The long interdialytic interval in thrice-weekly hemodialysis (HD) is associated with excess cardiovascular risk. The mechanisms behind these adverse consequences are not fully understood.
In a recent study published in AJKD, Tsilonis et al investigated the interdialytic changes in right and left ventricular function during the two- and three-day intervals. Corresponding author Dr. Pantelis A. Sarafidis (PS) discusses this article with Dr. Kenar Jhaveri (AJKDblog), AJKD Blog Editor.
AJKDblog: Can you discuss the results of your study?
PS: For the first time, this study aimed to provide a comparative evaluation of changes in systolic and diastolic heart function indices during the two- and three-day interdialytic intervals in patients receiving thrice-weekly HD. In both interdialytic intervals, we noted left ventricular chamber dilatation, left ventricular filling pressure elevation, and left atrial enlargement. We also observed increases in right ventricular systolic pressure (RVSP), right atrial volume, and inferior vena cava diameter, which suggest pulmonary circulation overload. However, increases in left atrial volume index, RVSP, and inferior vena cava diameter were significantly greater during the three-day interdialytic interval, suggesting further loading during the third day. Lastly, changes in weight gain, right ventricle diastolic function, and pulmonary vascular resistance were independently associated with changes in RVSP, indicating that volume excess is in the causal pathway of elevated pulmonary circulation and right ventricular loading. These results are adding to the mechanistic background of the observed excess cardiovascular mortality towards the end of the long interdialytic interval.
AJKDblog: Residual urine output is slowly becoming a mortality indicator in patients receiving HD as it has been in patients receiving peritoneal dialysis (PD). Did you look at patients who had residual urine output in two- versus three-day interdialytic intervals and their cardiac markers?
PS: Indeed, residual urine output increasingly appears as an indicator of mortality both in HD and PD patients. However, data regarding residual urine output were not captured in the present study. It is known that urine output in HD is decreasing faster than it is in PD. The average dialysis vintage in our study was 58 months; thus, only a very small minority of patients would have important residual diuresis. A similar study on cardiac index changes during different interdialytic intervals in incident HD patients with preserved urine output is a good idea, as a possible absence of difference in weight gain between the two intervals may yield different results.
AJKDblog: What are the limitations of this study and how did it affect your results?
PS: The major limitation of most echocardiographic studies in HD populations is the relatively small sample sizes, and this also may have affected the significance level of some borderline comparisons in our study. Another limitation may have been the observational design of the present study. However, performing a study randomizing patients to either two- or three-day intervals is not easy and would be rather impractical, as we wanted to capture real clinical practice. Hence, the crossover randomized order of the evaluations in our study appeared as the best solution. Finally, the cardiologist performing the echocardiograms was unavoidably unblinded to the sequence of study visits, but for this reason echocardiographic measurements were conducted offline by another experienced physician who was blinded to the chronologic sequence of the echocardiograms.
AJKDblog: Besides increasing dialysis time, can any medical therapy decrease the mortality difference between the three- vs two-day groups?
PS: No medical therapy can change this difference. More dialysis may help to decrease the three-day interval by some hours, but I don’t think it can be a solution to this problem. More frequent dialysis, e.g., eliminating the three-day interval, may be the best solution, as indicated recently by the extended follow-up data of the Daily Trial of the Frequent Dialysis Network. In contrast, current evidence (e.g., data from the Nocturnal Trial of the Frequent Dialysis Network) suggests that both longer and more frequent dialysis does not confer any mortality benefit. An option with the fewest implementation difficulties would be alternate-day dialysis, i.e. only eliminating the three-day interval; however, this would need to be tested in outcome studies.
AJKDblog: Do the results of this study change your clinical practice?
PS: By documenting these changes in cardiac function and remodeling, our study contributes to the complex mechanistic background of increased cardiovascular events during the long interdialytic interval. Hence, our study adds to the central idea that the conventional thrice-weekly HD schedule may not be the best for patients treated with HD. However, for clinical practice of dialysis patterns to be changed, we and the whole world need hard data from outcome studies in the field.