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Professor Pete. Good afternoon and welcome. My name is um Steven Marks. I'm professor of pediatric nephrology and transplantation at University College London and practice clinically in Great Th Street Hospital for Children NHS Foundation Trust as a pediatric nephrologist and also as the director of an N I HR and sponsored clinical research facility. Today, I'm going to introduce some concepts about uh protein urea and um hematuria. Can I just check um that you can all hear me and see me and that uh you just got one slide present on the monitor. Um No, I've got two slides present in the monitor. Yeah, lovely. Now, everything's clear. Thank you. You're welcome. So I'm going to start with some case presentations. Look a bit about an understanding of an hematuria, thinking about Frank macroscopic hematuria. So that's when you see blood itself compared to microscopic hematuria, which is either your microscopy where you see red cells and or a urine dipstick being positive for hematuria without visible blood, we'll then talk a little bit about proteinuria and evidence based medicine and try and bring it all together. And in the end, if you'd all and for those of you just joined, just remember to put your name, your details and um your medical school, but also where you currently are from in the chat, that would be great. And it's good to see so many of you joining and our thoughts are with you. Uh whether you've come from the conflicts in either Ukraine or Sudan. So I'm gonna start with the case presentation because very often we have the answer in the clinical information. So the first is a 12 year old boy, he was admitted with a four day history of severe left loin pain. He had a three week history of afebrile recurrent episodes of macroscopic hematuria. So visible Frank hematuria, he had decreased oral intake and examination review, severe left loin tenderness and investigations. He's got normal um renal functions. So his plasma creatins normal as is his albumin. He's only got a trace of proteinuria, but he's got four plus of hematuria. Um and no cast seen. So does MD have any ideas what we're thinking about with uh this 12 year old boy who's got painful macroscopic hematuria. So we've got some suggestions of um acute pyelonephritis. Well, I said he didn't have a temperature but you are correct that if you look at um the totality of visible blood, the most likely is uh an infection. So, uh either an upper lower urinary tract infection, but he's got uh evidence of pain specifically on one side, any other, right ears. Ok. So others saying urinary tract infection as well. Well, the most likely is actually going to be a calculus because he's got pain over one of his kidneys and very often it can cause obstruction. But here you can see a small non obstructing renal calculus on the ultrasound. And what you can see here is the acoustic shadowing. So you have some people putting stones up. So thank you um that posterior acoustic shadowing that you can see from the area of calcification within the kidney. So the next case is a comparison. So this is a young girl. She's three years of age. She's got a six month history of recurrent episodes of frank macroscopic hematuria. Again, it's associated with a precipitant of a viral upper respiratory tract infection, but she's otherwise eating and drinking. Normally, there's no vomiting, there's no past medical history or family history of importance. She's got normal examination. And again, investigations show that she's got normal renal function, normal plasma creatinine and albumin. And there's no evidence of protein urea hematuria and it's three plus on dipstick, but there's no cast and there's no calculi on the ultrasound. So people are putting in the chat as well. Nephritic Syndrome, but there's a nephrotic syndrome having said that she's a Dema but we'll talk about that. But we've had um three people um put or no even more. Now, um putting um an sort of iga nephropathy or Berger's disease. So well done. Everybody I think um this is a case of iga nephropathy. Obviously, if there had been um evidence of a rash that would obviously make you think of HSP nephritis or an iga vasculitis nephritis. About the last case is a six year old girl who developed a viral upper respiratory tract infection with a sore throat and cough. Three weeks ago, both parents and a younger sister also had an upper respiratory tract infection. And in this case, um she um had a 48 hour history of vomiting with Coca Cola colored urine and a 24 hour history of Perper edema with reduced urine output. An examination shows that she's hypovolemic. She's got evidence of peripheral edemic. She's uh hypertensive with systolic BP of 1 30 millimeters of mercury. She's got evidence of renal dysfunction with the plasma creatinine of 150 micro per liter. She's hypo aic at 22 g per liter because she's got nephrotic range, proteinuria with three plus some proteinuria, three plus of hematuria and evidence of red cell or cas. And uh we've got quite a few different answers coming up, but the majority are seen post streptococcal glom nephritis, which of course may be the commonest that you see. I would normally say a postinfectious glomar nephritis because obviously, it's not always streptococcal, you can have other infections and both bacteria viral um as well. But I agree with you. So you can see just in giving you a snippet of clinical information, you're able to discern exactly what the likelihood is of the um etiology of the blood in the urine. So, does hematuria matter? Well, for me, the simple way to look at this is actually, should you investigate? And really if you see visible macroscopic hematuria, then the answer is inevitably yes. And I hope that I can convince you that although you may want to follow patients up and do initial screening, if you've got ongoing persistent microscopic hematuria, then really longer term investigations are really not required as long as the patient doesn't develop proteinuria hypertension or renal dysfunction. And why do we say this? Well, if we look at the epidemiology with macroscopic hematuria, very often, it's a clear diagnosis. It happens in about one in 500 as a rate of prevalence and the resolution can vary. But what we find with microscopic hematuria is the definition varies, sad results and a huge varies in the prevalence. Are you talking about more than five red cells by high power field? If you do urine microscopy and phase contrast microscopy or does it mean that you've got a urine dipstick being positive? And then remember the urine dipsticks are very, very, very sensitive and the prevalence can be up to about one in 50. So anything from 0.5% to 1.5% but the majority of cases will resolve within about six months. So normally about 70% and the reason is very often it's associated with a bit of glomerular bleeding because of uh an infection uh or a postinfectious phenomenon which actually resolves quite quickly. So one has to think about hematuria, does it matter only if you have recurrent episodes of macroscopic hematuria, always making sure if you've got proteinuria in between the episodes of macroscopic heter, exclude another cause, exclude a familial cause. But consider actually if you're going to label the child and give them a diagnosis and that might have huge implications for their life. It may mean that they're not able to apply for certain jobs. It may affect their applications for both life insurance and also thinking of a mortgage. So how can we be so certain? Well, here is um uh some studies which have been done into going um patients who went a percutaneous renal biopsy, either for recurrent microscopic hematuria or intermittent attacks of microscopic hematuria. And what you can see here is that about a quarter have Alport syndrome, a quarter will have iga nephropathy. About a six will have thin basement membrane, another six will be normal and about 1/5 will be miscellaneous. So very often they will have evidence of mes aio proliferation. But if these patients do not have any evidence of proteinuria hypertension or renal dysfunction at present, there is very little to offer and I agree there is potentially clinical trials, gene therapy, for example, for Port Syndrome, for specific um genetic mutations. But apart from that, apart from treating the hypertension and proteinuria, there's no direct um diagnostic or prognostic implications if the other features of proteinuria, hypertension and renal dysfunction are missing. So one can say that one can clinically continue to evaluate these patients and maybe treat without necessarily knowing the underlying diagnosis. And of course, if I've got a patient that I suspect an Alport syndrome with recurrent episodes of macroscopic hematuria, then actually undertake genetic screening before a percutaneous renal biopsy. So let's first of all, talk about microscopic material. So once you start seeing blood in the urine, which is visible in frank microscopic hematuria may actually only contain very small amounts of blood. So for example, if you do a finger prick and you put one drop of blood into a liter of urine, then it will turn rosy. A microscopic immature may contain significant numbers of red blood cells. But you may only get that bright red blood staining with clots. If you've got heavy bleeding from trauma or coagulopathy, if you've got cloudy urine, then there may be pus cells present. So again, urine microscopy and culture and sensitivity to exclude a urinary tract infection. And if there's history of gravel or even history of some grit or of a painful microscopic material, then I will very often ask the patients and the families to sift the urine and see if there is any debris which is held back, which we can send off for physical chemical analysis, seeing if there's any evidence of calcium phosphate stones, urate crystals, cysteine or Strube light being present as well. But the important thing is is that sometimes you may see blood urine but it's actually not blood. And one of the commonest is actually red food coloring or dye, either from ingestion of food coloring, which is added to foodstuffs, especially red dye, but also beetroot. So drinking beetroot juice and or a high intake of beetroot beetroot soup may actually lead to discoloration of the urine and making it look red. And this can actually be found in some people just with a very small amount. And every year I get referred to a few patients and I get the history and I've seen recently a kid who his mother was really insistent that he had five fruit and vegetable a day, but he wouldn't take anything apart from beetroot. So he had beetroot soup every single day for those of you that are aware, antituberculous medication with rifampicin. Very often we're told that uh it gives you red tears and can potentially stain um your contact lenses. Well, again, you can get red discoloration to the urine as you can have with hemoglobinuria, myoglobinuria or even porphyria is an inborn error of metabolism, but it's very, very rare uric crystals which are more commonly an orange discoloration which can be seen particularly in newborn babies, especially if it's the first baby to a mother who's aiming to breastfeed. And initially the it takes some time for the colo and good milk supply. So the baby is a little bit dry, dehydrated at the start. And that might result in the patient management and being to increase the amount of fluids to get rid of the crystals I put here as well. Fictitious macroscopic hematuria, what we used to call moises syndrome by proxy. And this may be where an adult, usually a parent or a step parent is putting blood into the urine of the child. And one needs very close liaison with the safeguarding team and working closely with social work and police and looking to see if there is evidence on the chain of command to ensure that one is able to detect. For example, if there is blood being put into the urine by um by the perpetrator. And for this actually to be caught um either in hospital and visualized and or even if we're able to prove that the urine and the red cells do not come from the same person. So one possibility is uh sending the urine sample to hematology to look at the blood group. Noting that of course, the child and the perpetrator may have the same blood group, but also potentially looking at the DNA. But it's really important that you work very closely and with your safeguarding team to ensure there's a chain of command so that we know that the urine specimen has been delivered from person to person. And indeed, we've had a recent admission to our ward for this very principle to actually see if the child has ongoing microscopic Hema material. So the take home message here is you need to always confirm the presence of red cells in urine microscopy. But please note that may be the situation that you've got a patient um who's managed in primary care. And by the time the urine sample is actually sent um to the laboratory, the red cells may have nice. So here you can see um a stone which is being released um from um the left kidney and you can see it uh being obstructed here in the pelvi ure junction coming down here into the ves ureteric junction where it can also obstruct. But to be honest, as long as you have a S A kidney which is functioning normally on the other side, you will have overall normal kidney function. However, if you did have an obstructing calculus and solitary kidney or you had bilateral evidence of calculi obstructing both kidneys, then it would only be then that you'd have evidence of renal dysfunction. And here you can see that uh there is the possibility of the calculus getting stuck within the urethra itself. So the the timing of the hematuria may help. So if it's throughout micturition, then it may be a real cause itself. If you have terminal hematuria, it may be as a result of a problem with the bladder or potentially nonspecific urethritis. But usually if it's bleeding within the urethra, it will happen at the start of micturition itself. So this is what I was discussing um earlier and I have no apologies for using this um old slide which I discussed with junk finger recently when she was over visiting in London. And this is because there isn't really much more recent data, but this shows that most causes of macroscopic hematuria. As you said in the case, presentations are due to a proven or suspected urinary tract infection or evidence of infection or uh inflammation such as perineal irritation, trauma and with medical causes such as acute glom nephritis, a coagulopathy, stones and tumor being less common. But the other causes that 1 may see specifically with blood in the urine, potentially if you're exercise induced. So this may