DW: How does multiple myeloma impact the kidneys and increase risk for kidney disease?
Dr. Raje: So again, you know, kidney disease is really very important in the context of myeloma and if you think about kidney disease in the course of a myeloma patients’ disease state, at the time of presentation, we find sort of renal insufficiency in about 20% or 30% of patients that can go all the way up to 50% or 60% in patients over the course of their lifetime with myeloma. Now why does this occur? This occurs because, again, it’s part of the CRAB criteria, so the R in the crab is renal disease. And the reason that occurs is the myeloma protein, the immunoglobulin, as well as the light chains associated with myeloma the capitalize chain or the Lambda light chain, they tend to be sticky proteins. The sticky proteins have a tendency to attach to the kidney tubules and by doing so they can cause tubular damage and myeloma kidney and can impact kidney function.
Again, really important to pick up on this, and the reason it’s important to pick up on this is one you want to prevent kidney related problems. The reason for that is you want to, you know, some of the treatments we have for myeloma are impacted by kidney dysfunction, so there are certain limitations to what you can or cannot use in the treatment of myeloma. So prevention is always the best strategy—if not prevention, treat early, so that you can reverse that kidney dysfunction in patients and be extremely careful with monitoring kidney function in the course of a patient’s lifetime.
DW: What treatments or approaches can be used to mitigate or treat these complications?
So I’ll start out with mitigation strategies. Mitigation strategies—know that your kidneys are really important in the context of myeloma, that’s number one. So education, education, education. Number two is avoid sort of nephrotoxic drugs, so I will always tell my patients stay away from non-steroidal anti-inflammatory drugs, so NSAIDs like ibuprofen, Advil, so on and so forth should be avoided because they can be kidney toxic. And simple things like when you’re getting imaging and you have a diagnosis of myeloma, you want to be careful and you want … do not want to get contrast because IB contrast can negatively impact kidney function. Other things we’ve talked about hypercalcemia earlier on in the context of bone disease, high calcium levels can be toxic to the kidneys. So try and avoid that as well. And then certain drugs that we use.
You know, the other thing to remember is the renal dysfunction is myeloma generally occurs in patients were in their fifties, sixties and seventies. There are other sort of medical problems, which crop up in that age group, such as hypertension, diabetes, and all of those can affect kidneys as well. So if you have chronic renal insufficiency, make sure your hypertension is well-treated, diabetes is well-treated, and make sure you try and understand what the contribution of these other medical conditions are in the context of kidney dysfunction. So that’s mostly sort of prevention. The other big thing in the prevention category would be hydration, hydration, hydration. And the reason to use hydration is by hydrating, you’re actually diluting out the protein, you’re diluting out the light chains, and you’re trying to protect those kidneys from kidney toxic problems.
We’ve come a long way with treatments for myeloma, so I think if you have a myeloma kidney as a consequence of active symptomatic myeloma, it’s critical that you start treating immediately. And the drugs, we have a very effective at reversing kidney function. If you catch it early and treat it imminently. And the treatment for that would be drugs like bortezomib. In patients with kidney dysfunction, I will use drugs like cytoxan because they are able to get the myeloma protein down quickly and they’re safe in the context of kidney failure, and you don’t have to do a lot of dose adjusting. Once that kidney failure reverts, then you can go back to your immunomodulatory drugs, another drug, which is less taught off in the context of kidney function, but I think we should be using it more, is the monitoring antibodies. The reason to use monoclonal antibodies is they’re not excreted by the kidneys. They excrete it, or they’re metabolized by your reticuloendothelial system, so it’s independent of the kidney. So drugs like daratumumab and isatuximab now are CD38 monoclonal antibodies, very effective in the context of myeloma, combining them with a drug like bortezomib, for example, would actually help control the myeloma and reverse kidney function quite effectively.