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)*

**References**

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**.