Routine Blood Sampling Frequency and Outcomes in Patients on Hemodialysis

Among patients receiving maintenance hemodialysis, routine measurement of biochemical and hematologic parameters is a key part of the surveillance provided. Routine laboratory testing reveals data that are used to measure adequacy of dialysis and to inform management of complications associated with dialysis such as anemia, electrolyte disturbances, and abnormalities associated with chronic kidney disease-mineral bone disorder (CKD-MBD).

Routine testing also provides information that can be used to improve patient outcomes. More frequent testing may be associated with improved outcomes; however, there are few data available to support any particular monitoring interval. Alison Thomas, MN, and colleagues conducted a study designed to compare clinical outcomes associated with two testing interval strategies for routine blood testing among individuals receiving maintenance hemodialysis. The researchers sought to determine whether there was an association between monthly testing and lower risk for death, cardiovascular disease, and hospitalizations compared with testing every 6 weeks. Results of the study were reported in the American Journal of Kidney Diseases [2020;75(4):471-479].

The study included all prevalent hemodialysis recipients in Ontario, Canada, as of April 1, 2001, and a cohort of incident patients initiating maintenance hemodialysis in Ontario, Canada, between April 2, 2011, and March 31, 2016. The primary outcome of interest was all-cause mortality. Secondary outcomes included major adverse cardiovascular events, all-cause hospitalization, and episodes of hyperkalemia.

The retrospective population-based cohort study utilized Cox proportional hazards with adjustment for demographic and clinical characteristics to evaluate the association between blood testing interval and all-cause mortality. To allow for potential recurrent events, the Andersen-Gill extension of the Cox model was used to evaluate secondary outcomes.

The prevalent cohort included 7454 Ontario residents receiving maintenance hemodialysis on April 1, 2011, who met inclusion criteria; the incident cohort included an additional 10,666 eligible patients who initiated hemodialysis between April 1, 2011, and March 31, 2016. During the entire study period, of the 27 hemodialysis programs in Ontario, 17 performed routine sampling on a monthly basis (high-frequency cohort; 5335 prevalent and 7752 incident patients), and eight did so every 6 weeks (low-frequency cohort; 2119 prevalent and 2914 incident patients).

In the prevalent cohort, median follow-up was 1089 days; in the incident cohort, median follow-up was 641 days. During the study period, two programs (1143 prevalent and 1590 incident patients) changed their blood work policy. Both programs transitioned from monthly to every 6 week intervals; those patients were excluded from the primary analyses.

In both the prevalent and incident cohorts, baseline characteristics were generally well balanced between patients receiving hemodialysis at programs with monthly and every 6-week intervals. The frequency of pre-existing conditions was also similar in patients exposed to both blood sampling strategies. There were some differences, however: mean time on dialysis was longer in patients receiving monthly testing compared with those receiving testing every 6 weeks, and, in both cohorts, patients exposed to monthly blood sampling were more likely to be white, have lower incomes, and receive care at programs affiliated with teaching hospitals.

In the prevalent cohort, there was no association between more frequent blood sampling and a lower risk for all-cause mortality. Mortality tended to be higher in patients exposed to monthly blood sampling (185 vs 150 per 1000 patient-years at centers with every 6 week testing; unadjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.99-1.54). Following adjustment, in comparison with patients treated at centers with every 6 week testing, the HR for mortality in those receiving monthly testing was 1.16 (95% CI, 0.99-1.38).

In the incident cohort, there was no significant difference in crude time to mortality between those treated at monthly testing centers and those treated at centers with every 6 week testing (205 vs 175 per 1000 patient-years; unadjusted HR, 1.15; 95% CI, 0.91-1.46). Following adjustment, results were similar (adjusted HR, 1.15; 95% CI, 0.96-1.37).

There was no evidence of an association between blood work frequency and any of the secondary outcomes in the prevalent cohort. However, in the incident cohort, there was an association between exposure to monthly blood sampling and a higher risk for cardiovascular events (adjusted HR, 1.18; 95% CI, 1.00-1.39), all-cause hospitalization (adjusted HR, 1.11; 95% CI, 1.03-1.20), and episodes of hyperkalemia (adjusted HR, 1.20; 95% CI, 1.00-1.44).

In subgroup analyses, morality was accentuated in patients exposed to monthly testing at teaching hospitals (interaction P<.001 and P<.02 in the prevalent and incident cohorts, respectively). Patients >65 years of age in the incident cohort who received monthly blood testing were at higher risk for mortality (interaction P=.02).

The researchers cited some limitations to the study: the inability to account for potential variability in clinician or center-wide practices in response to blood results; unmeasured confounding; limited data regarding center practices other than blood sampling frequency; and the lack of data on the frequency of unscheduled blood work performed outside the prespecified sampling interval.

In conclusion, the researchers said, “Monthly sampling compared to sampling of blood parameters at 6-week intervals did not show evidence of associating with lower mortality, a reduction in cardiovascular events, or fewer healthcare encounters in maintenance hemodialysis recipients. Hemodialysis programs that perform routine blood work sampling on a monthly basis may consider a de-escalation of their sampling interval. Randomized controlled trials are needed to define a frequency of blood testing that will be both optimally beneficial to the health of hemodialysis recipients and maximally impactful in the use of healthcare resources.”

Takeaway Points

1. Researchers reported results of a retrospective population-based cohort study designed to compare clinical outcomes across two testing interval strategies for routine blood testing among patients receiving maintenance hemodialysis.
2. The study compared monthly versus every 6 weeks frequency of blood work testing. Outcomes of interest were all-cause mortality, major adverse cardiovascular events, all-cause hospitalization, and episodes of hyperkalemia.
3. There were no associations between any of the outcomes of interest and monthly versus every 6 week blood work testing frequency.