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Everybody. Thank you everyone for joining today. It's good to see so many of you here and um thank you for putting all your details in the chat. Um Unfortunately, the situation Ukraine still goes on, but our thoughts are with you all. Good to see that you're all um here and well, and I can also see you're all around the world. So actually from the UK to India and Chennai actually were, I've just set up a twinning program with transplantation um but also as far a field as um Nigeria. Um so welcome everybody. I'm just going to share my screen. Hopefully you can see that well and you can hear me and see me well. So I'm professor Pediatric Nephrology at University College London. I'm one of the kidney specialist, but I lead our kidney transplantation program here, which is um the largest in the United Kingdom, one of the largest in the world. Um We did um 39 kidney transplants last year, but in fact, that would be counted as quite small in an adult center, but obviously, we deal with more complex um Children. Also, I'm the director of our clinical research facility where we do to kind of high impact clinical trials. So a lot of the phase one work. So very exciting gene therapy studies going ahead from the future. So maybe we won't need kidney transplantation moving forward. So I thought I'd start with a bit of a case presentation, try and share with you the functions of the kidney. Talk a little bit about what is normal kidney function. And when is it abnormal? I'm thinking of renal dysfunction from the severe reversible acute kidney injury um to the um irreversible kidney damage that happens in uh chronic kidney disease. But very often, what we typically see is patient's presenting with acute kidney injury on top of chronic kidney disease, which may in fact not be known. And those patient's with end stage kidney disease management and I'll touch a little bit about a newborn babies, kidney failure and management as well. This just gives you a flavor of a premature male infant born at 34 plus six weeks, gestation weighing 3.35 kg. His mother had previous pregnancies which were successful in this child in neutral as a fetus. His mother had normal antenatal sounds at six and 12 weeks. But by 20 weeks, they had diagnosed congenital anomaly where the left kidney looked bright in the right kidney, had some evidence of hydrogen froze is so, therefore, the the pregnancy was more closely monitored. And here you can see the kind of fetal medicine imaging here for that bright kidney, the child ended up having developing bilateral hydronephrosis is and that ecogenicity increased, the bladder became distended and the like er volume decreased. So at 34 weeks, gestation, there was induction of labor, the baby was born and with respiratory distress syndrome required ventilation for five days, an admission to the neonatal intensive care unit for just over a week and had neonatal interventions including a suprapubic catheter being inserted for five weeks, feeling that there was obstruction. So, bilateral nephrostomy, he's were inserted for a couple of weeks and the crown in of 288 managed to reduce. But due to ongoing anemia and interventions and the child required blood transfusion. So here we can see a mixture rating cystourethrogram. And here you can see the dilated posterior urethra and you can see kind of a small trabeculated wall bladder that you can see here. And this confirmed an obstruction due to posterior youth revolves which very often can be associated with one of the most common congenital anomalies. The kidney and urinary tract, what we call dysplasia or bilateral reno dysplasia. So, dysplastic kidneys. So there was no evidence of other obstructions such as physical ureteric function. And he went on to have resection of the posterior through evolves. But due to the increased pressure in neutral, that very often will cause damage to the kidney in neutral. And despite the fact of removing the obstruction and going back a month later and redoing the resection because you still see evolve leaflet, you may not always get normal kidney function. So, does anybody have any ideas? What factors are predictive of long term prognosis is just having a look to see if anybody in you can either run mute or you can put in the chat. So the in factors to think about is if there's evidence of both kidneys not being formed correctly. So, bilateral renal dysplasia. So you may get cystic dysplastic kidneys where they're cysts within both of the kidneys. If you go bilateral visa clear to reflux and you go abnormal bladder function and that can impact but obviously, it's difficult sometimes to work out longer term due to children's development both in bladder and renal function. So normally you see the kidney function improving in the first year. But in patient's with posterior use evolves, we looked at the series that was up to a median of over three years, 3.2 years. Those Children that have multiple hits to the kidney having episodes of pylon arthritis or begin coming on well within uh inter current infections, developing hypertension and dehydration and the development of protein, urine hypertension. So, patient's need to be followed up at 17 months of age and this particular patient was growing and developing normally abnormal BP, there was no evidence of protein urea. He was salt wasting required some bicarbonate supplementation, some iron supplementation and um antibiotic, prophylaxis, but actually he had normal kidney function. So a creatinine of 97. So it can be difficult to predict from those infants start with any natal course, including intensive care. So, what do the kidneys do? Well, the kidneys are brilliant at removing waste and foreign materials at the least cost and useful materials and energy. They regulate the whole meal status and the body's water electric levels and asset based bounds and all they do a lot of actions such as production of metropolitan