Fetal Intervention in Setting of In-utero Renal Failure (IURF)

But we want to move on to my, uh, long, long time partner next, uh, Doctor Muira Habli. I'm going to um. See if I can share my screen with you here. So, um, again for those that just joined, um. We, we are having a good time so far, um, with Genetic testing as well as uh fetal imaging for renal condition and uh Doctor Hab Lee is going to share with us um from maternal fetal medicine perspective about this condition and uh potential uh fetal intervention uh for these conditions and um Mira had been with Cincinnati uh for a long time and she had been my, uh, partner in crime for many years. Uh, she's currently the director of Tri Health Fetal Care Center as well as the chair of Perinatal Research Committee at Gumton Hospital, uh, in Cincinnati. Neera, um, are you ready to share your talk? Yes. Good morning, everybody. Good afternoon, depending on which uh time zone you are. Thank you for the organizing committee for inviting me and thank you for our attendee for their time in the weekend here. I'm gonna share my slides and we'll go from there. Perfect. You're in presenter mode, when you. OK. Is it good mood now? Perfect, perfect. Today I'm going to speak mainly about fetal intervention in the setting of in utero renal failure. I have no disclosure except some of the images I got from Dr. Jose Perro, my partner. The outline or the objective of my talk mainly to speak about the renal function and embryology, diagnosis of fetal renal failure radiographically and chemical. What are fetal intervention we offer either am infusion via amnio port or percutaneous amnio infusion, and Dr. Taba, my partner, will present some of the cases. fetal anomalies in general are detected in 2% of all fetuses, and the GU abnormalities are the most common one. They constitute about 50 to 30% of structural anomaly that are present at birth or at the time of prenatal ultrasound. The kidney usually or the glomeruli develop between 8 to 9 weeks, and they start by 10 weeks make urine. By 12 weeks, the kidneys are completely functional. By 14 weeks, major contributor to amniotic fluid, and after 20 weeks, more than 90% of the amniotic fluid is kidney related and not placenta. That's why most of the diagnosis usually of renal anomalies occurs between 15 to 20 weeks of gestation at the anatomy scan when we do at 20 weeks of gestation. As for the nephron, they continue to develop until birth, but at birth, the number of nephrons, they remain static, but there is increased in size to in order to be compatible with the changes in the babies. Now the placenta acts as an in vivo dialysis unit in the fetal life where the fetal electrolyte and fluid are usually regulated by the placental correlation with the mom and the maternal blood, as seen in this graph, there is an inverse relationship between the fetal electrolyte and gestational age. If you look at the y axis, it's sodium concentration, and the x axis is gestational age. With increasing gestational age, there is a decrease in the sodium concentration, and this is really important because it is secondary to increase in maturity of the renal tubular system. If we have renal failure, then you will see the sodium electrolyte increase because we have dysfunctional renal tubular system regardless of the etiology. Now how we diagnose renal disease, as Dr. Marianne has mentioned, either by ultrasound, our primary diagnosis for me as the maternal fetal medicine, and the MRI is always complementary to our diagnosis. The checklist that we use in general first look at the amniotic fluid. The presence and the size and the appearance of the kidney, the location of the kidney if it's pelvic or abdominal. Look at new Doppler arteries to check for renal arteries, and look at the bladder shape, volume, and wall thickness, the sex of the baby, because this helps us and also diagnosis and umbilical cord abnormalities if it's present. Now it is hard. When I was looking at the literature to find what is the definition of in utero renal failure, I honestly did not find a single paper that tells me this is the definition of in utero renal failure. However, what we use in general in most of the literature and in our workup is whenever we have amniotic fluid, oligohydremnius, anhydramnia. defined by deepest vertical pocket less than 2 centimeters plus or minus the total AFI less than 5 centimeters based on gestational age or less than the 5th percentile. In addition to a renal pathology, this constitutes about a sensitivity of 0.6 and specificity of 0.7 for the diagnosis of in utero renal failure. That means anhydremnias or oligohydremnius associated with abnormal renal function or structure, then this is considered in uterrenal failure. What are