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

INTRODUCTION — 

This topic reviews methods of assessing small-solute removal in peritoneal dialysis, including the Kt/Vurea and the creatinine clearance.

An overview of prescribing an adequate amount of peritoneal dialysis, the management of inadequate solute clearance in peritoneal dialysis, and the mechanism of solute clearance by peritoneal dialysis are discussed elsewhere:

●(See "Prescribing peritoneal dialysis".)

●(See "Inadequate solute clearance in peritoneal dialysis".)

●(See "Mechanisms of solute clearance and ultrafiltration in peritoneal dialysis".)

GENERAL PRINCIPLES

Small solute removal — Although solutes of many different sizes likely contribute to uremic symptoms (see "Uremic toxins"), the delivered dose of peritoneal dialysis is typically determined by measuring the removal of small solutes. Metrics commonly used to assess small solute removal include the weekly urea clearance normalized to total body water (Kt/Vurea) and the weekly creatinine clearance (CCr) normalized to body surface area (BSA). Although Kt/Vurea is generally preferred [1-3], some clinicians use both metrics since the Kt/Vurea and the CCr are occasionally discrepant [4-6]. (See 'Differences between Kt/Vurea and creatinine clearance' below.)

Calculation of Kt/Vurea and creatinine clearance — Kt/Vurea and CCr have peritoneal dialysis and residual kidney components.

●Peritoneal Kt/Vurea – The daily peritoneal Kt/Vurea is calculated from the daily peritoneal urea clearance (Kt), which is the product of the daily drain volume and the ratio of the urea concentration in the pooled, drained dialysate 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 of peritoneal Kt/V urea'.)

●Peritoneal creatinine clearance – Similar to the calculation of the peritoneal urea clearance K, the peritoneal CCr is calculated by multiplying the drain volume by the ratio of dialysate creatinine to serum creatinine (D/P creatinine). Clearance is normalized to 1.73 m² BSA, estimated by the Dubois formula [8].

●Addition of residual kidney function – If the patient has significant residual kidney function, the solute removal provided by the kidney should be added to the solute removal provided by peritoneal dialysis to obtain an assessment of total solute removal. Significant kidney function is defined by National Kidney Foundation (NKF)-Kidney Disease Outcomes Quality Initiative (KDOQI) as a urine volume >100 mL/day [9].

The calculations for kidney Kt/Vurea and kidney CCr are the same as for peritoneal Kt/Vurea and peritoneal CCr, respectively, except daily peritoneal drain volume is replaced by 24-hour urine volume and drained dialysate measurements of urea and creatinine are replaced by urine measurements of the same factors. (See "Prescribing peritoneal dialysis", section on 'Addition of residual kidney function' and "Calculation of the creatinine clearance".)

Both the total Kt/V and total CCr are expressed as weekly values; thus, the residual kidney daily value is multiplied by seven, and the peritoneal daily value is multiplied by the number of days per week on dialysis (usually seven but sometimes less for patients on incremental peritoneal dialysis). (See "Prescribing peritoneal dialysis", section on 'Kt/Vurea'.)

WEIGHT AND NORMALIZATION — 

We do not use the actual weight to calculate Kt/Vurea and body surface area (BSA)-normalized creatinine clearance (CCr); rather, we use the ideal body weight or, for patients with obesity, the adjusted body weight (calculator 1) [1]. This practice accounts for the fact that adipose tissue is not part of the true volume of distribution of urea or creatinine and avoids over- or underestimating the delivered dialysis dose in malnourished and obese patients, respectively, as follows:

•In malnourished patients, the decrease in weight causes a decrease in V (and BSA) while Kt and CCr are unchanged; thus, Kt/V and BSA-normalized CCr tend to increase. This is one reason why one often finds Kt/V and CCr values that are near or above target in malnourished patients. If, in this setting, the ideal body weight was used in the calculations, the Kt/V and CCr would not be as close to target as when actual weights are used (table 1).

•In patients with obesity, the situation is reversed. Using the actual weight in the calculations often results in what appears to be low Kt/V and CCr values that are often incongruous with a patient’s good appetite, lack of uremic symptoms, and normal serum albumin concentration. In this setting, substituting the adjusted weight (or ideal weight) results in clearance values more predictive of their nutritional status (table 1).

