Managing and Monitoring Urea and Creatinine Levels in Hemodialysis Patients
Target Dialysis Dose
For patients on thrice-weekly hemodialysis, target a single-pool Kt/V (spKt/V) of 1.4 per session, with a minimum acceptable dose of spKt/V 1.2, or alternatively target a urea reduction ratio (URR) of 70% with a minimum of 65%. 1, 2
The 2006 KDOQI guidelines increased the target from the previous 1.3 to 1.4 because analysis of HEMO Study data revealed a within-patient coefficient of variation of approximately 0.1 Kt/V units—meaning that targeting 1.3 would result in approximately 21% of treatments falling below the minimum threshold of 1.2. 1 Targeting 1.4 provides 95% confidence that delivered dose will not fall below 1.2 per dialysis. 1
Measurement Methods and Timing
Pre-dialysis BUN Sampling
- Draw blood immediately before dialysis initiation, avoiding any dilution with saline or heparin. 1
- For arteriovenous fistulas/grafts: obtain specimen from arterial needle prior to connecting tubing or flushing. 1
- For venous catheters: withdraw 10 mL (adults) or 3-5 mL (pediatrics) to clear heparin/saline before drawing the actual sample. 1
Post-dialysis BUN Sampling
Use the slow-flow/stop-pump technique to obtain accurate post-dialysis samples. 1 This method prevents sample dilution with recirculated blood and minimizes confounding effects of urea rebound. 1
- Timing is critical: sampling immediately at dialysis end captures recirculated blood with falsely low BUN, while waiting 30-60 minutes captures complete urea rebound but is clinically impractical. 1
- The slow-flow technique (sampling at 0.25-0.50 minutes after slowing blood flow) provides the most accurate and reproducible values for single-pool Kt/V modeling. 1
Both Samples Must Be From Same Session
Draw pre- and post-dialysis BUN samples during the same hemodialysis treatment and have the laboratory analyze both specimens simultaneously. 1 This minimizes interassay variability, which accounts for most variation in adequacy measurements (4.0% coefficient of variation for Kt/V, 2.4% for URR). 1
Monitoring Frequency
Measure Kt/V or URR within the first month after initiating dialysis and at least once every 4 months thereafter. 2 For patients with frequent missed or shortened treatments, increase measurement frequency. 1
Incorporating Residual Kidney Function
For patients with residual urea clearance (Kr) ≥2 mL/min, measure and include residual kidney function in adequacy calculations; for Kr <2 mL/min, it can be ignored. 1, 2
This cutoff is somewhat arbitrary but serves a practical purpose: 1
- Residual urea clearance of 2 mL/min equals approximately 20 L/week of clearance, representing about 0.67 weekly Kt/V units in a patient with volume (V) = 30 L. 1
- The 2006 guidelines reduced this threshold from the previous 5 mL/min (average of urea and creatinine clearances) to 2 mL/min of normalized urea clearance alone. 1
- Recheck Kr at least quarterly (every 3 months) in patients whose dialysis dose has been reduced based on residual function. 1
Rationale for Including Residual Function
Observational studies demonstrate that residual kidney function contributes more to improved outcomes than equivalent dialyzer clearance, likely due to removal of larger molecular weight solutes, maintenance of salt/water balance, and preservation of hormonal functions. 1 The HEMO Study excluded patients with Kr >1.5 mL/min and showed no mortality benefit from increasing dialysis dose above standard targets, suggesting that unnecessary dialysis compromises quality of life without improving outcomes. 1
Creatinine Monitoring
While urea-based measurements (Kt/V, URR) remain the primary adequacy metrics, creatinine clearance can be used in conjunction with urea clearance to assess residual kidney function. 1 The average of urea and creatinine clearances was previously used to define significant residual function (≥5 mL/min/1.73 m²), but current guidelines focus on urea clearance alone for simplicity. 1
In patients with residual function, residual creatinine clearance is approximately 2.8 times higher than residual urea clearance, while residual phosphate clearance is about 1.2 times higher than urea clearance. 3
Special Populations Requiring Higher Targets
Women
Consider targeting higher dialysis doses in women, as HEMO Study subgroup analysis showed mortality benefit only in women assigned to higher doses (URR 75%, spKt/V approximately 1.7). 1 However, recent observational data suggest Kt/V may have weaker prognostic value in women compared to men. 4
Small Patients
The Work Group recommended possibly increasing target doses in small patients, though specific thresholds were not definitively established. 1
Treatment Compliance Monitoring
Every dialysis center must have mechanisms to monitor and minimize missed and shortened treatments. 1, 2 Studies demonstrate that poor compliance, particularly missed treatments, is an important predictor of mortality and hospitalizations. 1 US patients miss approximately 4% of treatments monthly—more than counterparts in other countries like Japan. 1
Factors Affecting Adequacy
Recent evidence confirms multiple determinants of dialysis adequacy: 5
- Blood flow rate: Increasing from 200 to 250 mL/min significantly improves Kt/V and URR. 6 Blood flow rate is an independent determinant of adequacy. 5
- Dialyzer type: High-flux dialyzers achieve higher Kt/V than low-flux dialyzers; surface area >1.2 m² is recommended. 5
- Treatment duration: Directly correlates with adequacy. 5
- Anticoagulation: Dialyzer clotting decreases Kt/V. 5
- Blood pressure control: Adequacy inversely relates to pre-dialysis systolic blood pressure. 5
- Gender: Females achieve higher Kt/V values, though male gender paradoxically predicts adequacy in regression models. 5
Common Pitfalls
Diluted samples: Failure to properly clear heparin/saline from catheters or needles falsely lowers pre-dialysis BUN, artificially elevating Kt/V and URR. 1
Improper post-dialysis timing: Sampling too early captures recirculated blood (falsely low BUN), while sampling too late captures urea rebound (falsely high BUN). 1
Ignoring residual function: Failure to account for Kr ≥2 mL/min may lead to excessive dialysis that compromises quality of life without improving outcomes. 1
URR limitations: URR cannot adjust for volume changes during ultrafiltration, cannot incorporate residual kidney function, and approaches zero with daily dialysis—making it unsuitable for frequent dialysis schedules. 1
Missed treatments: Even adequate Kt/V per session becomes meaningless if treatments are frequently missed or shortened. 1
Prognostic Thresholds
Both URR and Kt/V demonstrate equivalent prognostic value for all-cause mortality. 4 Survival improves progressively with higher doses: