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um, so good afternoon. My name is Steven Marks. I'm one of the kidney specialists from Great Orman streets, and I'm going to speak to you today about chronic kidney disease and kidney transplantation. I'm one of the pediatric nephrologist and professor of pediatric nephrology and transplantation at University College London and also, um, leader of clinical research facility as a director at Great Ormond Street Hospital as well as the kidney transplantation team. So I'm going to start with the presentation of a case. Talk a little bit about how the kidneys work a little bit about age related kidney function and about when you have abnormal kidney function, whether it be acute kidney injury, which is a sudden reversible compared to irreversible chronic kidney disease. Where there's been damaged will be very commonly see, which is undiagnosed cases of chronic kidney disease, where they have an inter current infection or dehydration, and then present with the acute kidney injury on top of the undiagnosed chronic kidney disease. An end stage kidney disease or Stage five chronic kidney disease when the kidney function is less than 15% and the likelihood is that patient's require kidney replacement therapy with Dallas is and or transplantation to survive. And then I'll talk a little about about specifically about neonatal kidney injury and, um, and management of acute kidney injury. So I thought I'd start with the case. This is a premature boy who was born at 34 plus six weeks gestation, weighing 3.35 kg. His mother was a multi gravitated previous pregnancies, and she had normal antenatal ultrasounds at six and 12 weeks gestation over the 20 week gestation ultrasound, there was an antenatal diagnosis of right hydrn of froze is with the other kidney being bright and a bright kidney. Antony Italy actually may mean that there's abnormality in that kidney as well as the hydronephrosis is on the contralateral kidney. And here you can see the changes that described on that kidney on the antenatal ultrasound. So this, uh, neonate was born with, um, respiratory distress syndrome. There was no pneumothorax, and that's very often due to oligohydramnios, where there is a reduction in the like, er volume. And that's what happened in this case. There was bilateral hydrin of froze is the kidneys got increasingly echogenic. The bladder got more distended. There was less like or volume. And that's why this, uh, unit was born because the labor was induced early at 34 weeks gestation after birth. This, uh, required ventilation 55 days. It was a neonatal intensive care unit for eight days. And apart from the usual respiratory distress without pneumothorax, there were some other neonatal interventions due to the renal disease and that include an insert, a question of the suprapubic catheter for five weeks and the feeling that there may be obstruction. So insertion of bilateral nephrostomy is for two weeks and, uh, and evidence of kidney dysfunction. So a maximum plasma kratom of 288 and also the requirement for receiving a blood transfusion. So this is a make sure rating cystourethrogram. So this is where you put in a catheter into the bladder. Um, this is, um, area that you can see here, and then you can see there's a little bit of narrowing, and then you can see an area here does empty know what you might be seeing in this? Make sure ratings history throw gram. So this is in fact, the dilated, um, posterior urethra, and you can see shelf like here, and this is what you're seeing is a posterior. You throw valve. So this is an obstruction. So the M C u G confirmed posterior you throw valves. There was no evidence of obstruction at the physical. You're a Terek Junction and the frost a gram. And the way to manage these kids is to actually resect that valve leaflet. And very often you'll be in the situation where there's already been damage to the kidneys. And that's the chronic kidney disease. Potentially. But they did cystoscopy redo resection of the left sided remaining posterior through one month, and I kind of wanted you to think about what are the factors which are predictive of this patient's long term prognosis? What might you want to know? Well, the kind of things that might be important is actually, what does the kidney look like on ultrasound? Is there a good parenchyma or are these kidneys small? Do they have evidence of system? So is it a bilateral cystic dysplastic kidney? And what does the bladder function, which, of course, will evolve during this neonate as he grows up into an infant and a young boy? But have there been intermittent infections. Has there been times where there's been urinary tract infections and urosepsis episodes of hypertension or dehydration, and actually the development of protein, urea and or hypertension both independently. We mean they're more likely to have chronic