happen um after running a marathon loin pain hematuria syndrome where the macroscopic hematuria is associated with loin pain hemorrhagic cystitis, which is bleeding from the bladder may cause due to example, cyclophosphamide been giving and that causing ali uh induced uh toxicity to the bladder epithelial layer. Any causes of hypercalciuria or hyperuricosuria, increasing stone formation and other causes more rarely with uh bladder tumors such as rhabdomyosarcoma or melaka. So, what about macroscopic hematuria without protein urea? Well, if there's no protein and you've got visible urine, then it's important after the dipstick to send the urine off for a midstream sample of urine if they're an older child and sending off for a culture and sensitivity, but also with a urine calcium to creatinine ratio. And we'd undertake a Doppler renal ultrasound to exclude neph devices or renal Carli renal stones, hydronephrosis, papillary necrosis, that Doppler looking specifically for evidence of renal venous thrombosis, any urethral bladder abnormality, for example, such as a neo arterial venous malformation, evidence of glomar nephritis such as lupus or iga vasculitis, sickle cell disease or sub bacterial subacute bacterial endocarditis. So, the important thing in the management is to confirm the presence of red cells on your microscopy. Take a full history and physical examination. Don't forget to check the BP or urine dipstick. Send it off for a MRE sample of urine and treat if they have a urinary tract infection. But if non confirmatory and the family history and urinalysis with further investigations, then they should include a full blood count coagulation screen, looking for evidence of inflammation infection with sr erythrocyte sedimentation rate and c reactive protein checking on the renal function with plasma creatinine serum electrolytes albumin, an autoimmune screen with A T two complement C three C four immunoglobulins, iggig and IgM A N double stranded DNA and en. Um And uh rarely we we require a GBM antibody unless there's evidence of renal dysfunction. But thinking about sending off a urine after dipstick for my cost culture, an albumin to creatinine ratio together as a and calcium to creatinine ratio. I'm thinking about doing a Doppler renal tract and bladder ultrasound with consideration of abdominal x-ray. But noting that abdominal x-ray rarely um gives any additional information. The feeling being is that potentially may miss um a renal calculus uh which is behind uh the ureter as um as it descends into the bladder. And remember we want to know about them in pediatric nephrology if there's evidence of hypertension protein urea, when there's no evidence of macroscopic immature and renal dysfunction. So, let's talk about microscopic hematuria. Well, we advocate for patients to undergo urine dipstick testing because the urine dipsticks are convenient. There's widespread juice, we recommend to store in a dry environment. We get automated results with a printout and blood is detected by proxies like action and detects very small quantities with a negative result excluding hematuria. Remember, protein urea um is also sensitive and the albumin demonstrates better binding and but it is important therefore to send a urine albumin to creatinine ratio to look at how much glomerular bleeding. Because obviously a proteinuria and dipstick may detect both um tubular and glomerular protein urea as well. So if you've just got a dips stink positive microscopic hematuria and there's no microscopic hematuria, then the child may in fact be completely asymptomatic. Then this may be family screening, joining a new GP practice, moving to a different country may just be changing from one GP to another. But if there is evidence of microscopic hematuria, one must check to exclude proteinuria, consider doing the BP and check your renal function, sending off um a urine albumin creatinine ratio, evidence of proteinuria. And considering um other investigations and sometimes actually genetic information may be valuable prior to undertaking a renal biopsy which can be delayed if there's no evidence of hypertension, um proteinuria or renal dysfunction. If a child has symptoms and or signs, which are more generic such as fever, lethargy, hypertension and edema, then more investigations would be required just like if there was urinary tract and symptoms with dysuria, urgency, frequency and enuresis. We'd be looking more at the bladder and undertaking bladder ultrasound as a minimum investigation and looking at the pre and post void residual. If there is systemic signs of non urinary tract such as rash, purpura arthritis, jaundice or gastrointestinal um symptoms, then we may want to think about the underlying etiology. Patients may have fever, illness, trauma and extreme exertion and that might induce hematuria. So having a febrile vile upper respiratory tract infection, there's seen an accident