to stimulate bone marrow production. They're able to do a lot of these tasks over a wide range of water salt and protein dietary and to get intakes and degrees of muscular activity. And very often we know from probably unethical studies in the past where they take a group of medical students, they don't give them enough to drink, give them high protein loads and get them to do figure eights exercise going on um a marathon and then seeing what happens and when you take a blood test, what's the first thing that you might detect as an abnormality? What do you think? Well, some people think the cramping may go up is acute kidney injury. But again, that doesn't happen initially. What about hypernatremia dehydration and getting an elevated sodium? Well, actually, as I said, the kidneys can cope usually over a wide range of activity. But yes, that may happen. But the first thing you're probably going to see happen is an elevated um urea and so well done. I've seen you put that in the chat. So thank you for that. But if you think of the dialysis machines that we have, the two main functions they do, has he removed fluids that's called the ultra filtration and they get rid of the waste products and that's the dialysis itself. So, what about newborn babies? Well, newborn babies are at special risk of developing kidney failure because of their relative state of chronic insufficiency. They have much lower BP with an elevated renovascular resistance. Their renal blood flow is reduced as is their overall kidney function or glomerular filtration rate. So here we can look at the arctic BP and very low birth weight weight, infants of 715 g and a kilogram of weight birth. And you can see here that the systolic blood pressures and and the values measured in the first hours of life are between about 44 49. So very relatively low with very low diastolic blood pressures of 24 to 26 depending on the size, but hygienically assess their kidney function. Well, people do a lot of research and often talk about biomarkers, but I use a biomarker all the time and that's the plasma crackin. Initially, the values reflect the maternal crotan. Um So shortly after birth, it's important to know what the mom's crackin is. If you do a blood test and find the nina, it's creatinine is elevated, that plasma cran in rises progressively throughout childhood. Basically, according to the height and muscle bulk, because we use plasma croutons as a biomarker because the only place that's released is in the muscles. And we know that the only place that the croutons got rid of is in the kidney. So a normal newborn plasma craning will be around 20 can rise to 100 micromoles per liter after pubertal development and adolescents. But that's really only in a very muscular teenager who's going to the gym. It does not rise until the renal function has have. So it's actually a poor marker of overall kidney function. A note the Crandon may not be raised in a child who is small and thin due to chronic kidney disease. So here we can see the relationship between the fetal and maternal plasma craning being around one as you can see here, although can vary from anything from about 10.7, up to about 1.5, but really just showing them the first few days that the creatinine of the knee in it will very often resemble that of the mom. And here you can see changes in the creatinine from over time based on gestational ages. Um so a relatively high plasma Kratt in between 60 and 70 from anywhere between less than 27 weeks to 31 to 32 weeks, gestational age increasing to 1 20 in the very small and then it's um under 27 weeks due to usually other issues and having multiple hits. But here you can see the plasma cracked and coming down to normal by about 7 to 8 weeks of age. And if you look at the overall plasma kratom, and according to the timeline, you can see that very often those initially high plasma croutons very often reflecting the mother will come down to a steady state usually by about one month. So four weeks and here, if you look at the first four weeks, you can see that that reduction continues and actually is more significant in the smaller infants who generally are born at an early gestational age and have higher plasma croutons which come down with time. Now, there are many, many ways that you know of estimating your glomerular filtration rate. So if any adult, the United Kingdom has a blood test, for example, they will get an estimated G F R based on their age, their sex, their ethnicity, and the plasma crackin an adult Bryant is very often it's checked with a Cockcroft Gold equation where you take a function multiplied by 100 and 40 minus the age of the adult multiplied by the weight and divided by plasma Kratt. And because actually it's more the muscular weight, which is really important. So you've got to use the lean body weight in these patient's and in Children, we very often go and move to what we call the Schwartz formula, modified Schwartz formula or Schwartz haircut, where we take a constant, we multiply by the heightened centimeters and divided by the plasma Kratt and the micromoles be liter. And invariably, we take a measurement about 36 a half. People have said between 33 34 it's very well change dependent. So actually, we would be up to 40 is potentially in adolescents, but we generally use 36.5 through the different age ranges. Noting that if you want more exact measurement, then you might have to use the S statin. See estimation, there are other measures apart from cystatin C in measuring the formal glomerular filtration rate. And that can be by the clearance of a substance which can be 51 chrome EDTA iohexol, which we use more readily. But in fact, and the results depending on how many sample sizes you do an in house issues. Such a example, the timing of the blood tests can influence the overall and results. But remember, you can always take a time during collection and see what the creatinine clearance is of your patient's