There is a lot of depth that we can go into as far as renal replacement therapy in the hospital. For starters, there is an alphabet soup of acronyms that describe modalities of renal replacement therapy -- this can be confusing. Secondly, there are details involved in running continuous renal replacement therapy (CRRT) that we will consider to be out of the scope of this introduction. We are going to cover the types of renal replacement therapy used most in our hospital. This information is tailored to the medical student or resident rotating though nephrology and as such, we will try to present the most important information in a straightforward manner. Below are our learning objectives:
Cover the terminology of renal replacement therapy
Introduce the three main types of renal replacement therapy used in our hospital
Discuss the mechanisms by which each modality cleans the blood and removes fluid
Briefly present the “dialysis circuits” of the main modalities we use in the hospital
Mention limitations, advantages of each modality in the hospital setting
The terminology of renal replacement therapy is one of the most confusing aspects of this section. Let’s dive in. The term “renal replacement therapy (RRT)” is the granddaddy of umbrella terms which encompasses all of the types of dialysis and related things. Humans are a creative species and as such, have come up with a menagerie of ways to “replace” the function of a kidney. The chart below covers the organization of RRT.
Figure 1: RRT = renal replacement therapy; HD = hemodialysis; PD = peritoneal dialysis; CRRT = continuous renal replacement therapy; CVVH = continuous venovenous hemofiltration; CVVHD = continuous venovenous hemodialysis; CVVHD = continuous venovenous hemodiafiltration
The three main types of renal replacement therapy we use in our hospital are intermittent hemodialysis (IHD), peritoneal dialysis (PD), and continuous venovenous hemodiafiltration. HD is the default type of dialysis we use in the hospital and it’s great. The second type of RRT we use in the hospital is PD. Sometimes patients are on peritoneal dialysis prior to coming in the hospital and if so, we continue this while they are in the hospital. This type of dialysis involves putting what is essentially IV fluid into the peritoneal cavity and this process cleans the blood. Lastly, CVVHDF is a type of continuous renal replacement therapy that we use in the ICU.
How Renal Replacement Therapy Works
Now for the nitty gritty of how these types of RRT do what they do. There are many types of RRT, but just know that they all work using only three concepts -- diffusion, convection, and ultrafiltration. The difference between every type of RRT is due to differences in how they employ those three main concepts.
Diffusion
We all know what diffusion is… nothing complicated here… it’s just the net movement of particles from an area of higher concentration to an area of lower concentration. This is the main mechanism by which HD and PD clean the blood, and one way that helps the frankenstein modality that is CVVHDF clean the blood.
Figure 2: diffusion is the process of particles moving from an area of high concentration to low concentration over time.
Convection
This is really not a hard a concept to grasp, but the definitions given in textbooks seem to make it as mysterious as cytokines, unicorns, or whatever actually happens beyond that small mesh curtain between first class and coach airline seats (no one will ever know). To explain this concept, we are going to employ the method of the pour over coffee brew. So grab your handlebar mustache, fixed gear bike, Apple laptop, and let’s dive in.
I first heard of this analogy from a website and I think it explains it in a nice way. In short, convection is what happens when some particle is dissolved in a liquid (like water) and is then forced through a filter by something (like gravity or hydraulic pressure). It’s what happens when coffee dissolves into water in the brew basket and then falls out of the bottom of the filter due to gravity -- that’s it. The net result is that something that is small and dissolved in water is able to go through a filter and larger particles stay in the filter. In the coffee example, our rich, bold, hearty brew drips down into our mug and the coffee grounds (which are larger particles that we don’t want in our mug) stay in the filter. When we are performing renal replacement therapy, small particles like potassium, urea, sodium, ect goes through the filter into the waste bin and larger particles like WBCs, RBCs, albumin, and a variety of large particles helpful for life, stay in the body. This is all convection is. It’s not rocket surgery, but it’s really helpful for cleaning the blood and we love it.
