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.
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.
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.
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:
considering HCO-HD in patients with AKI due to cast nephropathy:
1.
Chemo-sensitive regime;
bortezomib is frequently employed
Chemo-sensitive regime;
bortezomib is frequently employed
2.
High serum FLC levels (>500mg/l;
usually much higher)
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)
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.
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.
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.
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?