Please review Chapter 3 at this time. Many concepts developed in Chapter 3 will be only briefly touched on here.

 I.  UREA AS A MARKER SOLUTE. Although uremic toxicity is due to both small- and large-molecular-weight solutes, small toxins appear to be of greater importance. For this reason (and there are practical, laboratory measurement issues as well), the amount of dialysis prescribed is based on removal of urea, which has a molecular weight of 60 Da. Urea is only slightly toxic per se, and so its plasma level is only reflecting concentrations of other, presumably more harmful, uremic toxins.

     A.  Urea removal versus serum level. Both removal and serum level should be monitored when checking dialysis adequacy. Monitoring of urea removal is more important. If removal is inadequate, then dialysis is inadequate, regardless of the serum level. On the other hand, a low serum urea level does not necessarily reflect adequate dialysis. Serum level depends not only on the rate of removal but also on the rate of urea generation. The generation rate is linked to the protein nitrogen appearance rate because most protein nitrogen is excreted as urea. A low serum urea level may be found in patients in whom removal is poor but in whom the generation rate is also low (e.g., due to poor protein intake).

     B.  Measures of urea removal. These are the urea reduction ratio (URR), the single-pool Kt/V (spKt/V), the equilibrated Kt/V (eKt/V), and the weekly standard Kt/V (stdKt/V) (see Chapter 3).

     C.  Dose of dialysis in terms of urea removal for thrice-weekly dialysis. In a secondary analysis of the randomized National Cooperative Dialysis Study, the rate of treatment failure increased dramatically in patients dialyzed three times per week when spKt/V was <0.8, compared with when values were >1.0. In large observational studies, similar results were found. For this reason, the KDOQI Adequacy Workgroups have recommended a minimum spKt/V for dialysis patients of 1.2, with a target value of at least 1.4. This translates to a stdKt/V urea value of 2.1 when stdKt/V is calculated using modeling or by a method that takes volume contraction into account. The European Best Practice Guidelines recommend a slightly higher minimum amount of dialysis, defined as a minimum eKt/V of 1.2. Values for eKt/V values tend to be about 0.15 units lower than spKt/V, the amount depending on the rate of dialysis. High-level evidence guideline recommendations depend on randomized studies, and in the field of dialysis adequacy, the only other larger randomized study that has been done is the HEMO study, where an spKt/V of 1.7 was compared with an spKt/V of 1.3 (the study doses were actually defined in terms of eKt/V). Patients assigned to the higher dose of dialysis did not live longer, were not hospitalized less frequently, and were not found to manifest nutritional or other benefits. Apart from these two studies, there is little high-quality evidence regarding dialysis dose and outcomes, and almost all recommendations and guidelines in this area are primarily opinion-based.

        1.  Effect of gender. In the randomized analysis of the HEMO trial, the women assigned to the higher dose of dialysis survived longer than the women assigned to the standard dose. Survival in the men assigned to the higher dialysis dose was slightly worse, so the overall effect of dose in the HEMO trial was negative, and it is not clear whether this dose–gender interaction was real or just a statistical fluke. If women need more dialysis, the reason is unclear. As detailed in Chapter 3, an alternative method of scaling dialysis dose might be to scale to body surface area (BSA) instead of by urea distribution volume (V). In healthy patients and in children, glomerular filtration rate (GFR) naturally scales to BSA, and an adult man and woman with similar values for BSA will have similar levels of GFR (Daugirdas, 2009). Because the ratio of V:BSA is about 12%–15% different in men than in women, under current dosing guidelines, if a man and a woman have the same level of V, they will get the same dose of dialysis; however, BSA in the woman will be 12%–15% higher, so theoretically one might argue that women need about 15% more dialysis than men. If one wishes to increase the dose of dialysis in terms of stdKt/V, the increase in spKt/V has to be increased by about twice as much. So this line of reasoning would suggest that the minimum spKt/V in women should be about 25%–30% higher than that in men. However, the optimum method of scaling dialysis dose is not known, and there are no firm data other than the HEMO study and a few observational studies to suggest that BSA should be used to scale dialysis dose instead of V.

        2.  Smaller patients. One can come up with four reasons why smaller patients should get relatively more dialysis when dose is measured as spKt/V:

            a.  Small patients (those with small values for V) would get a larger amount of dialysis if dose were scaled to BSA.

            b.  The KDOQI dose targets are in the form of spKt/V and not eKt/V; postdialysis urea rebound tends to be larger in smaller patients.

            c.  It is fairly easy to deliver a high Kt/V to small patients (and also women) in a short session length (e.g., 2.5 hours). Such short session lengths may not be sufficient to allow for removal of middle molecules, nor for adequate removal of excess fluid, and this may result in a chronically overhydrated patient.

            d.  Short session length treatments may give a seemingly adequate Kt/V level, but in patients who gain large amounts of fluid between treatments, short session lengths may require a relatively high ultrafiltration (UF) rate to remove this fluid and high UF rates are associated with a poor outcome.

