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Case 7: Dialysis Related Amyloidosis

“Ouch my wrist hurts.” Your nephrologist may be able to help.

You see an 82 year old African American male with history of ESRD secondary to polycystic kidney disease, who has been on hemodialysis for the last 12 years via a left brachiocephalic AVF. He is otherwise in surprisingly good health and very functional. While you are rounding in the dialysis unit, he tells you that he has been having left shoulder and left wrist pain and was told that he may have carpal tunnel syndrome in his left wrist. You are concerned that he may be developing dialysis related amyloidosis.
This is correct!

Dialysis related amyloidosis is caused by tissue accumulation of β2 microglobulin (in synovia, bones, and rarely visceral organs) in patients with renal failure who typically have a long dialysis vintage (more than 8-10 years). Carpal tunnel syndrome is one of its manifestations. With the use of modern high flux dialyzers, the prevalence of dialysis related amyloidosis has declined considerably, however it can still be seen as the endogenous production of β2 microglobulin far exceeds its removal even with modern dialysis. There is also a significant rebound in plasma levels of β2 microglobulin post dialysis. Therefore increasing dialysis treatment time such as with daily nocturnal dialysis as well as using a high flux dialyzer to improve convective clearance of β2 microglobulin helps this condition (Choice 3). Changing to a high efficiency dialyzer with a high KoA (Choice 2) would not help, as β2 microglobulin has a low diffusive clearance. Ligating AVF (Choice 4) is sometimes used as treatment for steal syndrome which this patient does not have. Increasing dialysate flow (Choice 1) will not help β2 microglobulin clearance.

This is incorrect. Try again.

 

Access Recirculation Debrief

CLINICAL PEARLS:

  • The higher the blood pump flow rate, the higher the chances of access recirculation.
  • 25% of patients with a drop in Kt/V tend to have access recirculation issues.

Case 6: Access Recirculation

Round and round we go! A case of access recirculation.

You see a 72 year Asian male with history of diabetes, hypertension, and ESRD on HD via a left radio-cephalic AVF while rounding in your dialysis unit. His dialysis Rx is a dialyzer D flux 250, Qb of 400ml/min, Qd- 600 ml/min for a duration of 4 hours. His Kt/V on three times a week hemodialysis has ranged between 1.6-1.8. Your dialysis unit nurse reports that most recently checked Kt/V has dropped down to 1.0 confirmed on 2 different checks. He has been compliant with his dialysis treatments and has completed the full 4 hours as prescribed. Patient feels fine. His physical exam is unremarkable with blood pressures ranging between 130-150 systolic and trace edema.
This is incorrect. Try again.
This is correct!

A drop in Kt/V can be due to multiple factors. Inaccurate post dialysis BUN measurement, shortened dialysis treatment (affecting T), low access blood flow or access recirculation (the latter two affecting K), are some of the common ones. Poor access flow is the most common cause of a drop in Kt/V (40% of cases). In our patient, access flow seems maintained at 400ml/min and his treatment time has not been reduced. Access recirculation is seen in about 25% of cases of reduced Kt/V. If this is suspected, a fistulogram (Choice 3) should be done to evaluate for access stenosis. Increasing treatment time (Choice 1) and dialysate flow (Choice 2) will likely help improve Kt/V to varying degrees, however access recirculation should be ruled out first if suspected. Since the low Kt/V has already been confirmed on 2 separate occasions, monitoring and repeating in one month (Choice 4) will simply delay intervention.

Let's look at access recirculation now.

Case 5: Dialysis Disequilibrium Syndrome

 Lets slow things down! A patient at risk of dialysis disequilibrium syndrome

58 year old Caucasian female with history of systemic lupus erythematosus, hypertension, stroke, alcoholic cirrhosis and chronic kidney stage 5 is being initiated on hemodialysis for worsening uremic symptoms (worsening nausea, vomiting and headaches over the past couple of months) via a left arm brachiocephalic AV fistula. Her predialysis laboratory data is as follows: BUN- 140mg/dl; creatinine- 8.0; Serum K- 5.2meq/l; serum bicarbonate-12meq/l. Serum Na-135meq/l. Choose the best dialysis Rx for this patient for his first hemodialysis treatment.
This is incorrect. Try again.
This is incorrect. Try again.
This is incorrect. Try again.
You have selected the best dialysis Rx for this patient
Qb = 200ml/min
Qd = 300ml/min
KoA = 600
Time = 2hours or 120min

Patient is at a risk of dialysis disequilibrium syndrome given this is her first dialysis treatment and she has a high BUN, chronic uremic symptoms, severe metabolic acidosis and a history of stroke and alcohol liver disease. The rapidity and magnitude of osmotic shifts associated with dialysis can lead to cerebral swelling and neurologic compromise. The goal here is to avoid abruptly high urea clearance with the first few hemodialysis treatments. Using a low blood flow, low dialysate flow, a small dialyzer with a low KoA, and short treatment duration will avoid high urea clearances. Qb and treatment time can be increased in a step wise manner over the next 3-4 daily treatments.