as well. So what about the overall glimmer, local attrition rates? So here you can see the G F are improving. So if you're preterm infant, you've got very, very poor kidney function, which can improve to about 50 mils per minute per 1.73 m squared in the termini in eight. And by about fifth of around 50 mils per minute for 1.73 m squared at a month. And this chemo basically just shows you that if we talk about end stage kidney disease being a G F are less than 15 mils per minute per 1.73 m squared. You'll see that mostly mean it's have very poor kidney function, but the difference is their kidney function will improve by 123 months, increasing about 50 mils per minute per 1.73 m squared. And any value of mils per minute per 1.73 m squares is roughly um equating to percentages invariably by one year, it'll be about 100 and 215 10 years may go up to 100 and 20 and beyond. So, trying to discern what happens in the nets is important because they may have acute kidney injury, what we used to call acute renal failure, acute on chronic kidney disease or acute kidney injury. On top of a chronic kidney disease, chronic kidney disease that sell for end stage kidney disease requiring dialysis as kidney replacement therapy. When we talk about cute kidney injury, we mean the rapid reversible deterioration of G F are associated with nitrogenous waste product accumulation. And depending on individual series. In a prospective study, about 8% of babies in NICU experience some form of acute kidney injury and pre renal failure is the most common type of acute kidney injury. In around about three quarters of all neonatal cases, severe acute kidney injury can be defined in the neonate as plasma Cranham, which is increasing by more than 50 micromoles per liter per day or 5.65 mg per liter per day. We sometimes use the terminology of oliguria, which is defined as a reduction and the urine, I put two less than 20.5 mils per kilogram per or in Children, but it can be one mil per kilogram per are in units and that it should be compared to one little per kilogram per day of an urea due to the transitional epithelial layer in the bladder being secretary and producing fluid, acute kidney injury associated with perinatal asphyxia is predominantly nonoliguric. So uh I mean it will continue to produce some urine. So all forms of acute kidney injury depending on the age can be pre reno. So this is fluid getting to the kidneys renal itself. So, intrinsic renal parenchymal disease or post renal is usually obstruction by prerenal. We usually mean decreased to intravascular volume very often. This can include third space losses of sepsis and nephrotic syndrome, but can happen even in pump failure. So, circulatory failure with congestive cardiac failure, pericarditis and or cardiac tamponade. Intrinsic kidney disease can include acute tubular necrosis is um uric acid nephropathy, which can be seen with tumor lysis syndrome very often though. And then it's you might for example, have an orange tinge to the urine. And that very often is babies who are born usually first time moms. Um the colostrum is just coming through. The babies are intra dry vascular e um dehydrated because they're not getting a lot of milk and the baby can put out some urate crystals in the nappy. However, we can see drug induced or idiopathic interstitial nephritis very rarely in mean it's and infants is a, is a Frank Glamorama fighters. But we have seen it with COVID obviously talking about vascular lesion's with hemolytic uremic syndrome, cortical necrosis or in larger of intestine bosses and infectious causes of sepsis and pilon arthritis. And remember we've got two kidneys. So if one kidney is otherwise doing well, then there shouldn't be a problem. But obviously, if you've got a solitary kidney which is obstructed, that can result in acute kidney injury if you've got obstruction on both sides. So, thinking of bilateral Euro Terek urethral obstruction. So, when I consider neonate, it's they have very similar um causes of acute kidney injury with prerenal, post renal and intrinsic renal. So, hypoxic anoxia prerenal giving hypoxic ischemic encephalopathy, dehydration, hypovolemic hypertension and congestive cardiac failure, organ failure with hyperplasia, dysplasia, vascular disorders, um acute tubular necrosis, nephrotic agents and pylon arthritis and post renal urethral obstruction or diverticulum uterus, you and Urogenic bladder. So, thinking of fluid electrolyte and acid base and balance. So, patient's may get fluid overload because you're quiggle opathy, disseminated and vascular coagulation. You're having to give lots of fluids and replacement development of acidosis is electrolyte imbalances with hyponatremia, hypochelemia and hypercalcemia, which of course can lead to convulsions and overwhelming sepsis or renovascular. It's from bosses or it'd really hypertension. So, if you think about presentation and chronic kidney disease, um so very often it can be acute on chronic kidney disease which may or may not be diagnosed with antenatal information and it can be precipitated by infection or dehydration. Those who have had an antenatal diagnosis of bilateral anomalies should really worry you. But those with symptoms and signs of chronic kidney disease with anorexia, lethargy politics see a polyuria failure to grow. So, faltering growth failed to thrive bone abnormalities with renal osteodystrophy and Ricketts as well as hypertension and M protein urea. We should suspect chronic kidney disease when the croutons above the normal range hematological and biochemical abnormalities with anemia, hyperkalemia, hypercalcemia, hyperphosphatemia and secondary hyperparathyroidism. The patient's having bilateral renal anomalies and antenatal scans or bilateral renal defects or having a family history of chronic kidney disease, persistent protein urea after an episode of acute kidney injury. This is some work when I was in North America where their data really