kidney disease. And I showed you this case because, actually, because there was an acute obstruction and there wasn't too much damage in neutral that when you followed this infant up. At 17 months of age, he was growing and developing normally with a height on the 50th percentile weight just above the 25th percentile. He had normal BP without protein urea. He didn't have any urinary tract infections he was on trimethoprim. Prophylaxes required a bit of iron supplementation and sodium bicarbonate because of salt wasting. But he actually had normal glomerular filtration rate at 97 mils per minute per 1.73 m squared, or 97% with the normal being above 90 with the plasma kratom of 33. So let's consider the kidneys themselves. Well, obviously they're amazing, um, Oregon's that removing waste and foreign materials, and it's always best to think about what does the dialysis machine do? Well, the two things it does is remove fluids. So that's ultra filtration, especially if you don't produce any urine and also removes the waste products. So that's the dialysis itself. And the kidneys are able to regulate homeostasis so the body's water electrolyte balance acid base balance above and beyond what normally would be able to and they can do over a wide range of water, salt and protein, dietary intakes and degrees of muscular activity. But they allow the cells to act on the blood as an ultra filtration and remove the fluids. And there's always additional body functions, such as the production of re through Puritan. But the newborn infant is at special risk of developing renal failure because really the kidney function is very poor. There's a relatively lower BP with an elevated renovascular resistance, and the lower Reno blood flow will actually accumulate and result in a lower glory Markkula filtration rate, or kidney function. So this is looking at the BP within the art of very low birth weight infants of 750 up to about 1 kg, and you can see here that the mean BP that you can see is between 33 35 with a systolic of only 44 to 49 but ranging as you can see here from 34 to 59 these are the values during the first few hours of life. So where do you go about assessing the kidney function of a knee net when they're just born? Well, the plasma Cranham we use as an indicator and in fact, as a bio marker of kidney function, although initial values actually reflects more the maternal crackin. So you might have a situation where the mother has been unwell and the bloods that you're taking in the neonate are just reflecting maternal, chronic kidney disease or acute kidney injury. But because craning comes from the muscles and the only place the body can get rid of them is through the kidneys. We are in the situation that it is a relatively good biomarker of kidney function, but obviously depends on what your muscle mass is. And that's why an infant whose got faltering growth or failure to thrive, who's got low muscle mass, who has a crack in in which is even within the normal limits but at the upper limit of normal main facts have chronic kidney disease under diagnosed because for that infant you'd expect too much lower plasma kratom because of the low muscle mass. Normally, you'd expect the crackin to be in the twenties, rising to about 100 maximally. But that's really a postpubertal boy who's got big muscles and that we see in adolescence. Um, but invariably, until your renal function is about half, you may not actually see any change in the plasma Kratzmann, and it may not be raised in a child who's small and thin. So this is a relationship between the fetal and maternal plasma kratom, and, as you can see, according to the various weeks of gestation, and this is the plasma cracking and then premature. Nein, it's going down from less than 27 weeks gestation here according to how old they are, and what you can see here is that there's an increase in the plasma kratom after birth. But then, within the first week, it equilibrates and starts reflecting the neonatal plasma kratom from the maternal plasma kratom, and you can see here that the rate of decline of the kidney function is obviously faster in those born of lower gestational age, where it's much higher initially, and that shows you the relationship in the neonatal plasma crackin going onto an infant and you can see your values really rarely but can be in the hundreds but coming down, as I say within the first 7 to 10 days. And if you look at the first four weeks again, similar curves, um, looking at the birth weight of infants from 1 kg 1.5 kg, 2 kg in term. And you can see here that the smaller the infant, the higher the plasma crack in in when you can see slightly longer taking time to come back to normal. So we kind of use the estimated liberal infiltration rate to work out what the kidney function is. An adults as MDRD to formula. So wherever you have a blood test taken as an adult in many