Acute Kidney Injury: The Basics

Welcome to another edition of MedPods, the podcast on important topics related to medicine brought to you by the Department of Internal Medicine at AFMC. In our previous editions, we spoke on very relevant topics of stroke and its management and anemia and we also spoke on a specific condition of iron deficiency anemia in the last podcast. Today we shall be discussing a very relevant topic, the topic of acute kidney injury which we often encounter in our clinical practice. The students need to understand this topic in relevance to the fact that most often the outcome of a patient in the intensive care unit and any other emergency also depends on how the patient responds to treatment of acute kidney injury. To talk on this, today we have with us Colonel Parikshit Chauhan who is a nephrologist and associate professor in medicine in the Department of Internal Medicine at AFMC. Nephrologist who has qualified from the prestigious PGI-MER Chandigarh shall be talking about the various aspects of acute kidney injury that the students and the practitioners of medicine should understand. Welcome Parikshit. To talk about this topic today, what we shall follow the way we have been doing in earlier podcast is that I would request you to start from the very basics so that our students understand what topic we are going to talk about in the background and thereafter going into certain details of it. So to start, could you elaborate on what is the comprehensive definition of acute kidney injury? Thank you sir for giving me an opportunity. So the definition broad definition for acute kidney injury is reversible loss of kidney function but to be exact exact definition is rise in serum gratinine by 0.3 milligram per deciliter over 48 hours that is 2 days and rise of creatinine by more than 50 percent over last 7 days over the baseline creatinine and there is another criteria of urine output. If the urine output is less than 0.5 ml per kg per hour for at least 6 hours it is it qualifies for AKI. Now the requirement for this exact definition is to bring uniformity in diagnosis of AKI as well as for use of term AKI in different clinical and epidemiological studies. So from what I understand, there are two aspects to it one the absolute increase in the value of creatinine and also what is the percentage rise in the creatinine. So what are the three key criteria that you use in clinical practice and you have these various parameters when you are diagnosing AKI. These are the only two criteria that is serum creatinine and urine output which help us in diagnosing AKI diagnosis these two are required. Now the normal creatinine level in a healthy adult female is less than 1 milligram per deciliter while in an adult male it is less than 1.2 milligram per deciliter. I just told that it is rise of 0.3 milligram per deciliter above the baseline. Now what is baseline creatinine? If an individual has remained healthy throughout so we presume that his or her creatinine was always in the normal range and if the previous reports are available you take the average of creatinine over last one year. Now what is normal output? It is 700 to 3000 ml per day and it depends on the fluid intake by an individual and the surrounding weather conditions. Urea is also serum urea is also an indicator of renal function but it is highly variable. It depends it varies with fluid status, the diet and use of drugs like steroids or in a hospital patient something like parenteral nutrition and one more important thing that before labeling someone as AKI one has to ensure that hydration status is corrected. Good, so like most other topics that we have discussed till now it is very important to take proper history to understand the background of the patient where the patient has actually settings in which the patient has developed this AKI. What is his baseline creatinine? If it is available from the past reports or just go by the normal range that is known. Similarly the urine output also is part of history when patient first comes to us otherwise we go by the normal range and the way the urine output is measured while the patient is in hospital. Okay, so are there any different classifications or stages of acute kidney injury that our students should be aware of? So over the last almost two and half decades there have been three classification criteria for AKI again for uniformity and for use in studies. So in 2004 it was rifle criteria, in 2007 it was akin criteria and since 2012 we have been using KDGO criteria that is kidney disease in improving global outcomes and it is being universally used in day to day practice. Now there are three stages after diagnosing AKI what we should put them in any of we should try to level them in any of these stage. Stage one is when the creatinine is more than 0.3 milligram per deciliter of the baseline or it has risen by 1.5 to 1.9 times, broadly 1.5 to 2 times and the urine output has been less than 0.5 milligram per deciliter per hour for 6 to 12 hours. So minimum is 6, now stage two is creatinine has risen by almost 2 to 3 times and the urine output is low for 12 to 24 hours same value 0.5 milligram per deciliter per hour. Stage three when the creatinine has risen by three times of the baseline value or in a patient with presumed normal baseline creatinine it absolute value is more than 4 