1 00:00:01,000 --> 00:00:04,040 Welcome to KD GO Conversations in Nephrology. 2 00:00:04,360 --> 00:00:08,119 This episode titled Challenges of implementing evidence based 3 00:00:08,119 --> 00:00:13,520 Guidance for IGA Nephropathy is provided by KD Go and supported 4 00:00:13,520 --> 00:00:16,680 by Trevier. Here's your host, Doctor Donna 5 00:00:16,680 --> 00:00:20,320 Ryzik. Hello and welcome to KD Go 6 00:00:20,320 --> 00:00:23,560 Conversations in Nephrology. I am Doctor Donna Ryzik. 7 00:00:23,560 --> 00:00:26,640 I'm Professor of Medicine in the Division of Nephrology at the 8 00:00:26,640 --> 00:00:30,040 University of Alabama at Birmingham, where I also serve 9 00:00:30,040 --> 00:00:32,960 as the Associate Dean for Clinical Trial Research in the 10 00:00:32,960 --> 00:00:35,840 School of Medicine. Joining me today to discuss the 11 00:00:35,840 --> 00:00:39,520 challenges of implementing evidence based guidance for IGA 12 00:00:39,520 --> 00:00:43,720 nephropathy is our distinguished guest doctor, Sunil Udani. 13 00:00:44,080 --> 00:00:47,160 Dr. Udani is a consulting physician at Nephrology 14 00:00:47,160 --> 00:00:52,080 Associates of North Illinois, also known as Nanny and medical 15 00:00:52,080 --> 00:00:55,560 director of Nanny Research. His clinical and research 16 00:00:55,560 --> 00:00:58,640 interests include glomerular diseases and cardiorena 17 00:00:58,640 --> 00:01:00,840 syndrome. Doctor Udani, welcome to the 18 00:01:00,840 --> 00:01:02,720 podcast. Doctor Ryzik, thank you so much 19 00:01:02,720 --> 00:01:04,720 for inviting me and having this conversation. 20 00:01:05,239 --> 00:01:08,400 Great. So Sunil, I know of course you 21 00:01:08,720 --> 00:01:11,800 are aware of the updated KD GO guidelines. 22 00:01:12,280 --> 00:01:16,360 And so my first question to you today is what are the most 23 00:01:16,360 --> 00:01:19,840 significant challenges to adopting these guidelines in 24 00:01:19,840 --> 00:01:22,960 your practice? As you well know and has been 25 00:01:22,960 --> 00:01:25,680 outlined, you know this is a rapidly evolving time in hygiene 26 00:01:25,680 --> 00:01:28,240 nephropathy and the guidelines that have been just been updated 27 00:01:28,240 --> 00:01:30,880 are quite recent and we know there's definitely always a lag 28 00:01:30,880 --> 00:01:34,400 between them being published and then you know global awareness 29 00:01:34,400 --> 00:01:37,080 especially in the community nephrology space. 30 00:01:37,080 --> 00:01:39,920 So I think the first step is awareness and awareness of the 31 00:01:39,920 --> 00:01:42,320 specific changes that have been highlighted. 32 00:01:42,640 --> 00:01:45,840 The first being the partner threshold and that you really a 33 00:01:45,920 --> 00:01:49,480 much lower partner threshold than we are previously used to 34 00:01:49,520 --> 00:01:52,640 or previously had been targeting has been outlining the 35 00:01:52,640 --> 00:01:56,400 guidelines to really getting down to as low as possible. 36 00:01:56,400 --> 00:02:00,600 If you can get under 0.5g per gram ideal, but you know, really 37 00:02:00,600 --> 00:02:05,400 as low as possible as opposed to simply being OK with the UPCR of 38 00:02:05,640 --> 00:02:07,520 you know, 1g or is slightly below. 39 00:02:07,760 --> 00:02:12,400 And the second thing I think is a key thing that'll be a new 40 00:02:12,400 --> 00:02:17,360 change in the guidelines is the idea of simultaneous therapy of, 41 00:02:17,360 --> 00:02:19,680 you know, multiple targets of they're treating renal 42 00:02:19,680 --> 00:02:22,600 protection with our conventional agents such as Ras inhibitors, 43 00:02:22,600 --> 00:02:26,200 SGL 2 inhibitors as well as endothelium receptor antagonists 44 00:02:26,280 --> 00:02:29,960 while also treating the immune and inflammatory nature of IG 45 00:02:29,960 --> 00:02:33,160 nephropathy. This is a very different concept 46 00:02:33,160 --> 00:02:34,720 than that was previously outlined. 