Prenatal Imaging of Cystic Kidneys

So I'm going to uh introduce the next speaker, um, Doctor Mariana Meyers, and uh let's see if you can See my slide show here. Um, again, for those that just joined us, um, this is, uh, recorded and it's going to be made uh viewable on demand, uh, in this same link, uh, should you have missed that wonderful talk that Leandra just gave in genetics related to renal uh dysplasia. The future, um, um. Session session number 3 in June is also going to be on the same link and I want to introduce, uh, my good friend Maryna Meyers next, uh, who will be, uh, sharing with us her, um, Experiences in prenatal diagnosis of renal conditions, especially when it comes to renal dysplasia. She is currently the director of fetal imaging at Children's Hospital Colorado. Good morning, everybody. Thank you, um, Vong, for having me. It's an honor. All right, um, so this is kind of my favorite topic. I am really passionate about GU pathology. Um, I have no disclosures, and I literally have one objective for this talk. Um, I want to show that not All cystic kidneys are MCDK and as a radiologist, I received a ton of clinical um indications when ordering renal ultrasounds that says MCDK and then you change the diagnosis and that can have a huge impact on the family and the physicians in their treatment to the patient. So briefly, we're gonna talk a little bit about embryology. We're gonna do a review of MCDK or multicystic dysplastic kidney. Then we're gonna move on to talk about renal cystic dysplasias and I'm gonna show you some cases in between and mainly I'm gonna concentrate on prenatal imaging. So, embryologically, in the 1st 4 weeks of life from the cloica arises the mesonephric duct, which is gonna function as a temporary kidney until week 4 of life. Then in week 5, the metanephric duct arises, which is gonna be leading to the final kidney. The metanephric duct is gonna give origin to the ureteric bud and the renal mesenchy. And as you see here in red, the ureteric bud is gonna grow cephalide until it touches the renoblastoma, and it's very important to know that these two structures, they need to touch, they need to connect in order for some signals, some substances with signaling functions such as these that I have listed here to be released, which are going to um stimulate the development and the branching of the collecting system at the renal pelvis and in the intrarenal level. So in MCDK what happens is there is no touching, no connection of the ureteric bud and the renal mesenchyme of some sort, can be a complete atricia, a partial attricia, or some sort of disconnect. Therefore, these substances are not released. These bud branching, branching signaling factors cannot be released. Therefore, the nephrons fail to develop. And leads to a dysplastic tubular system and failure and ramification of the ureteric butt. By imaging, the MCDK is going to be seeing um a cysts all over the kidneys involving the cortex and the medullary region. There's gonna be an absence of normal renal parenchyma and that's mainly gonna be a histologic diagnosis, of course, and by imaging, we may see a scant amount of very ecogenic renal parenchyma without corticomedullary differentiation. The renal size will decrease over time as the cyst becomes smaller. Typically, there's no renal pelvis, and that's actually a good hint to figure out if this is MCDK or it's something else. And the normal renal parenchyma, as I said, is not formed, although, again, that's a histologic diagnosis. So, why is this important? Because MCDK has low to no risk of hypertension, the risk of cancer originally thought, is now, uh, very low, as you can see here, and there's some citations at the bottom. It is associated with contralateral UPJ obstruction, therefore, you have to work up the other side as well. And there are different appearances in the ultrasound and cross-sectional imaging compared to renal cystic disease entities, and I will show you a little bit, although it's not so straightforward. There is some overlap and it can be confusing. And in general, MCDK is not associated with genetic syndromes because as I showed you, it's an embryologic problem, not genetically associated. So, in the fetal imaging, we're gonna see, for example, this is a 22 week fetus that had a very um large left kidney with multiple cysts that didn't communicate with each other. And when we say they didn't communicate with each other, we imply that this is not hydronephrosis. This is not a renal collection system uh misleading us to think that these are um hydronephrosis rather than cysts. So in the fetal MRI we can see that there is a decent amount of amniotic fluid. There is a very large amount of uh cyst with enlargement of the abdomen on the left, and in the sagittal view, you can see how the anteroposterior diameter of the baby seems to be enlarged by all these cysts. The good thing is that there is normal amniotic fluid and there's a normal bladder and the contralateral kidney was normal. So the baby was born and this is how the kidney looked and as you can see, there is very abnormal appearance of some parenchyma in the liver um sorry, the