The concept of HCO-HD is based on a new technology of protein permeable dialyzers which efficiently remove FLC molecules.
18–
21 The new haemodialysis membrane has a molecular weight cutoff similar to that of the normal kidney (approximately 65 kD).
18 On the other hand, conventional dialysis is limited to remove only large uraemic toxins by their specific molecular weight cut-off. The recent introduction of the HCO-HD technology allows clinicians to use these membranes for the treatment of MM nephropathy with efficient elimination of high cut-off FLC molecular weight.
18–
21 In contrast, previously described plasma exchange (PE) removes only intravascular FLC in significant quantities; however, shortly thereafter, there is a rapid accumulation of FLC from the extra-vascular compartment into the intra-vascular compartment.
24 Accordingly, the FLC levels return to their pre-treatment baseline without change.
24 In contrast, HCO-HD allows an extended treatment, with subsequent redistribution of extra-vascular FLC into the intravascular compartment. By using this method, there are no significant additional side effects recorded in our cohort beyond the conventional haemodialysis. However, at least, in an ex-vivo study, there might be an increased plasma protein loss including albumin, coagulation factors, growth factors and hormones.
25 Therefore, specific trials to examine this theory are warranted.
Our study was conducted under the assumption that; HCO-HD was an efficient way to reduce FLC concentration in MM patients; HCO-HD is more effective when the patients are diagnosed and treated early; and that chemotherapy is a necessary part of the treatment therapy.
2,
11Our study showed that HCO-HD is an effective means of reducing FLC concentration in MM patients, as all of the patients, except for patient 3, showed a large decrease in their FLC concentration and improved renal function as a result of the HCO-HD. Patient 3 may not have shown the same results because he had relapsed MM and therefore HCO-HD and salvage treatment did not achieve a favorable outcome. From this a further point can be drawn that patients who achieved a low FLC level and restored their renal function early on during the treatment of MM had a better chance of becoming dialysis-independent.
2,
11Patients 1, 2 and 4 had de-novo myeloma and when treated they became dialysis-independent. Patient 3 had relapsed MM and showed little response to the treatment. Patient 3 remained dialysis-dependent. This may be due to established myeloma nephropathy and possibly more renal damage, such as scarring and possible fibrosis to the kidneys and in particular the nephrons. This highlights that early treatment provides a greater likelihood of the patient becoming dialysis-independent.
This study demonstrated that the FLC concentration would rebound on successive days unless the chemotherapy was effective. Consequently whilst HCO-HD is effective in managing myeloma nephropathy, chemotherapy is also an important component of the treatment as it treats the actual disease. The chemotherapy treatment must be suited to the individual or it will not work as well. Patient 2 initially started with thalidomide and dexamethasone but showed little to no results, the chemotherapy was changed to a bortezomib containing regimen and thereafter the patient’s response was dramatically improved. This may be explained by the fact that different therapies have different effects on the myeloma kidney disease. For example bortezomib inhibits the 26S proteasome inhibitor and works down that pathway.
14,
22 Studies have also found that bortezomib is ideal for patients with renal injury because it reduces the serum cystatin-C level and also interferes with active nuclear factor kappa-B in renal epithelial cells and hence improves renal disease.
11,
14 Other drugs may not work in this way. Thus it is important to use the most appropriate course of therapy for the individual patient.
Our study also showed that HCO-HD is effective when combined with specific myeloma therapy, especially bortezomib. Without long-term effective control of MM with proper chemotherapy, patients with renal failure will inevitably have a progression of their renal nephropathy because the underlying disease has not been addressed. Thus, mechanical removal of serum FLC through HCO-HD only, is not enough without specific myeloma therapy. When HCO-HD is coupled with other therapies it can be used to manage the disease and its effects; hence improving patient’s survival. Other studies have also found that overall survival increased, from no less than 2 years to 7 years with the introduction of novel therapies.
11 An increased efficiency of HCO-HD could further increase the overall survival while improving quality of life, as recent studies emphasise the importance of this aspect of the treatment.
23Multiple myeloma associated with some degree of renal impairment is responsible for approximately 1% of malignancies, 13% of these malignancies being haematological malignancies.
11 Therefore, it is important that patients with unexplained renal failure undergo specific investigations to exclude MM, especially with the easily performed serum FLC test among other tests. If the nephropathy can be linked to MM, specific treatment for MM with HCO-HD and chemotherapy should start without delay. This would result in a favourable outcome as we demonstrated in our study.
The outcome of our study is consistent with findings from other studies.
14–
16 However, in our cohort of patients we found that early reduction of serum FLC led to an increased likelihood of the patient becoming dialysis-independent, with HCO-HD combined with chemotherapy being most effective. The favourable results demonstrated in cases 1, 2 and 4 should be interpreted carefully, as employing bortezomib is associated with favourable outcome in cases of myeloma nephropathy.
11 However this was not the case in patient 3. It was most likely the combination of HCO-HD and bortezomib, which produced the favourable outcomes in patients 1, 2 and 4.
