Fetal Obstruction Uropathy and ESRD - Urologic Management

Uh, Doctor Defore is a professor of surgery at the University of Cincinnati College of Medicine, and he is a pediatric urologist at Cincinnati Children's, where he serves as the co-director of the Pediatric stone Center. Uh, his other clinical interests include uro-oncology and vesicoureteral reflux. Uh, his research interests include antioxidant modulation of apoptosis and crypt orchidism, and pediatric urologic surgical outcomes analysis. Using an evidence-based medicine approach. And today, he'll be discussing bladder management in children with in utero renal failure. Doctor Defour, thank you very much, and I appreciate the offer to um be here today. So, again, um, my name is Bob Defour. I'm one of the urologists here at Cincinnati Children's, and I am very honored to um be here this morning and talking to, um, this audience. And I want to thank Doctor Hali and Doctor Lim. And uh that was a fantastic uh overview of fetal MRI by Dr. Nagaraj. So my task is to talk about what to do with the baby after they're born. Um, my role is fairly limited prenatally. After the baby is born, our role becomes more intense. And I'm going to share actually just a series of 3 cases that I think are very illustrative of some of the challenges that we face uh in these most complicated children. And um, So case number one was, uh, just like Doctor Nagaraj, uh, showed some examples of, uh, was a prenatally diagnosed bladder outlet obstruction with anhydramnios, underwent a, um, vesicoamniotic shunt in an outside institution and then had some amnio infusions, was born fairly early at 1.3 kg with a multitude of other, uh, issues going on, uh, that were very severe. Uh, including some severe pulmonary issues. So, um, The baby was diagnosed with urethral atresia and was taken to the operating room where a vesicostomy was performed, as you can see right here. The bladder looked pretty awful, very thick-walled and severely inflamed, and we removed the shunt under the same anesthetic. Despite that, uh, the baby's creatinine continued to rise, uh, as you can see here at the time of the vesicostomy up to a peak of about 7. And the serum sodium progressively got worse. The baby was severely edematous, um, and not doing well clinically, was not quite big enough, uh, for peritoneal dialysis at 1600 g. It was very fluid overloaded. The kidney was very echogenic and didn't show much hydronephrosis, but the ureter was massively dilated. So after a lot of discussion and, and some realistic conversations with the family, we took the baby to the operating room and performed a cutaneous ureterostomy, as you can see here. And the cre creatinine trended down. The baby began to have a massive postoperative, uh, post-obstructive diuresis, and the creatinine actually nadired at about 1.9. And that gave us a bridge to dialysis, uh, that then occurred when the baby was much bigger at 4100 g and where the peritoneal dialysis catheter could work much better. The next steps in this child were fairly complicated. Of course, here's a little drawing of the anatomy, had a ureterostomy, had a vesicostomy, had a very thick-walled bladder. But after several months, uh, and, um, of diversion, we did an integrated nephrostogram. And now the, the, uh, ureter vesicle junction was now open and the hydroureter had resolved. And so we were able to attempt a rescue of the atretic urethra. We're able to, to perform cystoscopy and dilate the tract and start intermittent catheterization. Unfortunately, the family uh induced a false passage and we lost the urethra. We then did a two-stage orchidopexy laparoscopically and then got the baby ready for a transplant by closing the ureterostomy, sending the urine back down to the bladder, and then ultimately transplanted into the vesicostomy. So bladder out obstruction, uh, is, is one of the issues that we're discussing today. And these babies are at very high risk of chronic renal insufficiency and obstructive neuropathy and typically is a poor prognosis if the maybe your creatinine is over one after one year. We've advanced a lot in our management for valves, NICU supportive care with uh ventilatory and nutrition, end-stage renal disease management. Like I mentioned before, PD has offered as early as 1800 g at our institution. This is just sort of uh an example of the valve and then after the ablation of the valve. And that is helped by the miniaturization of the instruments that we're able to use. In the fetal care center era, though, we have sort of the most severe of the most severe patients, the, the ones that Doctor Nagaraj mentioned with hydramnios or severe oligohydramnios, um, that have severe pulmonary issues at birth and are quote, fetal care center survivors, uh, pulmonary