        3.  Malnourished patients. When a patient’s weight is substantially below the weight of his or her peers, or when a patient has lost a large amount of weight, one opinion is to scale dialysis to the patient’s optimum “healthy” weight, and not the current reduced weight. The thinking is that the increased amount of dialysis will help return the patient to his or her healthier, premorbid condition.

        4.  Residual renal urea clearance (Kru). Whether patients with substantial residual kidney function can be managed with lower doses of dialysis is an unanswered question. In one large study, when patient urine volume was >100 mL per day, the amount of dialysis delivered had little impact on survival (Temorshuizen, 2004). Methods of adjusting dialysis dose for residual kidney function are entirely opinion-based. There are a variety of modeling-based adjustments that can be used. Readers can look to the European Best Practice recommendations (2002) and to the NKF-KDOQI 2006 adequacy guidelines for some suggested guidance.

     D.  Adequacy targets for schedules other than three times per week. There is no high-level evidence that can guide us in terms of dose titration when dialysis is given other than three times per week. One approach is to maintain a minimum stdKt/V (calculated using modeling or the FHN equation) of 2.1 across all dialysis schedules (Table 11.1). The value of 2.1 was chosen because it corresponds to a three-times-per-week schedule with an spKt/V of 1.2 (NKF-KDOQI, 2006).

        1.  Four to six sessions per week. In one randomized trial that showed a benefit of more frequent dialysis, the FHN Daily Trial, the average delivered stdKt/V averaged 3.7, considerably higher than the 2.1 minimum dose suggested by NKF-KDOQI. The average number of treatments delivered per week was 5, and the average delivered session length was 154 minutes (FHN Trial Group, 2010).

        2.  Twice-a-week dialysis. In the developing world, many patients are dialyzed only twice a week for economic reasons, and in the United States, this was not unusual in the recent past. Kinetic modeling using an stdKt/V approach suggests that twice-a-week dialysis is not appropriate in patients without some modest degree of residual kidney function. On the other hand, there are preliminary data suggesting that starting incident patients out on twice-a-week dialysis may result in longer preservation of residual kidney function (Kalantar Zadeh, 2014). One observational study of twice-a-week dialysis done in the United States was unable to show an adverse association for this treatment strategy, and outcomes were actually a bit better than in patients dialyzed three times per week. Lack of harm may have been due to preferential selection of patients with some residual kidney function (Hanson, 1999), but there was no definitive evidence that this was the case.

Assumes session lengths of 3.5–4 hr; Kr = residual kidney clearance.

^a Target spKt/V values should be about 15% higher than the minimum values shown.

^b Frequent dialysis (five and six times per week) is more completely discussed in Chapter 16.

Adapted from NKF-KDOQI Clinical Practice Recommendations. Hemodialysis Adequacy. Update 2006. Am J Kidney Dis. 2006:48:(Suppl1):S2–S90.

     E.  Adequacy targets based on metrics other than urea removal.

        1.  Dialysis time. Urea removal is only one measure of dialysis adequacy. For solutes such as phosphorus and middle molecules, total weekly time is the major determinant of removal. Short weekly time also makes it difficult to remove excess salt and water from patients safely and effectively. The US KDOQI 2006 adequacy work group recommended a minimum session length of 3 hours for patients dialyzed three times per week with little residual renal function. The European Best Practices Group (2002) recommends a minimum 4-hour treatment time. The benefits of dialysis sessions longer than 3.5 hours are not clear, and seem to be greatest in Japan and intermediate in Europe; benefits are difficult to demonstrate in the United States (Tentori, 2012), perhaps because of the more intense dialysis given in that country. Also, dose-versus-outcomes data may be confounded by dose-targeting bias, a situation where survival is higher in patients who are meeting whatever dose target is being applied (Daugirdas, 2013). In the United States, the average dialysis time is about 3.5 hours and is increasing toward 4 hours, similar to the practice in the rest of the world. A large randomized study (TiMe trial) is currently underway in the United States to determine whether setting a minimum dialysis time of 4.25 hours for all new (incident) patients, regardless of body size, will result in meaningful outcome benefits. A substantial number of patients in the United States dialyze in-center overnight for about 6–9 hours per treatment. This strategy is described more completely in Chapter 16.