emergency, there's evidence of microscopic hematuria, but there's no evidence of hypertension proteinuria renal dysfunction. Then that could just need to be seen a couple of weeks later to check. If the hematuria resolves and if it doesn't resolve, then they need to ongoing check for proteinuria and hypertension until it does resolve where hematuria is related to non renal disease, it should disappear and there should be complete resolution. But if the child has ongoing microscopic hematuria, then what we want to see is resolution and we can discharge if the microscopic he material resolves or is intermittent over six months. And there's otherwise normal family dipstick renal ultrasound and urine calcium to creatinine ratio if it's associated with proteinuria. So there's microscopic hematuria and proteinuria or you have persistent microscopic hematuria associated with complex disease or family history. Then again, we'd want to see these Children. So in summary, the investigations for microscopic hematuria without protein uria. Mainly three, we want patients undergo a machine, sample of urine to be sent to the bacteriological lab laboratory for microscopy culture and sensitivity. We're going to undertake a urine calcium creatinine ratio to exclude hyperchol. And we're going to take an ultrasound to exclude renal calculi and hydronephrosis. Mostly I have to say I've been in the situation that I've not done a percutaneous renal biopsy for patients with microscopic hematuria in the absence of macroscopic hematuria, hypertension, uh proteinuria or renal dysfunction. And the reason is that it is an invasive procedure and very often it will not add to the treatment unless the patient develops proteinuria hypertension or renal dysfunction. But obviously, some parents really want the diagnosis because it involves later investigations. Um but patients can undergo genetic counseling, for example, if you have a positive result, reassurance or potentially even follow up, um can be mitigated if you've got an underlying diagnosis without proteinuria, hypertension or renal dysfunction. So, although a different population in Japan, they undertake annual urine dipstick testing of Children um in school. And that shows that you can see here, about one in 500 have isolated microscopic hematuria with about a half having asymptomatic microscopic hematuria. And 46% have a specific cause of microscopic hematuria. And the majority of cases that you can see here are actually asymptomatic isolated with 100 and 36 cases. It's a normal phenomenon that may in fact involve menstruation in about a third of cases, 35%. But a urinary tract infection with pyelonephritis or ve reflux that you can see here in about 6% about 2% have evidence of hyperglycemia and 1% will have evidence of renal calculi or Neri lithiasis. And although you can take a good past medical history, ig a vasculitis or HSP nephritis was evident in three patients to 1.2% a much smaller number with HSP nephritis or iga vasculitis and get the history um of um papic rash, especially in the lower limb hydronephrosis, uh which happens in about one in 50 cases and uh polycystic kidney disease, which happens in one in a million. So what happens if we follow up patients who have asymptomatic isolated microscopic hematuria with a mean follow up um of 7.5 years. So this means that um about 1% of patients will have evidence of protein injury, but hypertension renal dysfunction is not a concern. So this is really the schema that we've come up with. And from when I was working in North America, looking to see what the underlying investigations may be according to microscopic hematuria. Without protein urea, the middle panel with microscopic hematuria without protein, urine with microscopic and macroscopic hematuria. So you you can think of my schema that you can have for patients if they've got evidence of glomerular proteinuria and hematuria, which is persistent and heavy, we will consider a renal biopsy but it it's very, very minimal proteinuria with just ongoing glomerular hematuria. Then continuous evidence of um Masco hematuria and a family history, especially in a first degree relative will push us to consider um percutaneous renal biopsy in those where it is rejected. And the reason being is that we can offer reassurance in most of the cases where it's intermittent. The microscopic hematuria resolves the parents have negative dipsticks. Uh and otherwise there's no family history of having to have end stage kidney disease, having dialysis or requiring transplantation. So, thinking about developing um protein urea when we use the dipsticks because it's a clinical evaluation. Um don't send the urine off for protein or albumin's creatinine ratio. If this patient is an adolescent menstruating, think very clearly if they've got evidence of edema and or hypertension, could there be an element of nephrotic syndrome? Always remember that you