Measurement of solute clearance in continuous peritoneal dialysis: Kt/V and creatinine clearance

INTRODUCTION — Dialysis adequacy is an important issue for patients treated with maintenance hemodialysis or peritoneal dialysis. Dialysis attempts to remove all solutes that native kidneys normally remove. However, the assessment of dialysis adequacy by measurement of all solutes is not feasible. Thus, the removal of a few substances, such as urea and creatinine, by dialysis is measured as a surrogate for removal of all solutes.

The minimum effective dialysis dose is typically determined by measuring small solute (eg, urea and creatinine) clearance. Common methods used to measure this include urea clearance normalized to total body water (Kt/Vurea) and the peritoneal creatinine clearance (CCr) normalized to body surface area (BSA). Both Kt/V and CCr utilize clearance of a surrogate solute (ie, urea or creatinine, respectively) to estimate overall small solute clearance.

The weekly Kt/Vurea is now the preferred method for measuring small solute clearance [1-3]. However, the CCr may still be used in some areas. Although the Kt/V and peritoneal CCr usually correlate, they are occasionally discrepant [4-6].

This topic reviews methods of measuring solute clearance in peritoneal dialysis, including the Kt/V and the CCr.

An overview of prescribing an adequate amount of peritoneal dialysis and the mechanism of solute clearance by peritoneal dialysis are discussed elsewhere. (See "Prescribing peritoneal dialysis" and "Mechanisms of solute clearance and ultrafiltration in peritoneal dialysis".)

DEFINITIONS AND CALCULATION — The daily Kt/Vurea is calculated from the daily urea clearance (Kt), which is the sum of the product of all drain volumes (peritoneal and residual kidney) and the ratio of the urea concentration in the pooled, drained dialysate or urine to that in the plasma (D/P urea). Kt is normalized to total body water, which is the volume of distribution of urea (V). V may be estimated from published formulas such as the Watson formula [7]. In general, V is approximately equal to 60 percent of ideal body weight for men and 55 percent ideal body weight for women. In practice, most centers use a kinetic modeling program to determine V and Kt/V, although the Kt/V may be manually calculated from the serum urea, pooled dialysate urea, total drain volume, and estimated V. (See "Prescribing peritoneal dialysis", section on 'Calculation'.)

Calculation of the peritoneal CCr is similar to that for the Kt/Vurea. The mean daily drain volume (peritoneal and residual kidney) is multiplied by the ratio of total dialysate and urine creatinine to the serum creatinine (D/P creatinine). Clearance is normalized to 1.73 m² body surface area (BSA), estimated by the Dubois formula [8].

Both calculations measure total clearance of either urea or creatinine. In order to determine the residual renal component of the total clearance, a 24-hour urine collection is performed. When the CCr is calculated, we estimated the glomerular filtration rate (GFR) from the average of the urea and CCr. This is because CCr alone typically overestimates the GFR since creatinine is not only filtered but also secreted into the tubules. (See "Calculation of the creatinine clearance".)

Both the Kt/V and CCr are expressed as weekly values; thus, the total daily values are multiplied by 7.

CORRELATION BETWEEN Kt/VUREA AND CREATININE CLEARANCE — In most peritoneal dialysis patients, Kt/Vurea and CCr correlate fairly well. In some patients, there is discrepancy between Kt/Vurea and CCr. The correlation between Kt/Vurea and CCr is affected by three factors:

●The relative contribution of residual kidney function to total solute clearance

●The rate of peritoneal transport, which varies between patients

●Extremes of weight in either direction (ie, patients with malnutrition or obesity)

The relation between total urea clearance and CCr reflects the sum of the renal and dialysis clearances.

●The ratio of CCr to Kt/V tends to be higher in patients who have significant residual kidney function. Significant residual kidney function is common when peritoneal dialysis is first initiated. A commonly used historical reference value is the ratio of CCr/Kt/V of 60/2.0 = 30.

●The patient's ratio of CCr to Kt/V falls as the patient becomes anuric.