showed that about a third of patient's have congenital anomalies of the kidney and urinary tract. A third have primary glomerular disease. So, thinking of glomerulonephritis, thinking of patient's with Falkland cemented glomerulosclerosis, causing steroid resistant nephrotic syndrome, which doesn't respond to other treatments and about a third of other including other genetic causes of kidney disease as well. So this kind of structural malformations being around 40% glomerulonephritis. Up quarter, hereditary nephropathy is about 1/5 and 1/10 being systemic diseases. And this has very much been merged in our UK renal registry data. You still receive the whole data and you can see about a third of patient's having dysplasia with or without physical ureteric reflux. You can see that if you add in the posterior to valve, you get over half of the patient's with congenital anomalies. Thinking in your new tracked much less about six with the merlot diseases. And you can see 7% of Children, sexual disease and congenital nephrotic syndrome and smaller amounts for metabolic renovascular polycystic kidney disease. This is an innate who was born that you can see unfortunately was a stillbirth and had what we call absent abdominal wall musculature. So this is associated with Meghan ureters, but also bilateral cryptorchidism. And as a result of um reduced like our volume, not maturing the lungs because of reduced fetal urine production. Then you result in the problems that the kidney doesn't allow the lungs to mature because that like or is not going into the respiratory. So here we can see some of the appearances which maybe suggestive on ultrasound. So you can see here that if you've got cysts in your kidneys because you've got small dysplastic kidneys you might be in the situation that you've got a multi cystic dysplastic kidney. So this was felt to be a separate entity, a multi dysplastic kidneys, one where there's actually no functioning parenchyma. So if you did a DMSA scan, there would be 0% function and, and basically, that would be associated with the new traffic ureter. Whereas renal dysplasia itself will have cysts, but there'll be function from the kidney and also more recessive, an autosomal dominant polycystic kidney disease, increasing predominance, as well as other genetic inherited diseases such as tubular sclerosis or glamour polycystic disease. Just having small kidneys, we tend to suggest renal dysplasia. But important to know if there was any vascular insults, either venous territorial and all causes may result in small kidneys, uh end stage kidney disease. So by the time you've got small kidneys, even at presentation, we wouldn't move forward to do a percutaneous kidney biopsy because of the risk of bleeding. If you got normal kidneys, it may happen as a glomerulonephritis. A familiar nephropathy nephrotic syndrome, again, tend to have big bright kiddies at the start, but they generally settle down and in front of these is maybe cystic. So kind of an overlap between the renal dysplasia and the juvenile in front of visas. And there's also the tribune opathy is to consider if there's obstruction, then you may have pursue it revolves or dysplasia with physical Eurotech junction or pa the ureter junction obstruction and then you're a plastic bladder. And remember it's always important to exclude and nephrolithiasis. So, seeing if there's any evidence of renal calculi, basically from the history with recurrent urinary tract infections with or without obstruction or reflux. Thinking about the development of pureeing disorders, cystinuria, hyperoxaluria, and costume disorders. So what is the most common genetic cause? Friends age kidney disease in the first two decades of life does empty have an idea if so you can put it in the chat very often. People think it's polycystic kidney disease. But in fact, it is indeed, as you said, juvenile and from a thesis, a recessive cystic kidney disease caused by genetic mutations M P H P one gene all the way up to double figures now and very often they will have genetic testing in Children presenting with end stage kidney disease. Here you can see and the stages of chronic kidney disease from stage 1 to 5 stage ones where you have normal kidney function with an estimated glomerular filtration rate above 90 miles per minute for 1.73 m square. But either this renal parenchymal disease present or these are patient's who have bilateral potential insults in the future. So for example, a child with insulin dependent diabetes, myelitis by stage two chronic kidney disease, where the kidney functions between 60 to 90 miles per minute for 1.73 m squared or 60 to 90% they usually aren't any symptoms, but it may develop biochemical abnormalities and you may find that some results on the lower end of the G F R range between 30 and 60. You start getting biochemical abnormalities. In addition, patient's may develop pro growth in appetite, but the symptoms start getting more severe with the lethargy by time, it's dropped to stage four chronic kidney disease with EGFR between 15 and 30 and usually kidney replacement therapy is required if it's less than 15 most per 1.73 m squared. Although nenets can be actually tolerate lower um G F R s and not required kidney replacement therapy. It's important to take a good history in an older child as well. But in Nina two younger child, you want to know how often they're feeding. Obviously, breast feeding can be difficult but are they having temperatures and losing excess fluid? Do they have diarrhea, vomiting? Um As soon as they've been fed, is there any insult to the baby? Any problems with urinary flow? Thinking about any excessive losses through hemorrhage or burns, taking a full drug history, especially in adolescence, thinking recreational drug use and making sure you've got antenatal antenatal information as well as well as past medical and surgical history, including your new tract infections, the growth and overall failure