Thursday, July 18, 2013

Extended High Cut-Off (HCO) Hemodialysis for Myeloma Cast Nephropathy

There has been much recent interest in novel extra-corporeal treatments for removal of nephrotoxic free light chains (FLC) in myeloma cast nephropathy. HCO dialyzers employ high flux membranes with particularly large pores (up to 50kDa Vs 15kDa for conventional high flux) facilitating the removal of large plasma proteins such as FLC (kappa and lambda light chains have molecular weights of 22kD and 45kD respectively). HCO-HD may also be potentially beneficial in rhabdomyolysis with myoglobin having a molecular weight of 17kDa.

Extra-corporeal removal has primarily been achieved using plasma exchange and has long been a controversial topic in nephrology. HCO dialyzers are much more efficient at clearing FLC compared to plasma exchange. Multiple case reports have suggested a benefit to early use of HCO-HD in cases of cast nephropathy and a study by Hutchinson CA et al demonstrated an early reduction in FLC to be associated with renal recovery. Another paper from the same group reported on 67 patients with AKI due to cast nephropathy who received HCO-HD with modern chemotherapy. The majority of patients had sustained reductions in serum FLC concentrations (76%) and a high rate of independence of dialysis (63%). The HD regime used Gambro HCO 1100 dialyzers and was aggressive, with almost daily 8-hour sessions for the 12 days. After this, the schedule drops back to alternate days and finally to three 6-hour sessions per week after day 21. My limited experience with this regime in 2 patients demonstrated a need for regular phosphate and albumin repletion and careful monitoring of other electrolytes.

Obviously HCO-HD will only remove FLC and will not stop their production. Therefore, for a sustained response, patients need to be a on a chemo-sensitive regime. The above studies have demonstrated that patients who need a break in chemotherapy do worse, as do those with signs of chronicity on renal biopsy.

The following criteria are suggested before considering HCO-HD in patients with AKI due to cast nephropathy:

1.       Chemo-sensitive regime; bortezomib is frequently employed

2.       High serum FLC levels (>500mg/l; usually much higher)

3.      Low levels of interstitial fibrosis & tubular dropout on biopsy (i.e. evidence of salvageable kidneys)

A randomized controlled trial, led by Dr. Hutchinson, in the UK is currently on-going (Eulite Trial) which will compare conventional high flux HD with HCO-HD in patients receiving chemotherapy (bortezomib or thalidomide plus dexamethasone). HCO-HD certainly appears to be more efficient than plasma exchange at reducing FLC levels but at this point, its precise role in the management of cast nephropathy is unclear. We await the Eulite trial to hopefully clarify the potential benefit of HCO dialysis in this situation.


Wael Hussein said...

Thanks for an interesting review. Hutchinson's 67 patients cohort showed the only factor that correlated with renal recovery was the reduced load of FLC. To my mind, if everything else is fixed, what makes the difference between those who achieved a reduction and those who did not would be the rate of generation; ie, the aggressiveness of their underlying myeloma. Results of the current RCT will be interesting as the all patients need dialysis anyway.
Do you use your current protocol for patients with high levels of FLT who have AKI NOT requiring dialysis by "traditional" indications? And is there any data that shows they probably end up with less severe renal outcomes?

Paul Phelan said...

Hey Wael. This protocol has been used in patients with AKI requiring HD, including the 2 patients in whom I have had experience. I agree that it is paramount to switch off generation of SFLC. However, chemotherapeutic regimes take time to reduce SFLC and as interstital scarring and subsequent irreversible renal injury may occur quickly (e.g. over several weeks), HCO-HD may be beneficial in quickly dropping the SFLC levels. We await the RCTs with interest.