Figure 3: Convection: something dissolves in water. The tiny particles dissolved in water pass through a filter when something like gravity forces it through. The filter lets small particles pass through, but retains large particles (like coffee grounds).
ultrafiltration
We’ll let you in on a secret. The process that accomplishes convection is the same process that accomplishes ultrafiltration. The only difference is that we use the term “ultrafiltration” to denote that we specifically care about the volume of fluid that passes through the filter. In our coffee example, water with coffee dissolved in it passes through the filter. We could talk about this process in two ways. Firstly, we can talk about it in terms of convection and how we now have a delicious mug of coffee that we now can enjoy. We appreciate that the water with coffee in it was “cleared” from the brew basket into our mug. On the other hand, we could talk about this same situation in terms of ultrafiltration… speaking specifically about how much volume passes through the filter. Let’s say we pour a little too much water into the brew basket and it’s about to overflow. As gravity forces coffee through the filter into the mug, a certain volume is ultrafiltered and we now appreciate that coffee is no longer about to spill over onto our countertop. When we perform renal replacement therapy, we have two goals: cleaning the blood and removing fluid. In convection and ultrafiltration, the exact same thing is happening, but we use different terminology to talk about which goal of RRT we are achieving.
Dialysis circuits
We’ll now talk about the mechanical strategies for using diffusion, convection, and ultrafiltration to achieve the two main goals of RRT -- cleaning the blood and removing fluid.
hd
Below is the circuit for hemodialysis. The two mechanisms HD utilizes are diffusion and ultrafiltration.
Figure 3: Circuit for hemodialysis. The important things about this are that blood comes into the dialyzer (filter) from the patient and is exposed to dialysate (essentially IV fluid with an electrolyte composition that the blood could aspire to be like) through the medium of a semipermeable membrane. This membrane allows small particles like electrolytes, urea, and creatinine to pass through, but keeps the important things like WBCs, RBCS, and albumin in the blood where it belongs. The small particles in the dialysate and blood equilibrate with each other and this changes the composition of the plasma into a more desirable state.
Figure 4: if we create a pressure gradient from the blood side of the membrane to the dialysate side, the we induce ultrafiltration which essentially wrings the plasma out of the blood into the dialysate. This is helpful to remove fluid from a volume overloaded individual and this process can happen at the same time we clean the blood via diffusion.
PD
Peritoneal dialysis accomplishes the goals of RTT via diffusion and ultrafiltration. In PD, the semipermeable membrane that separates the blood from the dialysate (which we call “PD fluid” in this case) are the capillaries in the parietal and visceral peritoneal membrane. The process is the same though and diffusion happens as usual. We fill the peritoneal cavity with ~2L of PD fluid (essentially creating ascites) which then equilibrates with the blood. At the end, the BMP of the blood and the PD fluid will be the same. At that point, we drain the fluid out of the belly and fill it with fresh PD fluid for the process to start again.
Figure 5: PD involves filling the peritoneal cavity with fluid. Diffusion of uremic solutes, out of capillaries lining the peritoneal cavity, into the PD fluid via diffusion cleans the blood. Of note, ultrafiltration in PD also helps clean the blood via convection and we consider this in our calculations of adequate blood cleaning.
Creating ultrafiltration in PD is a little different than in HD. Instead of using hydraulic pressure to push fluid through the semipermeable membrane, we use osmotic pressure (through high dextrose concentrations in PD fluid) to pull fluid into the peritoneal cavity. The higher the concentration of dextrose, the more fluid we can pull into the peritoneal cavity. We use color coding to denote the dextrose concentrations of the bags. In addition, a different molecule called icodextrin is sometimes used to create ultrafiltration through colloidal pressure (colloidal pressure because it’s a large molecule). Icodextrin can exert ultrafiltration for long periods of time and it’s useful for us in certain situations. The main point is to have a general idea of the # of liters someone puts into their belly at home and the colors of the bags they typically use. Literally as the the patient this exact phrase: “What color bags do you use and how many of each do you use each day?” Write this information down on your prerounding sheet, report it to the nephrologist and you will look like an all star.
1.5% dextrose: yellow bag
2.5% dextrose: green bag
4.25% dextrose: red bag
Icodextrin: purple bag
cvvh
Now, let’s talk about CRRT. If we do routine HD on a patient, this treatment will last 3-4 hours. Let’s imagine that instead of turning the machine off at 3-4 hours, you just let it run for a full 24 hours. Congratulations, you just performed CRRT and specifically did so via continuous venovenous hemodialysis. The circuit for CVVHD is the same as HD. The only difference is that you run CVVHD for at least 24h, but more often, for days at a time. The venovenous notation in CVVHD refers to the fact that when you place a temporary dialysis catheter in a patient, the catheter only goes into a vein. In the old days, they would place an arterial catheter and a venous catheter and use the heart as the pump that forced blood through the machine. We of course no longer do this because we have now electricity and technology, but it’s an interesting bit of history. That’s it. Now you understand CVVHD.