kidney with lack of corticometillary differentiation and all these cysts which don't communicate with each other. So this was indeed MCDK. The patient later on, at 3 months of age, had a MAC 3 which confirmed that there is no function within that left kidney. As we can see here, there is no radio tracer uptake and the renographic curve shows only activity on the right kidney. So, this was very straightforward MCDK. What happens when you have bilateral affection? Well, this is lethal, um, although I know that with amnio infusion and the rough trial, that could be questionable, but we'll leave that for a different talk. So, on the left, we have ultrasound images from a 21 week fetus and you can see how these images are, are actually kind of ugly because there's no amniotic fluid and ultrasound depends on having the amniotic fluid to be able to visualize the fetal structures properly. So here we have the echogenicity of the fetal ribs, so we have the chest over here, the belly of the baby over here. And at the level of the kidneys, we have a bunch of cysts in both sides. The MRI is really not dependent on amniotic fluid. We get to see a lot more and you can see all these cysts of different sizes occupying the cortex and the medullary region of the fetal kidneys as we can also see in this axial view of the baby. These babies sadly died in utero, although I'm sure we're not surprised to hear that. So let's move on to renal cystic dysplasia. If you Google renal cystic dysplasia definition, you get an MCDK definition. And if you go to OMI, which is one of my favorite, uh, web pages, and you type renal cystic dysplasia, you get over 3600 entries. So it's obviously not a very straightforward topic. I'd like to divide the pathophysiology of renal cystic dysplasia into multifactorial, syndromic, genetic, and obstructions of the lower urinary tract, although I know that was discussed in the prior session, so I'm, I'm not gonna address that topic. So, by imaging, renal cystic dysplasia may or may not have a normal parenchymal formation. It's gonna have diffuse cysts all over the parenchyma or it could have a rim, um, like appearance of cysts as we can see here in this diagram, or the cyst may have different sizes and be anywhere. The renal parenchyma is typically abnormally hyperechoic and may or may not have a visible renal pelvis and calluses. It is associated with syndromic or genetic abnormalities, as we heard from Leandra as well. It can be associated with hypertension and other GU and non-GU anomalies, therefore, we need to image the entire fetus. We may have some renal function in contrast to MCDK which has no function, however, some of these entities can progress to have no renal function at all. The risk of malignancy is not the same as was thought originally for MCDKs. However, if the syndrome it is associated with has a risk of malignancy, of course, then you will encounter that. And in general, my imaging has a different appearance, but as I mentioned, it's not too straightforward. So, I like to uh divide the renal cystic dysplasias into two broad categories, genetic etiologies and developmental or obstructive. So within the genetics, we have the HNF1 beta or the celiopathies. So, let's start with the HNF1 beta, and it's a hepatocyte nuclear factor 1 beta with transcription of a factor 2, and it's an autosomal dominant um disease important for family counseling and recurrence. It can present with diabetes, renal cyst, or renal cell carcinoma, and it may affect also the liver, pancreas, thymus, genitalia, and other organs. This is an example of a twenty-week pregnant uh patient with a proven mutation of an um HNF1 beta where we could see in the ultrasound multiple cysts, particularly at the, at the border of the kidney, at the cortex bilaterally, and there was some echogenic parenchyma in between, but the cysts were also um going into the pituary region. By fetal MRI we can see how large and um hyperintense these kidneys are. There's no amniotic fluid, therefore, the lungs didn't really develop. There is um small appearance and dark appearance of the lungs which is characteristic for pulmonary hypoplasia and the cysts are all over, but again, there seems to have more of a predisposition in the cortex of the kidneys. Um, this baby, uh, this family opted for termination of pregnancy, and while we did the fetal MRI, we got to see the mom's kidneys, and she only had a tiny cyst at the right lower pole, but mom was unaffected, although she did express the same mutation. All right, let's move on to celiopathies, and this is a very large category. So celiopathies can be divided into single-gene or multi-gene celiopathy. So, what are celiopathies is a group of clinical and genetically overlapping disorders with a common problem which is the, the problem in the primary celia or centrosomal complex. There's a wide variation of presentation, um, but mainly what happens in the kidney is celial dysfunction is associated with renal cysts and, um, can lead to renal failure. So for single gene, we have the typical ARPKD or ADPKD while for multi-gene we have the nephronopticsis which are cysts restricted to the corticomedullary