countries around the world, you'll get an automatic estimated glomerular filtration rate based on as an adult your age, your sex, your ethnicity and what the plasma cracklin is. There are very formulas which are used and the Cockcroft gold as an equation historically, which was used very commonly from called G. But we're in the situation of trying to work out what would be the best for Children. And that's when we start going to what we call the shorts formula. Where you take the heightened centimeters of the patient. You multiply by K factor and you divide it by a plasma cran in the micromoles per liter. And that gives you the estimated glomerular filtration rate and mils per minute for 1.73 m squared, which actually equilibrates quite closely to the percentage of overall kidney function. And we generally use values 33 34 36 a half would be the highest. But you can see here that it can be up to about 48. Um, that you can see here, even 60 to an adult Mills. Um, so you've got to be really careful about getting the right formula according to your Kratt, and whether you're in the house, Sassy is a yeah method or whatever is used in your analyzer in the biochemistry laboratory. And then you can get more formal measurements, and this is where you inject very often a nuclear medicine. So 51 chrome any D t a. Also, um, I Hexalen Mulan, and you watch the calculation in the clearance of the substance by taking samples peripherally, not from the same cannula over a period of time and because kidney function basically improves in the first year of life. We would normally do this before 12 months, correct today. But to be honest, I've actually grown away from checking the formal G f r. And by looking at the Cystatin C, which is a measurement which again you can get a formula to estimate the kidney function. And obviously you could do a time during collection for cramping, clearance and looking that and the individuals that you see. So this is some work. And again, I adapted this from the G f r N Nenets and, as you can see here that the relative kidney function in premature nenets is very, very small. And it's not until they get to about four weeks that the kidney function is actually coming to about 50% of normal. So what is the normal G f R. Well, if we look at it in mils per minute per 1.73 m squared, or as I said to your percentage, you will see that even a healthy term. Nein, it has endstage kidney disease because their kidney function is less than 15 mils per minute per 1.73 m squared. Although of course we don't say that because we know that in mostly in its it will improve over the first few months and especially up until about a year of life. And here you can see that the normal G f r. For infants age 123 months is still in the 50 mils per minute per 1.73 m squared. And it's not usually until about one year that you get a normal estimated g f R. So what about acute kidney injury? Well, this is a rapid, reversible deterioration of the G f R. And it's associated with nitrogenous waste products. Accumulation and acute kidney injury is very common in the in its but it depends on what you look at. So if you look at a neonatal intensive care unit which has got a cardiac unit, which is will ventilate level three down to 22 weeks, or you're going to catch a lot more acute kidney injury, where pre renal failure what was previously called Vasomotor nephropathy really is the most common type of acute kidney injury in about 72% of all neonatal cases. So what is acute kidney injury? Well, very often we will say that's when the increase in crown and is more than 50 micromoles per liter per day. And that's equivalent America to 5.65 mg per liter Per do oliguric is defined as a reduction that urine output to less than half a mil per kilogram per hour in Children, but less than one meal per kilogram per hour in the units and acute kidney injury is associated with asphyxia is predominantly nonoliguric, so the fact that they will continue to produce urine. So here you can see we divide acute kidney injury in to pre Reno. So that's about the fluid getting in to the patient or the losses of fluid renal, where there's something intrinsic to the kidneys and post renal is where you've got an obstruction. So pre renal failure is usually due to decrease true intravascular volume due to losses from dehydration, gas in to Stein ALS, salt wasting diabetes, insipidus and third spacing that we see in sepsis and nephrotic syndrome. Circulatory failure with congestive cardiac failure, pericarditis or cardiac tamponade is much, much rarer, but actually intrinsically within the kidney. We can see sometimes acute tubular necrosis with an hypoxic ischemic injury, with drug and toxin mediated. But uric acid nephropathy or tumor lysis syndrome can be seen in older Children who develop, for example, a malignancy, and you then either start treatment or the cells start breaking