want the first urine in the day, that's the most concentrated sample and to undertake an orthostatic Proia, which is an early morning urine sample in the United Kingdom. We very rarely do 24 hour urine collections, but you can do spot urines throughout the day and see if there's a change or reduction in the amount of protein urea. Um But it's important to also send off to the lab for first urine of the day, early morning urine albumin or protein to creatinine ratio. And looking to see if there's been any change in the senior al albumin level or plasma creatinine with estimated GFR indicating what degree renal dysfunction is. So this slide just highlights the differences that 1 may see in normal urinal to creatinine ratios which as you can see here um uh do vary and then tend to be higher in the first week to six month um age group. But really um reducing down as you can see um after the initial peak in uh the first few weeks. So normally you have a, you're not creatin ratio in double digits. So let's now consider um protein uria. So it's important to always look at the specific gravity. So if you have a patient who's nephrotic, they have four plus a protein urea, they drink two liters before they come to clinic and they micturate for you in clinic and give you a sample and it's got no protein urea because they're drunk and diluted urine down. So you may in fact have specific gravity of 1000. And a patient who's got no evidence of um protein urea. But in fact, even if you send off to the laboratory, they may have a very low urine. And so it's important to always quantify the protein urea, looking to see if there's 01 plus two plus. But in fact, if there's 3 to 4 plus of proteinuria, anywhere from 3 to 20 g per liter, then that's usually pathological. So though normal proteinuria can be less than 60 mg, meter per per day in a rest a day, febrile child, that's indicative of no um normal level, low levels of proteinuria. We use the terminology orthostatic or partial um um proteinuria. And we use this for patients that have proteinuria during the upright position and it basically changes over the day compared to renal disease, which gives proteinuria um every day in itself, postural proteinuria is more commonly in adolescent men can be transient or variable in nature, was normally less than two g per day and is previously a benign condition with about 45% total abnormalities of glomeruli and about 8% more a renal disease. Here, you can see glom nephritis screen and we're wanting to detect if there is any difference in the autoimmune profile, but checking the full blood count, there's no evidence of renal dysfunction, but specifically concentrating on the complement C three C four levels, um A or TTER A N double stranded DNA en a extractable nuclear antigens, as well as anchor Antin cytoplasmic antibodies, serum immunoglobulins, iggig and IgM and a percutaneous renal biopsy. So, I've worked in a couple of units both in this country and overseas where we used to spin the urine down ourselves in the centrifuge in the emergency unit, um or the ambulatory care units and seeing the red blood cell count actually makes you quite confident that you've probably got a case of post infectious glom nephritis. It's important to get the terminology, right. So if you have a nephritic syndrome, then that is very often where there's evidence of microscopic hematuria with some leakage of protein proteinuria, but not as significant as nephrotic range. Um hematuria, which is more than 40 mg per meter square per hour or one g per meter square per day. And this can be associated with acute kidney injury, nephritic syndrome with uria and uh salt and fluid overload giving you have hypertension. However, if you've got proteinuria, um which is nephrotic range, but associated with al anemia. So, an album less than 25 edema and evidence of hyperlipidemia, then you'll have evidence of nephrotic syndrome. And the commonest cause of a Nephritic syndrome is um a post infectious glomar nephritis and the commonest cause of a nephrotic syndrome itself. So, proteinuria, hyper edema and hyperlipidemia is minimal change disease or minimal change nephrotic syndrome. And if you've got features of the two, then the commonest cause again, would be like that with just Nephritic syndrome. With the post infectious glomar nephritis. Here is the caption to think about how to manage these patients. So if you've got increased urinary protein, you've got nephrotic range proteinuria with edema, we want to repeat um uh with a first morning urine, um augment creatinine ratio. And then if that's just normal, then you can be reassured. It may be orthostatic in an older boy. But if it is um abnormal, you're going to want to undertake ongoing follow up to check that we don't develop significant proteinuria. But if patients have nephrotic range protein urine edema, we want to check the renal function, see if there's any