border and is due to a mutation in this specific gene. In some entities. And if it is associated with renal, retinal issues, liver fibrosis, or cerebellar vermis hypoplasia can lead to Scher syndrome. If it is associated with retinitis pigmentosa, polydactyly, developmental delay, hypogenitalism can lead to Barrett-Betle syndrome. You can also find Meckel-Gruber and glomerulo cystic kidney disease. And I graded that out because there is this misconception that glomerulocystic kidney disease is a celiopathy and reality it's not. It's a mutation in one specific gene which is a UMOD that can be familiar or sporadic, but it tends to be associated with other celiopathies. They come along, that's why sometimes it's, it's um thought to be a celiopathy. So what happens in glomerulocystic kidney disease, there is an enlargement of the Bowman space and as you can see in this dichromic um stain at moderate power, you can see the glomeruli here, so that's the bundle of the capillaries with enlargement of the Bowman space which is this white appearance. So, if you look in the top part of this slide, you can see that there's dilatation of tubules, which is characteristic of sometimes a DPKD with cyst formation. So this is a patient that has ADPKD with terminal cystic kidney disease. All right, let's go to the single gene. So ARPKD is an autosomal recessive transmission um with mutation of the gene PKHD1. It has a variable presentation, it can go from decreased renal function to complete end-stage renal disease. The kidneys are gonna be large, hyperintense in MRI or hyper-echoic in ultrasound. The borders of the cyst are gonna be very um poorly defined because they're very, very small. So that's what's gonna explain the echogenic or the bright appearance of the kidneys by imaging. If this is diagnosed in utero, we're gonna have oligo or inhadremnius, smaller absent bladder, which will lead to pulmonary hypoplasia, and it may or may not be associated with hepatic disease and there are many uh publications talking about Crohn's Disease Association. So this is an example of a 33 week gestational age fetus with anhydremmius and you can see the kidneys are really large, there is no amniotic fluid and the kidneys are ecogenic but they have these kind of dots of hypoechogenicity with, which represent fluid. By MRI imaging, there's this homogeneous hyperintensity and it's really hard to pinpoint where the cysts are, but this is very typical for ARPKD. This patient did not have, at least in utero, any um dilatation of the biliary ducts. Postnatal images can show all this detail of the tiny, tiny cysts throughout the kidneys and uh the enlargement, of course. This is another example of a fetus at 29 weeks that had ADPK ARPKD sorry, and had abnormality of the kidney in utero. So the kidneys are very large, echogenic, and you can see here all these white areas in the liver, that is dilatation of the biliary system. And in this movie, you can see the branching pattern of the biliary ducts, um, particularly in the posterior aspect and the very, very large kidney. So this was a fetus that already in utero, we could see that there was, um, involvement of the liver aside from the fact that it was tested positive for ARPKD. All right, let's move on to multigens. So it's, it's very broad and sometimes it's not so straightforward to make a diagnosis. So this was a case of a neonatal one day of life, um, that was IUGR in utero, had a normal prenatal ultrasound up to 20 weeks. Then develop oligohydremias and pulmonary hypoplasia. And in these images, what I want to highlight is the presence of these cysts um that are primarily located at the cortex of the kidneys. They have different sizes, but the um medullary region seems to be somewhat spared. The baby also had abnormal um head ultrasound that showed midline abnormalities, abnormalities of the formation of a vermis and some um cystic formations with CSF in the posterior fossa. So this baby was, uh, showed a mutation in this specific gene and apparently it wasn't that straightforward because it could be associated with all these syndromes. So we may find a celiopathy but not particularly associated to one single gene. And sadly, this baby died at 2 days of life due to respiratory insufficiency. Schubert syndrome is an autosomal recessive celiopathy, uh, with mutation in multiple different genes, but characterizes by vermian hypoplasia, has the typical molar tooth sign shape of a brain stem as we can see right here in this MRI could have retinal dystrophy and renal cysts. This is a movie of a baby that has Schubert's syndrome. There is anhydramus and you can see something really bright on only one side of the abdomen, so we couldn't find the, the baby's um original ultrasound and they couldn't find the right kidney and when we did the MRI we noticed that this was actually a cross fsectopia with abnormal appearance of the kidneys, so the kidneys were in this distribution. Um, and they were obviously hyper intense, but if you notice, they are not as large as the ones I showed you for ARPKD, so that is helpful also in the diagnosis. This baby had abnormal brain, um, appearance with