down themselves. You only need one doors to develop interstitial nephritis from a drug, although it can be a dope, a thick. Other medications, such as non steroidals, but you can also get an incision of writers. Do two antibiotics. We see patients with inflammation within the kidney, glomerulonephritis, vasculitis, Lupus nephritis or vascular lesion such as hemolytic uremic syndrome. Um, cortical D crozes or renal artery? Uh, venous thrombosis or infectious causes such as sepsis and pylon arthritis. As long as you have a normal contralateral kidney, you actually will do okay. But having obstruction in the sultry kidney will result in Reno dysfunction, and that can also be seen if you've got bilateral your it Eric obstruction or, in fact, a urethral obstruction. So these are some of the things to consider in a neonate with acute kidney injury. Could it be that they've got chronic kidney disease? Could it be a prerenal in origin? So hypoxic Insult, dehydration, hypervolemia, hypertension, congestive cardiac failure. But considering also, could it be intrinsic to the kidneys? So hypoplastic or dysplastic kidneys do they have vascular disorders? So venous thromboses has been evidence of acute chewable in necrosis nephro toxicity or pilot nephritis and post renal failure is where you have obstruction, usually urethral, such as posterior. You throw bulbs or diverticulum are you to a seal or a neurogenic bladder? And it's important to really look quite closely the fluid alleged like an acid base balance. To make sure that you treat fluid overload, make sure you minimize acidosis, hyponatremia, hypochelemia, hypercalcemia and prevent convulsion. Sepsis, as you know, venous thrombosis and episodes of arterial hypertension. So how many patient's present with chronic kidney disease? Well, it may be an acute kidney injury on top of a chronic kidney disease, which may be precipitated by infection or dehydration. You may have an antenatal diagnosis of bilateral renal anomalies, and it's likely that they will have continued their maybe the history of chronic kidney disease with polyps. See a Polidori, anorexia, lethargy failed to grow or the development of bony abnormality such as CKD, mono been disorder or renal osteodystrophy. You may, in fact, detect hypertension or an incidental finding of protein urea, and it's always important to measure the BP. Check an early morning urine dipstick and albumen to creatinine ratio to see if there's evidence of hypertension and or protein urea. And when should you suspect chronic kidney disease? Well, that's normally when the creatinine is higher. And, as I said, sometimes it can be falsely stated that it's a normal creatinine, when in fact you've got low muscle mass and it's very, very high. You may want to look at the degree of renal dysfunction, how it's changed over time, looking specifically hematological biochemical abnormalities such as anemia, hypercalcemia, hypercalcemia, hyperphosphatemia and secondary hyperparathyroidism. There may be abnormalities detected aunt in Italy, so bilateral renal anomalies, or in fact, even posting Italy with renal defects. It's important to make sure you follow patient's up very, very closely. Make sure there's no family history of chronic kidney disease, that there is persistent protein urea and make sure that you monitor and see what happens after an episode of acute kidney injury. So this is a pie chart, which I devised when I was in the North America. We basically cut down to see what were the causes of Children having chronic kidney disease and in their cohort about third restrict of your opathy third glomerular disease, such as steroid resistant nephrotic syndrome, due to Focalin cementicle, Maryland's closes the third word other, which was mainly miscellaneous, hereditary, cystic or secondary glomerular diseases. But here you can see over 40% or structural malformations, and if we include the obstructions as well, then very often you're getting towards About 50% have abnormalities. So can gentle anomalies of the kidney and urinary tract. With bilateral renal dysplasia, you can see here about a quarter of glomerulonephritis, 1/5 hereditary nephropathy. He's and about 1/10 systemic disease. And this is similar data that we did in the United Kingdom. Looking at the renal registry pediatric data where if you take the Green group, which is as as plastic with or without physical eurotech reflux, very often, with or without obstructive uropathy, you'll see that that actually corresponds to most of the patient's and has a number in Kakuta, usually of above 50% over half of patient's now affected. You can see here, though, that we do have a distinct number with glomerular diseases Chamblin, Stich or nephritis content a nephrotic syndrome. And then we decreased down to rear causes such as, you know, vascular hypertension, metabolic disorders and polycystic kidney disease. So