milligram per deciliter. Third is if there is requirement of renal replacement therapy not because of hezotemia but maybe for any other indication which we will discuss. Here the urine output criteria is not 0.5 but it is 0.3 ml per kg per hour for 24 hours or if the patient is enduric for 24 hours. So usually the we start the for practically we start the dialysis when the patient qualifies for the stage three. So like in most other conditions it is very important to understand the stage of AKI because that decides how severe the presentation is and also decides how we are going to manage the patient and the aggressiveness which we are going to manage. And also the prognosis. Correct. So prognosis of the patient is also decided based on the stage in which he has presented. So coming next to a very important topic which which we discuss in every system failure that we encounter is this organ acutely involved or is there an underlying chronic disease which on top of which there is an acute insult. So when it comes to kidneys how do you differentiate between a patient having acute kidney injury from a patient who has a chronic kidney disease and has now come with an acute worsening. So as already discussed AKI is reversible and the duration of renal dysfunction has been for less than 7 days. One qualifies for chronic kidney disease when the duration of the renal dysfunction is for more than 90 days. Now what comes in between these 7 days and 90 days is acute kidney disease. It is a new term coined a few years ago. While AKI is reversible and patient requires no follow-up if the patient has remained healthy before this episode. But CKD patients require regular follow-up and and they require to be told about the progressive nature of the disease. CKD is irreversible and they require regular follow-up in the OPDs they are managed for complications of CKD like anemia, mineral bone disease, they are vaccinated for hepatitis B, pneumonia, seasonal influenza and they are mentally prepared for requirement of renal replacement therapy in future which may be near or later and AV fissure access creation. So chronic kidney disease is a condition that we must always watch out for in a patient who comes to us with acute kidney injury because that is going to decide on whether it is completely reversible and if there is underlying CKD then the whole concept of management and follow-up of this patient is going to change. So that is the importance of knowing if there is any underlying chronic kidney disease. So in clinical practice when you encounter patients with acute kidney injury, what are the common causes that you see of in patients who are presenting with AKI? So there are numerous causes of acute kidney injury and one should try to divide them into for easily remembering into pre-renal that is there is some problem, there is compromise of blood supply to the kidneys, something happening in the kidney that is renal and post-renal after in the collecting system, pre-renal, renal and post-renal. So pre-renal blood supply to kidney is compromised, so it could be hypovolemia, in community it could be diarrhea or vomiting, heart failure with forward pump failure, blood is not reaching the renal artery, cirrhosis where there is pooling of blood in the splenchnic circulation as compared, which should have been in systemic circulation that is the mechanism for hepatorenal syndrome, nephrotic syndrome, all the blood has gone into, has extravaceted to the, from the intra, and thus reducing the intravascular volume and some drugs like NSEITs, ACE inhibitors and cyclosporine or tecrolimus, they decrease the perfusion pressure of the glomeruline. So they can cause pre-renal AKI, now these drugs also cause renal also by acute interstitial nephritis or TMA, so these are the major causes of pre-renal one should remember and pre-renal is easily reversible with fluid depletion. Now renal we can divide into the according to the structural, structural involvement, it could be glomerular, something like glomerulonephritis, now we come down it could be tubular interstitium that is tubular interstitial disorder, commonly seen if the hydration, pre-renal can progress to ischemic ATN, if patient has remained hypotensive for a long time. Some drugs commonly like amphotoracin, amicasin, antibiotics like cephalosporine, they cause tubular interstitial disorder and many antibiotics are implicated. Now it is vessels, vessels around the glomeruline that is capillaries, it could be involved vasculitis, anchor related vasculitis or thrombotic microangeopathies. So these are the renal causes of acute kidney injury, post renal easy to remember is if there is bladder outlet obstruction, if there is single sided ureteral obstruction does not cause AKI, the other kidney takes over. So bladder outlet obstruction or if there is bilateral calculate obstructing the ureter intra-luminally or there may be something extra-luminal causing the impairment of drainage, something like C.A. cervix is commonly implicated, it causes post renal AKI. So one should remember it is pre-renal, renal and post renal, it helps in also how do you manage the individual which I will be discussing later. So students must understand that it is very important like in all other topics in medicine to classify when we are approaching ideology so that we can understand why it is happening