Jonathan Barratt, PhD, FRCP: Moving now to a challenging concept of how we make a diagnosis. And the fact that patients don't present to us with a label, they present with perhaps an abnormal blood test, an abnormal urine analysis. When you see a patient in your general nephrology clinic who's presented perhaps with hematuria or proteinuria, what's the thought processes that go through in terms of how you come up with a differential diagnosis? What are you looking for that will help you make that diagnosis?

Anuja Java, MD: When a patient comes to you, like you said with hematuria, proteinuria, with those 2 things, the differential can be broad. For somebody who has just isolated microscopic hematuria, of course IgA is one. But you would also be thinking about somebody with Alport syndrome, thin basement membrane disease. A very close mimic of IgA nephropathy could be Post-Infectious GN because both these patients could present with after like Dr Nester mentioned, you have an upper respiratory infection and then they have developed these symptoms. Another close cousin is the IgA vasculitis, where in addition to what is happening in the kidney, you get these extrarenal manifestations of somebody with a rash, joint pains, abdominal pain. Lupus, another common GN, is also in the differential when you're seeing these patients with blood and protein in the urine. And of course, C3G, the other disease we are talking about today is a close differential as well. You have to keep all these in mind when you are taking a good history, when you're looking, when you're finding out what the trigger is, looking for a good family history. And this is all critical because of course, the natural history for these different diseases varies. A Post-Infectious GN patient will resolve and will get better versus the fibrosis and the scarring and the underlying pathophysiology of IgA or C3G and is not going to stop. It's not going to go away. Similarly, the disease, which is the IgA, dominant GN, which is associated with staph, which you see in the older patients with diabetes, you would want to treat them with antibiotics and not hit them with immunosuppression like you would for some of these. When you see these patients, I think taking a good history, keeping these in the differential, looking for a family history as said. And the labs, as you mentioned, you do a urinalysis, a protein-creatinine or a 24-hour. And then to rule out these, you would look for complement levels. You would be looking for ANA, if you're worried about lupus. And something earlier in the discussion we talked about some of the disease could be associated with secondary factors, like if there's liver disease, you want to look for that, hepatitis, things like that. You must start from the basics and do a comprehensive workup and a history-taking to be able to kind of tease down what it is that you're dealing with and ultimately do a kidney biopsy that's going to give you the diagnosis and finish the diagnosis.

Jonathan Barratt, PhD, FRCP: For IgA, we are sadly lacking a biomarker, aren't we? We have double-stranded DNA and complement levels help us with lupus. We've got ANCA for ANCA-associated vasculitis. We've now got PLA2R for membranous. For IgA nephropathy, we don't have anything that helps us drill down to that diagnosis. And as you say, a kidney biopsy is our go-to investigation. And because really the challenge for me about kidney biopsy is when to do it. My personal view is we leave it too late. And, some of my colleagues we mentioned earlier, if there's no treatment, why do a kidney biopsy, subject someone to a kidney biopsy if you're not in the treat? But I think what we are beginning to understand is that we leave things too late if we have a certain proteinuria threshold for a biopsy or a certain GFR threshold. We must have the patient prove they've got progressive kidney disease before we make a diagnosis to give them treatment to prevent them developing progressive kidney disease. And that's the issue that is going to be forced when we have new therapies available.

Transcript Edited for Clarity