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Casino FG, Lopez T

The equivalent renal clearance: a new parameter to assess dialysis dose

Nephrol Dial Transplant (Aug) 11:1574-1581 1996

This article is a technical description of a method for quantifying dialysis that allows direct addition of residual native kidney clearance to the dialyzer "equivalent renal clearance," both measured in ml/min. The new index of dialysis, which is based on the concept of equivalency of time-averaged BUN values (TAC), has potential value as a universal measure of both dialyzer and native kidney function that is more intuitive than KT/V and may allow direct comparisons among different treatment modalities and schedules. The report is accompanied by arguments in favor of its use and a set of patient data representing an example of its use.

Inclusion of residual clearance (Kr) in the KT/V formula for hemodialysis seems reasonable but has been largely been ignored during the campaign in recent years to set minimum standards for adequate dialysis. The importance of Kr is acknowledged by its inclusion in the KT/V formula for peritoneal dialysis but it is routinely omitted in the hemodialysis formula not because of insignificance but because the dialysis community has never agreed on a standard method for its inclusion.

The relatively simple method for incorporating Kr in KT/V by multiplying residual clearance by the number of minutes in the week to obtain a weekly "KrT" and then dividing by three times V for patients dialyzed three times a week before adding it to dialyzer KdT has been criticized by Gotch who points out that this method underestimates the effect of Kr (1). Since Kr is a continuous clearance, it is intrinsically more efficient than an intermittent dialyzer clearance (Kd) which exerts its effect only during the relatively short duration of treatment. The average solute removal per unit of Kr is higher than solute removal per unit of Kd. If the goal is to control the predialysis BUN instead of the time-averaged BUN (TAC), the discrepancy between the simple averaging technique described above and the real contribution of Kr to total clearance is even greater. Gotch developed approximation formulas for including Kr in KT/V using an approach that controls the midweek predialysis BUN (1). Other formulas assess the effect of Kr on KT/V when TAC is controlled instead (2).

Casino and Lopez have taken the latter approach, basing their method on the assumption that no matter how much the BUN fluctuates, patients with the same TAC and PCRn have equivalent risks. They reversed the usual method of modifying Kr to allow its inclusion in the KT/V term and converted the sum of both clearances to a term they call the "equivalent renal clearance" (EKR). Since removal of urea is equal to urea generation in the steady state, the clearance for continuously dialyzed patients can be approximated as G/TAC. For intermittently (hemo) dialyzed patients, since G and TAC can be calculated using formal modeling of urea kinetics, an equivalent clearance for hemodialyzed patients can also be calculated as G/TAC. For these patients EKR is a total clearance that includes the effect of residual function; the dialyzer component can be extracted from it simply by subtracting Kr. The dialyzer component of EKR is is always lower than the time-averaged dialyzer clearance because the new method of quantitating dialysis ignores the inefficiency of intermittent dialysis that necessitates a higher time-average clearance to achieve the same TAC. EKR in hemodialyzed patients is the continuous clearance necessary to maintain the equivalent TAC at the same protein catabolic rate (PCRn).

When EKR is normalized to the patient's volume of urea distribution (EKRc), the result is a universally applicable measure of dialysis that can be compared among patients of all sizes. When normalized to a 40 liter patient, the minimum consensus-derived KT/V of 1.2 per dialysis for thrice weekly dialysis translates to an EKRc of 13.0 ml/min according to the authors' method. This could be any combination of residual and dialyzer clearances. For example, if residual clearance is 3.0 ml/min, then dialyzer clearance need only be 10 ml/min to meet the minimum standard. Standards for EKRc do not change with dialysis frequency so the EKRc of intermittent hemodialysis can be directly compared to standardized clearances obtained with continuous replacement therapy like CAPD, with the EKR of patients dialyzed daily, or with the clearance of continuously functioning native kidneys. This universal applicability to patients before starting dialysis and after starting any mode of dialysis or transplantation is an attractive feature. It has the potential for removing the current celebrated difference between standards of adequacy (KT/V) for hemodialysis versus peritoneal dialysis. It also allows the application of a familiar expression, used to quantitate native kidney function, to the artificial kidney. Dialysis providers using this EKR might have less difficulty communicating among themselves and with patients and others not familiar with the principles of solute kinetics.

Comment: The method described for calculating both the target and the delivered dose of dialysis from the constant relationship between TAC and PCRn independent of the dialysis schedule and day-of-the week has been in use for several years (2). EKR is a simple concept but is not simple to calculate. The method requires measurement of G and TAC, variables that are not available if simplified methods are used for dialysis quantification. In addition, when the minimum standard dose of dialysis is not achieved, EKR does not offer a method to correct the problem. For hemodialyzed patients, KT/V must be calculated to predict the necessary adjustment in K or T.

The Keshaviah/Teschan formula for adjusting Kt/V for Kr should underestimate the effect of Kr, not overestimate it as stated in this article. Gotch's formula gives an apparent overestimation of Kr because it seeks to maintain predialysis BUN rather than TAC. The older methods for accomodating Kr were designed to adjust intermittently measured Kt/V, not the derived continuous equivalent, EKR. Therefore the statement that the previously described methods cause an overestimation of kinetic KT is misleading because the correction has been applied to the wrong parameter. EKR is always lower than its intermittent dialysis counterpart even in patients with zero Kr.

The stated miminum standard of 1.0/dialysis for KT/V should be updated to 1.2/dialysis which corresponds to a minimum EKRc of 13 ml/min (using the authors' formula) for patients dialyzed 3x/week. The authors' computer algorithm for calculating EKR and TAC from Kt/V calculates whole blood water clearance which is 7% lower than the usual expression of clearance for PD or the native kidney. This brings the minimum standard for EKR up to 14 ml/min (and requires adjustments in the authors' graphs). However, the single compartment model is well known to overestimate G, so EKR will be falsely high (since EKR is G/TAC) in all hemodialyzed patients. In addition, for a 40 liter peritoneally dialyzed patient, the recently updated minimum standard for Kt/V of 2.2/week translates to an EKRc of 8.7 ml/min (2.2 x 40000/10080). If the minimum for hemodialysis is adjusted downward to 12 ml/min to account for the two-compartment phenomenon, the standard for PD remains substantially lower than HD. The difference suggests that this method of quantifying dialysis may not be comparable among modalities of treatment. It suggests that another solute with a whole body mass-transfer coefficient lower than urea might be a more appropriate marker of effective clearance. (Thomas A. Depner, M.D., University of California at Davis)

1. Gotch FA: Kinetic modeling in hemodialysis. In: Clinical Dialysis, edited by Nissenson AR, Gentile DE, and Fine RN, Norwalk, CT:Appleton and Lange, pp. 126-129, 1990.

2. Depner TA: Prescribing Hemodialysis: A Guide to Urea Modeling, Boston: Kluwer Academic Publishers, pp. 187-190, 1991.

The full text of this abstract is available from Oxford Press at this site.