this is a picture of a neonate who, unfortunately, died when I was doing neonatology, and you can see here that he's got lax abdominal wall musculature go slightly low set years, and this baby, unfortunately, died. The feeling had been that he might have renal dysplasia, but in fact he had two kidneys, neither which works. He had a multi cystic dysplastic kidney on each side so didn't produce any urine had associated prune belly or absent abdominal wall musculature syndrome. But we also see this constellation in those with Reno hyperplasia, Franko to renal syndrome, other genetic defects and Bardi Beetle syndrome, as well as megacystis megaureter. So that just gives you a breath of some of the things that you might see when you're investigating Children. So If they've got cystic kidneys, it might be cystic dysplastic kidneys. It may be on some recessive and dominant polycystic kidney disease, and if it's the latter, you'd want to undertake ultrasound of the parents, especially over the age of 35. It could be that they've got cysts that could be part of tubular sclerosis or glomerulus cystic disease. If you've got small kidneys, then it's as plastic with without musical. Your reflux and vascular insults could be the cause, and for those patient's with small kidneys. But all causes after a while may result in Children having small kidneys, and that includes those with normal sized kidneys at the start, where maybe do two glomerulonephritis familiar nephropathy nephrotic syndrome in front of thesis or tubal opathy. And it's only when you've got obstruction, usually with dysplasia, with pursue you through walls, physical, your stereo junction obstruction or pelvic ureter junction obstruction. You get more problems, and that's why we advocate an early um, investigation of these patient's as well. And never forget obstruction due to calculi, especially if patient's are presenting with the current urinary tract infections or noted to have hypercalciuria or hyperoxaluria. Um, noting that periphery Azaz, Um, and Cystinuria are much more rare. So does MD know what's the most frequent genetic cause for end stage kidney disease in the first two decades of life? Well, normally, for this question, people would consider ob samel dominant polycystic kidney disease or even not so more recessive. But actually the most common is Jevon all nephron a thesis. This is recessive cystic kidney disease, which is a caused by genetic mutations, including M. P H. P 1234 and many, many more genes. It's diagnosed by having a positive genetic tests and Children presenting with NCH kidney disease. So if you look at the stages of chronic kidney disease, Stage one is where the kidney function is above 90 mils per minute for 1.73 m squared, or 90% when we know parenchymal disease is present. But usually there are no other clinical features of chronic kidney disease. Even with a G, F are between 60 and 90 miles per minute per 1.73 m squared of what we call grade two um, chronic kidney disease. There's usually no symptoms, but patient's may present and developed by chemical abnormalities, especially when they're G F R sitting 60 and 70 miles per minute per 1.73 m squared, but it's usually not until between 13 60 miles per minute per 1.73 m squared. Do have biochemical abnormalities. In addition, patient's may develop poor growth appetite. Um, and their symptoms may become more and more severe, especially as you get near to having kidney function with the G f r of about 15. And it's not until your kidney function drops below that magical 50 number that you're able to be admitted to the dialysis unit and consider commencement of kidney replacement therapy. And obviously we'll have discussions about those therapies. Are it supports to get a history of how much fluid was I/O in the 24 hours before with the excessive losses from fever, hypovolemia, diarrhea, vomiting burdens? Was there any evidence of hemorrhage looking to see if there's anything in the drug history or neonatal medical and surgical history, but also taking a very detailed family history to see if there's any family history of renal problems, hypertension, a renal replacement, therapy and transplantation, and it's important to look at the patient assess them and go back and reassess, looking to see the state whether they're, um, dehydrated. And I've been in the situation before where patient's have been reviewed and have been acutely unwell, not realizing just how dry they are. So knowing the baseline heart rate and BP and what the syrup lots of those are is really, really helpful. Obviously, patient's developing hydration problems so looking for the peripheral profusion or edema would be seen earlier, especially those with chronic, um, cardiac congestive failure and looking to see if clinical clues of multisystem disease or palpable kidneys or bladder rations. So the important thing is to go back and