the molar tooth configuration and the abnormal vermis, and it was diagnosed indeed with Schubert syndrome. Mecker-Gruber is an autosomal recessive lithoceliopathy, as a mutation in the TMEM231 gene, and I think I practiced all night to say that. Um, it can be characterized by uh renal cyst, um, cystic dysplasia, particularly with nephronopticis type, CNS abnormalities, um, specifically a posterior, more, uh, occipital parietal encephalocele, postaxial polydactyli and hepatic abnormalities. So here we have a case of a baby at 20 weeks that had 7 toes, had very large kidneys with the renal pelvis identified and a tiny appearance of cysts all over the kidneys. And indeed was found to have this specific mutation. On top of that, had an occipital encephalocele, as we can see, here's the forehead, the top of the head, the encephalocele and also had micrognathathia and you can see here perhaps, although it looks a little bit pixelated, um, the tiny cysts that are all over the kidneys. Um, this is very lethal, so it's hard to find postnatal images of Michael Gruber. That's the only patient that I was able to find in my, um, files. All right, tuberosclerosis, um, is an autosomal dominant mutation in specific chains, the TSC1 or TSC2. It characterizes by hamartoma in multiple organs, and that's what we mostly see by imaging. And it can also be associated with angiomyolipomas, cysts, renal cell carcinoma, or ADPKD, and that is because the mutation of this TSC1 or 2 gene is right next to the mutation for the PKD1 gene in chromosome 16. So, therefore, we have two types of presentations. We have those who only have angiomyolipomas and maybe a couple of cysts, but um nothing major to that, or you may have the florid spectrum of an ADPKD pattern of. Atherosclerosis. So, in utero, I only have this case where you could see there's bilateral involvement of the kidneys with large and small cysts, and there is abnormally echogenic parenchyma in between. And the MRI shows the differences in the size of the kidneys. One side seems to be more affected than the other. This baby had subependyal nodules, as we can see these black dots over here in the axial brain MRI and also had a rhabdomyoma in the heart which was proven by the fetal echocardiogram. Um, lastly, I want to talk about, well, I'm gonna very briefly talk about the obstructive pathology. So the only thing that I want to highlight is that Um, the bladder outlet obstruction that creates the backup of urine into the proximal GU system can lead to renal damage, and that renal damage can be presented as cyst. So that's why I included this in the renal cystic dysplasia because it's not, um, that the cysts are originally formed, these kidneys may form originally but because of an insult later on, developed this cyst as a response to that. So this is a 2 week, uh, fetus that had the typical keyhole appearance of a bladder outlet obstruction in posterior urethral valves, but if you see in the ultrasound, you see multiple cysts at the periphery of the kidney with abnormally echogenic renal parenchyma. There's no amniotic fluid as you can. see surrounding the baby and the fetal MRI highlights the rim uh appearance of the cyst in the um fetal MRU sequences and also you can see it in the axial Two weighted images and again you see partially the dilated bladder over there. Um, this is an interesting case of poster urethral valves in twins, both of which had posterior urethral valves, although one was more affected than the other. And by imaging, we had an echogenic appearance of the kidney with hydronephrosis, and the MRI highlights the thinning of the cortex of this twin, which is more pronounced than on the other. And the bladder was enlarged, however, it didn't have the massive um dilatation as we are used to seeing. But in the postnatal imagings, we can see that this baby developed this peripheral cysts with a very abnormal hypeechoic appearance of the kidneys. So keep in mind that we may not see the renal cyst. Dysplasia in utero, but this takes time to develop and we may end up seeing this later on. And if we start seeing this, at least in my, uh, fetal care center, people counsel the families that if you start seeing renal cysto dysplasia in utero, that tends to lead to, um, sooner rather than later renal failure in the postnatal state. And this is a VCUG of the same baby after the ablation of the, uh, valves, although it still shows some dilatation. So in conclusion, I think the only thing that I would like for you to remember from my talk, uh, is that not all cystic kidneys are MCDK. Think about something else. Imaging can help by showing if there is or not a collecting system. Um, if there is, typically it's not MCDK, so take a look for something else and particularly look for other GU or non-GU abnormalities since this can lead you to a specific syndrome and proper uh counseling of the patient. And I think the correct diagnosis, as Leandra um talked about, is really important for parental counseling, recurrence risk in other pregnancies, and to make sure we treat these patients properly. Thank you. Thank you, Mary Anna. I um I don't know, um, what to say except that, you