evidence of hypia and refer if they've got abnormal features such as an older child who's got systemic disease with hypertension and microscopic hematuria. And we consider treating as a potential steroid sensitive nephrotic syndrome with prednisoLONE therapy up to 60 mgs once a day. Um And watching the response here is the schema which I developed looking for proteinuria, which you're going to repeat if it's transient because it's negative and repeat, then it's not significant and you can be more reassured if the reevaluation at 12 months is normal. If they've got ongoing positive dip stick for proteinuria, then it's persistent proteinuria, which may be as a result of an orthostatic test. And which case, if it is orthostatic. You're going to continue to reevaluate if it's not orthostatic but significant, then you're going to quantify in the 24 hour. And then we'll be thinking about if there's evidence of glomerular protein urea. So your creatinine ratio being elevated, then thinking about under doing um a check of the renal function and autoimmune process and considering a renal biopsy. But if you have evidence of tubular dysfunction with glycosuria, aminoacidemia, phosphaturia, renal tubular acidosis, impaired urinary concentration. Um then that be a cause to look specifically for tubular protein urea with a urine and amino delucas andina to creatinine ratio or a urine retinal binding protein to creatinine ratio. The important reason to know about proteinuria is because if it is ongoing, is it due to active inflammation or is it due to chronic damage or scarring? So, if there's active glom nephritis, we might want to institute immunosuppression. So both ace inhibitors and angiotensin receptor blockers can treat hypertension and proteinuria. And the efferent arterial dilatation can reduce glomerular pressure and remember to commence enalapril at 0.1 G per kilogram per day. Noting the side effects of hyperkalemia and renal dysfunction. So, requiring to repeat blood tests one week after commencing or at least every two weeks after an increase in dose and considering side effects. Counseling for the family if the child develops a nonproductive cough, which can be very irritating but generally improves with time or any evidence of teratogenicity. So, putting this all together if you've got macroscopic hematuria. So, recurrent and confirmed red blood cells, you want to check the timing of the blood during the urinary stream to help isolate the causes. You want to investigate, to exclude common conditions such as urinary tract infection and renal Carni. If you've got evidence of microscopic hematuria, if it's condition and con continuous and confirmed red blood cells, then check if the family members, especially the parents have positive urine dipstick because they may have proteinuria unlike the child and or hypertension and they may warrant the investigations rather than the kid. And we need to discuss with the family options with a more conservative approach where possible to just follow up without undertaking a percutaneous renal biopsy. Remember if there's evidence of proteinuria, one you to always investigate if it's either persistent or non orthostatic and make sure that you exclude nephrotic syndrome and glomerulonephritis. Thank you very much. Indeed. And I'll be happy to answer any questions. So I'll just stop um sharing my slides. It's good to see so many of you on line today. And thank you for putting in where you are. I see some people in my native Scotland, um from Sudan. Um and also around the world. We got people graduated from Sudan, still studying third to fifth year and some people already working in the UK. Oh, very warm. Welcome to you all. Everyone's welcome. And please do pass on about the crisis Rescue Foundation. And we've been doing this course really, um during the pandemic and especially when the Ukraine trouble started. I'm happy to answer questions and I see your hand up first of all by Ada. Hello, as Azad. Hello. Uh, I think in one of your previous, uh, yeah, in one of, uh, your previous lectures, I think it was about sle uh the, and so I don't, I, I don't remember much but the process of hematuria and proteinuria could be present in sle but not in a, not in like se will affect everything if possible. But uh protein UDA, we can say doing u there is a uh possible way to diagnose it because for sle we, for the other indicators, main indicators. But sle is not the one which will come to our mind directly when we see proteinuria and hemato. Yes. No, very good question as that. So thank you for that. So I'm just gonna um share my slide again, which hopefully, can you see the slide there? Yeah, basically. So basically, when you've got microscopic hematuria, the question is always um relation to whether it's part of systemic symptoms or signs. So if there is for example, a malar rash and a child's got microscopic hematuria, but there's no protein. You're