High cut-off (HCO) dialyzers are specialized extracorporeal membranes designed with larger pore sizes and molecular weight cut-offs of approximately 45–60 kDa, permitting enhanced clearance of middle and large molecular weight solutes. Unlike conventional high-flux membranes, HCO dialyzers effectively remove pathogenic proteins such as serum free light chains (sFLCs), myoglobin, β2-microglobulin, and inflammatory mediators while preserving most essential plasma proteins. Their primary clinical application has been in multiple myeloma-associated cast nephropathy; however, recent evidence supports an expanding role in severe rhabdomyolysis-associated acute kidney injury (AKI).
The rationale for HCO dialysis is based on the molecular dimensions of pathogenic circulating proteins. Myoglobin, a 17.8 kDa heme protein released during rhabdomyolysis, readily passes through HCO membranes but is inadequately removed by standard high-flux dialysis. Excess circulating myoglobin contributes to renal vasoconstriction, oxidative tubular injury, and intratubular cast formation, culminating in pigment nephropathy and dialysis-dependent AKI. HCO membranes facilitate rapid extracorporeal myoglobin removal through enhanced diffusive and convective transport.
Recent literature has highlighted the utility of HCO dialysis and related extracorporeal blood purification strategies in severe rhabdomyolysis. In a 2024 case report of dengue-associated rhabdomyolysis with AKI, creatine phosphokinase (CPK) levels exceeded 2,000,000 U/L. The patient underwent extracorporeal blood purification using CRRT combined with cytokine adsorption therapy, resulting in progressive reductions in CPK and myoglobin levels alongside renal recovery. The report emphasized the growing importance of extracorporeal techniques capable of clearing large molecular toxins in severe rhabdomyolysis.
Similarly, studies evaluating HCO membranes in rhabdomyolysis-associated AKI have demonstrated marked reductions in serum myoglobin concentrations compared with standard high-flux membranes. One report showed a 50% reduction in serum myoglobin within four hours using HCO haemodialysis, whereas conventional high-flux dialysis failed to achieve meaningful clearance. Intermittent HCO haemodialysis has been reported to achieve myoglobin clearances up to 20-fold higher than standard modalities.
We have used this High cut off dialyser for a patient admitted with statin induced rhabdomyolysis with CPK of 21000 units and with reduction to 1200 units and significant symptomatic improvement in the patient.
The best-established indication for HCO dialyzers remains multiple myeloma-associated cast nephropathy. Removal of nephrotoxic κ and λ free light chains can reduce tubular injury and facilitate renal recovery when combined with rapid initiation of bortezomib-based chemotherapy. Trials such as MYRE and EuLITE demonstrated superior sFLC reduction with HCO dialysis compared with conventional high-flux dialysis, although survival and dialysis independence outcomes remain heterogeneous. Consequently, HCO dialysis is currently regarded as adjunctive therapy rather than definitive treatment.
Despite promising efficacy, HCO dialyzers are associated with important limitations. Albumin loss remains the principal adverse effect, especially during prolonged sessions, occasionally necessitating albumin supplementation. Additional drawbacks include higher treatment costs, need for extended dialysis sessions, and limited randomized controlled trial data. Nevertheless, the emergence of medium cut-off (MCO) membranes and adsorption-based technologies has renewed interest in extracorporeal large-molecule removal strategies in critical care nephrology.
In conclusion, HCO dialyzers represent an important advancement in extracorporeal blood purification. While their established role is in myeloma cast nephropathy, recent evidence supports expanding use in severe rhabdomyolysis-associated AKI, particularly in patients with markedly elevated myoglobin and CPK levels. Rapid extracorporeal toxin clearance may reduce renal injury, improve biochemical recovery, and potentially shorten dialysis dependence in selected critically ill patients.
References:
- Samarasingha P, Karunatilake H, Jayanaga A, et al. Dengue rhabdomyolysis successfully treated with hemoperfusion using CytoSorb® in combination with continuous renal replacement therapy: a case report. J Med Case Rep. 2024;18:329.
- Bottari G, Guzzo I. How I treat rhabdomyolysis-induced AKI? A different perspective. G Ital Nefrol. 2024.
- Gubensek J, Persic V, Jerman A, et al. Extracorporeal myoglobin removal in severe rhabdomyolysis with high cut-off membranes. Crit Care. 2021;25:97.
- Heyne N, Guthoff M, Krieger J, et al. High cut-off renal replacement therapy for removal of myoglobin in severe rhabdomyolysis and acute kidney injury: a case series. Nephron Clin Pract. 2012;121:c159–c164.
- Xing Y, Yan J, Yu Z, et al. High-cutoff hemodialysis in multiple myeloma patients with acute kidney injury. Front Oncol. 2022;12:1024133.
Dr Rashmi Shivram
Associate Consultant, Department of Nephrology,
Kauvery Hospital, Chennai.[1]
Dr. Balasubramaniyam. R
HOD, Department of Nephrology,
Kauvery Hospital, Chennai.[1]
Dr. Balaji Kirushnan
Senior Consultant, Department of Nephrology,
Kauvery Hospital, Chennai.[1]