to thrive. It's always important to ask about the family history and it's really an important lesson that every year I get told the patient's don't have any history when I go up to them, ask one question. I come back and tell the juniors they do. And the reason is, is that if you've had a kidney transplant, the feeling by lay public is the fact that that person is cured from their kidney disease. So it's important to ask is Emily and the family got significant kidney problems and he had high BP, dialysis or kidney transplantation. It's important to assess patients' and go back and reassess them and have a overview of them, especially if there's been a change in their overall management. What's happened if they become more tachycardic, they drop the BP and do they have cooler peripheries? They need another bolus. Are they in palmyra edema? In which case, you don't want to bolus getting syrup, lots of weights, heights and head circumference, making sure that you um um look after the patient's and look at their state of hydration and see if it changes as well as looking for signs of cardiac failure, multi system disease, palpal kidneys, bladders and masses. The blood tests, if you're trying to work out acute on chronic or chronic kidney disease is to see that the iron evidence of iron deficiency anemia and the anemia and chronic kidney disease is very often normochromic normocytic and thinking of clotting cross match, especially if you might need to go to theater for Dallas is access, looking at the serum electrolytes, the acid base status, the renal function. What's happening is that deteriorating, seeing what else there is infections such as using blood cultures and CRP. But thinking about calcium homeostasis and bone health thinking of ionized calcium P th um and then special investigations as suggested by the underlying cause. If we get a drop of urine, please do a urine dipstick and see if there's any protein urea center off to laboratory for urine albumin and protein to creatinine ratio, whichever you have locally do Mike Austrian culture. A check for urine electrolytes, especially in the face of hypernatremia and calculate the fractional excretion which is urine over the plasma study and multiplied by the plasma over the urine, the urine, um Crichton, other investigations as outlined but definitely an ultrasound to exclude obstruction. But it will also show you large big bright kidneys if there's an acute process or small kidneys or chronic kidney disease, I may consider doing a percutaneous renal biopsy but not if the kidneys are small and shrunken because there's a huge risk those kidneys are going to bleed. But considering doing an X ray of the left wrist in hand, looking for rickets. It's about assessing patients' clinically as we said, but going back and recessing and seeing the rate of rise or fall of that plasma croutons important, making sure you keep an eye on the bone health calcium phosphate product as well as the albion alkaline phosphate, ease a daily full blood count and your analysis as well as urine electrolytes but try and do them when the patient's not just received diuretics and ultrasound and to be repeated, especially if the initial images suggest and follow up. So this maybe you after the lecture going to the pub. But thinking of your hydration status, it's important that if you're euvolemic or dehydrated, you're going to give a flu challenge. Normally we start with 10 to 20 miles per kilogram per hour over an hour and then assessing if they're euvolemic, you might want to consider giving frusemide. If there's no response and consider giving 2 mg per kilogram, followed by 2 mg per kilogram. Although the textbook see up to five months free kilogram, it's always good to challenge your patient but do it slowly and with the frusemide because you're wanting to reduce the evidence of them auto toxicity. If they are clinically fluid overloaded, their tachycardic, they've got a gallop rhythm. They've got an elevated jugular venous pressure. If they've got Dhiman hypertension, then again, you might want to give frusemide if the fluid overloaded, severe and use dialysis if there's no response to treatment. So that's your further fluid boluses as indicated by the clinical state. You're going to monitor with daily or twice daily weight. Thank your input output recording and at least four hourly BP monitoring of the peripheral core temperature gap. Once you've given your fluid bolus, you may want to cut back, especially on the fluid status of the patient but you may want to give insensible loss is 400 mils per kilogram per day. But replacement of the urine output of the euvolemic maybe restricting to a half to three quarters urine output if they are overloaded and modified to the fluid restriction, if on dialysis or urine output is established. Impala uric recovery phase. Remember to replace the urine output with insensible loss is for 24 hours and set a target especially if the renal function continues to improve. So does MG know how to manage some of these points? So what about hyperkalemia was a patient? There were in any and they had hyperkalemia. What would you do? Well, the first thing to think does it would it matter if they were an older child and able to sustain it? Does it matter if they run in it? Because younger kids and Nina, it's actually managed with hyper claim a fairly easy. But I think putting on electoral um or a 12 D C G. Hello. Never. Please meet the microphone. Yeah, I've meted other people. And so if you've got hypochelemia, thinking about putting them on a cardiac monitor, giving themselves beautiful sodium bicarbonate. We've got zirconium. Now, frusemide, calcium rezoning and insulin dextrose infusions. If they've got low sodium, that was probably due to fluid overload. So you want to restrict, but you may have to remove fluid with kidney replacement therapy, either with dialysis or intensive care. Very rarely. Would I ever give hypertonic ceiling, you