47 00:02:34,720 --> 00:02:36,800 And I think, you know, disseminating this information 48 00:02:36,800 --> 00:02:39,480 is going to be the first key. It's also a shift in the 49 00:02:39,480 --> 00:02:43,600 paradigm and nephrologists are not used to, and I was 50 00:02:43,600 --> 00:02:46,840 comfortable with implementing multiple therapies at once. 51 00:02:46,840 --> 00:02:48,840 There are certain disease states where we've done this, you know, 52 00:02:48,840 --> 00:02:51,200 lupus nephritis perhaps, and certainly in the transplant 53 00:02:51,200 --> 00:02:54,360 arena we've done this, but not for IGAIGA. 54 00:02:54,360 --> 00:02:57,000 It's been trying to find a single therapy that is an 55 00:02:57,000 --> 00:02:59,120 effective or a single therapy that's been helpful. 56 00:02:59,640 --> 00:03:03,240 We know that's you know, with the advent of multiple new 57 00:03:03,240 --> 00:03:05,720 therapies available demonstrating reductions 58 00:03:05,720 --> 00:03:09,760 pertinaria or preservation of renal function and knowing the 59 00:03:10,160 --> 00:03:13,480 natural course of this disease being quite severe for young 60 00:03:13,480 --> 00:03:15,720 people in terms of an expectation that they will 61 00:03:15,720 --> 00:03:19,120 progress to NCH kidneys ease. We know that this sort of multi 62 00:03:19,120 --> 00:03:22,120 targeted or simultaneous approach and treating the the 63 00:03:22,120 --> 00:03:24,720 whole aspects of IG nephropathy become key. 64 00:03:24,880 --> 00:03:27,520 So I think it's definitely a hill that nephrologists have to 65 00:03:27,520 --> 00:03:30,160 sort of climb in terms of their understanding, their adoption, 66 00:03:30,360 --> 00:03:34,160 integrating that into their not only their cognitive approach to 67 00:03:34,160 --> 00:03:36,800 IG nephropathy, but their day-to-day therapeutic 68 00:03:36,800 --> 00:03:39,040 interventions. Yeah, absolutely. 69 00:03:39,040 --> 00:03:43,160 And you mentioned changing the therapeutic goal of proteinuria. 70 00:03:43,160 --> 00:03:46,520 As you mentioned, the bar is much higher and we try to target 71 00:03:46,520 --> 00:03:48,120 lower and lower levels of proteinuria. 72 00:03:48,120 --> 00:03:52,240 And I think the guidelines also for the first time kind of 73 00:03:52,240 --> 00:03:56,080 recommend performing a kidney biopsy to diagnose the disease 74 00:03:56,080 --> 00:04:00,440 once you see a proteinuria of .5g per day, which was not 75 00:04:00,680 --> 00:04:02,560 really spelled out in the previous guideline. 76 00:04:02,560 --> 00:04:05,960 So again, increasing hopefully detection of the disease at an 77 00:04:05,960 --> 00:04:10,160 earlier stage. I think we've been so complacent 78 00:04:10,160 --> 00:04:12,800 with our approach because we thought there was nothing to do 79 00:04:12,800 --> 00:04:16,240 or at least the things that were available, IE glucocorticoids or 80 00:04:16,240 --> 00:04:18,959 conventional suppression like cyclophosphamide, they'll prove 81 00:04:18,959 --> 00:04:21,279 the previous guidelines really highlighted that we should move 82 00:04:21,279 --> 00:04:23,240 away from those because of the toxicity. 83 00:04:23,440 --> 00:04:25,800 And so there was I think the people exactly to your point 84 00:04:25,800 --> 00:04:29,360 that people would .8g per gram or you know, right around one 85 00:04:29,360 --> 00:04:32,080 that had microscopic hematuria, they said yeah, we think 86 00:04:32,080 --> 00:04:33,720 asidegian nephropathy, we're not going to do anything 87 00:04:33,720 --> 00:04:35,080 differently. We're going to treat with RAST 88 00:04:35,080 --> 00:04:37,360 inhibition etcetera. And so we didn't make a 89 00:04:37,360 --> 00:04:40,320 definitive diagnosis, but I think, you know, I'm, I'm hoping 90 00:04:40,320 --> 00:04:43,080 that it's not just IGA that changes with this, but really a 91 00:04:43,080 --> 00:04:48,240 global direction of, you know, really defining kidney diagnosis 92 00:04:48,520 --> 00:04:52,960 more precisely so that we really can then provide the specific 93 00:04:52,960 --> 00:04:54,680 recommendations for patients that help them. 94 00:04:55,240 --> 00:04:59,280 Yeah, I couldn't agree more. So there have been a flurry of 95 00:04:59,280 --> 00:05:02,880 new clinical trials and new therapies as we just mentioned. 96 00:05:02,960 --> 00:05:06,360 What are the key learning points that we can take away from the 97 00:05:06,640 --> 00:05:10,000 clinical trials in IGNF property, their design, the 98 00:05:10,000 --> 00:05:13,000 outcomes? And you know, conversely, what 99 00:05:13,000 --> 00:05:16,560 key knowledge gaps have been also highlighted in adopting the 100 00:05:16,560 --> 00:05:18,640 new classes of therapy? Yeah. 101 00:05:18,640 --> 00:05:22,120 It's such a great time in terms of the evolution of trials and 102 00:05:22,120 --> 00:05:23,360 therapy. And I think naturally one of the 103 00:05:23,360 --> 00:05:27,440 key steps and as you were, I'm sure involved with this idea of 104 00:05:27,480 --> 00:05:30,240 looking at print nerve reduction as a surrogate outcome for 105 00:05:30,240 --> 00:05:33,480 kidney protection. And the idea of the FDA adopting 106 00:05:33,480 --> 00:05:38,000 that through the partnership between KHI and industry and and 107 00:05:38,000 --> 00:05:41,920 ASN and the FDA that allowing for an accelerated pathway of 108 00:05:41,920 --> 00:05:44,520 approval. And then of course then waiting 109 00:05:44,520 --> 00:05:46,640 for the two year data to get confirmation. 110 00:05:46,640 --> 00:05:50,280 And what we've seen really so far to date is that that is 111 00:05:50,280 --> 00:05:53,720 translated over each time the protein air reduction that's 112 00:05:53,720 --> 00:05:56,800 been achieved has also translated into preserved kidney 113 00:05:56,800 --> 00:05:59,240 function. So it's reassuring to see that 114 00:05:59,240 --> 00:06:02,600 surrogate outcome that has been sort of accepted is 115 00:06:02,680 --> 00:06:07,080 demonstrating a better validity. I think the other sort of stark 116 00:06:07,080 --> 00:06:11,040 reality that we've seen is what happens to folks in the control 117 00:06:11,040 --> 00:06:14,320 arms, in particular the degree of GFR loss. 118 00:06:14,320 --> 00:06:18,640 And I think it's again, easy to overlook in these young folks 119 00:06:18,640 --> 00:06:21,600 with fairly well preserved kidney function, oftentimes at 120 00:06:21,600 --> 00:06:24,800 diagnosis and even, you know, as we're seeing them, but they are 121 00:06:24,960 --> 00:06:27,120 when we look and, and it you know, it's certainly in the 122 00:06:27,120 --> 00:06:29,920 clinical trial set and we can see they're losing 5ML per 123 00:06:29,920 --> 00:06:33,000 minute per year in the control arm variable. 124 00:06:33,000 --> 00:06:37,000 Of course, it's been a harsh reminder of the Natural History 125 00:06:37,000 --> 00:06:39,520 of the disease and why it's so important for us to act. 126 00:06:39,640 --> 00:06:41,640 I think it's a couple other things have been notable. 127 00:06:41,640 --> 00:06:44,200 I think it's been great that the more recent trials are allowed 128 00:06:44,200 --> 00:06:47,880 for SGL 2 inhibition and in addition to Ras therapy. 129 00:06:48,080 --> 00:06:50,440 So I think it's told us two things, you know, 1 is that the 130 00:06:50,440 --> 00:06:53,400 use of SGL Geneva is more helpful does not providing our 131 00:06:53,400 --> 00:06:56,240 treatment as their overall people still need specific 132 00:06:56,240 --> 00:06:58,640 therapies for IGN nephropathy, but it hasn't attenuated the 133 00:06:58,640 --> 00:07:01,640 benefits either. Also, it's been key that there's 134 00:07:01,640 --> 00:07:05,280 been a wide variation in terms of where people are in the 135 00:07:05,280 --> 00:07:08,840 disease state where I think that the idea of complacency and 136 00:07:08,840 --> 00:07:11,120 saying oh, this person had a biopsy five years ago, they have 137 00:07:11,160 --> 00:07:13,360 this much protein area. These are folks that are 138 00:07:13,360 --> 00:07:16,000 enrolled the trials and then they're still eligible for these 139 00:07:16,000 --> 00:07:18,000 new therapies that are becoming about. 