Figure 6: HD or CVVHD circuit… they’re both the same
CVVH
Moving onto continuous venovenous hemofiltration, we now use the process of convection for the first time. One of our goals of RRT is to clean the blood. If we’re trying to decrease the BUN of a patient, then this involves physically removing urea molecules out of the body. We can do this by essentially wringing plasma out of the blood via a pressure gradient through a filter.
Figure 7: Convection in CVVH
This certainly removes urea out of the body, but it leaves us volume depleted. An easy way to combat this is by replacing volume. We can do this by our favorite method -- infusing isotonic crystalloids into the blood. That’s the whole rationale behind CVVH… wring plasma out of the blood through a filter and then essentially replace that same volume with Plasmalyte. During CVVH, we call the fluid (which is essentially Plasmalyte) replacement fluid and the process of convection and volume replacement happen at the same time in the CVVH machine.
Figure 8: Circuit for CVVH. blood comes from the patient and a pressure gradient pushes plasma through a semipermeable membrane, hemoconcentrating the blood. The plasma that goes through the membrane is captured and disposed of. After the filter, replacement fluid gives the same volume back to the blood that was removed with convection.
CVVHDF
Let’s imagine that we are currently not in a COVID-19 pandemic and you invite friends over for dinner. You’re going to make the one acceptable entree you know. Everything is all and well until you find out, 1 hour prior to dinner, that your friends invited 10 more friends. You’re screwed. You are so pumped that everyone is coming and you think you may have enough food, but just to make sure, you order a few pizzas to be delivered just to be on the safe side. This is essentially what CVVHDF is. It is continuous venovenous hemodiafiltration. Hemodialfiltration is the compoundish word that refers to a combination of hemofiltration and hemodialysis. CVVHDF accomplishes the goals of RRT (cleaning the blood and removing fluid) through the mechanisms of diffusion, convection, and ultrafiltration. The figure below may look a bit complex, but it’s essentially just a CVVH circuit with dialysis stuck on top. On the surface, it appears to be the El Camino of RRT circuits, but because of the sheer performance characteristics, some nephrologists consider it to be the Porsche of CRRT. As already mentioned, we use the Prismaflex machine, made by Baxter, at our hospital. Prismaflex performs CVVHDF so we often use the words, CRRT, Prismaflex, and CVVHDF interchangeably in our notes.
Figure 8: Circuit for CVVHDF. The duckbill platypus of renal replacement therapy, CVVHDF involves a mixture of CVVH and CVVHD
limitations of each modality
Lastly, let’s talk about some benefits and limitations of HD, PD, and CRRT.
HD
This is our default. It can clean the blood and clean it fast. It can also remove fluid via ultrafiltration fast. Because of this, it’s great for fixing a K+ of 7.0 quickly or removing a few liters of fluid in a pulmonary edema patient. It really can drop blood pressure during treatment though and that’s it’s downfall. In hemodynamically unstable patients, it can drop blood pressure even more and that sometimes prevents us from using it. In addition, because it cleans the blood so quickly, it can result in next water movement into the brain, exacerbating cerebral edema in those with an intracranial catastrophe.
PD
If someone is on PD at home, we continue this in the hospital. We can continue PD even if someone is on multiple vasopressors. It does have the limitation of not being able to remove large amounts of fluid in a short period of time. Lastly, if someone has to have surgery that breaches the peritoneal cavity, then we have to transition these patients to HD temporarily to give the peritoneum time to heal so we avoid leaks.
CRRT
We use CRRT in hemodynamically unstable patients or those with some large intracranial event (think increased intracranial pressure). Because CRRT cleans the blood slowly and because we can remove fluid over the course of 24h rather than 3-4, CRRT is more gentle on the hemodynamic status. Access is an important consideration. We have to use either a non-tunneled dialysis catheter or non-tunneled dialysis catheter to run CRRT. We cannot use an AV fistula. Lastly, it does not really matter if we use CVVH, CVVHD, or CVVHDF -- they all work and we use whatever a particular hospital has.