may have an elevated sodium. So again, considering of sodium retention that may respond to freeze. Um I'd in if not dialysis and you may be hypercalcemic in thinking that might be multifactorial and giving supplementation with one alpha hydroxycholecalciferol. If you've got a high phosphate, then again, dietary phosphate restriction using phosphate binders may be required. But if you're not eating, then it's very difficult to normalize. Hyperphosphatemia may not improve so much with Dallas is and acid doses with sodium bicarbonate replacement. If you've got high BP, secondary to fluid overload or alternation, your vascular tone, then think about diuretics with medical management. Dallas is of the failed to respond to diuretics analysis. If they've got pom radium A and oliguria, remember the nutritional aspects and the drug aspects of kidney failure. So it can be associated with the cata polic state and thinking about malnutrition is not good. Um So you need to ensure you've got adequate calories and nutrition to improve the long term outcomes. Babies should be reviewed by the dieticians and if they've got acute kidney injury with hypokalemia, hyperphosphatemia and they're beginning to eat, then they should have a restricted diet. But you want to get at least 0.6 g per kilogram of protein intake and to maintain calorific intake and start nutritional feeds. And we try and do orally or via nasogastric tube to minimize catabolism uremia and the anxieties of total parental nutrition. Remember, it's always important to look up um some resources. So for example, the British National formally for Children to see that if you've got a drug and you've got evidence of renal dysfunction. Do you space the doses out more widely and or are you in the situation of being in the situation where you have to reduce the total doors are and make sure the two and what happens when the kidney function improves or deteriorates? You've got to make sure that you look at that every single day. Um I see some of you put um some of the answers and apologies. The the chat seemed to go from my screen. That's just come back just now but try and avoid nephrotoxic drugs where you possibly can. How do patient's do well, there's various reports depending on your definition of acute kidney injury. But it's important to look at the longer term outcomes especially if um acute kidney injury, which may be the morbidity and mortality. How much are you able to get people? Patient's off Dallas is and how many have got chronic kidney disease? It depends whether you're including mean, it's for example, that I've got congenital heart disease going to intensive care. So once we've got your kidney function, that estimated G F R is less than 15% or 50 mils per minute for 1.73 m squared, we're going to want to do where possible. A preemptive kidney transplantation. That's not always possible and some patient's require particle dialysis which can be done at home or in hospital. Uh hemodialysis invariably in the past was just hospital. But can I be performed with new technologies at home? But we would try to do a pre emptive kidney transplantation before the patient ever required dialysis. And as opposed to doing deceased donor transplant, which may be heart beating or non heart beating, we would try to do a living related donor. We can take unrelated donors, but we would look to see whether the immunological match was good, the right blood group, although we do do blood group A B on compatible in HLA incompatible transplant and think about period cooled exchange. So let me give you an example of a patient. Here's a patient presenting it two years of age with an acute illness and you can see that he's dropped his kidney function with an acute kidney injury with a estimate ically morale filtration rate of around three quarters of normal and 75 miles per minute for 1.73 m squared. After as acute kidney injury, you follow him up and you see that the kidney function is dropping to 60%. Two years. Follow up. It's dropped to 45% and three years follow up. It's hit 25. So we start planning for living related kidney transplantation, but he has an inter current infection. As you can see 3.5 years after follow up. So six months after this planning for a living related kidney transplantation, there's been problems with the work up in the donor and the patient ends up requiring Dallas is but very shortly, we're able to proceed with a living kidney donor transplant from mom. And our outcomes in the national data show that patient's do relatively well. Um If you have only a short form of Dallas is by five year follow up. That's one year after kidney transplantation, he has acute kidney injury. He's got acute rejection episodes with infectious complications and has worsening kidney function. He has worsening function at um two years after his transplant with EGFR just below 40 miles from, from 1.73 m squared and this drops to 20%. Um at seven year follow up for three years after his kidney transplant with planning for his next transplantation. If you follow him up for eight years. So four years after his transplant, he's got worsening kidney function. Yet again, he's nearing Dallas is but he's able to receive a second transplant at nine years follow up. So this is five years after his first transplant and you can see 12 year follow up, um which is eight years after his first transplant and three years after a second kidney transplant when he's transferred to an adult um nephrologist just before his 18th birthday. So thinking of the overall end stage kidney disease management and patient's that have got normal kidney function. But those with abnormal were wanting to try and see whether we can do kidney transplantation where as possible and it would be good to be blood group compatible. Um living donor kidney transplantation from a healthy individual with a good immunological match at least a 111. So acute kidney injury and chronic kidney disease. I think