even at that stage, then you're quite rightly that I would be worried of the systemic symptoms and signs and we'd undertake investigations at that point because 1 may have for example, a very mild um form of systemic lupus er hematosis and lupus nephritis. So when we do a biopsy, a percutaneous renal biopsy, we may see a more mild International Society of Nephrology Renal Pathology Society Working Group and class two lupus nephritis at that stage. And actually, if you pick them up earlier, then you may be in the advantage that you're going to be able to make a diagnosis. Please remember to complete the feedback form because it's essential for us to have feedback in order to continue with online medical lectures, the link is in the chat. So if you just click on that, you get the Google Docs. If you quickly fill that in, then you'll also be sent um your CBD forms for attendance. So there's a question in the chat from Daniel. So thank you for a 21 year old patient has recurrent microscopic hematuria with a family history of renal failure. What are the differential diagnoses? Well, if there is evidence of renal dysfunction in particularly of a chronic kidney disease, then I would really think about in that instance of there being evidence of port disease. Obviously, one can get X linked recessive autosomal recessive autosomal dominant. Um you sometimes can get um genetic forms of thin basement membrane disease. Um And again, that would only really be detected on genetic screening or evidence of um patients um when you're doing uh percutaneous renal biopsy, and you're looking at the electron microscopy, there can be genetic forms of um iga nephropathy. So we sometimes can see that um running in families, but it's really, really important and to do full screens on families and making sure that you get all the information together. And under taking early genetics. If there are older family members that have got already evidence of renal dysfunction or proteinuria, you may want to get them investigated first so that you're able to get the diagnosis and especially as it may impact a child and you may want to wait until the child, for example, is 18 years of age. But then to make the, the sense of they actually want to, I wait time before they get the diagnosis themselves. Remember, the genetics are really important if you do have an Alport Syndrome, as you said, if there is um this patient who's got a family history of renal disease. So for example, if you have an autosomal recessive form of Alport syndrome and you're homozygous or col four a three or a four, you have over a 90% chance of developing end stage kidney disease and requiring kidney replacement therapy. Usually with the median age of onset of around 15 years. Whereas if you're an autosomal recessive all courses, but it's only just a heterozygous co four, a three or four, a gene mutation, then you're talking about a less than 5% lifetime risk of end stage kidney disease with a median age at onset of about 50 years and also dominant in membrane disease on biopsy with the same heterozygous co four, a 34 mutations, again, less than 5% developing and usually a little bit later to the age of 60. Whereas if you've got an X linked Ports disease and it's a hemizygous in a, in a male with a col four A five gene. And then you have over 90% estimated lifetime risk of developing endstage kidney disease at median age at onset of 30 years compared to the carrier girls who have a heterozygous mutation with a 15% risk of endstage kidney disease, usually much later with median age at onset of 65 years. So I hope that answers your question of that just having a look around the room and to see if there's any more hands up and anything else in the chat as well. Thank you for your thumbs up and for your positive comments in the chat. And if I could just remind you all again to complete the feedback form, we always take your feedback seriously and we change the talk. So please do let us know and hopefully we will see you all very soon at the next lecture. Thank you for your very nice comments as well about the lecture and my explanation and look forward to seeing you soon. Is there anything else you want to add? No, not really. Thank you very much again. Professor. I really, really enjoyed the lecture. I really enjoyed the enthusiasm. I thank every single person for the lectures today. It was quite a long day. But thank you everyone for joining. Um If no one has no more comments or questions for the professor, I think we can end it here today. Yeah, thank you. Because I know you've had lots of teaching today. I've got the graveyard slot at the end of the day. I wish you all um a good evening. Wish you all safety wherever you are around the world. And thank you for joining us again and thinking of you all all the best. You too. Goodbye. Thank you very much, professor. Have a lovely evening. Have a lovely evening. Take care. Bye.