This is incorrect. Try again.

Case 4: Dialyzer Size

Is a bigger dialyzer, a better dialyzer?

You are the Medical director of a dialysis unit. A dialyzer manufacturing company is trying to sell you high efficiency dialyzers with a KoA of 2000ml/min. You are currently using dialyzers with a KoA of 1000ml/min. Having a great understanding of urea kinetics, you know that buying the high KoA dialyzer (albeit expensive) would be a great investment for your dialysis unit and would double the average Kt/V of your patients.
This is incorrect. Try again.
This is correct!

Kt/V rises with increase in KoA. However, KoA >1000 ml/min are of marginal benefit especially with standard (Qb) blood flows of 400-500ml/min. Qb limits the benefit of dialyzers with excessively high KoA. Qb >500ml/min are difficult to achieve due to access flow limitations and needle resistance. Also higher blood flows may be un-physiologic and increase risk of access recirculation. Dialysis urea clearance can never exceed Qb. If all of the blood is cleared, clearance is the Qb.

Case 3: Access Flow

Poor access flow is a big problem!

55 year old Caucasian male with history of diabetes, hypertension, coronary artery disease, and end stage renal disease secondary to diabetic nephropathy is on hemodialysis three times a week via a dialysis catheter due to previously failed fistulas. His catheter is malfunctioning and providing a Qb of 200ml/min for the last 2 treatments. You are his rounding nephrologist. You schedule him for a catheter exchange through interventional radiology but patient refuses to go any sooner than the following week as he is “tired of all these procedures.” His current dialysis prescription is as follows: Dialyzer D-flux 180 (KoA 1000ml/min), Qd-500ml/min, and a current Qb of 200ml/min with an EDW of 70kg. The renal fellow in the unit is worried about low urea clearance given poor access blood flow and decides that until the catheter is exchanged, he will change him to a larger dialyzer (D-250) with a KoA of 1600ml/min.
Incorrect. Try again.
Correct! The increase is only 3.6%.

Remember:

  • Dialyzer urea clearance (K) is determined by the lowest of the 3 parameters: Qb, KoA and Qd.
  • At low blood flow (Qb <200ml/min), K is linear to the Qb and is flow-limited so a high KoA or a high Qd does not matter.
  • A bigger dialyzer or higher dialysate flow are helpful in improving K at higher Qb (>400ml/min).
  • Review the graph below:

    Case 2: Constrained T

    Not a minute more than 3.5 hours!

    67 year old African American male with history of diabetes, hypertension and advanced chronic kidney disease has been initiated on dialysis in the hospital. He has received 6 treatments so far and has done well without significant issues with hypotension or cramping. He will now be transitioning to your outpatient dialysis unit. The patient weighs 70kg and has a well functioning AV fistula. You have done your smart calculations (Case 1) and know that he needs to be dialyzed for 3.9 hours for a goal sp Kt/V of 1.4. However, the patient is adamant that he will not stay for more than 3.5 hours because that’s what his friend does. How would you calculate the initial dialysis prescription now?

    STEP 1: Start with T since it is a non-negotiable for the patient
    T = 3.5 hours or 210 min

    STEP 2: Calculate your V
    V = 60% of 70kg = 42L or 42,000 ml

    STEP 3: Remember your goal spKt/V
    spKt/V = 1.4

    STEP 4: Plug in the known variables for Kt/V
    [K x 210min] / 42,000ml = 1.4
    K = [42,000ml x 1.4] / 210min = 280ml/min

    STEP 5: Assume that you would like to prescribe a Qb of 400ml/min and a Qd of 500ml/min

    STEP 6: Refer to any normogram or calculators easily available online to decide what your dialyzer’s KoA should be in order to achieve a spKt/V of 1.4

    STEP 7: Check the normogram to make sure the in vitro KoA of the dialyzer should at least be 766ml/min.

    CLINICAL PEARLS:

    • As mentioned in the earlier case, in vitro KoA values (provided by manufacturer packet insert) are about 20% higher than in vivo values. Therefore when using in vitro K and KoA values to calculate dialysis prescription, it is important to confirm delivered spKt/V and adjust treatment as needed to meet goal.

