SPEAKER 1: In this video, we will be discussing the condition of acute kidney injury. The second video in this module will cover the causes and effects of chronic kidney disease. In preparation, you will want to review the structure and the function of the renal system using your notes from 1203 or appropriate pages from the class textbook. To begin with, there are three terms that we need to define. The first term is BUN, which stands for blood urea nitrogen. The second term is creatinine, which is not the same as creatine. And the last term is GFR, otherwise known as glomerular filtration rate. These terms will commonly arise during our exploration of acute kidney injury and also of chronic kidney disease. And we will begin now by defining and explaining them. The first term that we're going to describe is BUN, or blood urea nitrogen, which, by the way, is always pronounced B-U-N, and never "bun," and is a concentration of urea in the blood. This value shows the degree of functioning of two kidney characteristics. The first is glomerular filtration. Urea is a small molecule that is filtered completely at the glomerulus, which means that 100% of it will come through into the filtrate. Therefore, as the amount of blood that is filtered by the glomerulus drops, there is an increase in the amount that is retained in the blood, which means that as the amount of blood that is filtered through the glomerulus drops, the BUN level will rise. The second kidney function that is revealed by the BUN value is the reabsorptive capacity of the tubule. And this is due to the fact that urea is actually reabsorbed at a couple of places further down the nephron. So as the speed of the flow of the filtrate through the nephron drops, it allows for more opportunity for urea to be reabsorbed. And the BUN value will rise. The second term we want to describe is the plasma [? creatine ?] concentration. [? Creatine ?] is a compound that is produced by muscles at a fairly constant rate and then, like urea, is filtered 100% at the glomerulus. But, unlike urea, it is never reabsorbed or secreted-- or in very, very, very small amounts. Therefore, plasma creatinine concentration is a reasonable indication of the amount of filtration that is occurring at the glomerulus. If the glomerular filtration decreases, the plasma creatinine concentration will increase. The last term that we're going to describe at this point is GFR, or glomerular filtration rate. And this is the rate of production of filtrate by the glomerulus, which is typically about 125 mils per minute per 1.73 meters squared. The 1.73 meters squared is considered to be the surface area of an average person. The GFR is considered to be the best measurable value for the overall function of the kidney as it is affected by three things, the supply of blood to the kidney, the conditions within the kidney, and obstruction of flow of the filtrate or the urine. So pretty much anything that can affect the functioning of the kidney will affect the GFR. The GFR would be most accurately measured by injection into the patient of a compound that is filtered but never reabsorbed or secreted in the kidney. For example, a compound called inulin. The patient then would be injected with a known amount of inulin. And then a 24-hour urine sample would be taken and analyzed. And also a serum analysis to determine the amount of inulin remaining in the body would be done. The amount of inulin then appearing in the urine is compared with the amount remaining in the blood. And this would reveal how much inulin had actually passed through the kidney, and thus would give a very exact value for the rate at which blood was filtered through the glomerulus. However, in practice, it is much more convenient to just use creatinine. This is a compound that the patient makes naturally. It doesn't have to be injected into the person. And it also, remember, is only minimally reabsorbed or secreted by the tubule. In practice, only one serum sample is taken. And then the GFR is estimated from the creatinine concentration with the use of a calculation that adjusts for age, sex, and race, all of which will affect the GFR. So two people who have the same serum creatinine levels could have very different GFRs. For example, a 45-year-old black man and a 65-year-old white woman could both have a serum creatinine level of 1 milligram per deciliter. But after application of the equation, the man would be classified with normal kidney function while the woman would be evaluated with stage 3 chronic kidney disease. And, by the way, using the equation that is involved in estimating the GFR from the serum creatinine is useful only for chronic kidney disease. It is not something that is accurately used when estimating acute kidney injury. Speaking of which, let's move on to our discussion of acute kidney injury. Consider the following case. Peter S. was brought into hospital with massive internal injuries following a car accident. He underwent successful surgery to repair the damage. However, on the day after the surgery, his urine output had diminished to 10 to 20 mils per hour, which is significantly lower than normal. Analysis of BUN and creatinine yielded values higher than the normal value. Efforts to increase urine output by increasing blood volume were unsuccessful. Peter's case involved a decrease in the functioning of the kidney that occurred within hours or days of an initial trauma. This outcome falls under the category of acute kidney injury. Acute kidney injury involves a sudden decline in kidney function, usually occurring in a patient in critical care with a decrease in glomerular filtration and accumulation of nitrogenous waste products in the blood. And this would be indicated by an increased BUN value and increased plasma creatinine. There may or may not be a reduction in the amount of urine produced, known as oliguria, depending upon the initial cause of the kidney injury. An important characteristic of AKI, or acute kidney injury, is that it can be completely reversible once the initiating problem has been dealt with. However, this does depend upon the extent and type of damage done to the kidney. Because the likelihood of full renal recovery is increased if the harm that is developing in the kidney is discovered quickly, there is a necessity of an objective uniform system for categorizing the level of injury. Several systems have been suggested, the first of which