The 2-day gap between hemodialysis (HD) sessions among patients on a thrice-weekly HD schedule is associated with increased hospitalization and mortality rates compared with the 1-day interval, regardless of HD session pattern, researchers concluded.

“Planning an intervention to reduce mortality over the long break should clearly be focused on re-evaluating the standard dialysis pattern,” investigators wrote in a paper published in Kidney International (online ahead of print).

In a study of an incident cohort of 5,864 HD patients, James Fotheringham, MD, of the Sheffield Kidney Institute, Northern General Hospital in Sheffield, U.K., and colleagues found that the hospital admission rate was 2.4 per year after a 2-day gap compared with 1.4 per year after 1-day intervals, regardless of whether thrice-weekly HD commenced on a Monday or Tuesday (rate ratio 1.7). Dr. Fotheringham’s group observed the greatest differences in admission rates among patients admitted with fluid overload or with conditions associated with a high risk of fluid overload.

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The overall mortality rate on HD was 17.3 deaths per 100 patient-years. It was 20.5 per 100 patient-years after the 2-day gap compared with 16.7 per 100 patient-years for the rest of the week (rate ratio 1.22), with the increased rate driven by out-of-hospital deaths (rate ratio 1.59 vs. 1.06 for in-hospital death).

Of the 5,864 patients, 606 died outside of the hospital. Of these, 79% died on dialysis days without a corresponding HD session being coded, suggesting that the majority of deaths occurred before HD was due, according to the researchers. They called the increase in out-of-hospital mortality “thought provoking.” The findings “suggest that excessive fluid removal necessitated by the 2-day break is unlikely to be a major factor accounting for the observed excess mortality.”

The study cohort had a median follow-up of 1.3 years. HD session patterns were as follows: Monday, Wednesday, Friday, 50.2%; Tuesday, Thursday, Saturday, 47.3%; and Tuesday, Thursday, Sunday, 2.5%.

“This study adds new insights to the underlying mechanisms and at-risk sub-populations of the long interdialytic gap,” Connie M. Rhee, MD, MSc, and Kamyar Kalantar-Zadeh, MD, MPH, PhD, of the Division of Nephrology and Hypertension at the University of California Irvine, wrote in an accompanying editorial. Higher hospitalization rates observed on Monday, Tuesday, and Sunday for patients on the Monday-Wednesday-Friday, Tuesday-Thursday-Saturday, and Tuesday-Thursday-Sunday HD schedules, respectively, “do not support the weekend lag effect as an explanatory factor for higher admission rates on the day after the long interdialytic gap,” they noted.

Based on collective data from the new study and others, Drs. Rhee and Kalantar-Zadeh said they believe that both excess fluid and uremic toxin accumulation during the long interval and rapid removal with the first dialysis treatment of the week may contribute to the heightened morbidity and mortality of the day after the long interdialytic gap.

They offered some potential strategies to ameliorate the adverse effects of the long interdialytic gap, such as incremental fluid/solute removal by aiming for higher dry weight at the beginning of the week, a lower fluid removal goal, and a lower dialysis dose the day after the long interdialytic gap compared with midweek targets. Other possible approaches include eliminating the long interdialytic gap with more frequent HD sessions in patients with negligible residual kidney function and longer and more gentle HD sessions immediately following the long interdialytic gap.