LISA CLARK: I'm Lisa Clark. Welcome, and thank you for joining us for this webcast. Many cases of kidney disease in the United States are linked to other serious medical conditions like high blood pressure or diabetes, but there are other forms of kidney disease which may strike with no known cause and have serious repercussions. For the next few minutes, we're going to take a closer look at one of these diseases called focal segmental glomerulosclerosis, or in shorter form, thank goodness, FSGS.
Joining our discussion this evening, Dr. Leonard Stern, immediately to my left, and Dr. Jai Radhakrishnan. Welcome to both of you and thank you for being here.
I am going to stick with the abbreviation for this, FSGS, and Len, I'll ask you to describe what this disease is.
LEONARD STERN, MD: Well, the kidney consists of many parts. One of them is called the glomerulus, which is the main filtering part of the kidney. This illness attacks the glomerulus, the filtering function of the kidney. There are two forms. One is an inflammatory form, and one is a relatively bland form. They both produce the injury to the filtering part of the kidney where protein leaks into the urine, and the consequences of protein leaking into the urine over time is that the protein acts as a toxin which injures the remaining parts of the nephrons. So this, once it's initiated, is progressive and indolent in some patients, rapid in others, but will eventually result in kidney failure requiring dialysis or transplant.
LISA CLARK: People may actually know a little bit about this because two pro basketball players were recently diagnosed with FSGS -- Alonso Mourning and Sean Elliott. When you have a big-name celebrity who is diagnosed with a disease, does that immediately lead to a lot more interest and study on the disease?
JAI RADHAKRISHNAN, MD: It's usual, but as nephrologists, we see this every day. It's nothing unusual for us. That I'll tell you.
LISA CLARK: How common is it?
JAI RADHAKRISHNAN, MD: If you look at diseases that cause kidney failure, it's not common, but when you look at kidneys that cause protein to be leaked to the urine, it is probably one of the most common diagnoses that you can find in what we call nephrotic syndrome, which is a syndrome where you lose a lot of protein, you swell up, and the protein in your blood drops. It's probably the most common cause of nephrotic syndrome in certain populations.
LISA CLARK: Len, who is most at risk for developing this disease?
LEONARD STERN, MD:/ Well, there are a variety of things. It largely affects males, African Americans more so than white Americans. It has some association with drug use, illicit drug use. There is some association with HIV and AIDS, but on the other hand there is an association with obesity, with urinary tract infections and mechanical reflux of urine from the bladder into the ureters. But reasonably speaking, when an illness is associated with so many different things, the reason for that is that we don't know the cause.
The issue with this illness is that it is a relentless disorder unless it's treated, and the difficulties with the illness of the protein leaking in the urine, that's really the target of the therapy. Since we don't understand the primary cause in the vast majority of patients, all we do is we treat the features of the illness, and those might be related to the high blood pressure that the illness causes, and we directly attack the protein leaking into the urine by a variety of means to try to eliminate that.
LISA CLARK: Jai, one of the articles that I read about this said this is -- they didn't say definitively-- but they said it's a suspected autoimmune disorder. Where do you come down on that?
JAI RADHAKRISHNAN, MD: The word autoimmune means that the body produces immunity against itself, and in doing so it damages organs. So there's data which was recently published from both France and from the United States that there's a protein or there's a substance in the blood that goes and destroys the filters of the kidney, causing it to become more leaky, and it's not yet known what this protein is, but there's a lot of research being done in this direction.
LISA CLARK: I'm not sure about the individual cases of the NBA players that I mentioned, but I assume that a general medical screening picked up the protein in the urine. What other ways might this disease present? Would people have symptoms?
JAI RADHAKRISHNAN, MD: The most important or the most common presentation would be to find protein in the urine, but also equally common would be that the patient would present with swelling of his body, essentially, because of salt and water retention, or he could be diagnosed with a high blood pressure, and not uncommonly it can progress without any symptoms, causing kidney failure.
LISA CLARK: How is a definitive diagnosis made, Len?
LEONARD STERN, MD:/ Definitive diagnosis, kidney biopsy, where actually one of us might, in a controlled setting in the radiology suite, using an ultrasound apparatus, localize the kidney, and do a needle biopsy of the kidney. Then the tissue is examined under a microscope by a trained renal pathologists, and there we can make a definitive diagnosis.
LISA CLARK: How important is a prompt diagnosis in the ability to treat effectively?
LEONARD STERN, MD:/ I guess in our field, if we know what the diagnosis is in a reasonable time frame, then we could direct specific therapies toward that illness. It's very difficult to treat a patient with kidney disease without actually knowing the type of kidney disease, because some illnesses we treat with one set of medications and others with different sets of medications.
LISA CLARK: What sorts of medications might be used in this case, Jai?