140 00:07:18,600 --> 00:07:21,440 There certainly are unanswered questions though, as you alluded 141 00:07:21,440 --> 00:07:23,480 to. I think, you know, first is what 142 00:07:23,480 --> 00:07:26,320 happens when patients, you know, are freshly diagnosed really, 143 00:07:26,320 --> 00:07:28,320 you know, these are patients that have had an established 144 00:07:28,320 --> 00:07:30,560 diagnosis. Usually the by the time they 145 00:07:30,560 --> 00:07:32,520 have diagnosed, they've had to have established disease. 146 00:07:32,520 --> 00:07:35,080 They've run through at least supportive care. 147 00:07:35,280 --> 00:07:37,600 So what about patients that are newly diagnosed? 148 00:07:37,600 --> 00:07:40,080 What's the role of these therapies upfront as opposed to 149 00:07:40,080 --> 00:07:43,320 going through our conventional markers of RASA vision 1st and 150 00:07:43,320 --> 00:07:47,200 sort of watchful waiting? We have not had at least to date 151 00:07:47,200 --> 00:07:51,600 more information on which subtypes in terms of biopsy for 152 00:07:51,600 --> 00:07:54,200 histological classifications, Oxford classifications may 153 00:07:54,200 --> 00:07:57,000 respond to different therapies and you know really how long 154 00:07:57,000 --> 00:07:58,320 those therapies need to be maintained. 155 00:07:58,440 --> 00:08:01,280 The trials are all fairly similarly designed of two year 156 00:08:01,280 --> 00:08:05,280 trials of open label extensions. And so we know at least that's 157 00:08:05,280 --> 00:08:07,160 how long people were on the trial and how long to be on 158 00:08:07,160 --> 00:08:08,840 therapy. But is there an endpoint? 159 00:08:08,920 --> 00:08:11,480 And I think we don't know yet. And naturally patients want to 160 00:08:11,480 --> 00:08:13,000 know. And I think that's unfortunately 161 00:08:13,240 --> 00:08:16,720 we just have to be very honest and transparency. 162 00:08:16,720 --> 00:08:18,720 We don't know yet. Certainly we hope to know, but 163 00:08:18,920 --> 00:08:21,320 at least for now we'd say that if this is helpful now and 164 00:08:21,320 --> 00:08:23,520 intolerable and safe that we should implement. 165 00:08:23,960 --> 00:08:26,200 And with the flurry of therapies, the other sort of a 166 00:08:26,200 --> 00:08:28,920 good problem to have is you know which therapy is best for each 167 00:08:28,920 --> 00:08:30,320 patient. And I think with session with 168 00:08:30,520 --> 00:08:34,600 multiple pathways being looked at, we know that the supportive 169 00:08:34,600 --> 00:08:38,200 pathway of endotheam receptor antagonism and anterotensive 170 00:08:38,200 --> 00:08:41,480 receptor antagonism. But in terms of targeting the 171 00:08:41,480 --> 00:08:46,200 gut with an enteric budesonide or targeting April and bath or 172 00:08:46,200 --> 00:08:48,200 targeting complement, which of these pathways is going to be 173 00:08:48,200 --> 00:08:50,800 important for each patient? I think that's what's certainly 174 00:08:50,800 --> 00:08:53,480 the next question. And for clinicians is the 175 00:08:53,480 --> 00:08:55,960 hardest part is going to be saying, OK, well, how long do I 176 00:08:55,960 --> 00:08:59,720 wait before potentially, you know, modifying therapy? 177 00:08:59,720 --> 00:09:01,160 How do I know they're responding? 178 00:09:01,440 --> 00:09:03,760 And you know, what's the sort of the the best response they're 179 00:09:03,760 --> 00:09:05,160 going to get? And I think, again, these are 180 00:09:05,160 --> 00:09:07,080 questions that we ultimately need to know. 181 00:09:07,360 --> 00:09:09,560 Yeah, you mentioned great point, Sunil. 182 00:09:09,880 --> 00:09:12,840 Thank you for all that. And just to remind the audience 183 00:09:12,840 --> 00:09:15,960 that we are still writing this chapter, writing the story, 184 00:09:15,960 --> 00:09:17,600 right? I mean, it's been tremendous 185 00:09:17,600 --> 00:09:20,160 success so far and hopefully it will continue. 