                 Another argument against Kt/V is that a focus on urea removal tends to drive high-efficiency dialysis, with use of large dialyzers and rapid blood flows; the high efficiency of such treatments may result in solute disequilibrium and intradialytic side effects. Also, high blood flow rates delivered using the requisite larger needle sizes may engender more blood turbulence and platelet activation, as well as access dysfunction. A related question is whether one should make “optimum” use of the dialysis time by prescribing the highest blood flow that is consistently achievable, and using the most efficient (high K₀A) dialyzer that one can afford. An alternative “slow and gentle” approach remains popular in Europe, according to which low blood flow rates and relatively small dialyzers are used. There are no randomized trials available to help choose between these two options. The best approach may be to set targets on the basis of both Kt/V (perhaps with higher minimum targets for women and smaller patients) and dialysis time. Changing the Kt/V target to a surface-area-adjusted value by itself solves the problem of short dialysis time given to smaller patients and women, as the amount of dialysis given to such patients based on surface area needs to be considerably larger, and this takes more time to deliver.

 II. WRITING THE INITIAL PRESCRIPTION

     A.  The dialysis dose: K ×t. A dialysis prescription involves two main components: K, the dialyzer clearance, and t, the dialysis session length. K, in turn, depends on the dialyzer size used and the blood flow rate. The dialysate flow rate also plays a small role as discussed in Chapter 3.

        1.  K usually ranges from 200 to 260 mL/min. For adult patients dialyzed using a blood flow rate of 400 mL/min, dialyzer clearance K will usually be about 230 ± 30 mL/min. One can use a urea kinetics calculator or a nomogram such as Figure 13.6, to get a reasonable estimate of dialyzer clearance from the blood flow rate and the efficiency of the dialyzer (K₀A) being used. If we assume that K will be 250 mL/min for a dialysis session length of 4 hours, K × t will be 250 × 240 = 60,000 mL or 60 L. This represents the total volume of blood cleared of urea during the dialysis session.

        2.  Targeting K ×t on the basis of patient size and desired Kt/V. Assume that we have a clearance of 250 mL/min and a session length of 4 hours. How large a patient could we dialyze and still meet KDOQI guidelines? Remember that the guidelines suggest using a prescribed (K × t)/V of 1.4 to ensure that the delivered dose stays above 1.2. Over the 4-hour session we are delivering 60 L of K × t, and if we want a prescribed Kt/V of 1.4, V must be 60/1.4 = 43 L, corresponding to a weight of about 78 kg. See Tables 11.2 and 11.3 for some additional examples.

Step 1: Estimate the patient’s V.

Step 2: Multiply V by the desired Kt/V to get the required K × t.

Step 3: Compute required K for a given t, or the required t for a given K.

Step 1. Estimate V. This is best done from anthropometric equations incorporating height, weight, age, and gender as devised by Watson (Appendix A). If the patient is African American, add 2 kg to the Watson value for V_ant. Alternatively, one can use the Hume–Weyers equations or the nomogram derived from them (Appendix A). Assume that, in this case, the estimated V is 40 L.

Step 2. Compute the required K ×t. If the desired Kt/V is 1.5 and the estimated V is 40 L, then the required K × t is 1.5 times V, or 1.5 × 40 = 60 L.

Step 3. Compute the required t or K. The required K × t can be achieved with a variety of different combinations of K (which depends on K₀A, Q_B, and Q_D) and t. A variety of urea modeling programs are available that will do a computer simulation of various scenarios and come up with many possible combinations of K and t. Internet-based calculators can be accessed via the Web References cited at the end of this chapter.

Given a desired session length t, how to compute required K.

One approach is to input a session length t and then ask: What kind of dialyzer, blood flow rate, and dialysate flow rate would I then need to achieve the required K × t? Again, simple algebra is sufficient. From the previous example:

Desired spKt/V = 1.5; V_ant = 40 L, K × t = 60 L

First, convert K × t to milliliters to get 60,000 mL. If the desired session length is 4 hr, or 240 min:

Desired t = 240 min

Required K = (K × t)/t = 60,000/240 = 250 mL/min

Now that we know the required K, how to choose K₀A, Q_B, and Q_D.

How does one now choose K₀A, Q_B, and Q_D? A simple way is to select the most rapid value of Q_B that can be reliably and consistently delivered. Assume in this patient that a blood pump speed of 400 mL/min will be possible. One can then go to the K–K₀A-Q_B nomogram (Figure 13.6) to find the approximate dialyzer K₀A value that will be required to achieve a K of 250 mL/min at a blood flow rate of 400 mL/min.

To find the required dialyzer K₀A, find 400 (which is Q_B) on the horizontal axis, then go up until you find 250 (desired K) on the vertical axis. At this point, you are on a K₀A line of about 900, so a dialyzer with a K₀A value of at least 900 mL/min will be needed. If such a high-efficiency dialyzer is not available, one will need to dialyze longer than 4 hours. Some 5%–10% improvement in K can be obtained by increasing dialysate flow rate to 800 mL/min. However, with some modern dialyzers that include spacer yarns to optimize dialysate flow around the fibers, increasing dialysate flow from 600 to 800 mL/min was shown to have very little impact (Ward, 2011).