and also easy to remember by calling the criteria of firstly using the criteria for diagnosis and thereafter looking for the ideology based on whether it is pre-renal, renal or post-renal. Now once we have a clinical suspicion of acute kidney injury which we have confirmed by the various criteria that you just mentioned, what are the various diagnostic investigation modalities that you have to all various lab tests or imaging that you do to diagnose these patients about their cause of AKI and further management. So first how you suspect already discussed like there is rising creatinine and the patient is low urine output, again we go back to taking good history whether individual was taking any drugs which could be nephrotoxic, some alternative medications also on OPD basis. History of lightheadedness, suggestive of hypotension, more on change of posture is suggestive that patient was fluid depleted, history of any infection anywhere in any other organ like lung or it could be urinary tract infection also they can cause AKI. So history taking is very important, after that you come for the clinical examination you do for tachycardia, hypotension, maybe suggestive of pre-renal AKI. With investigation you start with basics like hemoglobin or peripheral blood smear. If it is low and there is hemolysis on peripheral blood smear, it could be hemolysis induced acute tubular necrosis or maybe thrombotic micro angiopathy. If the leukocytes are raised, it is suggestive of infection and may indicate some infection related glomerular nephritis or sepsis related atlases, platelets are low it could be some tropical fever like the tropical infection like dengue or thrombotic micro angiopathy. You expect urine and creatinine to always be high in a case of AKI. If there is hyperuricemia, hyperphosphatemia, hyperkalemia with low calcium, please suspect it could be tubular lysicentral and if associated CPK is high that is in 5 digits more than 10,000, then suspect reptomyelosis. Very important urine examination, it is the liquid kidney biopsy. So if there are active sediments which are dysmorphic RBCs or RBC cast, they suggest some glomerular involvement, glomerular disease. Other in urine examination are which is not very sensitive and specific but always mentioned in the textbook and we do not do it commonly is fractional excretion of sodium. If it is less than 1%, it means the kidneys are functioning still and the cause is pre-needle. Greater gravity and osmolarity increases in pre-needle AKI while it may be low or normal in renal or post-needle AKI. Serology, if there is some systemic disorder we are suspecting with immunological phenomena. Something like vasculitis so angka, serological markers can be ordered, angka vasculi C angka, P angka, ANA. Some other autoimmune disorder extracted nuclear antigen profile can be ordered. Imaging is very important. So we start with ultrasound KUP. It tells us about the size of kidney. It normal size is 9 to 12 centimeters. If it is less than 9 centimeters, we get a hint that patient may be having chronic kidney disease 8 centimeter kidney and now has presented for the first time it may be acute on chronic or may be a progression of CKD. Ultrasound also tells us about the any obstruction and it helps in measuring the IVC diameter and coaxiality thus helping in guiding the fluid therapy. Sometimes CT scan is also required in acute kidney injury. Stones can be missed by ultrasound but if there is bilateral urethral obstruction and nothing can be seen then we go for CT scan which is NCCT that is non-contrast. In case of AKI when contrast is in SKB, there is a condition known as acute cortical necrosis. In spite of deranged renal function we have to order contrast in a CT scan. Acute cortical necrosis is usually seen with postpartum AKI or snake bite and the prognosis is very poor renal prognosis. So, we are very comprehensively addressed and I think starting from basic investigations like hemogram or urine routine examination which you mentioned is something like a liquid biopsy for the kidney if you get into the actual details of the urine examination and of course then subsequently the electrolytes, the urea, creatinine and of course specific tests for looking at the ideologies. Now, we discussed about the classification of various types of AKI, so with investigations how do you differentiate between pre-renal, post-renal and intrinsic renal involvement using investigations. So, we look for one upon creatinine ratio that is very easily available. If it is more than 20 is to 1, it is suggestive of pre-renal that is urea has risen more as compared to creatinine, it is suggestive of pre-renal, it may be less than 10, the ratio is less than 10 in renal and post-renal. Already discussed about the fractional excretion of sodium, it is less than 1 percent in pre-renal while it is more than 2 percent in renal and post-renal. The other thing is specific gravity which no one looks at in the investigation report and the osmolality although it is difficult to get this investigation done routinely. So, specific gravity and osmolality rises in the pre-renal suggesting that kidneys are still functional and they are able to concentrate the urine. So, these are the basic investigation which helps in differentiating between pre-renal versus renal and post-renal. Good, I think this is something these