186 00:09:20,160 --> 00:09:23,800 But some of these questions will be answered, hopefully with more 187 00:09:23,800 --> 00:09:26,320 science coming out. To your point, and I think 188 00:09:26,320 --> 00:09:28,560 that's what is also hard about adopting these in clinical 189 00:09:28,560 --> 00:09:32,040 practice is this idea of the unknown for clinicians doing 190 00:09:32,040 --> 00:09:34,080 things every day. You know, we sort of have all 191 00:09:34,080 --> 00:09:37,240 these things we relied on these sort of things that we've been 192 00:09:37,240 --> 00:09:40,520 using for the last 30 years. And with all these unanswered 193 00:09:40,520 --> 00:09:43,560 questions, we have to be comfortable with that lack of 194 00:09:43,560 --> 00:09:46,600 knowledge and still think, hey, I got to do as best for my 195 00:09:46,600 --> 00:09:49,240 patient even though we don't have all the answers right now. 196 00:09:49,480 --> 00:09:51,960 Again, as long as we're looking at safety and all those things. 197 00:09:52,480 --> 00:09:55,840 Yeah, absolutely. And again, have the confidence 198 00:09:55,840 --> 00:09:59,200 that these questions, you know, science is still trying to 199 00:09:59,200 --> 00:10:01,760 answer. If you're just tuning in, you're 200 00:10:01,760 --> 00:10:06,320 listening to the KD Go podcast on challenges of implementing 201 00:10:06,320 --> 00:10:08,680 evidence based guidance for IG and nephropathy. 202 00:10:08,800 --> 00:10:12,080 I'm Doctor Dana Risik and I have the pleasure of speaking today 203 00:10:12,080 --> 00:10:16,320 to Doctor Sunil Udani. So Sunil, with all the, you 204 00:10:16,320 --> 00:10:19,040 know, again, exciting news, but also challenges that we've been 205 00:10:19,040 --> 00:10:22,240 talking about. What in your mind are strategies 206 00:10:22,240 --> 00:10:24,680 to increase the implementation of these new guidelines? 207 00:10:24,920 --> 00:10:27,960 I think we can learn from some of the experience that we've had 208 00:10:27,960 --> 00:10:29,960 with evolution and renal therapeutics as of late, 209 00:10:29,960 --> 00:10:32,920 including the SGLT 2 inhibitors in the sense of, you know, 210 00:10:32,920 --> 00:10:37,160 seeing how did adoption come about with those therapies. 211 00:10:37,160 --> 00:10:39,040 And I think that, you know, first, of course, the 212 00:10:39,840 --> 00:10:41,840 distribution of knowledge. And I think that, you know, it's 213 00:10:41,840 --> 00:10:45,040 no longer the case where people are always reading journals or 214 00:10:45,040 --> 00:10:47,080 if they are reading journals, it's no longer the case that 215 00:10:47,080 --> 00:10:48,640 everyone can go to scientific meetings. 216 00:10:48,920 --> 00:10:51,080 So we have to be, you know, innovative. 217 00:10:51,080 --> 00:10:54,040 And I think things like this where either, you know, podcasts 218 00:10:54,040 --> 00:10:56,360 or webinars that are asynchronous so people can 219 00:10:56,360 --> 00:11:00,280 listen in, you know, when they have the time, I think that's 220 00:11:00,280 --> 00:11:03,080 key. I think that identifying the 221 00:11:03,080 --> 00:11:04,800 local people that are helpful, right? 222 00:11:04,800 --> 00:11:07,560 I mean, I think ultimately physicians want to do the right 223 00:11:07,560 --> 00:11:10,600 thing, but they, you know, when it's a new therapy, there's 224 00:11:10,600 --> 00:11:13,600 natural anxiety about it. And so who do they trust 225 00:11:13,600 --> 00:11:15,600 locally? Because naturally there are, you 226 00:11:15,600 --> 00:11:17,760 know, guidelines and, and there are, you know, national 227 00:11:18,000 --> 00:11:20,280 speakers, but ultimately you want to have someone that it's 228 00:11:20,280 --> 00:11:21,760 local you can be comfortable with. 229 00:11:22,120 --> 00:11:25,240 And I think that's the key in terms of this idea of, you know, 230 00:11:25,240 --> 00:11:28,800 hub and spoke model of expertise or identifying local centers of 231 00:11:28,800 --> 00:11:32,360 excellence or local experts that you will feel comfortable with 232 00:11:32,360 --> 00:11:34,000 approaching. And then for the people that are 233 00:11:34,000 --> 00:11:38,320 experts, you know, being open to and, and accessible to people to 234 00:11:38,360 --> 00:11:41,480 so that they can walk through cases and walk through concepts 235 00:11:41,720 --> 00:11:44,040 so that these things become less intimidating. 