Correspondence

Correction

Rhabdomyolysis and Acute Kidney Injury

N Engl J Med 2009; 361:1411-1413October 1, 2009

Article

To the Editor:

Bosch and colleagues (July 2 issue)1 observe that although conventional hemodialysis filters do not remove myoglobin (molecular weight, 17.8 kD), hemodiafiltration with super-high-flux dialyzers may be effective.2 We used a hemodialysis prescription with a super-high-flux dialyzer (HCO-1100, Gambro) that efficiently removed molecules of up to 60 kD. In two patients with rhabdomyolysis and acute kidney injury, the mean serum myoglobin clearance with a single dialysis treatment was 59%.3 A 4-hour dialysis treatment cleared myoglobin from the equivalent of 9 liters of extravascular fluid (twice the intravascular volume). The kinetics of myoglobin that we observed were similar to the kinetics of free light chains (25 to 50 kD).4

The experience gained in the use of super-high-flux dialysis to remove free light chains in myeloma kidney (or cast nephropathy) should expedite the development of a randomized trial of the removal of myoglobin. A randomized, controlled trial of the use of super-high-flux dialysis to remove free light chains is 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@bham.ac.uk

5 References

1. 1

   Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med 2009;361:62-72
   Full Text | Web of Science | Medline

2. 2

   Ronco C. Extracorporeal therapies in acute rhabdomyolysis and myoglobin clearance. Crit Care 2005;9:141-142
   CrossRef | Web of Science | Medline

3. 3

   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
   CrossRef | Web of Science

4. 4

   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
   CrossRef | Web of Science | Medline

5. 5

   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 | Web of Science | Medline

To the Editor:

In their review article on rhabdomyolysis and acute kidney injury, Bosch et al. summarize the limited efficacy and prognostic impact of extracorporeal myoglobin removal by standard blood-purification techniques. New options are now possible given the availability of protein-permeable, high-cutoff filters in Europe (filing for approval by the U.S. Food and Drug Administration is in preparation). These filters are currently under investigation for elimination of nephrotoxic free light chains in cast nephropathy associated with multiple myeloma.1 With an in vivo molecular cutoff at 45 kD, high-cutoff filters are effective in eliminating the 17-kD molecule myoglobin.2 We have used high-cutoff hemodialysis for myoglobin removal in severe rhabdomyolysis. Myoglobin clearance with high-cutoff filters, corrected for membrane-surface area, is up to 20 times as high as myoglobin clearance with standard high-flux hemodialysis in intraindividual comparison. With the use of full-size, high-cutoff filters 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 plasma myoglobin concentration.

Nils Heyne, M.D.
Martina Guthoff, M.D.
Katja C. Weisel, M.D.
University of Tübingen, Tübingen, Germany
nils.heyne@med.uni-tuebingen.de

Dr. Heyne reports receiving lecture fees from Gambro.

No other potential conflict of interest relevant to this letter was reported.

2 References

1. 1

   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 | Web of Science | Medline

2. 2

   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

Author/Editor Response

Basnayake and colleagues comment on the potential use of extracorporeal removal of myoglobin with the use of super-high-flux dialysis membranes, and Heyne and colleagues suggest the use of high-cutoff membranes for this purpose. Although the experience with super-high-flux membranes or high-cutoff membranes may be encouraging, it is still limited. A number of questions about myoglobin metabolism, kinetics, and body distribution have not been answered, and these issues may complicate the application of the appropriate extracorporeal treatment in terms of frequency, duration, and intensity.1 In addition, high-cutoff membranes with reported molecular-weight cutoff values of approximately 50 kD (100 kD in the article by Naka et al.2) may be associated with unwanted losses of albumin or other components that may be dangerous for the patient. We believe that although these techniques are promising, randomized, controlled clinical trials will be necessary before they can be recommended. Therefore, we would emphasize that since conventional dialysis or standard hemofiltration has not achieved clinically significant myoglobin removal,1,3 and the experience with high-cutoff membranes or super-high-flux membranes is limited, at present, these techniques cannot be recommended for the preventive removal of myoglobin in rhabdomyolysis.

In Table 3 of our article, we recommend that volume replacement with normal saline solutions should be used for the prevention or treatment of rhabdomyolysis-induced acute kidney injury. The use of solutions containing bicarbonate is optional because their benefits have not been firmly demonstrated. Although slightly hypertonic bicarbonate solutions have been used by some investigators and are commonly used in some countries as 1/6 M sodium bicarbonate (1.4% sodium bicarbonate),3 we agree with others4,5 that they should be isotonic or even slightly hypotonic. Since normal saline, commonly called isotonic saline is in fact slightly hypertonic (154 mmol per liter of sodium and chloride), the alternation with 100 mmol of bicarbonate in 1 liter of 5% dextrose is the most appropriate option if alkalinization is used. If 0.45% saline is to be used, it should be combined with 50 to 70 mmol of bicarbonate (rather than the 100 mmol listed in Table 3 of our article). As recommended in the text, volume repletion and alkalinization in patients with rhabdomyolysis should be monitored by the frequent measurement of levels of urine pH and 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@clinic.ub.es

5 References

1. 1

   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

2. 2

   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

3. 3

   Peltonen S, Ahlstrom A, Kylavainio V, Honkanen E, Pettila 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

4. 4

   Sever MS, Vanholder R, Lameire N. Management of crush-related injuries after disasters. N Engl J Med 2006;354:1052-1063
   Full Text | Web of Science | Medline

5. 5

   Vanholder R, Sever MS, Erek E, Lameire N. Rhabdomyolysis. J Am Soc Nephrol 2000;11:1553-1561
   Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Dinna N. Cruz, Sean M. Bagshaw. (2011) Does continuous renal replacement therapy have a role in the treatment of rhabdomyolysis complicated by acute kidney injury?. Seminars in Dialysis 24:4, 417-420
   CrossRef

2. 2

   Bertrand Gondouin, Colin A. Hutchison. (2011) High Cut-off Dialysis Membranes: Current Uses and Future Potential. Advances in Chronic Kidney Disease 18:3, 180-187
   CrossRef

3. 3

   Kevin V. Lemley. (2010) When to initiate ACEI/ARB therapy in patients with type 1 and 2 diabetes. Pediatric Nephrology 25:10, 2021-2034
   CrossRef