These differences are illustrated in the figure (figure 1), which shows total solute clearance represented by both Kt/V and CCr over time [9]. In this study, CCr from residual kidney function fell from 3.9 to 1.4 mL/min by two years. At the latter value (1.4 mL/min equals 14 L/week), residual kidney function continued to account for 23 percent of total CCr.

The effects of residual kidney function, peritoneal transport, and extremes of weight are discussed below.

Residual kidney function and solute clearance — As in any form of kidney replacement therapy, total solute removal consists of the removal of the solute in question by both dialysis and residual renal clearance. In peritoneal dialysis, it is standard to use total solute removal as a measure of dialysis adequacy. This is different from the standard practice in hemodialysis, in which only the dialysis clearance of a solute is used to measure dialysis adequacy.

Residual kidney function has historically been included in total clearance for peritoneal dialysis for the following reasons:

●Studies that defined peritoneal dialysis adequacy used total solute clearance. Most clinicians used the same practice in order for studies to inform clinical practice.

●It was considered relatively easy for peritoneal dialysis patients to provide 24-hour urine collections to the dialysis center since they were already providing 24-hour peritoneal dialysis effluent drain volumes.

●Residual kidney function is often preserved in peritoneal dialysis patients but not in hemodialysis patients. As a result, residual kidney function contributes a greater proportion to total clearance and typically for longer periods of time.

The contribution of renal clearance should not be ignored when calculating total solute clearance, since increasing the amount of peritoneal dialysis to meet minimum target values may unnecessarily increase the burden of dialysis for the patient. This important issue is discussed elsewhere. (See "Prescribing peritoneal dialysis", section on 'Addition of residual kidney function'.)

Like all solutes, creatinine and urea are cleared at specific rates by both peritoneal dialysis and by the kidney (ie, residual kidney function). The differences in individual clearances underlie the occasional discrepancy when Kt/Vurea and CCr are used to determine dialysis adequacy.

The residual CCr is an overestimate and the urea clearance is an underestimate of the glomerular filtration rate (GFR). This is because renal clearance is the sum total of glomerular filtration and net tubular secretion or reabsorption. Both creatinine and urea are freely filtered. However, whereas creatinine is also secreted by the tubule, urea is reabsorbed. As a result, tubular function increases the total CCr and decreases the total urea clearance.

Peritoneal clearance of solute — Peritoneal clearance of solute is primarily by diffusion, although there is also a small contribution from convection due to ultrafiltration. The rate of clearance of any solute by diffusion is inversely related to the size of the solute. Since urea is a smaller molecule than creatinine, the peritoneal clearance of urea tends to be greater than that of creatinine.

Peritoneal membrane transport characteristics may affect the relative clearances of various solutes.

As mentioned above, the diffusive clearance for urea is relatively greater than that for creatinine. Thus, for shorter dwells, the urea clearance per dwell tends to exceed that for creatinine.

This is most pronounced in patients who are low transporters. In such patients, the ratio of CCr to Kt/V is typically lower than in high (rapid) transporters (see "Rapid transporters on maintenance peritoneal dialysis"). During the typical dwells associated with continuous ambulatory peritoneal dialysis (CAPD), the dialysate to plasma ratio (D/P) for urea tends to be near unity (equilibration between blood and dialysate) in all patients, whereas the D/P for creatinine may approach unity only in high transporters (figure 2).

The net effect is that the weekly Kt/V in peritoneal dialysis patients is relatively independent of transporter type, while the weekly CCr falls progressively from high to low transporters (figure 3) [10,11].

These relationships were illustrated in a study of 309 anuric CAPD patients [12]. The Kt/V and the CCr were correlated to each other and with the peritoneal solute transport characteristics [12]. Weekly Kt/Vurea values were similar in the low, low-average, high-average, and high transport groups: 1.74, 1.66, 1.68, and 1.73, respectively. By comparison, the ratios of (nonnormalized) peritoneal creatinine to peritoneal urea clearance in the low, low-average, high-average, and high transport groups were 0.65, 0.76, 0.84, and 0.91, respectively.