students must remember and revise differentiating between pre-renal and renal because while post-renal is usually picked up on imaging, pre-renal and renal differentiation helps because the initial management of using fluids is different in both these settings. Now, coming to the aspects of management, what are the general principles when you are planning management of a patient of acute kidney injury? Sir, as already discussed we should try to differentiate which kind of AKI, pre-renal, renal, post-renal. So, I will start with pre-renal although with history taking and examination you can make out whether the patient has high potential or not and then you start with the fluids. Fluid is the only treatment for pre-renal and in between you if the patient has got a central line you can also measure the CVP and nowadays ultrasound is commonly available in all the ICUs. So, we should always look for IVC diameter and not only diameter, the collapsibility. It is the collapsibility which tells us whether the patient will respond to the fluids or not. So, you start with the fluids. The other thing is, so this is pre-renal and it is very dynamic. You cannot order 3 liters of fluid over 24 hours in pre-renal. So, it is very dynamic thing. So, you start with 200 ml per hour or after a bowl of 500 ml and keep on gauging the patient and titrate accordingly. If you are suspecting a renal AKI, first remove the offending agent and regarding the fluid you take an idea that I will be giving fluids of total of what was the output in 24 hours plus 500. Again, it is a dynamic if the patient remains oliguric or enuric, please stop the fluid, reassess again, patient should not develop pulmonary edema with power fluid administration. And if the patient starts passing urine, you can increase the fluid. So, it is a very dynamic fluid administration as is a very dynamic thing. Now regarding post-renal. Post-renal is something which requires immediate relief of obstruction. We should get into touch with surgeon in a peripheral centre or with a urologist and they can put in a DJ stand or two percutaneous nephrostomy and relieve the obstruction. And something if it is better outlet obstruction, a simple catheterization will resolve the AKI. So, pre-renal and post-renal, they are easy to manage and they respond beautifully to whatever fluids, oblique relief of obstruction. It is the renal, you remove the offending agent whatever is the cause and biopsy is indicated in renal causes. If you are suspecting something like glomerular disease, vasculitis or TMA. Classically, we say biopsy should be done in non-resolving AKI. What is non-resolving AKI if the kidney does not improve, the renal function does not come back to normal in 21 days because that is the time taken by tubular epithelial cells to regenerate. But go ahead with biopsy if you are suspecting some glomerular nephritis because these patients require immediate immunosuppression and if not treated on time, they progress to AKD and then CKD. So, that is how we broadly manage that. Okay. So, from what I understand the general principles of management approach the immediate resolution of offending agent when it comes to the renal AKI. And in pre-renal and post-renal, it is with hydration, maintaining the blood pressure and renal perfusion and in post-renal we are also addressing the obstructive nature of the disease and by relieving the obstruction since the kidneys are intrinsically okay, they will respond. So, however, in patients in home we see intrinsic renal involvement. There is an indication to do biopsy to find out the underlying disease and it should preferably be done after at least 3 weeks of the involvement so that the nature of the disease has manifested. But it should be done and the management should be proactive because it can lead to acute kidney disease and subsequently chronicity. Yes, one more thing sir regarding biopsy in renal the causes. So, biopsy should not be done with a creatinine of more than 5 because with this kind of uremic environment platelet have got functional defect. They do not adhere and chances of bleeding are very much. So, in such cases we provide dialysis 2 or 3 sessions and then do the biopsy one should not go upfront for biopsy in with uremia. Excellent. I think that is a very practical point which all the residents should remember. Now a very relevant decision that has to be made while managing acute kidney injury is when to subject the patient to renal replacement therapy or what we generally use as dialysis. Now what are the modalities available in such setting and what are the criteria which you have based your decision on. So, first I will tell what are the indications of renal replacement therapy. So, over the last decade there have been many studies multi-centric, but mostly they have been in the western world. So, in 2016 one Elaine trial came and they started providing dialysis in stage one AKI and then they said it affects the mortality the patient improve faster. After that four trials have come major trial AKI-KI 1 and 2 and start trial. What they have concluded that we stick to the textbook indications for renal replacement therapy and we do not provide dialysis till an indication arise like refractory hypokalemia refractory to medical management. First always try medical management. Other is refractory metabolic acidosis