236 00:11:44,120 --> 00:11:46,840 The new therapies and things that and that can be, you know, 237 00:11:46,840 --> 00:11:48,760 again, in a formal way, informal way. 238 00:11:48,760 --> 00:11:52,440 I think it now we know that there's online forums, ASM 239 00:11:52,440 --> 00:11:55,920 communities has one people have chat groups or their practice or 240 00:11:56,040 --> 00:12:00,280 the local communities that are key that can be accessed as ways 241 00:12:00,280 --> 00:12:03,080 to say, OK, yeah, I have this case, you know, how would your 242 00:12:03,080 --> 00:12:04,680 approach this? What do you guys, can you 243 00:12:04,680 --> 00:12:08,240 someone help me understand the new data on, you know, X 244 00:12:08,240 --> 00:12:10,440 therapy, et cetera. So I think you all of the above, 245 00:12:10,520 --> 00:12:12,680 we can't think of it, just saying like, put it out there 246 00:12:12,680 --> 00:12:15,120 and expect people to do it. And we have to engage people 247 00:12:15,120 --> 00:12:17,080 where they are and finding where they are is the key. 248 00:12:17,480 --> 00:12:21,360 And then ultimately, I think as we evolve, I think, you know, at 249 00:12:21,360 --> 00:12:25,680 some point we have to also have expectations to say, OK, this is 250 00:12:25,680 --> 00:12:28,360 the standard of Care now that we approach this and give 251 00:12:28,360 --> 00:12:31,080 clinicians feedback. And the last thing I'll say is, 252 00:12:31,080 --> 00:12:33,880 you know, what is more motivating than anything else is 253 00:12:33,880 --> 00:12:36,840 a motivated patient. And as we educate patients that 254 00:12:36,840 --> 00:12:39,560 there are better therapies available when they go into the 255 00:12:39,560 --> 00:12:42,040 nephrologist's office and say, hey, I've read about this or 256 00:12:42,040 --> 00:12:44,080 I've heard about this, can you help me understand? 257 00:12:44,080 --> 00:12:47,920 This would be helpful for me. I think that always spurs people 258 00:12:47,920 --> 00:12:50,880 to learn and do more. Yeah, keeping the patient 259 00:12:50,880 --> 00:12:53,600 central, absolutely. There are, you know, patient 260 00:12:53,600 --> 00:12:57,560 advocacy group and we're certainly making a lot of effort 261 00:12:57,680 --> 00:13:01,400 providing lay summaries of even scientific publications. 262 00:13:01,400 --> 00:13:05,680 So I think all that disseminates information both to physicians 263 00:13:05,680 --> 00:13:09,360 but also to patients. So what are in your mind 264 00:13:09,360 --> 00:13:13,240 remaining research or evidence gaps that we need to fill in? 265 00:13:13,960 --> 00:13:16,840 I think there's always been subgroups in each of the trials 266 00:13:16,840 --> 00:13:20,440 that have not been included. YG vasculitis has been one that 267 00:13:20,440 --> 00:13:22,520 has been excluded really from all the trials that I've 268 00:13:22,520 --> 00:13:25,040 observed. And so, you know, in adults 269 00:13:25,040 --> 00:13:28,160 particularly, they can be overlaps with, you know, 270 00:13:28,160 --> 00:13:29,520 conventional hygiene nephropathy. 271 00:13:29,520 --> 00:13:32,920 So obvious therapies would, you know, be implemented in their 272 00:13:32,920 --> 00:13:36,600 cases, the pediatric population. I'm an adult nephrologist, so I 273 00:13:36,600 --> 00:13:39,480 can't say see Pediatrics, but I know that my pediatric 274 00:13:39,480 --> 00:13:42,400 colleagues, you know, they need trials and data for their 275 00:13:42,400 --> 00:13:45,120 patients as well, or people that may have, you know, secondary 276 00:13:45,120 --> 00:13:47,160 forms of IGA. And, and again, which of these 277 00:13:47,160 --> 00:13:49,720 therapies that we see are, are safe and effective? 