monitoring changes in clinical status is paramount in kidney failure. It's important to have regular observations, checking the blood and urine and the most crucial element is fluid balance. But please remember to check clinically if there's evidence of acute on chronic kidney disease. Um A lot of this work came happens with her team here at Great Ormond Street, but also in the United Kingdom and internationally through world collaborations, especially with the certain registry. And I'm currently on the working group Children with chronic kidney disease and end stage kidney disease. Those that have transplanted versus Dallas is and those with living donor as supposed to deceased donor to give the best outcome. Looking at our research and future research plans are good and I've just got an advert out for another phd. Shouldn't to look at some of the aspects and we can predict outcomes with biomarkers. But I thought I'd make you think about the optimal periorbital BP for an 18 month old who um has only 10 kg but has had their kidneys removed because of congenital nephrotic syndrome and is on hemodialysis and is going to get a kidney from there, 80 kg father who's only 35 years old. Well, the important things to consider here are the donor BP, the recipient BP, what we're trying to achieve, we do do kidney transplantation of the the right blood group is that um consideration is always really important as well. If you look at some world data, you can see why we favor transplantation transplant. Two Children of uh two thirds lower mortality rate than Children who are dialyzed and the longer on dialysis, the higher mortality is in their sapir results in those that are transplanted well before dialysis. Um if you look at the overall outcomes, you can see the 20 year graph survival and we don't have time to show all of the data today, but basically is heading up towards about 20 years so that you can see the half life of kidneys. How long does it take for patient's to lose half of the kidneys? So this is when patient's may have abnormal kidney function, which is poor but not to the extent that require dialysis or transplantation. If you look at some of our national data, you can see that the number of patients that we've taken on with NSAID kidney disease below the age of 15 has dramatically increased over the last coming up for 40 years. And I'm sure you the changes from the eighties, nineties and early two thousands has really been because we had multiple patient's referred to us who have been refused. Dallas is that to other centers? And we were there last hope to try and see if we could get them a kidney. If you look at the number of UK deceased donor kidney transplantation, you can see that the relatively stable over the last decade. Um However, you can see here um in the total numbers, um the difference between adults and pediatrics and a growth as you can see here. Um up to the end of the decade and here you can see as well, the total number of transplants increasing in both adults and Children. But you can see a leveling off of the kids overall in the total of deceased and living donor kidney transplantation. If you look at the outcomes you can consider here, adults and Children, you can see that young infants do relatively well. Um longer term imitate the medications but have increased morbidity and graph loss at the start, usually due to the small vessels where they adolescents do very well initially, but they stop taking the medications and have a developing immune system which causes problems that we're able to reduce it. If you look at some of the data, Great Ormond Street, we performed the first kidney transplant in our unit um from the Royal Free in 1973. So Children less than five years old were transplanted from 1987 joined with the Royal free hospital. In 1997 a single transplant surgeon replaced with the team um of six surgeons that it is now. We treat one in five Children the UK with end stage kidney disease. But because we do transplantation in complex Children around the country, we do about one in four transplants. And we've had a living donor coordinator uh im post over the last 21 years. You can see here the complexity of patient's send from and patient's trying to do multiple organs or pancreas, liver, kidney, lung and kidney transplantation. But thinking about blood group compatibility and HLA incompatible transplantations. This just shows some of the data historically from gosh, showing you that the under fives have increased morbidity so that if you're an uric and your own Dallas is from birth, about a third of infants won't live to the age of two due to the complexities and very often the other organ involvement. So currently, we have 100 and 58 transplant recipients that we follow up and 20 patient's on call for deceased on a transplant and over 200 Children with chronic kidney disease. But some of these that you can see under one year of age, we have to see every week and tweet their medications and diet. Here, you can see your transplant numbers and um the hugely increased. Um um it's just fallen off the slide. But last um call, we had 39 kidney transplants with one um combined liver and kidney transplant um last year. And just thinking about the adolescents, Children are not small adults, we need to think about their challenging surgical techniques, the growth and development and also the developing immune system, which may have an impact on infections and the response to treatment with immune suppression. We have to really consider pediatric versus adult. We deal with pediatric is a very dependent child and a parent focus uh service. We've got a lot of crying Children and infants that the adolescents don't want to be around and quite personal and extensive team. But it is this adoration age group. And again, I've got a phd student trying to look at ways of improving longer term materials in these adolescents. This is one of the first papers over 20 years old, but