JAI RADHAKRISHNAN, MD: If it's the inflammatory type, we try to suppress the immune system, and we could do this by using cortical steroids, which is a form of hormone that's made by the body, given at high doses. If that fails or if the patient cannot tolerate this, we have something called cyclosporine, or there's another medication called CellCept. Some people have used a process called plasma exchange where this protein that's abnormal in the blood is removed by a process of purification and then normal plasma is given back, and this has been used successfully in transplants.
LISA CLARK: How effective are these treatments?
JAI RADHAKRISHNAN, MD: A ballpark would be about one-half of the patients would respond to one or the other kind of treatment, but what's also very important is that it's important to control blood pressure, because that alone could worsen the prognosis of this disease.
LISA CLARK: By responding positively to treatment, does that mean that there is a possibility that this disease can be cured or not?
LEONARD STERN, MD:/ I don't think the illness could be cured by our present medications, but we can place the patient in what we call a clinical remission. A responder would be someone whose blood pressure is well controlled and the protein in the urine is eliminated. In about half the patients we can achieve that result with a variety of different medication approaches.
When that happens, we hope that the patient can sustain that remission for a long period of time. One of the unknown variables we have is, how long do we treat the patient? It's the subject of much research, but not a lot of answers yet, so our strategy at the moment is to treat the patient for prolonged periods of time while they have sustained a remission in the hope that the illness will stop or burn itself out at some point.
LISA CLARK: Given the potential that this is an autoimmune disorder, how susceptible or prone to this type of disease would people be who have had other autoimmune disorders, lupus or Hashimoto's disease, or other autoimmune disorders?
JAI RADHAKRISHNAN, MD: There's no clear relation between these other disorders that you mentioned, because we know that only one kind of FSGS is associated with this protein, which is autoimmune in nature. But it's such a varied group of disease that you can't say definitely that it's one kind of mechanism that's prevalent in a given patient.
LISA CLARK: What would your advice be to an average person who doesn't consider him- or herself to be at risk for kidney disease? What kinds of tests do you need to do, have your GP do to make sure that something like this doesn't spring up on you?
LEONARD STERN, MD:/ During a normal physical examination, the blood pressure needs to be checked, and at some point an examination of the urine. An ordinary urinalysis will detect protein and inflammatory cells, and that's a superb screening test.
LISA CLARK: Indeed, it is. Again, thanks to both of you for joining us for this discussion. It's a very complex subject, and we hope it's been beneficial to all of you in our web audience. Again, thanks to Dr. Leonard Stern and Dr. Jay Radhakrishnan. Thanks very much. I'm Lisa Clark.
Joining our discussion this evening, Dr. Leonard Stern, immediately to my left, and Dr. Jai Radhakrishnan. Welcome to both of you and thank you for being here.
I am going to stick with the abbreviation for this, FSGS, and Len, I'll ask you to describe what this disease is.
LEONARD STERN, MD: Well, the kidney consists of many parts. One of them is called the glomerulus, which is the main filtering part of the kidney. This illness attacks the glomerulus, the filtering function of the kidney. There are two forms. One is an inflammatory form, and one is a relatively bland form. They both produce the injury to the filtering part of the kidney where protein leaks into the urine, and the consequences of protein leaking into the urine over time is that the protein acts as a toxin which injures the remaining parts of the nephrons. So this, once it's initiated, is progressive and indolent in some patients, rapid in others, but will eventually result in kidney failure requiring dialysis or transplant.
LISA CLARK: People may actually know a little bit about this because two pro basketball players were recently diagnosed with FSGS -- Alonso Mourning and Sean Elliott. When you have a big-name celebrity who is diagnosed with a disease, does that immediately lead to a lot more interest and study on the disease?
JAI RADHAKRISHNAN, MD: It's usual, but as nephrologists, we see this every day. It's nothing unusual for us. That I'll tell you.
LISA CLARK: How common is it?
JAI RADHAKRISHNAN, MD: If you look at diseases that cause kidney failure, it's not common, but when you look at kidneys that cause protein to be leaked to the urine, it is probably one of the most common diagnoses that you can find in what we call nephrotic syndrome, which is a syndrome where you lose a lot of protein, you swell up, and the protein in your blood drops. It's probably the most common cause of nephrotic syndrome in certain populations.
LISA CLARK: Len, who is most at risk for developing this disease?
LEONARD STERN, MD:/ Well, there are a variety of things. It largely affects males, African Americans more so than white Americans. It has some association with drug use, illicit drug use. There is some association with HIV and AIDS, but on the other hand there is an association with obesity, with urinary tract infections and mechanical reflux of urine from the bladder into the ureters. But reasonably speaking, when an illness is associated with so many different things, the reason for that is that we don't know the cause.