DIFFERENCES BETWEEN Kt/VUREA AND CREATININE CLEARANCE — 

In most peritoneal dialysis patients, Kt/Vurea and creatinine clearance (CCr) correlate fairly well. However, in some patients, there is a discrepancy between Kt/Vurea and CCr. The correlation between Kt/Vurea and CCr is affected predominantly by three factors:

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

●The rate of peritoneal solute transfer, which varies between patients

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

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

Residual kidney function — Like all solutes, creatinine and urea are removed at specific rates by the kidney. As such, the degree of residual kidney function affects the relation between CCr and Kt/Vurea. In patients on dialysis who have significant residual kidney function, the contribution of kidney CCr to total CCr is greater than the contribution of kidney Kt/V to total Kt/V, and the ratio of total CCr to total Kt/V tends to be relatively high. However, as kidney function decreases over time, the contribution of kidney CCr to total CCr decreases more than the contribution of kidney Kt/V to total Kt/V, and the ratio of total CCr to total Kt/V falls. These differences are illustrated in the figure (figure 1), which shows total solute removal represented by both CCr and Kt/V over time [10].

The phenomena above occurs because the residual kidney CCr is an overestimate and the urea clearance is an underestimate of the glomerular filtration rate (GFR). This is because kidney 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 membrane characteristics — Peritoneal membrane transfer (transport) characteristics affect the relation between CCr and Kt/V. In patients with slow peritoneal solute transfer (“low [or slow] transporters”), the ratio of CCr to Kt/V is typically lower than in patients with fast solute transfer (“high [or rapid] transporters”) (see "Rapid transport (fast solute transfer) in peritoneal dialysis"). This is because the rate of transfer 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.

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 patients with fast solute transfer (“rapid 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) [11,12].

These relationships were illustrated in a study of 309 anuric CAPD patients [13]. The Kt/V and the CCr were correlated to each other and with the peritoneal solute transport characteristics [13]. 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.

Patient weight — Although patient weight is used to calculate both Kt/V and body surface area (BSA)-adjusted CCr (see 'Weight and normalization' above), weight has a greater effect on Kt/V. This difference is related to different methods used to normalize total clearance of urea and creatinine and is most pronounced in patients with malnutrition or obesity when actual rather than ideal or adjusted body weights are used in the relevant calculations.

As previously noted (see 'Calculation of Kt/Vurea and creatinine clearance' above), the urea clearance (Kt) and the CCr are normalized by V (volume of distribution) and 1.73 m² BSA, respectively. 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. Although biological sex also contributes in a small way to differences between calculated values of V and BSA [14], the importance of weight is illustrated by comparing Kt/V and CCr 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.

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 delivered dose of peritoneal dialysis is typically determined by measuring the removal of small solutes. Metrics commonly used to assess small solute removal include the weekly urea clearance normalized to total body water (Kt/Vurea) and the weekly creatinine clearance (CCr) normalized to body surface area (BSA). Although Kt/Vurea is generally preferred, some clinicians use both metrics since the Kt/Vurea and the CCr are occasionally discrepant. (See 'General principles' above.)

●Weight and normalization – We do not use actual weight to calculate Kt/Vurea and BSA-normalized CCr; rather, we use the ideal body weight or, for patients with obesity, the adjusted body weight. Using the actual body weight tends to over- or underestimate the delivered dialysis dose in malnourished and obese patients, respectively. (See 'Weight and normalization' 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 – 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' above.)

•Peritoneal membrane characteristics – In patients with slow peritoneal solute transfer (“slow transporters”), the ratio of CCr to Kt/V is typically lower than in patients with fast solute transfer (“rapid transporters”). (See 'Peritoneal membrane characteristics' above.)

•Patient weight – Patient weight has a greater effect on Kt/V than on CCr. This difference is related to different methods used to normalize total clearance of urea and creatinine and is most pronounced in patients with malnutrition or obesity when actual rather than ideal or adjusted body weights are used in the relevant calculations. (See 'Patient weight' above.)