Is Hemodialysis (HD) more effective than Continuous Renal Replacement Therapy (CRRT) for removing myoglobin?

Myoglobin Removal: HD vs CRRT

Intermittent hemodialysis (HD) is superior to continuous renal replacement therapy (CRRT) for myoglobin removal in rhabdomyolysis-associated acute kidney injury, achieving clearances up to 44 ml/min with high cut-off filters compared to 3-22 ml/min with standard CRRT modalities. 1

Evidence for HD Superiority

Clearance Rates with Standard Filters

• Conventional HD achieves myoglobin clearance of 3.7 ml/min with standard high-flux filters, while CRRT (continuous venovenous hemofiltration) achieves similar rates of 3.3 ml/min with sustained low-efficiency daily dialysis (SLEDD). 1
• Standard CRRT modalities demonstrate limited efficacy for myoglobin removal due to the molecule's relatively high molecular weight of 17.8 kDa. 1, 2

High Cut-Off Filter Technology

• HD using high cut-off (HCO) dialyzers achieves myoglobin clearance of 44.2 ml/min, representing up to 20-fold higher clearance compared to standard filters. 1
• HCO filters with molecular cut-off at 45 kDa are specifically effective for myoglobin (17.8 kDa) removal, producing profound and sustained reduction in plasma myoglobin concentration. 1
• CRRT with HCO dialyzers achieves lower clearance (21.7 ml/min with SLEDD) compared to intermittent HD with the same filter type. 1

CRRT Limitations for Myoglobin

• The sieving coefficient for myoglobin in CRRT decreases significantly over time (from 0.6 to 0.4 within 16 hours), likely due to protein coating and blood clotting of the hemofilter, reducing overall efficiency. 2
• While CVVH at 2-3 L/h can remove considerable amounts of myoglobin (>700 mg during treatment), the declining sieving coefficient limits sustained clearance. 2
• A 2020 randomized trial comparing CVVHD with HCO dialyzer versus CVVHDF with high-flux dialyzer showed better myoglobin clearance with the HCO approach, but this still represents CRRT modality limitations compared to intermittent HD. 3

Clinical Context and Practical Considerations

When to Choose HD

• For hemodynamically stable patients with severe rhabdomyolysis requiring rapid myoglobin removal, intermittent HD with HCO filters should be the preferred modality. 1
• HD allows for more aggressive myoglobin clearance in shorter treatment times, which may improve renal recovery by reducing kidney exposure to nephrotoxic myoglobin. 1
• In tumor lysis syndrome (a similar scenario requiring rapid solute removal), HD achieves uric acid clearance of 70-100 ml/min with 50% reduction per 6-hour treatment, demonstrating superior diffusive clearance for middle molecules. 4

When CRRT May Be Considered

• For hemodynamically unstable patients, CRRT remains the preferred modality despite inferior myoglobin clearance, as it provides greater hemodynamic stability and better fluid balance control. 4, 5
• CRRT is indicated when pulmonary edema, severe volume overload, or cardiovascular instability preclude intermittent HD. 4
• In critically ill ICU patients with multiorgan failure, CRRT allows continuous metabolite removal and facilitates nutritional support delivery. 4

Important Caveats

Filter Selection Matters

• Standard high-flux dialyzers provide inadequate myoglobin clearance regardless of modality (HD or CRRT). 1
• HCO filters are essential for effective myoglobin removal but require careful monitoring for albumin loss, though studies show no measurable albumin clearance with appropriate filter selection. 3
• Medium cut-off (MCO) dialyzers in HD produce similar removal of β2-microglobulin and myoglobin as online hemodiafiltration without compromising nutritional status. 6

Treatment Frequency

• Daily HD treatments may be necessary in severe rhabdomyolysis given the continuous release of myoglobin from damaged muscle tissue. 4
• The timing and frequency of dialysis should be linked to the myoglobin generation rate and clinical response. 4

Mortality Considerations

• A 2022 secondary analysis of AKIKI and IDEAL-ICU trials found that CRRT as first modality conveyed no survival benefit compared to IHD and might be associated with less favorable outcomes in patients with lesser disease severity. 7
• In severe rhabdomyolysis, dialysis-dependent AKI doubles mortality, making effective myoglobin removal critically important. 1