What is monoclonal gammopathy of renal significance? So monoclonal gammopathy of a non-significance, it means that we have a protein that is M-spiked, and that M-spike is occurring with few cancer cells in the bone marrow. But there is no damage, there is no significance of those cells. Those cells have normal, those patients do not have any myeloma related symptoms. You have good hemoglobin usually, good bones with no pains. But then you look at a subset of patients that have this kind of small M-spike, and it's not enough to call it myeloma, but they do have kidney damage. And it's a very evolving area. This was a recent definition. I think the only way to diagnose monoclonal gammopathy of renal significance is to get a kidney biopsy. And the reason to get a kidney biopsy is you are going to treat those patients, or you are going to make a decision if the patient has a renal failure, if they need to go for a kidney transplant or not. So if you are evaluating a patient with bad kidneys and you find an M-spike, the next question is going to be, do we need to treat the benign condition to control the protein that's causing the damage to the kidney, or is the patient ready to go for a kidney transplant? And if the answer is yes to both of them, then a kidney biopsy is indicated an aggressive treatment of this M-spike to try to eliminate it as indicated so you can take them to a kidney transplant. But in general, monoclonal gammopathy of renal significance at this time is an evolving diagnosis, and a lot of centers are hesitant to treat those patients just by looking at an M-spike in kidney. I usually request a kidney biopsy to treat those patients. I don't know what other centers do. There is really no standard way of doing that. Does this mean that your myeloma protein is low enough to not be considered smoldering myeloma, but there is some damage to your kidneys because of myeloma? If you have damage, if you have no criteria to diagnose myeloma and you have a patient with renal insufficiency, most of those patients, especially in the older age group, will have hypertension, they have diabetes, or say have some other cause, then you can attribute the renal insufficiency or the renal damage to. However, if you cannot justify that, or if there is rapidly worsening kidney function, the patient had hypertension for 20 years, and then all of a sudden the creatinine that was 1.5 is up to 4, then this is the kind of patient that you detect an M-spike. I think the next question is going to be, are we certain that the M protein is causing the kidney damage? And if the question is yes, or the answer to that question is yes, then you need to go and get a kidney biopsy. And the kidney biopsy will help guide subsequent management, including a kidney transplant, if the kidney function worsens quickly. And you don't want to do a kidney transplant in a patient that has protein that's not controlled. So sometimes we get the biopsy, we treat them, and then we do the kidney transplant later on. Monoclonal gammopathy of renal significance is a relatively new term that we've been using in patients who have MGUS, or monoclonal gammopathy of undetermined significance. We start with having an M-spike, or a myeloma protein of less than 3 grams per deciliter, and less than 10% plasma cells in the bone marrow. But what we see in patients with renal significance is that they do have a kidney problem related to this abnormal protein. How can you manage monoclonal gammopathy of renal significance? Monoclonal gammopathy of renal significance is an area that we're very interested in, in terms of how to manage this disease. What we're thinking is that people are having damage from MGRS, that they actually need treatment for their monoclonal gammopathy instead of a watch and wait approach. Is the treatment for monoclonal gammopathy of renal significance the same as myeloma treatment? So in terms of treatment for MGRS, we're typically talking about myeloma-based therapies that we would use to treat somebody who has traditionally symptomatic multiple myeloma. What type of medications can be used with monoclonal gammopathy of renal significance? When people have a kidney problem, like MGRS, we have to pay special attention to the medications that we use. The medications that we use sometimes have to be dosed differently, or we have to pick different medications for treatment. But medications like linalytamide, bortezomib, and dexamethasone can still be used, we just have to pick the right doses for the kidney function. Even when patients go on dialysis, we can still use those medications, but again, we just have to be very specific in how we dose them.