survivors. And our, from a urology standpoint, our immediate postnatal management is to drain whatever can be drained. And so we either place, place a urethra catheter and then proceed with a valve ablation when stable. And then there's lots of other issues going on with NICU and supportive care. Nephrology is intensely involved in these patients, um, due to their severe neuropathy. And of course, we try to minimize infection. Now, the bladder function is important. Of course, bladder cycling helps later in life. Uh, we, we will rescue the bladder that's dysfunctional with clean intermittent catheterization and anticholinergic medication. This is a posterior urethra and the valve is here with a severely abnormal bladder with massive bilateral vesicoureter reflux. And this is after resecting the valve. Um, you can see the posturethra is much less dilated. The the bladder looks much happier and the reflux has resolved spontaneously. So despite the bladder function, we also, of course, uh, are more interested initially in the renal function and in the very worst of the worst cases, then we consider a urinary diversion. Um, we also manage the bladder actively with intermittent catheterization and these, uh, very severely affected patients. So this is a very abnormal bladder with cellules and diverticula and high-grade reflux. And so in our institution with these very severely affected babies, if they have worsening function despite the valve ablation or they have severe reflux with nephropathy or worsening hydronephrosis, or just a very markedly abnormal bladder appearance, then we'll empirically start them on intermittent catheterization. Your indication to do a diversion of the bladder is if the baby is just too small for our miniature scopes to go in and safely resect the valve, or if their family is unable to perform intermittent catheterization when it's indicated either due to urethral atresia or, um, you know, family or social concerns. This is a lot of work that we ask for the families to perform. To proceed with an upper tract diversion like a ureterostomy. Again, in, in rare cases, um, when we just have to optimize the kidneys to, to, um, get, um, the baby bridged to dialysis or just to save whatever function that we can. And this typically is from, um, so this is the renal pelvis and a very dilated, uh, distal ureter. And, and there's sometimes a secondary obstruction at the ureter or vesicle junction from a very thickened and abnormal bladder wall. So if you've drained your bladder with the with the catheter and the hydronephrosis worsens and the creatinine keeps rising, that would be an indication to place uh either a percutaneous nephrostomy or a cutaneous ureterostomy. Now, a percutaneous nephrostomy is leading less invasive, but you have to do something at some point after that because you can't leave that, that tube in for forever, certainly. And they tend to have a short half-life in the NICU. So they can get pulled out, they can, the family can inadvertently dislodge them. So, so they definitely um are a temporary um therapy. So this is another case. This is a fetal MRI baby with uh anhydramnios. You can see the bladder here on the T2 weighted image and uh with the dilated posturethra and then, and the bilateral hydronephrosis. The baby was born at 36 weeks with a little bit of um Echogenic kidneys, hydronephrotic kidneys, and a very thick-walled, very abnormal-looking bladder. And this is with the catheter in place. It's draining well. So despite this, the baby, um, and this is the BCG. So this is, we saw this before, so very markedly abnormal bladder, dilated reflux, massively dilated poster urethra, and an abnormal bladder. So this baby, despite um the well-draining catheter, the creatinine kept rising. We proceeded with percutaneous nephrostomies. And then once the baby had settled down, we converted that to low-end cutaneous ureterostomy. So you can see the baby here with a little fan instill incision to low-end cutaneous ureterostomies. The kidneys improved fairly markedly as far as the dilatation. Um, and then our next steps were we wanted to rescue the bladder. And so, um, this is a very motivated family. The mother is a physical therapist at our institution. We started them on the bladder cycling with intermittent catheterization, anticholinergic medication, and remarkably, that terrible bladder, um, which had been uh diverted and deffunctionalized, was able to be rescued to this nice smooth-walled bladder. Um, the posturethral valve was still in, uh, there at this point. So we proceeded with the valve ablation and then brought the ureters down from the skin, reimplanted them into the bladder, and then we're continuing them on very active bladder management for now. And then hopefully, we'll wean them