A common situation occurs when the maximum blood flow rate that can be reliably delivered is known. Often, one has a choice between using a larger (more expensive) or a smaller (slightly cheaper) dialyzer. Let us assume that one is constrained to use a dialysate flow rate of 500 mL/min. What would the dialysis session length then need to be to achieve a target spKt/V of 1.5? Let us assume that we are prescribing for the same patient, with an estimated V of 40 L, which means that K × t again must be 60 L, or 60,000 mL. Assume that the projected blood flow rate is 400 mL/min. Of the two dialyzers available, we look up their K₀A (maximum clearance) values and find they are 1,400 mL/min for the larger one and 800 mL/min for the smaller one. So how long do we need to dialyze this patient with each of the two dialyzers?

Step 1: From Figure 13.6 (which we can use because Q_D = 500 mL/min), find the K corresponding to Q_B of 400 mL/min (x-axis value) for each of the two dialyzers. K will be the value on the vertical axis that corresponds to the intersection of the 1,400- and 800-K₀A lines with a perpendicular rising from the horizontal axis (Q_B) at a point representing 400 mL/min. We find that the K values are about 270 mL/min for the bigger (K₀A = 1,400) dialyzer and 220 mL/min for the smaller (K₀A = 800) dialyzer.

Step 2: We know that spKt/V = 1.5 and estimated V = 40 L. Our desired K × t is 60 L, or 60,000 mL. By algebra:

Our calculations thus suggest that we will need to dialyze for 50 minutes longer using the smaller (K₀A = 800) dialyzer to achieve the same spKt/V of 1.5.

     B.  How weight change during dialysis affects the dialysis prescription. In patients who have large weight gains, one will need a higher Kt/V to get a given URR than in patients with minimal weight gain (see Figure 3.14 in Chapter 3). For example, to get a URR of 70%, one needs to prescribe a Kt/V of only 1.3 if no fluid is removed, but one needs a Kt/V of 1.5 if the weight loss during dialysis (UF/W) is 6% of the body weight (see the 0.06 UF/W line in Figure 3.14).

 III. CHECKING THE DELIVERED DOSE OF DIALYSIS. The dialysis dose is usually monitored on a monthly basis, according to KDOQI guidelines, by drawing a predialysis and postdialysis serum urea nitrogen (SUN). Alternatively and/or additionally, in vivo dialyzer clearance can be monitored during each treatment by checking the dialyzer sodium clearance, or delivered dialysis dose can be followed by tracking the UV absorbance of the spent dialysate, as described in Chapter 3.
    The pre- and post-SUN values are used to compute the URR, which is then combined with information concerning UF/W and with some other adjustments to compute the delivered spKt/V. One caveat: When checking the URR, one must be sure to use a properly drawn postdialysis blood specimen. In the presence of access recirculation, the postdialysis blood may be low due to admixture with dialyzer outlet blood unless a slow-blood-flow or a stop-dialysate-flow technique is used. Two KDOQI-suggested techniques for blood drawing are described in Table 11.4, and the reasons behind them are explained in detail in Chapter 3.

     A.  Methods of computing spKt/V from the pre- and post-SUN

        1.  Nomogram method. One uses Figure 3.14 as described before. Assume that a URR of 0.70 or 70% is measured. Depending on whether 0%, 3%, or 6% of the body weight was removed during the dialysis treatment, the delivered spKt/V for that treatment will be 1.3, 1.4, or 1.5, respectively.

        2.  More exact methods. The optimal method recommended by the KDOQI guidelines to calculate Kt/V is to use a urea kinetic modeling program. The basic principles of how such programs work are described in Chapter 3. These programs are available commercially, and one, Solute Solver, is available on the Internet (http://www.ureakinetics.org). An alternative method that is approved by KDOQI is to use the following equation (Daugirdas, 1993):

                 spKt/V = –ln(R – 0.008 × t) + (4 – 3.5 × R) × UF/W

                 where R is (1 – URR), or simply post-SUN/pre-SUN, t is the session length in hours, –ln is the negative natural logarithm, UF is the weight loss in kilograms, and W is the postdialysis weight. See Chapter 3 for a more complete discussion of this formula.

Principles

The effect of access recirculation will reverse quickly. When blood flow is slowed to 100 mL/min, the inflow urea concentration will rise in about 10–20 s (depending on the amount of dead space in the arterial line, usually about 10 mL).

Method

 1. Set UF rate to 0.

 2. Slow the blood pump to 100 mL/min for 10–20 s.

Related posts:

Dialyzer Reuse Volume Status and Fluid Overload in Peritoneal Dialysis Diabetes Obstetrics and Gynecology in Dialysis Patients Adequacy of Peritoneal Dialysis and Chronic Peritoneal Dialysis Prescription Bone Disease

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