just to show that in the olden days when you wrote a letter, Dear John, please see Bob who's had a kidney transplant and he didn't get the additional support that very often they would go off the rails within the first year to two years after transfer. We set up and published a decade ago or work with Oxford was showing that transition is important with um no unexpected um graft loss that you can see here and follow up um to about 10 years. So where are we in the future? Well, I think we need to consider increasing the donor pool, thinking of other ways of living related donor transplantation. A lot more altruistic uh the pair donations. So that's where I can't donate to my child and you can donate to your child, but we can do three ways throat because I donate my kidney to someone who's donor, donates to someone else who's donor donates to my child. And then I donate the second. So really, it's like buying a house and you getting involved in a chain, I think. However, stem cell research has come a long way. So we're able to grow kidneys and try and create replacement organs in the future. But in fact, the bladder is much easier as as delivered than the kidney. And basically using a cellular organ scaffolds, we can populate with stem cells to try and improve. But I think there's a lot that we need to do to try and improve renal holograph survival. Looking at the pitfalls and the biomarkers of transplantation, thinking of neuro Minister press of agents and indeed in all, making kidney transplants last longer, this shows some of the living donor options. So we plan for a preemptive living donor kidney transplantation where at all possible. But some people do go abroad for transplant tourism. And if they don't receive a kidney on the diseased on a waiting list and they don't have available um living donors here in the United Kingdom, any chest button transplant will promote to increase the living donation to match the best international um benchmarks within comparable funding systems. We want to promote a continuum of care for potential recipients and donors with increased living donor numbers provide coherent integrated approach, education and counseling and interface with primary care, more collaborative audit and research and more open access and equity of access to kidneys for our patient's and families moving forward. However, I think we also need to concentrate on prevention and detection of chronic kidney disease and think about preemptive living kidney transplantation as a kidney replacement mortality. Thank you very much. Indeed. Thank you for your time and thank you for joining and I would be happy to answer any questions. Please see in the chat if you wouldn't mind completing the two questions survey that you can see there. And once you do that, you'll be able to receive your certificate of attendance. Thank you very much as that. I see you've got your hand up. Uh go go back and repeat that year by your uh case much like 11 year. How if they're bosses are creating level of child was thank you for this ligation. Yes, you're talking about seeing the slide again, which shows what happens. You showed it a year by your attitude like yeah, I can, I can try and bring up here. It is. Oh, can you see that night? Who it's gone? Let me bring it up again. Yes. Yes. That one that went by the add uh the level of create impossible. Not this one the add away that one. No. So it's not. I had, it's small. I had what, what just tell me what the sliders. Sorry. There's a bit of a background noise. I can't 100% hear you. It was uh one with the arrows. Oh Yeah. Yeah. Yeah. So that was just an example of a patient. You mean that one? Yes. But it was much more indeed. Yes. So this is basically was showing just an example of a patient as that we follow up. That has an acute kidney injury, chronic kidney disease, you follow them up and very often their, their kidney, chronic kidney disease progresses with reduction and kidney function to the level that they start requiring Dallas is because you didn't have time for a preemptive living donor kidney transplant, but they received one. But actually when we follow patient's at post transplantation due to the vagaries of the medications and effort toxicity due to the complications, you see a deterioration in the kidney function with time and what the important thing is with failing allographs is to plan for re transplantation ahead of time. And again, we would aim for a preemptive re transplantation as well and just showing you how the patient does with follow up. But I just use that as an example, just clinical scenarios that we see every day in clinical practice and pursued, I think if you if you just all remember to um fill in your details as Well, that would be great. Um There will also be um some details being sent round um for you to be able to um fill in your information and then you can also download um that you can see just in the chat now, um information on getting your certificate as well as future online lectures. Thank you very much, Professor Steffen. I thank everyone else for attending the amazing lecture today. Um I've sent the certificate and please do book for future lectures which will be on Thursday from 9 March 10 to 16. Okay. Hope, hope to see everyone next Thursday. There's no any other questions. Uh Thank you for your, your nice comments in the chat and thank you for everybody joining and I know the time was changed. I think it was difficulty finding someone to adjudicate. So thank you for doing that today. I appreciate it. Thank you very much. I've posted the lectures for next Thursday. Please do book in advance and hope to see everyone on Thursday. Thanks, kids. Have a good day. All the best. You too. Goodbye. Just keep the meeting on a little bit longer so anyone can download the certificate and book for the links in the future. Thank you everyone for your time and I'll end the meeting. Surely. Have a lovely day. Goodbye, everyone.