off at some point. The last case I wanna talk about is an, is a, not a bladder outlet, but more of a, a, um, in the spectrum of renal agenesis, um, bilateral multicystic dysplastic kidneys. So this is a little girl. Um, this is a fetal MRI with anuria, um, uh, anhydramnios, bilateral quite cystic kidneys as you can see here. Um, the baby was born at 2 kg with, uh, massively dilated kidneys, um, with, uh, bilateral multicystic dysplastic kidneys, and was auric. Uh, at 3 days of life, uh, our transplant team took the baby to the operating room for a PD catheter and a, uh, hemodialysis catheter to start HD, uh, until the PD catheter matured. So now the baby's about 2 and the family is about ready, and, and the nephrologists are about ready for transplant. And the baby has had a lot of complications. Um, and so they're kinda ready to kinda move along. So at this point, we do, the urologist will step back in because for the 1st 2 years, we had very little role. But now we're gonna try to evaluate the bladder and we do that with a variety of things, of voiding cystourethrogram, urodynamics. Uh, and this baby, they were not able to place a catheter at the bedside for both, both of those tests. So we took her to the operating room to do a cystoscopy and found a, an Extremely small, probably the size of a thimble, uh, bladder that is just not gonna be useful, um, or not gonna be safe to transplant into. So we've discussed bladder cycling with the family. Uh, the prognosis in this case is fairly poor. So then your options are either to, uh, if the bladder can reach the skin, uh, as a stoma, you could transplant into a vesicostomy. But most likely in this patient, we'll have to just bring the Um, the allograft ureter out to the skin as a ureterostomy and that's sort of our last resort. But if the bladder can be cycled and can be rescued, that's our first choice. Um, so Doctor Lim asked me to talk a little bit about what we do later in life. So I'll just finish with 2 or 3 slides about what we can do down the road a bit, uh, to, to sort of rebuild, um, the lower urinary tract. And so this is when the child is older, like 5 at least. And this is a major abdominal procedure. We have to harvest bowel, do a bowel anastomosis. They're in the hospital for a while. Uh, remember, these patients are often immunosuppressed by now. They have a kidney transplant. And adherence is super critical because uh you just don't want this uh to perforate. So this is an example of um a channel, uh, abdominal wall channel called metrofenoff that is uh typically the appendix and we implant it into the bladder, um, as a catherizable channel. Um, and basically, so this is the, um, the cecum and the terminal ileum and the right colon. We sort of disconnect the appendix like you're gonna do an appendectomy, but leave it on its blood supply, swing it down to the pelvis, tunnel it into the bladder, and then bring the other end out to the skin. And that is a continent catheterrizable channel that the um patient can use. If the appendix is not available, then we take a little piece of ileum, reconfigure it using this Parker Kerr stitch, um, into a channel, leave it on its blood supply. And this is one of my favorite all-time pictures of this little boy, uh, in his, uh, GI Joe underwear, who is now dry for the first time in his life, uh, who has a little catherizable channel in his right lower quadrant that stays continent. And then if they are incontinent, we can do lots of things. This is kind of looking towards the feet. Um, this is the bladder neck. We can tighten the bladder neck and, uh, uh, do what we call a bladder neck reconstruction. Um, we can, this is a Penrose drain between the urethra and the rectum. We can lift that up with a, with a sling to kinda provide more, uh, continence. And then typically, in a case like this, you'll have to augment the bladder with intestine to make it, uh, a suitable capacity reservoir. And then the last thing I'll talk about is what if you do all these surgeries? What can happen as far as malignancy, particularly in immunosuppressed patient. Uh, and like our patient that I showed with the bilateral NCDK, she has no bladder. Essentially, she'll need a neo bladder. So sometimes we use stomach tissue and small intestine and sew it together like a baseball. And that's our new bladder, uh, with a continent catheizable channel. Um, the literature is poor, um, but it seems to be around 6% and a little bit higher if you stomach segments, uh, as far as developing bladder cancer. And again, these patients are often immunosuppressed. The latent time is, is probably about 14 or so years. So sometimes they are out of the pediatric system by the time this is an issue. Um. And then there's some other weak data comparing patients just with