the radiologic signs of in uteroo renal failure? If you look at this image, it is mainly hypoechogenic kidney and enlarged or atrophic or abscess in the setting of anhydremnius, we can define it as a uter renal failure. In the setting of anhydremnius or oligohydremnius, if there's no other etiology or. etiology and we look at the renal cortex appearance where you could see those cystic changes as Dr. Marianne Meyers in the previous lecture has mentioned. This has a sensitivity of 0.5 and the specificity of 0.84 that this represents in utero renal failure. Other things we look at, looking at renal Dopplers originating from the aorta, as you can see in this image, there is no renal arteries that indicate bilateral renal agenesis. In this image there is a unilateral renal artery abscess which is indicates unilateral renal agenesis. Other findings we look at. Ultrasound, the cortex, the renal pelvis dilation in this star as it's been seen, thinning of the cortex, if there's any ureter dilation, and also renal caliceal dilatation as seen by those errors, these are all in the setting of anhydremnius could be indicating different etiologies of in utero renal failure. Now, the other also definition of in uter renal failure is in addition to the geographic, we have to have some objective, objective findings. Two things we use either chemical or what's known, one of the proposed definition is using the percentage of bread bladder refilling if you have an obstruction, bla etiology. And this is defined as fetal bladder volume 48 hours after a vesicocentesis, that means a bladder tap minus the original fetal bladder volume before the bladder tap is done, divided by the fetal bladder volume before the tap multiplied by 100. A cut of 27% could predict a poor residual renal function, and there is an 80% sensitivity or a 75% specificity that this will progress into in utero renal failure. Other findings that could help us. It's like a puzzle. You get the radiographic findings, you do the bladder filling, you look at the chemical and you put all these together to say this is a fetal in uteuterrenal failure. The other things that help us or prognostically help us in the definition, chemical definition of in uterrenal failure is serial assessment by vesicocentesis every 48 hours. In general, or bladder tap and other words, the first urine sample is mainly when you do a bladder tap, is usually represents urinary stasis for a prolonged period of time. That means the numbers and the values of the urine electrolytes are not good yet a presentation of renal function. Then you do after 48 hours another secondary urinary sample. This also still represents the chronic renal collection from the upper urinary tract. All these electrolyte numbers. The third sample, the electrolyte represents the fresh urine excreted by the. Fetal kidney and it truly can reflect if there is the function of the kidney. Keep in mind with all of these radiographic and all of these chemical definitions that we use to help us in diagnosis, still the function of any organ is determined at the time of birth of the baby, but the literature supports that the fetus could have salvageable renal function if they demonstrate decreasing urine value defined by the following. If sodium is less than 100 mg per deciL, chloride less than 90, osmolarity less than 20, calcium less than 8, total protein less than 20, and the beta 2 microglobulin less than 6 mg per liter. All of, still we have a lot of research in the field of diagnosis of in uteroo renal failure, but these are the premium findings that we use now in our clinical practices. What are the consequences of having oligohydramus and hydramnius and renal failure? Whenever we have, regardless of the etiology, decreased in urine and fetal urine excretion, whether it's renal agenesis, cystic kidney disease, obstructive disease, this will lead to fetal compression and will lead to an acute umbilical cord compression and increased risk of asphyxia and stillbirth. In addition to the facial appearance of Potter's syndrome, defined as low set ears. Peaked nose, prominent epicanic folds, and downward slant to the eyes. Pulmonary hyperplasia is the main cause of respiratory failure and neonatal demise in these patients who have renal disease with oligo and anhydremnias. Limb deformities and contraction is also one of the consequences of anhydremnias and setting of renal failure. What are the causes of in utero renal failure? In my mind, I always do it as we do it in adults. There is prerenal. There is renal etiology, and there is post renal etiology. Prerenal etiology of in uterofenal failure that has been reported in the youth literature is mainly in some of the diseases such as in uteroro growth restriction. In twin