reassess is to look, examine the patient, to go back and see them again, see how they're feeling. And here we can see some of the initial investigations to look at to see what the potential cause. Maybe, and here you can have a full blood count Looking at blood film Kroger Relation Screen A cross match to get blood available, looking to check on serum electrolytes to check on calcium, magnesium and phosphate it blood culture and C reactive protein and Anna's calcium and P th But the PDH won't stop as managing the patient and taking onboard reticular site count and specific investigation, as suggested by the cause, with very often a feeling to undertake. Perk it in as you know, biopsy. So if you're looking at the urine, just one drop of urine would give us so much information. If we're able to check. The concentration and the fractional excretions are really important mode of doing that. Where you take the urinary sodium, you multiply by the plasma Kratt and you divided by the plasma sodium, multiplied by the urinary Cranham, obviously only going on two specific test if there's an indication, e c g chest secretary. But normally we will do echocardiography, especially if you think there's been longstanding high BP. And principally, an ultrasound is needed to refute and exclude obstruction. But we'll always pick up large, bright kidneys of an acute process or small kidneys that you see in chronic kidney disease and bilateral no dysplasia. And then you may consider for an investigation, such as a percutaneous renal biopsy and an X ray of the left wrist. But it's all about going back and reassessing, repeating the blood test, looking at the electrolytes, the acid base balance, the renal function. What's happening to the bone profile? The calcium, magnesium phosphate? What's happening to the albumin are we got excess urinary losses and alkaline phosphatase. He's keeping an eye on the urinary output looking, keeping an eye on the the urine, electrolytes, dipstick and urine albumin to creatine ratio and making sure that we do regular full blood counts, making sure there's not excessive loss and obviously doing a reen launches Sound of the renal images suggest the follow up is indicated. So this is just to take you through some of the fluid bounds. So thinking, if you're dehydrated, usually maker overloaded. And what the clinical features maybe is nothing if you're euvolemic, where you would assume that potentially, they were dehydrated. So this might be you afterwards, getting a B mission and the local pub. And here you can see that the flu challenges 10 to 20 mils per kilogram of normal saline over an hour, and we would give that if they're dehydrated and if there's no response in a euvolemic patient, then we would consider giving frusemide and I would normally give 2 mg per kilogram. Look for response after about half an hour and then give another 2 mg per kilogram as opposed to the 5 mg per kilogram which has suggested here, which may cause problems for patient's um So it's really important to consider, because if you give a one off big dose of frusemide, you might result in auto toxicity so the kidneys have recovered. But you've resulted in the patient having, um, hearing loss and then, if they're overloaded, sort of looking to see if they got evidence of tachycardia, gallop rhythm and elevated JVP a dumb a hypertension. And consider giving frusemide intravenously to try and offset the fluid pretty quickly. And consider dialysis if there's no response to the medical management. So you go back, you reassess. You're giving chris loads and Cologuard you're doing regular twice daily weights. There's no active input output measurement. You're measuring the BP every four hours and measuring the peripheral core temperature gradient as well at least every four hours. However, if it's, um, uh, younger infant or if there's concerns ago in the urine output, you can reduce the to insensible losses of 400 mils per meter square per day or 30 mils per kilogram per day. And if they're overloaded, you can actually kind of dampen down and give only a portion of what they've actually put out in the last hour, and that it would be a fluid restriction that based on what the urine output is. But we do know that Impala uric recovery phase that if you replace urine output with insensible loss is for 20 hours, then set a target of the renal function continues to improve, and that's really important in the overall kidney management. So the question is, do you manage some clinical scenarios? What do you do? You got a high potassium. So if there's evidence of hypokalemia, you're going to think about putting them on a cardiac monitor, giving them so beautiful with sodium bicarbonate. If they're acidotic with frusemide costume, Rizzo Knee um, and insulin dextrose infusions if they are hyponatremic. Secondly, to fluid overload, you might want to fluid restrict them. I