A 74-year-old gentleman presented with tiredness and lethargy. He was found to be in renal failure with a serum creatinine level of 800 μmol/l and commenced on haemodialysis. He has a background of ischaemic heart disease, previous coronary artery bypass grafting and emphysema. Further investigations revealed an immunoglobulin G (IgG) κ paraprotein of 32 g/l with reduction in IgA and IgM levels.
What treatment is most appropriate for this patient?
Is there a role for plasma exchange in patients with renal failure secondary to plasma cell myeloma (PCM)?
What are the different aspects of supportive care?
Not all patients with PCM are potential candidates for dose-escalation programmes, including autologous stem cell transplantation. The aim of therapy in these patients is to achieve disease control with minimal side effects, inducing improved quality of life. Melphalan and prednisone (MP) has been the mainstay of treatment in such patients and yields partial remission in 50%–55% of cases, with only occasional complete remission.1 Prednisone has been replaced with dexamethasone and directly compared to MP. The response rates were similar but there was considerably greater toxicity associated with dexamethasone.2,3 Cyclophosphamide is efficacious, especially when used in combination with steroids. Other combinations of alkylating agents, such as VBMCP (vincristine, carmustine, melphalan, cyclophosphamide and prednisone), have been utilized and, more recently, thalidomide has been added to MP with improved response rates but increased toxicity.4 The aim of MP therapy is to deliver maximum response followed by 3 months of therapy and, to date, no randomized study has shown a benefit to prolonging therapy beyond this time frame. The introduction of thalidomide to MP may alter this time frame, especially the notion of following maximum response to MP plus thalidomide with thalidomide monotherapy as a maintenance strategy, and is currently under investigation.
The approach to acute renal failure and the role of plasmapheresis
Plasma cell myeloma is associated with renal dysfunction in up to 50% of patients, with renal failure occurring in a significant proportion of patients. The presence of renal dysfunction/failure is associated with higher treatment- and disease-related mortality and limits clinical decision making when designing patient treatment strategies. The characteristic histopathological feature on renal biopsy is the ‘myeloma kidney’ or cast nephropathy due to excessive amounts of filtered intraluminal toxic light chains. Other causes of renal failure include hypercalcaemia, infection, dehydration and nephrotoxic drugs. General approaches to treat renal failure in myeloma include vigorous hydration, avoidance of toxins and nephrotoxic drugs, and aggressive treatment of infections and hypercalcaemia. However, these measures are often inadequate to reverse oliguric and advanced renal failure. Several case reports showed benefit from plasma exchange by acutely reducing levels of the light chain protein.5 So far, randomized studies have failed to demonstrate a significant benefit from plasmapheresis in this setting,6 though the clinical impact of such a strategy may be masked ...