Dr Barbara Grunseit
Director of Medical Services
Concord Repatriation General Hospital
Dear Barbara,
We like to submit the proposed protocol for treatment of acute renal failure due to cast
nephropathy to the hospital.
As outlined in the protocol attached, free light chain deposition in setting of multiple myeloma can
result in irreversible kidney damage associated with high morbidity, mortality and cost. Recent
observational and non randomised trials have looked at prompt removal of free light chains by
specialized dialysis membranes with very large pores (‘high cut-off membranes’) used in conjunction
with chemotherapy and have shown encouraging results in regards to recovery of renal function.
Like many other units in Australia, we agree that currently available evidence favours the use of this
therapy in a selected population with acute renal failure due to cast nephropathy. Inclusion,
exclusion and the treatment regimen are outlined in the proposed submission below. Current cost of
the membrane is at $1470.00 (ex. GST) per membrane. We anticipate having 1-3 patients per year
who would qualify to receive this therapy and each case to require an average of 18 membranes.
Predictions derived from the available economic model and pilot studies favour this therapy as more
cost- effective compared to conventional therapy in terms of the cost to the health care system of
permanent dialysis in these patients. Indeed the Victorian government is currently funding the
membranes for this reason.
As a unit, we appreciate your consideration in regards to approving this therapy in the hospital.
Yours sincerely
Proposed protocol for High cut-off membrane dialysis for treatment of cast
nephropathy
Rationale:
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Cast nephropathy due to overproduction of free light chains (FLC) is a common
and serious complication of multiple myeloma which can result in severe renal
injury.
Untreated this can cause irreversible renal injury with the requirement for
permanent dialysis and the subsequent high morbidity, mortality and costs.
High cut off dialysis membranes (HCO) have larger pore size than conventional
dialysis membranes, allowing increased permeability to larger molecular weight
proteins. Several prospective studies have shown that, in selected patients, using
such high cut off membranes in combination with chemotherapy provides a rapid
and sustained reduction in toxic FLC. These studies suggest such therapy is an
effective means of recovering renal function in the setting of acute renal failure
due to cast nephropathy and have been associated with improved renal function,
survival and dialysis independence.
Based on a cost analysis model, HCO- dialysis compared to standard
haemodialysis results in greater life expectancy (30.04 and 16.52 months
respectively) and cost savings due to avoidance of the need for chronic dialysis
Currently a multi-centre randomised control trial is under way to further evaluate
this treatment (EuLITE trial)
Inclusion:
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Dialysis dependent acute renal failure or severe acute renal failure (GFR < 15ml/min)
shown to be primarily due to cast nephropathy on contemporaneous (within 4 weeks)
renal biopsy
Multiple myeloma and planned for concurrent (Bortezomib based) chemotherapy
Abnormal free light chain ratio and serum free light chain > 500mg/l
Exclusion:
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Known advanced CKD (GFR<30ml/min) or evidence of significant fibrosis on renal
biopsy
Previous relapse on chemotherapy except when reasonable response to Bortezomib
based chemotherapy is expected
Hemodynamic instability precluding dialysis therapy
Advanced disease or other co-morbidities (cardiac dysfunction, liver dysfunction, and
peripheral neuropathy) with poor prognosis
Known allergy to mannitol or boron
Active sepsis or HIV
Pregnant or lactating women
Proposed protocol:
5 days of daily dialysis, then second daily dialysis to a total of 3 weeks of treatment
Day
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Date
HCO dialysis
single filter dialysis for 6 hours
theralite filter dialysis for 8 hour
theralite filter dialysis for 8 hour
theralite filter dialysis for 8 hour
theralite filter dialysis for 8 hour
theralite filter dialysis for 8 hour
theralite filter dialysis for 8 hour
theralite filter dialysis for 8 hour
theralite filter dialysis for 8 hour
Chemotherapy
Bortezomib+Dox+Dex
Dex
Dex
Bortezomib+ Dox+Dex
Bortezomib+Dex
Dex
Dex
Bortezomib+Dex
theralite filter dialysis for 8 hour
theralite filter dialysis for 8 hour
theralite filter dialysis for 8 hour
theralite filter dialysis for 8 hour
theralite filter dialysis for 8 hour
theralite filter dialysis for 8 hour
theralite filter dialysis for 8 hour
theralite filter dialysis for 8 hour
theralite filter dialysis for 8 hour
Dex
Dex
Dex
Dex
Bortezomib+Dox
Note: If a dialysis day falls on a Sunday, the session will be delayed to the next nonBortezomib weekday
Note:
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Albumin replacement at the end of each session
Pre and post dialysis urea and creatinine and electrolytes for each session
Pre dialysis Calcium and magnesium replacement (if low)
Pre and post dialysis FLC on days 1,5,12 and 21
If chemotherapy needs to be stopped or withheld for medical reasons, patients will be
withdrawn from HCO extended dialysis regimen and revert to standard care
Monitor:
 Individual case review by the haematologist and the nephrologist at completion of
first chemotherapy cycle (18th cycle of theralite filter dialysis) or earlier for
assessment response
 Demographic, clinical details and outcomes of each patient receiving this therapy
would be entered into a database
 The protocol would be revised at 18 months or earlier pending results of the ongoing
RCT or other emerging evidence