When to Start Renal Replacement Therapy
At this point, you have a good understanding of how renal replacement therapy works. Kudos and bonus points to you if you have also seen a dialysis machine or dialysis patient! There are distinct differences in dialysis management between inpatient and outpatient. This section will focus on when and how to do hemodialysis in the inpatient setting.
There are always some interventions and medications that can be used to facilitate renal injury/deficits. When those efforts fail, it is time to consider hemodialysis. The standard acronym used to remember indications for hemodialysis is AEIOU. Outside or absolute urgent indications for renal replacement therapy, there is currently no role for starting it early to get ahead of the curve. “Early vs late” starts for renal replacement therapy has been an ongoing area of investigation and the overall verdict is that there is no benefit to starting early before there are absolute indications for RRT. If you want to read more on this, read this write up on #NephJC.
A: Acidosis: Acidosis can be either metabolic or respiratory. Hemodialysis does nothing to correct a respiratory acidosis but can certainly correct a metabolic one. The dialysate used in both hemodialysis and CRRT contains sodium bicarbonate. The concentration of bicarbonate in the dialysate is fairly standard across the board (we use a 37 mEq/L), but can be customized if needed. If a patient presents to the hospital with severe metabolic or lactic acidosis (pH <7.1) that is refractory to IV sodium bicarbonate, adequate fluid resuscitation, and elimination of any potential acidosis inducing medications (think about metformin), it is time to try hemodialysis.
E: Electrolytes: Our kidneys like to maintain a homeostasis with electrolytes, and typically do this very efficiently and effectively. However, there are times when the kidneys fail to do this either because of excess intake of an electrolyte or lack of excretion. Often, the biggest threat in this category is potassium, followed by hypermagnesemia. Hyperkalemic emergencies are defined as serum potassium levels >6.0 meq/L or a sudden increase in serum potassium 1.0 meq/L above 4.5 meq/L within 24 hours associated with cardiac arrest, evolving critical illness, acute MI, or signs and symptoms of neuromuscular weakness. Such emergencies warrant immediate treatment with a dual purpose: to shift potassium back into the intracellular space and to facilitate potassium excretion from the body. At the same time, differential diagnosis development should be completed so that the potential source can be identified and remedied. In true hyperkalemic emergencies, medication administration is a way to buy yourself time, while dialysis access is placed and preparation of dialysis or CRRT machines is completed.
I: Intoxications: Does dialysis help? Think about SLIME!! S: salicylate; L: lithium; I: isopropanolol (rarely needed though); M: methanol and metfomin; E: ethylene glycol. Other potential poisonings that may warrant dialysis include overdose of acetaminophen, valproic acid, phenytoin, and barbiturates. Effectiveness of hemodialysis at removing toxins is based upon characteristics of the toxin (molecular size, lipid binding, charge), patient body habitus and volume of distribution, and the dialysis modality (PD vs HD vs CRRT).
O: Overload: Fluid volume overload is something that you will encounter frequently in the inpatient setting. Patients with CHF, CKD, and liver disease are at the highest risk of volume overload but there are a subset of patients with underlying kidney disorders that are at inherent risk too. Fluid overload is typically managed by escalation of diuretic therapies and most often will include a loop diuretic. A healthy diuretic response should be achievable in most cases. However, there are some scenarios in which patients will not diurese appropriately even with maximum diuretic therapies. In this case, hemodialysis should be considered to offset the hemodynamic/respiratory strain that is placed on the vital organs in the setting of volume overload. If the patient is hemodynamically stable, then conventional hemodialysis should be considered. If the patient shows high risk for hemodynamic instability or is on pressor therapy, CRRT should be the modality of choice. There is an option to do only ultrafiltration therapy, which only removes fluid from the body. This is often called SCUF.
U: Uremia (symptomatic): The kidney works to rid the body of urea. However, in the setting of AKI or advanced CKD, this process becomes altered and urea will build up in the body. Dialysis for uremia is an absolute indication in the presence of uremic encephalopathy or uremic pericarditis and should be strongly considered in patients with known CKD who are showing uremic symptoms: lethargy, nausea, poor appetite, weight loss, altered sense of taste.