twin transfusion syndrome or if there is maternal drug intake and non-steroidal anti-inflammatory. However, those prerenal, prerenal etiology, they are usually correctable or reversible etiology either in utero or immediately postnatal period. The renal etiologies include renal agenesis, multicystic dysplastic kidney disease, polycystic dysplastic kidney disease. Other postrenal include vesicoureteric reflux and lower urinary tract obstruction. Those that we offer in general fetal intervention defined by amnio infusion to restore amniotic fluid are mainly the renal and the postrenal group in the fetal life. What are the types of fetal amnio fetal intervention we offer for in utero renal failure? The aim for any intervention that we do during the fetal life, we cannot correct what has happened as damage in general, but we try to restore amniotic fluid, the cushion for the baby, and this is important for lung development, especially during the critical period between 16 and 26 weeks of gestation. Renal decompression also in some cases such as in bladder outlet obstruction is one of the causes of intervention. There are two types of amnio infusion that we do in relation to in utero renal failure either percutaneous amnio infusion or amnio infusion through an amnio port, which I will describe in detail in the coming slides. What are is the inclusion criteria that we use in order to confirm before we do or offer fetal infant intervention? First, we confirm diagnosis of renal failure using radiographic and the renal functional assessment either through bladder taps if it is based on the disease or through chemical. Findings age more than 18 years of age, no genetic or any other major anomalies. It's an isolated finding. Cervical lens more than 2 centimeters, single term pregnancy, no history of preterm delivery, and there is no technical contraindications such as abnormal presentation, accreta percreta, and definitely a motivated patient. Workup we do before we do any fetal intervention, a detailed anatomy scan and MRI to complement to make sure we have completely an isolated finding that is related to renal disease. We do a diagnostic amnia fusion first in the setting of oligoanhydremnias to confirm intact membranes. There is no rupture or any other obstetric indication, and to do genetic testing. We usually include patients that are diagnosed and the first am fusion before 26 weeks, and each of these patients go through multiple subspecialty meetings including pediatric surgery, nephrology, neonatology, MFM, transplant team, palliative care, social worker, and more and more, and they go through several meetings like that to make sure these patients are motivated and they fit the criteria for such intervention. The amni infusion protocol we use, we use a solution that is used mainly lactated ringer. The volume calculated in order to amni infuse those patients is gestational age in weeks, multiplied by 10, and the aim mainly is to achieve the deepest vertical pocket between 5 to 7 centimeters or an AFI total amniotic fluid index between 16 to 20. Frequency to maintain a DVP between 5 to 7 centimeters. In general once per week amnio infusion less than 26 weeks. If it is more than 26 weeks, we usually do it 2 times or 3 times per week based on the amniotic fluid measurement. We continue to do that till 37 weeks and gestation and the aim to do continue to do that to 37 weeks. Gestational age of delivery between 37 and 39 weeks unless indicated earlier. The amnio infusion is not indication for C-section in general. It's a spontaneous vaginal delivery unless C-section is for obstetric indications. We use lactated ringle because it's similar to what is the constituent of the amniotic fluid, and we use a warm LR as seen on this table in regarding sodium, potassium, calcium, all are compatible lactated ringer with what is in the natural amniotic fluid. For percutaneous needle or abdominal amnio fusion, we use usually a 20 or 22 gauge Eco-tip needle from Cook Company. We introduce it in a safer space than the amniotic fluid, and we infuse a sterile, warm, lactated ringer. As I said, the aim is to restore amniotic fluid and help in lung development in these patients with in utero renal failure. Complications of direct amnio infusion is mainly reported from cases that they have done in the literature and the Cochrane reviews and mainly from those that have done PPRM. We are working and now we are collecting our data to present MN port and MN fusion complications soon. The risk of choreoammonitis in those patients is 10 to 20%. As I said, this is the misleading complications in utero renal failure because most of the complications of amnio fusion is in the setting of premature rupture of membrane. 