Challenges of Managing C3G

EP: 1.An overview of IgA Nephropathy

EP: 2.IgA Nephropathy in Different Ethnic Populations

EP: 3.IgA Nephropathy in the Transplant Population

EP: 4.IgA Nephropathy in Pediatric Patients

EP: 5.An Overview of C3G

EP: 6.C3G in Pediatric Patients

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EP: 7.Challenges of Managing C3G

EP: 8.Consequences of a Late or Missed Diagnosis of C3G

EP: 9.Differential Diagnosis of C3G

EP: 10.The Pathology of IgAN on Kidney Biopsy

EP: 11.The role of electro microscopy in the diagnosis of IgAN

EP: 12.Kidney biopsy as a guide for treatment and prognosis

EP: 13.Diagnostic testing in C3G

EP: 14.Diagnosing C3G in pediatric patients

EP: 15.Kidney biopsy C3G

EP: 16.Building expertise in C3G

EP: 17.Clues to C3G in a biopsy

EP: 18.Barriers to kidney biopsy

EP: 19.Current standard of care for C3G

EP: 20.Clinical trial data on complement inhibition in C3G

EP: 21.Complement therapy in transplant patients in C3G

EP: 22.Clinical trial data on IgAN for therapies

Jonathan Barratt, PhD, FRCP: Anuja, in terms of your experience of C3G, how do you find your patients present and is it a challenging condition to manage?

Anuja Java, MD: It is a challenging condition to manage. As Dr Nester mentioned, patients who come to us again for looking for a kidney transplant, we know for sure that they're going to recur. And at that point, we tell them, yes, you have a disease, it's a slowly progressive disease, or it may be more aggressive. And then what? We don't have a way to tell them that there is a way to treat the patient. That is really something - a challenge for us, a challenge for patients. That's the biggest concern we have. There is nothing FDA-approved right now. And I know we'll talk about treatments and what's in there, but that's one thing I want to add. The other thing I want to mention, in addition to pediatrics and adults, the other thing we often see is the C3G that is associated with monoclonal gammopathy. In patients who are more than 50 years of age, when they have an underlying monoclonal protein, those patients are at risk of developing C3G. Now, in some ways, it's maybe a better condition because if you treat the underlying monoclonal gammopathy, the C3G does get better. That is one aspect that I wanted to add to the kind of patients that we see in the adult population. And then in addition to nephritic factors, there are some other rare autoantibodies that may be associated. But my experience is more looking at these from a post-transplant recurrence standpoint and not having much to offer to them at this point, but much to look forward to.

Jonathan Barratt, PhD, FRCP: And you picked an important question. The thing that I notice, and my patients find most difficult to deal with, is uncertainty. I can't give them a certain answer as to what's going to happen to me with C3G. Particularly, around the fact that they've developed end-stage kidney disease. They're having a kidney transplant. This is that gift that they are so desperate for to come off dialysis. And being able to understand and explain the uncertainty, which is very unsatisfactory, particularly when we don't have good treatment at the moment. That is a real challenge for patients, isn't it?

Anuja Java, MD: Absolutely.

Jonathan Barratt, PhD, FRCP: And Jerry, you mentioned seeing IgA nephropathy patients at every clinic. What do you think the challenge is for C3G patients where you probably don't see them as often? And actually, for C3G patients, what they want to have is a consultant, a nephrologist that really understands the disease. But because it's so rare, most nephrologists outside of big glomerulus disease centers won't have the opportunity to look after many of these patients. Is that your experience and how do you manage that?

Gerald B. Appel, MD: That is correct. It's been a real challenge and it's only the last decade that we've learned a lot about this disease. We've learned a lot about pathology. We've learned a lot about the pathogenesis and the alternate compliment pathway. And we've learned a little bit about treatment as well. If you talk to nephrologists a little over a decade ago, nobody will know what you were talking about. They would just say, "Oh, this is one of those rare diseases. I'm never going to see it in my lifetime. I'm not going to pay attention to it". Now, many people, many nephrologists are paying attention to it, not just because of the disease, but because as Carla said, it's the prototype for a complement involvement in glomerular systems and especially the alternative pathway. So, this is a major factor and it's changed a lot. We've learned a lot more about the pathogenesis. We've learned more about the patient population. Now, we automatically screen for monoclonal immunoglobulins in terms of especially the age over 50 that we can look for antibodies. The whole evaluation is worked out. But I still think most nephrologists, if they see one patient with C3 glomerular disease, glomerulopathy in their lifetime, that will be it. And therefore, they should be referring these patients to major centers where we can do the studies. It's amazing how many controlled trials are going on now for one of the rarest diseases you might see. But it's not just this disease. It can affect all the other glomerular diseases that involve complement.

Jonathan Barratt, PhD, FRCP: I couldn't agree more. And, that’s what patients tell us as well. Not just experts in glomerular disease. We need to have these patients looked after by experts. We need to have expert pathologists review the biopsy and we need to have access to clinical trials for these patients. Because the future's incredibly exciting now.

Transcript Edited for Clarity