neurogenic bladder like spinal cord injury patients on a catheter program to those who've been augmented and there really wasn't a difference. But the, but, again, lots of limitations and retrospective and, uh, and also very small numbers. So, um, why would they get bladder cancer? Theoretically, you know, they're immunosuppressed. They have, uh, stasis of their urine. They have pH changes when you use stomach and combine it with the urinary tract. They can have chronic infections and stones. This is a bladder stone, indwelling catheters. We really don't have any data with patients who have had a renal replacement therapy, uh, as a child. So in conclusion, so these are the most of the most severe sort of extreme spectrum of bladder outlet obstruction patients. Um, initial drainage of whatever's left is critical. Um, a ureterostomy may bridge you to the baby being big enough. To undergo dialysis. And then, uh, the nephrologist will tell you if there's some urine output, output that makes renal replacement therapy easier to manage. Uh, in other words, uh, if they're on dialysis, uh, making some urine helps them, uh, in that management. These patients all have bladder dysfunction and we are very aggressive with catheterization programs. And if that's not feasible, then a vesicostomy to, to provide a low-pressure drainage for the bladder. And then when it's time for transplant, it's important to have a low-pressure bladder that empties completely. Um, and a rehab cycle bladder is ideal. But if that's not available or there's just too much time pressure to get the graft done, um, then you either have to reimplant into the vesicostomy or a ureterostomy. Um, and then the ultimate bladder function effects are unclear after we divert. Um, but regardless, they all need active bladder management. And, and like I said, our policy, our sort of practice here is early institution of a catheter program anticholinergics. We try to prevent that progression of the valve, bladder, and bladder failure. And then once bladder reconstruction is felt to be feasible and they're older, we have lots of options, uh, channels, uh, augments, neobladders. And the bottom line is these patients need to be followed forever for, um, malignancy risk. So that's pretty much all I wanted to say. I want to thank my chief, Doctor Reddy, and then the fetal surgeons and the nephrologists who work, we work with very closely on these very challenging patients. So I'll be happy to take any questions at this point. Thank you very much, Doctor Defour. Um, I think we have two questions, um, coming in from the audience. Uh, the first question, uh, is from Doctor Lim, uh, and he asks, uh, if the fetus is auric, how often was the bladder, uh, not able to be rehabilitated, um, and is the lifespan of a renal graft affected if you have no bladder to transplant into? So I'll, I'll address the first one too. So in the patients who are completely anhydramnios and auric and have really um no bladder, the chances of us rehabilitating that to a normal bladder is low. Um, like I showed in the second case, you can certainly do it with a motivated family, but you probably have to have some bladder capacity to start with. And that patient had anhydrammias late in the, uh, in their third trimester, um, but earlier in the pregnancy, that was just oligo. But, uh, but yeah, it's very challenging. And I would say there, it takes a while. Uh, if, if you're, from the time you attempt to start cycling the bladder and until you get some Sort of feasible capacity increase, maybe 6 months, so, or more. So, so if you're really under a lot of pressure to get that transplant done, it's, it's not always, there's not always enough time for that. And then if you remind me that the second question was? Oh, the, the, uh, we've, we've shown actually that transplants into reconstructed bladders in valve patients, we've published this, this has similar outcomes to, um, patients who just have FSGS or some other, you know, nephropathy and normal bladders that have just been dysfunctionalized, uh, for whatever reason. So we, we can definitely take good care of these, uh, allografts. Um, but it's, it's a very active surveillance and very constant oversight of these patients and families. OK, thank you. And uh the other question from the audience from the audience says regarding case two, how did you cycle the bladder with CIC? So, um, what you do is you, you teach the family to do it. Um, and again, they have to be very motivated. They have to be fairly, um, sort of, uh, uh, socially, and they just have to have the, the resources and the time and the motivation to do it. But basically, we start very small. We have them learn how to in and out catheterize the bladder. We instill very small amounts initially, like 5 