know, this is, uh, one of those conditions that really, um, Impacted the spirit of the team sometime because of how difficult, um, you know, specific diagnosis, uh, can, can be made, uh, especially in places that, you know, you don't have the, the capability of a comprehensive evaluation, uh, and you only have uh access to, say, ultrasound and nothing else. Um, how, how would you, um, counsel, you know, or at least share with us, uh, what's your opinion about, you know, uh. Centers that um not able to um have the access to other imaging modality or genetic uh um uh evaluation. That's a great question. Um, I think that if you only rely on the ultrasound, I think that it's very important to make sure you educate your providers and your team that The appearance of the cyst and where they are located is very important because you may be locked yourself into a diagnosis that may not be the accurate one, so have an open mind and think about other renal cystic diseases. So once you start into the renal cystic disease category, um, I think most OBGYNs and MFMs know that it may not be just MCDK, but I have seen that happen. Many times we get patients referred to our center for MCDK and we end up changing the whole diagnosis. So, I think it's, it's about educating um team, your team and providers that um not every renal cyst may fall under the category of MCDK. Um, I think that educating is perhaps my only advice. Uh, and it, it, honestly, ultrasound is great. Ultrasound can, can be the main sole screening tool and many centers only rely on that. So as long as you know what you're looking for, you will find it, you know, uh, uh, but I think again, education will come first, um. In my thought Doctor Meyers, this is Stephanie Riddle. Um, I have a question for you about sort of an unrelated but related topic. You've done a lot of work looking at fetal lung volumes. Um, and can you comment about utilizing fetal lung volumes for patients like this, so other models of pulmonary hyperplasia other than things like CDH or space occupying lesions? Yeah, that's a great question. So, I'm always skeptical to do fetal lung volumes in patients that have anhydramus because you're gonna underestimate. It's like the lungs are sponges that are full of amniotic fluid. So if the sponge is dry, then the sponge itself is there, but you're just not distending it, right? So we might underestimate the fetal lung volume. I think that in cases where there is oligohydramus or severe oligohydramus near and hydrammias. We do it and perhaps it's just to add one more item in the checklist that parents may use to say, OK, I'm leaning towards comfort care or termination of pregnancy. Um, but we are very careful about counseling these patients regarding pulmonary hypoplasia and the risk, you know, the, the, the kind of like the PPLV and total lung volume, uh, cutoffs that we use for CDH because they don't apply to this. Um, so I think that it's, it's wise to call pulmonary hypoplasia based on the appearance of the anhydramus, but I wouldn't quantify it. I, I think that that can be very misleading. So I would say, don't do low volumes in these cases and don't quantify it. Just describe it if it is pulmonary hypoplasia of anhydramus or not. That's it. Arianna, um, that's a question from, um, your colleague, your old-time colleague, Maria Calvo. How can you tell apart TCF-2 mutation from cystic renal dysplasia? Uh, she commented that as not all stages of obstruction will show collecting system dilatation by the time you were doing the imaging. So that's a great question, Maria. Um, it's good to see you there. Um, so, I think that that is first of all, a genetic diagnosis. I don't think that by imaging we can distinguish and also because some of these patients early on may present with a pattern and then they will evolve into something else. Like at the beginning, you may see them just as a tuberculosis with a couple of scattered cysts, um, but then later on in life, it may evolve to have the florid appearance of let's say ADPKD associated. So, um, Again, when you first see these cases, it's hard to be locked into one diagnosis. I think that we can say this is, this looks like renal cystic dysplasia rather than MCDK and then from there, your genetic counselor could help guide the testing so you can be more um specific. About what this is and also look at the rest of the fetus. If you already see, you know, neurologic abnormalities, cardiac abnormalities, that can also help you think in your mind what it is. But again with the TS, uh, wait, I think I misunderstood tuber sclerosis by the TCF2 mutation. Um, so, wait, yes, so the TC, uh, the HNF1 beta, which I think that's what you, uh, are talking about, Maria, is that right? If you wanna type, yes. Um, so, uh, it's hard. Again, you see cysts, um, if it doesn't look like MCDK, it needs a genetic testing because you need to figure out what else it is. And again, the rest of the other body abnormalities may lead you into one category or not, um, but if you don't see anything else, it definitely requires genetic testing. Yes, sorry, I misunderstood at the beginning, I was thinking about tuber sclerosis.