Forget Kt/V. Dialysis is about replacing kidney function. That means fluid and toxin removal.
Here are a 2 facts: High flux dialyzer membranes allow all toxins to pass from the blood to the dialysate and back without restriction. Modern dialyzers are designed to clear all the toxins in the blood with BUN = 100 mg/dL, at 500 mL/min blood flow in one pass, assuming normal pathologies and dialysate flow = 30 L/H.
If I’ve got either wrong I’d really like to know.
Basicly, the dialyzer keeps the large molecules in the blood but allows all the smaller molecules to pass back and forth without restriction. It’s like mixing pink koolaid and clear water. The time factor is measured in microseconds.
The first mL of blood entering the dialyzer has lost half of all it’s toxins within the first half inch of flow at 500 mL/min and is completely clean by the time it reaches the other end. The second mL encounters dialysate already contaminated by the first but it doesn’t matter because in a minute the dialyzer is full of blood and the gradient of toxin concentration in the blood goes from max to zero over the length of the dialyzer. The dialysate has an equal and opposite toxin concentration gradient.
Now, what happens if the blood flow is reduced to 200 mL/min without changing the dialysate flow? Each mL of blood gets to spend more time in the dialyzer. Each mL gets completely cleaned sooner. Reduce the dialysate flow to 200 and it again takes the whole dialyzer to get the same result.
If the pre BUN is 50 instead of 100 the dialysate flow can be cut in half to achieve the exact same result. 50 BUN, 200 blood flow and 100 mL/min (6 L/H) dialysate is just as clean after dialysis as 100 BUN at 500 and 500.
There is nothing magic here. It’s 8th grade science and math. Hopefully I’ve got this right and we can move on to rebound and total toxin clearance in a 2 hour cycle.
Here is the most cited article on the topic I think https://www.ncbi.nlm.nih.gov/pubmed/11684546
Generally as Qb increases mortality decreases but there is a concern about recirculation, one needs to take in to consideration the fistula’s health to judge the appropriate Qb https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094923/
Why might this be? Only ~ 1/7th of the toxins are in your circulatory system with access to the artificial kidney or peritoneum. Most of the toxins in your body are in the cells ~ 4/7ths. To dialyze these toxins they have to pass through two biologic semipermeable membranes - cell wall then wall of a capillary - before they get to the dialyzer. The more blood that has been processed through the artificial kidney, the greater the gradient difference throughout out the circulatory system, between your blood space and the space between the cells. This gradient difference eventually causes a cascade of toxins from the cells into the blood, which then gives the artificial kidney a chance to remove them. The more blood that has lowered solute concentrations the faster toxins will be drawn out of your tissue.
Thanks Bill. Is there any reason to assume the larger molecule toxins are less soluble than urea? Are they harder to get from the blood into the dialysate?
The bigger they are the less likely they’ll fit. The pore sizes of each hollow fiber is a random distribution. Little things - urea, water - fit through them all and are sensitive to gradient TMP. Larger solutes - protein bound molecules - don’t have as many pores large enough to fit through and aren’t cleared by gradient differences, some bump through a pore that fits but it is more they are dragged across by the shear force along the membrane and convective clearance, or really any time UFR > 1.0 which is not a good idea unless you’re getting replacement fluids as you dialyze, for instance hemodiafiltration.
The shear force is little credited but plays a huge role in getting non-tiny things across the membrane. Each fiber inside the artificial kidney is a tube and as such the fluid traveling down the center of the tube will travel faster than the fluids bumping along the walls. The effect of this is that the density of solutes in the center of tube will be lower than the density along the walls. Think of all the solutes starting down the tube in a line, as the ones in the center move faster the density is decreased, this density imbalance causes molecules to be pulled from the wall to the center to keep the density the same.(atoms can not abide density differences, the same force creates the lift that keep A380s in the air). So now there is an opening on the one side of the membrane.
However, this is happening on both the inside of the tube and the outside. The fluid traveling fastest will have the most atomic-level suction force. TMP puts a thumb on the scale moving solutes into the dialysate, but when Qd > Qb everyone is pulling/pushing in the same direction.
Thanks Bill. Any idea the ratio between the quantity of large pores and normal ones in the standard High Flux membrane?
Taking your image of drag at the walls of the membrane allowing the blood in the center of each tube to move thru faster, don’t we get better clearance of the larger molecules by slowing the blood?
At slower blood flow, say 200 mL/min, each mL of blood gets to stay in the dialyzer 2.5 times longer than at 500.
We do that’s one of the benefits of nocturnal, being able to turn down Qb and maintain mandated urea based measures. Like anything there are tradeoffs and it is difficult to make general statements with all the variations. NxStage turns everything I’ve said on its head; I’ve been using it for 12 years without being able to explain its apparent efficacy
https://www.nature.com/articles/s41581-018-0002-x this article will cost you $9 but I think you’ll find it worth it if you want a deep dive into kidney membranes. One thing I took away: wall thickness matters as much/more than pore distribution. I saw a presentation by Dr Clark at the IDEAS Conference at the University of Washington last week, presenting this research. Another thing I took away a lot of what is done is done because it is observed to work by some measure.
Thanks Bill, That was helpfull, Couldn’t get the payment ap to work. Will try another browser later, But did get the figures & abstract.
My first intro to the idea of gradients between the blood and dialysate came in discussion with a Hosp Nephrologist. He used it to explain why more dialysate flow was better. After a bit of thought I concluded that it didn’t work because the membrane doesn’t inhibit the movement of water molecules, which are quite small, back and forth across the membrane.
There is a pressure differential that the dialyzer uses for UF but I don’t think it has anything to do with toxin clearance.
Anyway I think this article will help me understand.
Thank you. That piece on membrane design and manufacture was answered several questions.
An aside: Would you mind sharing your nocturnal dialysis parameters? Blood flow, dialysate flow, cycle time and typical pre & post BUN? I know it’s forward but dry wt helps to understand those other numbers,
I would not put my dialysis dose out there as an example, from what I have read I am given a lot more flexibility then most people. My example is finding a way to make this work and live a life I was meant to live through self care, being teachable (finding good coaches) and a willingness to learn. The particulars of my treatment are not an example, they work for me that is all anyone can say.
So that said, what I say is I get as much dialysis as I can stand as often as I can stand it. This morning I came off at 87kg Preferred Qb = 250 Qd is not set directly when using the NxStage, 30L over 7 hours Qd = ~70 BUN = lol