    Case 1: Dialysis Prescription

    Calculate an initial dialysis prescription (Rx), based on goal spKt/V

    67 year old African American male with history of diabetes, hypertension, and advanced chronic kidney disease has been initiated on dialysis in the hospital. He has received 6 treatments so far and has done well without significant issues with hypotension or cramping. He will now be transitioning to your outpatient dialysis unit. The patient weighs 70kg and has a well functioning AV fistula. How would you calculate the initial dialysis prescription based on goal spKt/V?
    STEP 1: Based on clinical practice guidelines, figure out your goal prescribed spKt/V.
    This is NOT the correct goal spKt/V. Try another choice.
    Correct! This should be your goal prescribed spKt/V.
    STEP 2: Calculate your V
    This is NOT the correct calculation for V. Try another choice.
    Correct! This is the best calculation for V. Move on to STEP 3.
    STEP 3: Review your known variables for Kt/V:
    Kt/42,000 = 1.4
    STEP 4: Calculate Kt = 1.4 x 42,000 = 58,800ml
    STEP 5: Assume K is known and is 250ml/min (based on choice of dialyzer (KoA)) and Qb is 400ml/min to calculate t t(treatment duration) = 58,800ml / 250 ml/min = 235 minutes or 3.9 hours
    Therefore, this patient will need to be dialyzed for 4 hours to achieve goal single pool Kt/V of 1.4.

    CLINICAL PEARLS:
    • The delivered Kt/V often tends to be lower than the prescribed Kt/V which is why we target a spKt/V of 1.4 to achieve a minimum goal spKt/v of 1.2.
    • When calculating treatment time using manufacturer’s provided in vitro K and KoA values (as we did in this case), it is important to remember that these values tend to be about 20% higher than actual in vivo values. This is one of the reasons why delivered Kt/V may be lower than prescribed Kt/V.
    • In smaller patients, determining treatment time using goal spKt/V of 1.4 may lead you to under dose dialysis since a low ‘V’, mathematically increases the ratio spKt/V, gives a false sense of reassurance and may prompt you to decrease dialysis time. Smaller patients have higher post dialysis urea rebound, so their eKt/V may be significantly lower than spKt/V. In addition, short dialysis treatments may not be adequate to remove middle molecules and other uremic solutes as well as may result in higher ultrafiltration rates and intra-dialytic hypotension. Therefore before reducing dialysis time, other variables such as BP, phosphorus and potassium control, ultrafiltration goals etc. need to be considered. US KDOQI 2006 recommends a minimum session length of 3 hours irrespective of Kt/V.

    Playground Debrief

    K INCREASES WITH INCREASE IN Qb

    CLINICAL PEARLS:

    • Dialyzer blood flow rate is a big determinant of K and ultimately Kt/V. Ideally Qb should be set between 400ml/min to 500ml/min as tolerated. Therefore when aiming for a goal Kt/V, ensure the delivered Qb is adequate.
    • Dialysis catheters tend to allow lower Qb than AVF and AVG.
    • K can NEVER exceed the Qb. If all the blood entering the dialyzer is cleared of urea in a minute, K is Qb.

    K INCREASES WITH INCREASE IN Qd, but…

    CLINICAL PEARL:

    • Higher Qd increases dialyzer urea clearance (K) but as Qb approaches Qd, K starts to plateau. Therefore, Qd should typically be 1.5-2 times the Qb to maximize diffusive clearance.
    • At a Qb of 400-500 ml/min, a Qd of UP TO 800ml/min makes sense.
    • An increase of Qd from 500ml/min to 800ml/min increases K only by 8-12% when the Qb and KoA are not limiting i.e. a high efficiency dialyzer is used and the Qb >400ml/min (as there is more effective surface area for diffusion).
    • Increasing Qd >800ml/min usually doesn’t add to the K or KT/V as the Qb becomes limiting (shown in graph). Dialystate is expensive, why waste it?
    • Qd of 500-600ml/min is often adequate to achieve target urea clearance with a conventional Qb of 400ml/min
    • An additional lesson is that with daily hemodialysis methodologies that have reduced Qds of 150 mL/min (for example, NxStage) or continuous veno-venous hemodialysis (CVVHD) techniques with Qds of 50–100 mL/min, there is no reason to employ higher Qbs or to use large dialyzers, as K will be limited by Qd.

    K INCREASES WITH INCREASE IN KoA

    CLINICAL PEARLS:

    • K increases with increasing dialyzer efficiency (KoA)
    • However, the increase in K is most pronounced at adequate pump blood flow.
    • At a Qb of <200ml/min, despite using a high efficiency dialyzer, K is low (the curves start to converge at a K of <170ml/min as shown in the graph).
    • At a Qb of >200ml/min, the curves start to separate and K rises in proportion to the rise in KoA. Rise in K at this point is therefore ‘membrane limited’. Hence, if you want the most benefit out of your high efficiency dialyzer, you need adequate blood flow preferably >400ml/min

    Feel free to go back to the playground case to understand how increases in Qb, Qd, and KoA impact K and Kt/V