278 00:13:49,880 --> 00:13:52,760 We have designed these trials based on previous KD GO 279 00:13:52,760 --> 00:13:57,040 guidelines, which was, you know, at 1g per gram UPCR as the 280 00:13:57,040 --> 00:13:59,280 threshold. But what about lower degrees of 281 00:13:59,280 --> 00:14:02,120 protein area? If we get people down to .6 or 282 00:14:02,320 --> 00:14:04,760 .4, but they still have hematuria, they still have IG 283 00:14:04,760 --> 00:14:07,240 nephropathy, do they also benefit? 284 00:14:07,240 --> 00:14:09,680 I think that you get, we don't know the answer to that question 285 00:14:09,680 --> 00:14:12,480 yet, but I have to believe that that is a critical thing for us 286 00:14:12,480 --> 00:14:15,680 to know so that we can really make sure that all patients have 287 00:14:15,680 --> 00:14:17,240 good options. It's been great. 288 00:14:17,240 --> 00:14:20,040 You know, there's been a lot of positivity in terms of the the 289 00:14:20,080 --> 00:14:23,560 clinical trials and the evidence of protein neural reduction and 290 00:14:23,560 --> 00:14:26,280 GFR preservation and many of them to date. 291 00:14:26,840 --> 00:14:30,040 But what we don't always have with those trials at the end of 292 00:14:30,040 --> 00:14:32,520 the granularity of understanding who doesn't respond. 293 00:14:32,840 --> 00:14:36,600 And I think that's going to be a key thing to say, OK, well, why 294 00:14:36,600 --> 00:14:39,400 does this person not respond to this therapy, but they respond 295 00:14:39,400 --> 00:14:41,320 to the other one? And kind of when is the point of 296 00:14:41,320 --> 00:14:44,520 saying there are there markers that we can look at that say, 297 00:14:44,520 --> 00:14:47,680 OK, this person's having a response And this is helpful 298 00:14:47,680 --> 00:14:50,400 beyond looking at simply proteinuria, beyond looking at 299 00:14:50,640 --> 00:14:53,520 GFR even, you know, and without repeating a biopsy. 300 00:14:53,520 --> 00:14:56,680 So non invasive ways that we can perhaps look at response rates 301 00:14:56,680 --> 00:14:58,920 and then get a better idea of who doesn't respond. 302 00:14:59,200 --> 00:15:02,200 Each of the trials have also included individuals with fairly 303 00:15:02,200 --> 00:15:04,080 significant kidney disease. You know, thresholds have been 304 00:15:04,080 --> 00:15:08,600 EGFRS of 30, but most of the exploratory cohorts of 20 to 30. 305 00:15:08,600 --> 00:15:11,760 And so again, you know, is there truly a point no return? 306 00:15:11,760 --> 00:15:14,600 I think the previous KD GO guidelines were very clear that 307 00:15:14,600 --> 00:15:17,480 there's a point no return and then to not instituting no 308 00:15:17,480 --> 00:15:20,040 suppression in those folks. But again, that was when we're 309 00:15:20,040 --> 00:15:22,400 using therapies that had higher toxicity profiles. 310 00:15:22,400 --> 00:15:26,000 So with therapies that are safer, is there truly a point no 311 00:15:26,000 --> 00:15:28,040 return where they don't benefit at all? 312 00:15:28,040 --> 00:15:29,480 Or what is that incremental benefit? 313 00:15:29,480 --> 00:15:32,240 And is it worthwhile with ultimately those folks 314 00:15:32,280 --> 00:15:35,120 progressing SH kidney disease is getting transplant then what 315 00:15:35,120 --> 00:15:36,480 happens to the post transplant period? 316 00:15:36,560 --> 00:15:39,400 We know IGA comes back in the allografts either at least 317 00:15:39,400 --> 00:15:42,000 histologically it comes back. But what about those folks that 318 00:15:42,000 --> 00:15:44,240 have more clinically relevant disease? 