mL. slowly increase that over the course of several months. Um, and this patient actually was able to get up to about 70 or so. So that's, and, and that's not bad. You know, a 1 year old should have a bladder capacity, uh, of about, you know, 80 to 90 mL. So, Um, so that wasn't too bad. And then we, then we add anticholinergic medications to sort of relax the bladder muscle and allow the bladder to store more. So, and that has side effects like constipation and dry mouth. So you have to start very, very slow with that and the baby too. So you're talking like 0.5 mg once or twice a day. And then you just have to just see the families. Uh, it, it helps that we have a, um, a valve nurse coordinator. Um, who manages our bladder cycling. And so she teaches the family, meets with them, has constant communication with them by phone and email and text. So it, it just, it takes a lot of support and a dedicated nursing team, um, but it can be done. Thank you. Um, I have a question myself. Um, we frequently use, uh, ves amniotic shunts in the, uh, in the, in the context of bladder outlet obstruction. Can you comment, comment on how the presence of that shunt affects your bladder management? Uh, you mean after, after birth, you mean after birth, yes. Um, I'm not sure I have a really good answer for you. Um, it certainly inflames the bladder, uh, uh, fairly significantly. And, but I'm not sure it is, I have enough data to kinda say that there's like an extreme effect one way or another. Um, these bladders look terrible, um, you know, whether they've been diverted or whether they've been obstructed for, you know, the entire pregnancy. Um, and they're very abnormal. But I'm not sure I can say it's, it makes it tremendously worse, you know, as far as, but there's gonna be a lot of inflammation like I showed in that very first case, the bladder just looked like a bomb went off in there. Bob, um, thank you for the, um, the excellent talk. Um, it's really comprehensive, um, and I hope, you know, some of the, uh, the pediatric surgeons and pediatric urologists in the audience, um, would enjoy how, you know, difficult. these cases could potentially be and how much um effort truly we're being put into, you know, caring for a baby like this. I know, um, Ellen and Kara are going to speak to some of those challenges. Um, my, my question is, um, given the topic today that we are focusing around The, the true bilateral reogenesis in some of our patient populations. And also um the trial that's going on, um, In North North America to perform amniocentesis sorry, amnio infusion for patients with um true um Bilateral renal agenesis pathology. I mean, by the time that these babies say that they got to the, um, the neonatal intensive care unit and then subsequently being cared for by um the, the multi-discipline team including pediatric urologist, um, Have you, how do you, you know, counsel this family to begin with, given all of those challenges and issues that you mentioned regarding trying to get these babies to transplantation first of all, and then second, you know, that's really No good data on how many of these babies truly have bladder or no bladder if they, they had uh bilateral renal agenesis. I mean, you know, uh, we, we just continue to, to have those kind of questions in our mind, um, when a baby is diagnosed with that condition. Is, is that, you know, Um, fair to get those babies to Survivor in the NICU and then, you know, undergo all of those challenges that one could even hardly imagine how difficult it is. Yeah, that's, those are great comments. And I, I, I really struggle with this in the prenatal counseling, um, team meetings and, um, consultations with these families because there's so many pathways and there's so, that, like, if we get the baby to deliver and if we get the baby to survive pulmonary-wise, if we can get the baby to, to await where they can get dialysis, Then we might be able to, you know, rescue the bladder and then we might need to be able to rehab and, and rebuild the bladder. And then your, your child might get cancer 20 years from now. So that is an overwhelming amount of information and I really struggle with how to present that to a family. In the fetal care center consultation setting and even immediately postnatally, it's just too, it's way too overwhelming and there, and, and there's so many hurdles that the baby has to, to, to get through, to get to the point of bladder reconstruction. But it's an enormously complex discussion, and I'm not sure they understand fully the vast consequences of all these decisions and, and, and I'm not sure I'm able to communicate it to them well enough, quite frankly. Thank you. Um, I don't know how, um, Uh, other centers are, are counseling patients with, uh, bilateral reneogenesis, but