12% reported literature of ruptured membrane in these patients after the first one of amn infusion, and some report 0 to 1% comparable to the estimated risk from amniocentesis. 2.6% risk of placental abruption preterm delivery is about 8% of patients. The second type of amnio infusion is MN port. The MU, these are the instruments we use in amnio port. This is the needle where we introduce in order to do amniotic fluid, and I will show a video of that. This is the catheter guide. This is the transducer, and this is the mediport that we use to infuse here using the power lock safety power lock needle in order to infuse amniotic fluid. This is some nice presentation I took from Dr. Jose Peru where the amnio port, medi port is put at the lower part of the ribs, and then we infuse it through this the amniotic fluid on this baby to maintain and restore this amniotic fluid, and I will share with the team a video. Show us the place to be. Mm And that's it, how we usually, that's it how we usually use the amnio port. You could see here minimal amount of amniotic fluid, and this is after the infusion, how we have no restoring a normal amniotic fluid. In Cincinnati Fetal Care Center, we have evaluated in the last almost 10 years about 439 patients with a genitourinary abnormality, 210 is bladder outlet obstruction, and 22, 20, 225 is other. renal disease, including MCKD and other disease. 67 of these have done amnio direct amnio percutaneous infusion, 40 due to a renal failure in the setting of bladder outlet obstruction. That means about 20% of bladder outlet obstruction that we see ended up with in utero renal failure. That means anhydremus, oligohydramus, with nonfunctioning or bladder capacity that is less than 27%. 27 of these in utero renal failure. The other 27 were secondary to other renal abnormality, about 12% of what we see. 25 patients have done MN port and as I mentioned, we are reviewing all of these patients to report the complications from direct percutaneous amnio fusion versus MN port in the setting of renal failure, not premature rupture of membrane as mentioned in the literature. Our first paper that I'm just going to mention, 8 patients that we reported their outcome, and this paper is published under the title of use of an amnio port to maintain amniotic fluid in fetuses with oligohydramnia secondary to either. Lower urinary tract obstruction or other fetal renal anomaly. We reported this is our first experienced serious cases. We had 8 patients that we did MU port. There were no fetal deaths on those 8 patients. We were able to successfully restore. And maintain amniotic fluid. There was one patient who died at birth with secondary to unrecognized laryngeal web, despite an MRI was done, and another one died from pulmonary hyperplasia after the patient has ruptured ruptured membrane after a few of the amnio infusion. None of the remaining 6 had pulmonary hypoplasia at birth. And these are the 8 patients that have been published in the literature. Most of them have infusion or diagnosis that started less than 26 weeks. You could see the 1st 3 patients were our first experience, and then we stick to our criteria. To start the infusion less than 26 weeks. Duration between infusion was about 4.3 days, and the gestational age at delivery was 34 weeks. The average gestational age with a range 31 to 37 weeks of gestation. 88% of these patients were surviving at birth and 70% in the neonatal period. There was no cases of infection. There was one catheter dislodgement, which was our first case actually that we have done because we did it at the pelvis, not at the chest as we do, and there was one malfunction of the port, and the patient at that point did not want to replace it or do another surgery, and there was one case of premature rupture of membrane. As I mentioned at the beginning, there still remains a lot for us to do in this area of fetal urology, from diagnosis, from therapy, from functional imaging, be creative in order to have an assessment of that biomarkers of renal function, and we, we are, you know, should be start doing randomized clinical trial in this aspect which there are still where there are few are already existing. I would like to thank our team and open for any discussion. Probably I'm actually gonna hold questions until after Taba, uh, Doctor Taba presents the cases and then pose the questions to you guys together if that's OK since we're staying on the same topic. Absolutely, I'm gonna stop sharing so that Doctor Taba can present his cases. Perfect. And I apologize for the video did not have the voice. I tried to correct it during presentation, but Dr. Lim will send a link, our fetal care center link in order for to be seen. It's on the chat box now, that link. I appreciate it. Thank you.