319 00:15:44,240 --> 00:15:47,440 Are these therapies safe to use with back her immune suppression 320 00:15:47,440 --> 00:15:49,720 already? Are they effective in the same 321 00:15:49,720 --> 00:15:51,640 pathways? And then those are interesting 322 00:15:51,640 --> 00:15:54,160 and naturally exciting questions as we learn more. 323 00:15:54,760 --> 00:15:57,680 So what I heard you say, Sunil, is we're going to need more 324 00:15:57,680 --> 00:16:01,480 clinical trials perhaps in some, you know, populations that we 325 00:16:01,480 --> 00:16:03,200 left out. We're going to need the real 326 00:16:03,200 --> 00:16:07,760 world data and we're going to need to just answer these 327 00:16:07,760 --> 00:16:13,360 questions as you alluded to by a hodgepodge of sources to fill in 328 00:16:13,360 --> 00:16:16,800 all these gaps as we start applying the guidelines. 329 00:16:16,800 --> 00:16:19,120 So great points. Thank you for sharing that. 330 00:16:19,600 --> 00:16:22,560 So before we close, are there any final messages you'd like to 331 00:16:22,560 --> 00:16:25,560 leave with our listeners? There are knowledge gaps, there 332 00:16:25,560 --> 00:16:28,000 are implementation challenges, but undoubtedly this is an 333 00:16:28,000 --> 00:16:31,000 exciting time for IH and nephropathy, the patients and, 334 00:16:31,040 --> 00:16:33,240 you know, the nephrology community and our clinicians. 335 00:16:33,560 --> 00:16:38,160 And we need to embrace the knowledge that we've learned the 336 00:16:38,160 --> 00:16:42,240 success of these new therapies that have demonstrated efficacy, 337 00:16:42,240 --> 00:16:47,240 tolerability, safety, as well as a more sort of insightful 338 00:16:47,320 --> 00:16:48,880 paradigm in terms of approach to therapy. 339 00:16:48,880 --> 00:16:53,000 Simultaneously treating the kidney specific targets in terms 340 00:16:53,000 --> 00:16:55,960 of things we've been doing supportively as well as novel 341 00:16:55,960 --> 00:16:59,320 pathways to do that, but also treating the immune related 342 00:16:59,320 --> 00:17:01,320 kidney disease. And as ultimately this is an 343 00:17:01,560 --> 00:17:05,119 autoimmune glomerular nephritis and so much are other immune 344 00:17:05,119 --> 00:17:08,520 glomerular nephritis, We need to find the effective ways to treat 345 00:17:08,520 --> 00:17:11,200 that immune concept. You know, it's a remarkable to 346 00:17:11,200 --> 00:17:14,599 be a Bevan part of some of these trials and to see the patients 347 00:17:14,599 --> 00:17:16,079 that have been willing to be part of that. 348 00:17:16,280 --> 00:17:18,200 None of these straws can be that big, right? 349 00:17:18,200 --> 00:17:20,440 The IGN nephropathy is not a common disease. 350 00:17:20,440 --> 00:17:24,520 So every patient counts so much. And it's incredible that this 351 00:17:24,520 --> 00:17:27,400 many patients have stepped up to, you know, be part of this 352 00:17:27,400 --> 00:17:29,680 process. And we are incredibly grateful 353 00:17:29,680 --> 00:17:33,000 to them for doing this and helping us advance the science 354 00:17:33,000 --> 00:17:34,880 as well as the whole research teams have been part of it. 355 00:17:34,880 --> 00:17:37,880 The Pi is the coordinators, the sponsors that have made a 356 00:17:37,880 --> 00:17:40,280 commitment to developing therapies that have been 357 00:17:40,280 --> 00:17:43,480 otherwise forgotten. So I'm very excited that this 358 00:17:43,480 --> 00:17:46,200 is, you know, really has changed the game in our way. 359 00:17:46,200 --> 00:17:49,600 We evaluate and treat hygiene nephropathy and now the key step 360 00:17:49,600 --> 00:17:52,360 is us doing the work to deliver these therapies to patients. 361 00:17:52,640 --> 00:17:55,640 So need I want to really thank you for joining me today. 362 00:17:55,640 --> 00:17:58,400 It was great having you on the podcast. 363 00:17:58,960 --> 00:18:01,120 Doctor Rizik, thank you so much for inviting me and the 364 00:18:01,120 --> 00:18:03,080 conversation. Always a pleasure to talk to 365 00:18:03,080 --> 00:18:04,600 you. Absolutely. 366 00:18:04,640 --> 00:18:08,280 I am Doctor Dana Rizik and to access this and other episodes 367 00:18:08,280 --> 00:18:13,000 in our series, please visit kdgo.org podcast. 368 00:18:13,360 --> 00:18:14,600 Thank you so much for listening.