It is important to be aware of individual patients' peritoneal membrane transport characteristics when writing the peritoneal dialysis prescription and interpreting solute clearance results. (See "Inadequate solute clearance in peritoneal dialysis", section on 'Reduced peritoneal dialysis solute clearance (Kt/Vurea)'.)

Weight and normalization — Patient weight has a greater effect on Kt/V than on CCr. A decrease or increase in weight causes the Kt/V to increase or decrease, respectively. As a result of this relationship, the Kt/V is often at or above target values in patients with malnutrition and low in patients with obesity if the actual (rather than ideal) body weight is used. This is the reason that, for calculating solute clearance, use of the ideal body weight is preferred to the actual weight.

The difference in the effect of weight on Kt/Vurea and CCr is related to different methods used to normalize total clearance of urea and creatinine. As noted above, the urea clearance (Kt) and the CCr are normalized by V (volume of distribution) and 1.73 m² body surface area (BSA), respectively. The effect of the patient's weight on this normalization is greater for Kt/V than it is for CCr. This becomes most pronounced in patients with malnutrition or obesity. If V is derived from the Watson formula [7] and BSA from the Dubois formula [8], the calculations are as follows:

In the BSA calculation, the numbers 0.425 and 0.725 represent the exponential power of the body weight and height, respectively.

It can be appreciated from these equations that weight has a relatively greater impact on the value for V than for BSA. This is illustrated in the figure, which compares Kt/V and CCr values for anuric males and females on 8 liters of therapy per day (figure 4). The Kt/V is higher in females compared with males, while there is little difference in the weekly CCr.

The effect of normalization also varies with the state of nutrition. In malnourished patients, the decrease in weight causes a decrease in V, while Kt is unchanged; thus, the Kt/V will tend to increase. This is one reason why one often finds a Kt/V value that is near or above target in malnourished patients. If, in this setting, the ideal body weight was used in the calculation, the Kt/V would not be as close to target as when actual weights are used (table 1).

The situation is reversed in patients with obesity. In patients with obesity who are eating well, feeling well, and have normal serum albumin concentrations, using the actual weight in the calculation often results in what appears to be low Kt/V and CCr values; substituting the ideal weight results in clearance values more predictive of their nutritional status (table 1).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dialysis".)

SUMMARY AND RECOMMENDATIONS

●General principles – The minimum effective dialysis dose is determined by measuring small solute clearance. Common methods used to measure small solute clearance include urea clearance normalized to total body water (Kt/Vurea) and the peritoneal creatinine clearance (CCr) normalized to body surface area (BSA). Although the Kt/V and peritoneal CCr usually correlate, they are occasionally discrepant. (See 'Introduction' above and 'Definitions and calculation' above.)

●Agreement between Kt/Vurea and CCr – In most patients on peritoneal dialysis, Kt/Vurea and CCr correlate fairly well. In some patients, there is a discrepancy between Kt/Vurea and CCr. The correlation between Kt/Vurea and CCr is affected by three factors:

•Residual kidney function – Both dialysis and residual kidney function contribute in varying amounts and differently to both CCr and Kt/V. The ratio of CCr to Kt/V is higher in patients with significant residual kidney function and falls as the patient becomes anuric. (See 'Residual kidney function and solute clearance' above.)

•Peritoneal membrane characteristics – Peritoneal membrane transport characteristics may affect the relationship between CCr and Kt/V. For shorter dwells, especially in low transporters, the urea clearance per dwell exceeds that for creatinine. Whereas the weekly Kt/V is independent of transporter type, the weekly CCr falls progressively from high to low transporters. It is important to be aware of peritoneal membrane transport characteristics of individual patients when interpreting solute clearance results. (See 'Peritoneal clearance of solute' above.)

•Patient weight – Patient weight has a greater effect on Kt/V than on CCr. A decrease or increase in weight causes the Kt/V to increase or decrease, respectively. As a result of this relationship, the Kt/V is often at or above target values in patients with malnutrition and low in patients with obesity. Using the ideal rather than actual weight may provide more accurate results. (See 'Weight and normalization' above.)