Filtering through the options: Renal considerations in disease management
Prof Paul Cockwell - University Hospitals Birmingham, Birmingham, UK
I’m here at the MyKE meeting in Barcelona and I’ve been asked to contribute through talking about kidney issues associated with multiple myeloma. Kidney problems are very common in people with multiple myeloma and have a big impact on how well people do in the short and long term. So for haematology specialists and oncology specialists it’s very important for them to have an awareness of kidney problems in myeloma and to have an understanding of the things that they can do to make sure that patients’ treatment in that area is as accurate as possible so the patient has an opportunity to recover the kidney function and to have better long-term outcomes associated with that.
How are these patients currently managed?
The current management of the patients with myeloma and severe kidney problems, and we call severe kidney problems severe acute kidney injuries, that is where the kidneys have got very little function in them as a consequence of the myeloma, the current management of those patients is to really focus as accurately as possible on high quality supportive care, which is making sure that the patients volume status is accurate, that drugs that can precipitate the damage to the kidneys such as diuretics and nonsteroidals are avoided, that factors that are important for contributing to kidney damage and the development of the renal lesion of myeloma called myeloma cast nephropathy such as hypercalcaemia are accurately treated. So that’s a real strong benchmark for good care is focussing on high quality supportive care. But then, from an oncology perspective, it’s about very accurate and prompt diagnosis and using chemotherapy in a way to target the light chains to get them down as rapidly as possible to give the kidneys the opportunity for a recovery and that’s crucial. This is a medical emergency; if you get kidney failure in association with multiple myeloma your best chance of recovering depends on your doctors getting a diagnosis quickly by doing diagnostic tests focussed on light chain levels and getting chemotherapy in as quickly as possible to get a good disease response and therefore take the pressure off the kidneys and give the kidneys the opportunity to recover their function.
What is the relationship between renal recovery and clinical outcomes?
The relationship between renal recovery from severe acute kidney injury and the long-term survival of the patient is best described by thinking about those patients whose kidneys stop such that they need dialysis treatment as an emergency for acute kidney injury. In those patients there’s a major difference between patients who continue to need dialysis treatment, that is don’t recover kidney function, and patients who do recover from requiring dialysis treatment. So the differences between those two groups of patients is major. The likelihood is that the average length of time somebody remains on dialysis will survive in current years with myeloma and acute kidney disease is between one to two years, whereas patients who recover kidney function have much better long-term outcome and probably have a median survival that’s not far off that which patients who don’t require dialysis have, probably around three to four years median survival. So this is an area where the difference between staying on dialysis and recovering kidney function so that you don’t need dialysis in a longer term has as big an impact as any single factor for the long-term survival of the patient.
When you then look at people who don’t have kidney failure that requires dialysis there’s relatively little known about how kidney function maps onto long-term survival but that’s going to become a very important area over the next few years because kidney function in most other disease settings has an impact on the long-term survival of the patient. So understanding what the kidney function is for somebody with myeloma at 12 months and 24 months and then mapping that kidney function on to long-term outcomes will start to lead us to understand what the relationships are between the kidney failure, myeloma and patient survival in the long-term. This becomes crucial as myeloma outcomes get better and better and it starts to move toward being more of a chronic long-term relapse in remitting condition rather than as a haematological malignancy that’s got a relatively defined survival time for the patient.
How can these patients be managed better in the future?
The best management of the patient depends on getting accurate immediate recognition of the fact that the patient’s kidney function has changed and they’ve lost their kidney function. That needs to be combined with prompt diagnostic assessment of the level of light chains in the serum of the patient. Because it’s the level of light chains in the serum that will tell you whether or not the acute kidney injury is likely to be due to the myeloma.
I would encourage people to think about configuring their clinical services so that they’ve got a within 24 hour turnaround of a serum free light chain test because if you have a high serum free light chain level in the setting of acute kidney injury that patient needs immediate treatment. By immediate treatment they’re likely to require dexamethasone at new presentation immediately once the likely diagnosis is made. In some centres that happens before the patient has a bone marrow biopsy; ideally the patient should have a bone marrow biopsy before you start treatment but you need to really work to get your clinical service as accurate as possible for that to happen. Then once that’s in place you then need to look at your chemotherapy regimen. The chemotherapy regimen that’s got the best evidence base at the moment for severe acute kidney injury and myeloma is a bortezomib and dexamethasone based triplet regimen and that appears to be the regimen that’s associated with best published disease responses in this setting with acceptable toxicity profiles for the patient.