pulmonary edema causing desaturation can be life threatening. Absolute value of 250 milligram per deciliter of blood urea and if the patient has three days of oliguria or if the patient develops uremic symptoms. In CKD we also mentioned uremic pericarditis and uremic incephalopathy as a as an indication for renal replacement therapy, but in AKI usually these complications do not arise you require a long standing uremia to cause pericarditis or incephalopathy. Now the modalities which we can use is peritoneal dialysis it could be with hard catheter or with a soft catheter and the other is hemodialysis it could be slow efficiency dialysis or CRRT in critically ill patients. These modalities we can discuss somewhere later in another part. Yes, I think it is very important to just understand which are the settings where we would like to subject the patient to renal replacement therapy and of course what are the modalities available and of course we will plan a subsequent podcast where we will discuss these modalities in detail. Now once we have managed a patient with AKI and he is recovered what are the likely long term implications for such patients and what is the follow up that you advise? Sir in a previously healthy individual something like a young serving soldier in our setting who developed AKI because of gastroenteritis or snake bite they get their baseline creatinine and no follow up is required in such cases but in a patient of chronic kidney disease who already had high creatinine maybe because of diabetes or long standing hypertension or some cardiac ailment or some drugs these patients require regular follow up whether they progress how fast is their CKD progressing? Now short term implication of AKI in hospitalized patient what has been found is if someone develops AKI the mortality which is around 20% in and in a critically ill patient high-potensive septic patient if they develop AKI and require RRT the mortality is around 80%. One common misconception which is there that AKI is totally reversible and after recovering the patient's kidneys are always well but what has been found recently that AKI an episode of AKI itself is a risk factor for CKD and someone who had an episode of AKI is 8 to 10 times more prone to develop CKD later in future as compared to one who never had. So that is very important to understand that AKI is not completely reversible although it may appear so there is always some amount of damage that happens and the patient is likely to develop CKD more likely than somebody who has never had AKI and also the fact that we must keep such patients on our follow up and lastly and one must remember that preventing AKI is also very important because if it has such implications which are long term. So coming towards the end of our discussion on this topic what are the recent advances which have come in the field of management of AKI that our students should be aware of. So the management of AKI revolves around the volume, status, maintenance, immunosuppression, relief of obstruction and renal replacement therapy. So recently what has been found that vasopressin as compared to noradrenaline helps in preventing AKI in septic patients, those patients who have got septic sepsis. The other newer modalities which are being explored but these are in phase one or phase two trials only that is use of nicotinamide and stencil therapy for prevention of our curing prevention and curing AKI. Now one another important thing is biomarkers for almost one and half decades we have heard of urinary, TIM, kidney injury molecule, NGAL, interleukin-18, something like tom, phosphol protein that is now labelled as Euromotubin. So these are diagnostic and diagnostic markers they have they did well very well in studies but in real world situation they have not benefited in diagnosing or managing the patients of AKI. One recent molecule that is insulin like growth factor binding protein 7 with TIM, TIM is tissue inhibitor metalloprotein is 3. So this molecule helps in early diagnosis of AKI stage 3 and now this molecule is being studied in our country also including armed forces institutions. So it may come out as a prognostic marker and as well as diagnostic for early detection of AKI and hence managing better management. So these are the recent advances that is also true. So thank you very much Kanul Chauhan I think in this very important topic of AKI we have considered various issues relevant to the initial diagnosis of AKI classification and various etiologies based on whether it is pre-renal, renal or post-renal. What are the investigations that need to be done and of course the management aspects which are very general. We have not gone into the specifics of the each cause of AKI which we shall be addressing in subsequent podcast and of course the most important aspect of following up such patients. So thank you for your time having spared for us to elaborate on this very relevant topic. We what we do in such podcast is that we gather feedback from the students and we also urge the students to ask questions which they have not understood well and we put them back to the faculty so that these points can be clarified and also the feedback that we receive from the students will also be given to you so that we can change the way we perform in the subsequent podcast. So thank you very much. Thank you sir.