I was wondering if, uh, Ellen and Sarah can comment if your pediatric urologist, um, were, were part of your, your prenatal counseling regarding those issues, those really important issues that, uh, Bob just raised. Yeah, so, um, we do, we start with a, it's a very long two days for these families of um a multidisciplinary approach with multiple. We have urology, nephrology, our MFMs, the neonatologists, nephrologist, um, and also our what we call compass, which is just our paleoty Care program talks with these families in China, you know, it, it's, you, you have to be realistic with these families. It's a commitment and it's a long shot. Statistically speaking, these children have, uh, are, are unlikely to get to transplant, um, but that doesn't mean that we don't have both anecdotal reports as well as case reports out there, and some kids are tough, and they do, uh, if, if they're able to get to transplant, they do incredibly well. So, uh, our approach is to first have, uh, educate as best we can at the very beginning, um, then we have a care conference first with the providers and then with the family within 24 to 48 hours after delivery, where we talk about the pulmonary status and then where we're gonna go from there based on how we're doing out of the starting gate. And then we have multiple um uh discussions along the way with the family, relatively regular care conferences to make sure that they understand the commitment, and my personal experience is, they never really understand it till they're living it. I'm, uh, surprised at how many families are able to rise to the occasion, uh, along the course, but to say that this isn't a phenomenal stress to families, uh, would be just blatantly untrue. I agree, you know, it's so difficult to kind of give these parents, um, even a good idea of what 1 month, 2 months, 3 months is gonna look like, much less get them on board with the time commitment it takes to go beyond our NICU and, you know, beyond hospitalization if these patients survive. Um, and so it's very important that you work with an interdisciplinary team very frequently, um, and keep parents in the loop, um, because it's a, it's a very large burden on these families. Thank you. I just want to point out that how important, you know, it is in terms of the dynamic of the multidiscipline team, um, especially during those really difficult stages. Um, I just want to point out, you know, one of the cases that Bob shared, um, that the creatinine keep rising and the baby was so small and really not a candidate for, um, any form of, um, sustainable dialysis, but, you know, at that time, the pediatric urologist jumped into the picture and created that, um, nephrostomy slash uh urologist, I believe it's a ureterostomy. Um, And, and really became the, the game changer at that period of time. I'm not saying that, you know, it's is always going to work, but it it's so important that sometimes, uh, you know, from the pediatric surgery standpoint, neonatologist standpoint, nursing standpoint, we just see that there's no other option of dialyzing that patient. But if, you know, the pediatric, um, urologist had not jumped into the picture, you know, we, we may miss out, um, Some of the options that could be offered uh to this family. So it looks like a, uh, another question just popped up from the audience as well. Um, and, and the question is, uh, you know, for a patient with suspected posterior urethral valves, what will your prenatal consult include and will it include talking about pregnancy termination. So, um, you know, I can, you know, I can also comment on, on that, uh, question. So, Uh, anytime we have a, uh, patient coming into our center with, uh, any complex, uh, renal anomaly, including lower urinary tract obstruction, uh, we include a, uh, maternal field medicine specialist, a neonatologist. Uh, a urologist, a nephrologist, a pediatric surgeon, and somebody from, um, our palliative care team. Um, they also, uh, meet with the, with our transplantation team, uh, as well. Um, and so they receive truly multidisciplinary comprehensive counseling, um, regarding how the pregnancy is managed, uh, prenatally, um, and what to expect, uh, in the, uh, in the years after birth. And, uh, we paint a very realistic picture. Um, of what the spectrum of outcomes would include, um, as well as the spectrum of care that the patients may choose to receive, um, during the pregnancy and after birth, and that does include counseling regarding pregnancy termination. Um, uh, in, in addition to that, uh, we discussed, uh, uh, comfort care, uh, palliative care measures, um, and the full, uh, spectrum, um, of care as you are, uh, hearing about his talk today. Um So that, that is typically um our evaluation of these, of these complex patients.