition, high-cutoff membraneswith reported molecular-weight cutoff values of approximately50 kD (100 kD in the article by Naka et al.2) may be associatedwith unwanted losses of albumin or other components that maybe dangerous for the patient. We believe that although thesetechniques are promising, randomized, controlled clinical trialswill be necessary before they can be recommended. Therefore,we would emphasize that since conventional dialysis or standardhemofiltration has not achieved clinically significant myoglobinremoval,1,3 and the experience with high-cutoff membranes orsuper-high-flux membranes is limited, at present, these techniquescannot be recommended for the preventive removal of myoglobinin rhabdomyolysis.
In Table 3 of our article, we recommend that volume replacementwith normal saline solutions should be used for the preventionor treatment of rhabdomyolysis-induced acute kidney injury.The use of solutions containing bicarbonate is optional becausetheir benefits have not been firmly demonstrated. Although slightlyhypertonic bicarbonate solutions have been used by some investigatorsand are commonly used in some countries as 1/6 M sodium bicarbonate(1.4% sodium bicarbonate),3 we agree with others4,5 that theyshould be isotonic or even slightly hypotonic. Since normalsaline, commonly called isotonic saline is in fact slightlyhypertonic (154 mmol per liter of sodium and chloride), thealternation with 100 mmol of bicarbonate in 1 liter of 5% dextroseis the most appropriate option if alkalinization is used. If0.45% saline is to be used, it should be combined with 50 to70 mmol of bicarbonate (rather than the 100 mmol listed in Table3 of our article). As recommended in the text, volume repletionand alkalinization in patients with rhabdomyolysis should bemonitored by the frequent measurement of levels of urine pHand serum bicarbonate, potassium, and calcium.
Esteban Poch, M.D., Ph.D. Xavier Bosch, M.D., Ph.D. Josep M. Grau, M.D., Ph.D. Hospital Clinic of Barcelona Barcelona, Spain jmgrau{at}clinic.ub.es
References
Mikkelsen TS, Toft P. Prognostic value, kinetics and effect of CVVHDF on serum of the myoglobin and creatine kinase in critically ill patients with rhabdomyolysis. Acta Anaesthesiol Scand 2005;49:859-864. [CrossRef][Web of Science][Medline]
Naka T, Jones D, Baldwin I, et al. Myoglobin clearance by super high-flux hemofiltration in a case of severe rhabdomyolysis: a case report. Crit Care 2005;9:R90-R95. [CrossRef][Web of Science][Medline]
Peltonen S, Ahlström A, Kylävainio V, Honkanen E, Pettilä V. The effect of combining intermittent hemodiafiltration with forced alkaline diuresis on plasma myoglobin in rhabdomyolysis. Acta Anaesthesiol Scand 2007;51:553-558. [CrossRef][Web of Science][Medline]
Sever MS, Vanholder R, Lameire N. Management of crush-related injuries after disasters. N Engl J Med 2006;354:1052-1063. [Free Full Text]
Vanholder R, Sever MS, Erek E, Lameire N. Rhabdomyolysis. J Am Soc Nephrol 2000;11:1553-1561. [Free Full Text]
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