would really give renal replacement therapy a hypertonic ceiling, but this has been done, and if they're retaining sodium considering frusemide or dialysis, and if they're hypercalcemic considering one alpha calcidol. So one alpha hydroxycholecalciferol calcium. Um, supplements, too if they've got evidence of hyperphosphatemia, an elevated phosphate, it's only really important if they're eating where you might want to reduce the dietary intake of phosphate and give phosphate binders to bind with the phosphate when they're eating acidosis. It's important if they're acidotic to consider giving sodium bicarbonate therapy, but we'd only want to do this if they got normal. Qasem if they got a normal level of their their calcium, because if they're a HIPAA calcium ache and you give sodium bicarbonate and you're going to lower the bicarbonate, and so it's important to get the calcium level up as much as you can initially, so that's an important lesson. Is always correcting the hypercalcemia before the acidosis is correcting acidosis. First will reduce the calcium level even more. If you've got hypertension, then that might be due to fluid overload. You considering giving diuretics medical management and if they're not responding to diuretics, you might be considering Dallas is, especially if there's pulmonary edema or oliguria. It's important to think about the nutritional aspects of acute kidney injury as well. If there's a Cata Bolic state and we would normally try and do this centrally with nutritional feeds via nasogastric tube as early as possible to try and minimize catabolism and your email. And try to avoid total parenteral nutrition because malnutrition itself will delay acute kidney injury recovery. And there's anecdotal evidence that good nutrition improves outcomes, always thinking about the drug doses as well. So for the purposes of correcting drug doses, you should always assume, especially if you're oliguric, that the G F R is less than 20 most per minute per 1.73 m squared. And every time there's a shift change in the G F R is important to relook at the drug doses and revise them accordingly. So some drugs require you to give less doses, so increase the dose interval between one dose and another and others it's reducing the total amount of dose so you're getting less of a peak. So it's always best to consult your for Marie and speak to a pharmacist for advice and avoid using nephrotoxic agents if you can. So how do patient's do? Well, they basically depend depending on what reports you do. So if you've got a definition of acute kidney injury, is it just the rise in the creatinine. Is there a percentage, or is it the fact that required kidney replacement therapy? The outcome of a kick in injury varies as well. Sometimes it's it's just deaf or survival versus those that you're able to get off to dialysis, and it's important that prevention is better than cure. So let's talk a little bit about irreversible kidney damage or chronic kidney disease or where we get to end stage kidney disease management. So this is when the kidney function is less than 15% of normal. And here we have the modalities of using personal dialysis, which can be hospital or home. So we generally trained for home personal dialysis. Most places and Children would always be able to, um, offer one form of dialysis, and it should be for the patient and family choice. But sometimes, for example, if it's for hemodialysis, some centers only offer this in center. So in the hospital coming to the hospital, which is a tertiary center in the United Kingdom, there's only 13 pediatric nephrology centers which do dialysis, of which 10 performed transplantation. We actually form a group here, so we've got home hemodialysis where families can be trained to perform home therapy with hemodialysis, just like we do with peritoneal dialysis. But we believe that the gold standard is a preemptive kidney transplantation. So that's a transplant before the requirement of dialysis. And we would aim for a living donor transplant where at all possible, although some will have to receive a deceased owner, which can be on block so both kidneys and a younger infant to see stoner. But it can be a heart beating. So a donation after brain death or a D B D deceased owner or non heart beating donation after circulatory death previously called Cardiac death kidneys from a deceased owner. We normally would go for a parental donation if we've got living donors. But sometimes we have unrelated donors so altruistic donors that can come forward. And this may be through the national Living kidney sharing scheme, where I can't in a my kidney to my child and you can donate your kidney to your child. There are other ways of doing living transplantation, and we've got this period pulled exchange, but we could do antibody removal, for example, if there's cases of blood group A beyond Compatible or