is the RIFLE system. The RIFLE system classification describes three levels of damage as shown by an increase in serum creatinine, a decline in GFR, and/or a decrease in the volume of urine produced. These three levels of damage are risk, injury, and failure, respectively. There are also two further levels that describe the result of proceeding through these levels of damage, known as loss and end stage renal disease. Categorizing a patient in one of these levels allows two things. The first is a more rapid identification of the degree of damage and the necessity of treatment. Remember, the sooner that kidney injury is identified and treated, the greater the likelihood that the patient will have a successful outcome. Categorization within such a uniform system also allows one more thing. It allows a gathering of statistics across numerous hospitals that can aid in the determination of the effect of a particular treatment. However, the RIFLE system does have flaws that involve, for example, the use of GFR. Remember, it had been mentioned previously that GFR can be very difficult to determine accurately in a traumatized patient. It is much more readily used with chronic conditions. Ongoing adjustments to the RIFLE system and the development of better, newer systems are continually being attempted to increase the accuracy of assessment of kidney function. There are many causes of AKI, with the result that this is a serious risk for patients, particularly those in critical care. Unfortunately, mortality rates have not changed significantly in the past 50 years. The causes of AKI have been placed into three categories. The first is prerenal, which involves a decrease in the supply of blood to the kidney. The second is intrarenal, which involves damage within the kidney itself, that is, damage to the glomerulus, to the tubules and/or any of the cells that support these structures. And finally, postrenal, which involves an obstruction in the flow of urine from the kidneys. As mentioned, prerenal failure is brought about through renal hypoperfusion, that is, decrease in the amount of blood that is supplied to the kidney. And this results in a decrease in GFR. This type of renal failure is strongly suggested by a greater increase in BUN values than in serum creatinine values as the slower movement of the filtrate through the tubule allows for greater reabsorption of urea. Hypoperfusion may be due to anything that interferes with the flow of blood to the glomeruli and the tubules, including renal vasoconstriction that's brought about through hormones or drugs, hypotension, that is, low blood pressure, hypovolemia, that is, low blood volume, hemorrhage, or inadequate cardiac output. It is important to note that if pressure continues to be low, the lack of oxygen delivery to the kidney can actually cause cell injury necrosis, which would then increase the damage through intrarenal means. Speaking of intrarenal means, that's our next topic. Although intrarenal failure is caused by conditions that harm any structure within the kidney, it usually results from something called tubular necrosis, otherwise known as acute tubular necrosis, or ATN. And this is actually damage and destruction to the cells lining the tubules as a result of occurrences, including such things as ischemia that is associated with prerenal failure as we've just discussed, sepsis, which is a bacterial infection of the bloodstream, and drugs that are toxic to kidney cells, such as some antibiotics or some chemicals that are used for imaging studies. Such a mechanism of damage can be suggested by a lower increase in BUN value, as opposed to serum creatinine due to the loss of reabsorptive capabilities of the tubules as the cells lining the tubules that do the reabsorbing are being damaged. The last category of injury is postrenal, which is caused by some obstruction in the fluid flow in the pathway from the nephrons to the exterior of the body. These conditions come under the heading of obstructive uropathy, which will be briefly described in class. Due to the ability of intact nephrons to compensate for poor or nonfunctioning nephrons, which we will discuss a little bit more in the video on chronic kidney disease, both kidneys have to be affected by the obstruction before postrenal injury occurs, that is, before the effects of the renal dysfunction are noticeable. Therefore, the obstruction must be one that affects both ureters, such as a tumor growing in the region, or emptying of the bladder itself, such as an enlarged prostate gland, which is actually the most common cause for postrenal AKI. The increase in pressure, which occurs due to the buildup of urine within the urinary tract because it's blocked from leaving, can actually extend upwards to the glomeruli resulting in a decrease in GFR. For treatment of acute kidney injury, it is vital to determine and correct the cause of the kidney injury itself. That is to say, to improve the perfusion if that's the problem, to stop the use of toxic drugs if that's the problem, or whatever is the initial injury that is occurring. This would then allow recovery of the kidney, perhaps even back to the original levels. Until the kidney recovery occurs, the patient's life obviously must be maintained. Since the kidney function has been compromised, the normal functions of the kidney must be supplemented, including maintaining normal fluid volume of the body and normal electrolyte levels. Nutrition levels must be kept up to stop the breakdown of body proteins, which would increase the production of nitrogenous waste in the body and add further stress to the kidney. Infections are common amongst those with AKI, and they actually form the major cause of death in this population of people. And so infections must be rigorously treated. Finally, if it becomes impossible to control the electrolyte and fluid balance and the level of nitrogen ice waste in the body, it will be necessary to perform renal replacement therapy. If the patient is very unstable, is in acute care and wouldn't tolerate large fluctuations in blood levels, the technique of continual renal replacement therapy, which is basically a 24-hour continuous hemodialysis with a very slow rate of exchange, may be used. Otherwise, traditional hemodialysis may be used. This is the end of our video on acute kidney injury. Please proceed on to the next video in this module, which deals with chronic kidney disease.