Patients on three times-weekly haemodialysis have increased mortality during the long, 2-day interdialytic interval
- Correspondence to Rajiv Agarwal
Indiana University and RLR VA Medical Center, 1481 West 10th Street, 111N, Indianapolis, IN 46202, USA;
People on long-term haemodialysis are dialysed three times-weekly such as on Mondays, Wednesdays and Fridays. Accumulation of volume and toxins over the longer 2-day interdialytic interval (eg, Friday–Monday) may provoke excess deaths. The cohort study by Foley et al asked the question whether compared with other days, morbidity and mortality is increased during the long interdialytic interval.
The participants were 32 065 adults in the USA who participated in the End-Stage Renal Disease (ESRD) Clinical Performance Measures Project at the end of calendar years 2004 through 2007. Patients were excluded if they were not receiving haemodialysis three times weekly. The outcomes were various causes of morbidity and mortality and their relationship with the day of dialysis. The mean follow-up was 2.2 years. Existing United States Renal Data System Standard Analytical Files were used to determine dates of hospitalisations, deaths and their causes. Poisson regression was used to calculate event rates of interest.
When compared with the short, 1-day interdialytic interval, the following event rates (per 100 person-years) were higher during the long, 2-day interdialytic interval: all-cause mortality (22.1 vs 18.0 deaths, p<0.001), mortality from cardiac causes (10.2 vs 7.5, p<0.001), infection related mortality (2.5 vs 2.1, p=0.007), mortality from cardiac arrest (1.3 vs 1.0, p=0.004), mortality from myocardial infarction (6.3 vs 4.4, p<0.001), and admissions for myocardial infarction (6.3 vs 3.9, p<0.001), congestive heart failure (29.9 vs 16.9, p<0.001), stroke (4.7 vs 3.1, p<0.001), dysrhythmia (20.9 vs 11.0, p<0.001) and any cardiovascular event (44.2 vs 19.7, p<0.001). These risk differences were mostly similar across the 25 subgroups.
It is quite plausible that a cause and effect relationship between lack of dialysis and excess mortality exists as has been shown in prior studies.1 Volume accumulation during the interdialytic interval provokes a progressive increase in systolic, diastolic and pulse pressure.2 Systolic hypertension is associated with cardiac arrhythmias. Accumulation of potassium and other toxins may also have deleterious cardiac consequences. Indeed in this study, the greatest risk of admissions after the long interdialytic interval was on hospitalisations that were cardiovascular in nature such as strokes, myocardial infarctions, dysrhythmias and most importantly heart failure.
The long interdialytic interval may not be related to mortality for the following four reasons: First, Monday spikes in myocardial infarctions have been reported even among people without ESRD.3 Second, it is possible, that patients on haemodialysis who dialyse three times-weekly may avoid hospitalisation, despite warning symptoms, until after the long interdialytic interval. In fact, the patients may avoid coming to the hospital even on the short interdialytic day despite symptoms; the authors showed that cardiovascular admission rates or death rates were lower on interdialytic days. Furthermore, patients on peritoneal dialysis who did not restrain to three times-weekly regimens do not show such trends of increased hospitalisations on Mondays.1 Third, volume and toxin accumulation and deaths may not be causally related. Those who are on dialysis for <1 year likely have better residual renal function, but these people did not have fewer deaths or cardiovascular hospitalisations. Lastly, the excess mortality on Mondays was not related to cardiovascular causes alone. Deaths due to liver or gastrointestinal disease were also more common on Mondays.
Kidney transplantation remains the best renal replacement therapy, but not all patients will be eligible. Although frequent dialysis slightly improves physical function and left ventricular mass, studies have not shown that patients on more frequent dialysis have less cardiovascular or infection related morbidity.4 Short of transplantation or daily-dialysis for everyone, what can be done now? Sodium restriction and achievement of dry-weight may blunt the volume expansion and therefore the rates of rise of interdialytic blood pressure.5 Furthermore, achievement of dry-weight without increasing treatment duration or frequency is associated with reduction in left ventricular mass comparable with that seen with frequent dialysis.6 Only one fourth of patients in this study received >4 h dialysis; this is far below 4 h minimum duration of dialysis recommended.7 The mantra to reduce excess deaths appears to be dialyse well, get to dry-weight and do-not-salt. These non-pharmacological strategies may at least be a partial, albeit an imperfect, solution to excess ‘Monday mortality’.
The author acknowledges the research support by a research grant from NIH 2RO1-DK62030-08.