Diagnosis and Treatment of Immune-Mediated Kidney Diseases - Episode 1
A panel of glomerular disease specialists provide an overview of immunoglobulin A nephropathy (IgAN).
Jonathan Barratt, PhD, FRCP: Hello, and welcome to this Peer Exchange titled “Diagnosis and Treatment of Immune-Mediated Kidney Diseases.” I'm Dr Jonathan Barrett, and I'm a professor of renal medicine at the University of Leicester in the UK [United Kingdom]. Joining me today in this discussion at the MGH studios are 4 of my colleagues Dr Gerald Appel, who is professor of medicine and co-director of the Glomerular Disease Center at New York Presbyterian Hospital and Columbia University Medical Center in New York. Dr Anuja Java is an associate professor in the division of nephrology at Washington University School of Medicine in St. Louis. Dr Sanjeev Sethi is a professor of laboratory medicine and pathology at the Mayo Clinic, specializing in the diagnosis of kidney diseases, and is affiliated with the Mayo Clinic Hospital in Rochester. Dr Carla Nester is a professor of pediatrics and nephrology, dialysis, and transplantation at the University of Iowa Carver College of Medicine in Iowa City. Today we are going to discuss management of immune-mediated kidney diseases. We will discuss challenges in diagnosis of IgAN nephropathy or immunoglobulin A nephropathy and C3 glomerulopathy or C3G. Current management and emerging treatment options for them. Let's get started on our first topic. And first, I want to move to Gerald Appel to ask him to describe your experience of looking after patients with IgAN nephropathy. How do they present and what challenges do you face managing their clinical care?
Gerald B. Appel, MD: Jonathan, IgA nephropathy is one of the most common diseases we see at the Glomerular Center at Columbia University. And this is true for many nephrologists. If you think of glomerular disease, it is the most common primary glomerular disease that's seen. The incidence has been said to be something like 2.5 per 100,000 around the world and one point something per 100,000 In the United States. It is very common. I can't go through a day full of patients without seeing somebody who has IgA nephropathy. And certainly, if we go through a week, we see many patients with it. It's not a rare disease for nephrologists. It is heterogeneous in its nature that some of the people, and most have just plain idiopathic IgA nephropathy, but IgA nephropathy has been associated with celiac disease. It's been associated with infections and these are things that should be considered when you see somebody with IgA nephropathy. The most common symptoms are usually hematuria red cells in the urine. Microscopic hematuria is almost always seen. It's unusual not to see it. Gross hematuria can be seen as well. And this is more common in the younger population that after sore throats sin pharyngitis or after exercise. It's not unusual to see a young person who goes out and plays basketball and he or she comes back and has dark urine, reddish brown urine, which goes away in a day or so. The other finding, which is very important, and we'll probably talk about later is proteinuria. Proteinuria is very important, prognostically, and again, over time, most patients with IgA nephropathy develop significant proteinuria. And then the other finding is high blood pressure. If you look at hematuria, proteinuria, and hypertension, those are the cardinal things that bring people to attention with IgA nephropathy. Now, we've learned a lot about the pathophysiology of this disease in the last few years. Many people talk about a 4-hit model of this, and that is, you start out because certain people have an abnormal IgA molecule, the immunoglobulin is abnormal in that it's galactose deficient at the hinge region of the IgA molecule. It turns out that their family members often have the same defect, but then something happens. These people have this defective IgA1 with galactose deficiency. They form antibodies against it, whether this is in response to an infection or some other stimulus, but that's factor two going on there, forming the antibodies. These form immune complexes, the immune complexes land in the glomerular filters, and this causes proliferation, inflammation, and eventually scarring of the filters. This is our 4-hit hypothesis, and this now is something that we're turning into thinking about pathogenesis in terms of treatment. If you take the risk factors for progressive IgA, that probably the most common risk factor that we think about is proteinuria. The heavier the proteinuria, the more likely somebody is to progress. If you can reduce the proteinuria through non-specific therapy, such as blocking the renin-angiotensin-aldosterone system, or by more specific therapy with certain immunosuppressive agents. If you can reduce that proteinuria, those patients are less likely to go to renal failure. But however, you look at it, this is a common and very important glomerular disease.
Transcript Edited for Clarity