The issue with this illness is that it is a relentless disorder unless it's treated, and the difficulties with the illness of the protein leaking in the urine, that's really the target of the therapy. Since we don't understand the primary cause in the vast majority of patients, all we do is we treat the features of the illness, and those might be related to the high blood pressure that the illness causes, and we directly attack the protein leaking into the urine by a variety of means to try to eliminate that.
LISA CLARK: Jai, one of the articles that I read about this said this is -- they didn't say definitively-- but they said it's a suspected autoimmune disorder. Where do you come down on that?
JAI RADHAKRISHNAN, MD: The word autoimmune means that the body produces immunity against itself, and in doing so it damages organs. So there's data which was recently published from both France and from the United States that there's a protein or there's a substance in the blood that goes and destroys the filters of the kidney, causing it to become more leaky, and it's not yet known what this protein is, but there's a lot of research being done in this direction.
LISA CLARK: I'm not sure about the individual cases of the NBA players that I mentioned, but I assume that a general medical screening picked up the protein in the urine. What other ways might this disease present? Would people have symptoms?
JAI RADHAKRISHNAN, MD: The most important or the most common presentation would be to find protein in the urine, but also equally common would be that the patient would present with swelling of his body, essentially, because of salt and water retention, or he could be diagnosed with a high blood pressure, and not uncommonly it can progress without any symptoms, causing kidney failure.
LISA CLARK: How is a definitive diagnosis made, Len?
LEONARD STERN, MD:/ Definitive diagnosis, kidney biopsy, where actually one of us might, in a controlled setting in the radiology suite, using an ultrasound apparatus, localize the kidney, and do a needle biopsy of the kidney. Then the tissue is examined under a microscope by a trained renal pathologists, and there we can make a definitive diagnosis.
LISA CLARK: How important is a prompt diagnosis in the ability to treat effectively?
LEONARD STERN, MD:/ I guess in our field, if we know what the diagnosis is in a reasonable time frame, then we could direct specific therapies toward that illness. It's very difficult to treat a patient with kidney disease without actually knowing the type of kidney disease, because some illnesses we treat with one set of medications and others with different sets of medications.
LISA CLARK: What sorts of medications might be used in this case, Jai?
JAI RADHAKRISHNAN, MD: If it's the inflammatory type, we try to suppress the immune system, and we could do this by using cortical steroids, which is a form of hormone that's made by the body, given at high doses. If that fails or if the patient cannot tolerate this, we have something called cyclosporine, or there's another medication called CellCept. Some people have used a process called plasma exchange where this protein that's abnormal in the blood is removed by a process of purification and then normal plasma is given back, and this has been used successfully in transplants.
LISA CLARK: How effective are these treatments?
JAI RADHAKRISHNAN, MD: A ballpark would be about one-half of the patients would respond to one or the other kind of treatment, but what's also very important is that it's important to control blood pressure, because that alone could worsen the prognosis of this disease.
LISA CLARK: By responding positively to treatment, does that mean that there is a possibility that this disease can be cured or not?
LEONARD STERN, MD:/ I don't think the illness could be cured by our present medications, but we can place the patient in what we call a clinical remission. A responder would be someone whose blood pressure is well controlled and the protein in the urine is eliminated. In about half the patients we can achieve that result with a variety of different medication approaches.
When that happens, we hope that the patient can sustain that remission for a long period of time. One of the unknown variables we have is, how long do we treat the patient? It's the subject of much research, but not a lot of answers yet, so our strategy at the moment is to treat the patient for prolonged periods of time while they have sustained a remission in the hope that the illness will stop or burn itself out at some point.
LISA CLARK: Given the potential that this is an autoimmune disorder, how susceptible or prone to this type of disease would people be who have had other autoimmune disorders, lupus or Hashimoto's disease, or other autoimmune disorders?
JAI RADHAKRISHNAN, MD: There's no clear relation between these other disorders that you mentioned, because we know that only one kind of FSGS is associated with this protein, which is autoimmune in nature. But it's such a varied group of disease that you can't say definitely that it's one kind of mechanism that's prevalent in a given patient.
LISA CLARK: What would your advice be to an average person who doesn't consider him- or herself to be at risk for kidney disease? What kinds of tests do you need to do, have your GP do to make sure that something like this doesn't spring up on you?
LEONARD STERN, MD:/ During a normal physical examination, the blood pressure needs to be checked, and at some point an examination of the urine. An ordinary urinalysis will detect protein and inflammatory cells, and that's a superb screening test.
LISA CLARK: Indeed, it is. Again, thanks to both of you for joining us for this discussion. It's a very complex subject, and we hope it's been beneficial to all of you in our web audience. Again, thanks to Dr. Leonard Stern and Dr. Jay Radhakrishnan. Thanks very much. I'm Lisa Clark.