HLA incompatible kidney transplantation, So let me take a snapshot through a patient. So this is a patient who presents a two years of age with an acute illness. They're G F R. You can see just above 70 mills permitted per 1.73 m squared, or 70%. This falls at one year to around 60% at two years to just over 40%. And three year follow up shows that this kidney function is 25% of normal, and at that time we would start planning for a living related kidney transplant. However, 3.5 years after follow up and the patient is now 5.5 years of age, there's an inter carton infection, so the kidney function is wiped out and this child goes into end stage kidney disease, requiring dialysis Four years after presenting so now the age of six, this child underwent living maternal donor kidney transplantation and the G F R was about 80% which is pretty good. But this dropped to 60% a year after transplant because of acute rejection, infection episodes, worse, overall kidney function and the six year follow up. So two years after transplantation with worsening kidney function that you can see here with the G f R dropping below 40% and seven years follow up. So three years after transplant, you can see this worse than kidney function. E J F. R. Is heading towards about 20% and we're planning for the next kidney transplant. But the interim four years after the transplant, so eight years follow up. There's whistling kidney function, and this child requires to go onto dialysis. You can see here, though, the again it takes a year. So a nine year follow up. Five years after the first transplant, they were able to receive the second transplant you can see here and the 12 year follow up data. So eight years after and the first transplant three years after the second transplantation, Um, and following that, the 15 year follow up. So 11 years after the first and six years after the second transplant, when the child has transferred to adult nephrologist with the G F are just above 50%. So this is the kind of circular model of endstage renal function where you have your the development of abnormal kidney function requirement for dialysis or transplantation, and trying to plan that with the family is really important. So it was a bit of a whistle stop tour through chronic kidney disease and transplantation. It's important to monitor changes in clinical status, in kidney failure and kidney dysfunction, looking at observations considering blood and urine test results. But the most crucial element to management is fluid bounds, and it's important to check if there's any evidence clinically of acute kidney injury. If there's evidence of chronic kidney disease or evidence of acute kidney injury on top of chronic kidney disease. Thank you very much indeed, and I'm happy to answer any questions. I'm happy if you want to add. Put any questions in the chat, or if you want to come off mute and ask me that's perfectly reasonable as well. Karsa. I think you've just come off mute. Did you? I think she's not got a microphone. No worries. So please remember to write your name in the chat the year of you study the city you're in and to um, also fill in the feedback, which Austin is just about to send. Yes, it's just come through OK, thank you very much. Indeed, We're getting some nice message. Just two years and I don't know if you can see. Yes, I can. I've just seen them come back, so thank you very much. My pleasure. Please do fill in the feedback form because we we need the feedback, Uh, in order to show our funders how well we're doing and also to keep improving, uh, the lectures and the quality and so on. Yeah, I know that you've some of you are still having a hard time in Ukraine. I know some of your outside, but our thoughts are with you because I know it's been a really challenging year and just wish everyone know the best in 2023. Let's hope we have better news in the world political arena as well as, um, the situation in Ukraine. I'm happy to answer any questions too. I've blown your minds because the end of a long day, probably of lecturing as well probably not helped. Thank you for your nice comments in the chat as well. Really appreciate it. So I can see you're all all over the place at the moment. Some in London, Ukraine, India, Southampton. Don't forget to tell us where you are Palestine as well. So a lot of, um, moved to different places, Probably back to your original countries. Have you got all the information you need? Austin? Um, yeah, I think so. Um, I'll be posting up the, uh, the certificate attendance certificate to shortly. Um, so if if? Well, while we're waiting for that, if you can fill out the the feedback forms, um, I'll also put in the the chatter linked to there's a student WhatsApp group where you can see more regular updates on what lectures are coming. Um, and I also put in the lectures that we have on on Thursday in the chat in just a moment.