Twice-Against Thrice-weekly Hemodialysis: the TATH Trial

Hemodialysis (HD) is the most worldwide prescribed renal replacement therapy for patients with end-stage renal disease. This treatment that relies heavily on technology has undergone major modifications in the last five decades in order to improve patients' outcomes. Those changes that aimed at reducing the morbidity and mortality of patients targeted mainly the water purification system, the membrane's permeability and biocompatibility, the dialysate composition and the dose of hemodialysis. However, the frequency of sessions per week remains a debatable issue influenced by the fluctuating scientific evidence and the patient's disapproval of being increasingly dependent on a machine.

In the majority of developed Western and Asian countries, patients on chronic hemodialysis are undergoing three dialysis sessions weekly.

In 2007 the European guidelines recommended the thrice-weekly hemodialysis with a session duration 3-5 hours. This dose of treatment will ensure hemodialysis sessions adequacy defined as urea reduction ratio >65% . However thrice-weekly hemodialysis has been established worldwide without randomized clinical trials. The rationale behind the thrice-weekly dialysis seems to be the uncertainty about dialysis adequacy and the risk of malnutrition, anemia and intra-dialytic hypotension with twice-weekly sessions. Several cohorts have also shown a favorable effect on survival with thrice compared to twice-weekly hemodialysis especially when duration of treatment per week of the twice-weekly schedule was less than 8 hours.

Incremental hemodialysis is defined as starting dialysis twice weekly for those who have a substantial renal urea clearance and switching after 3 months to three times weekly. A large retrospective study from the US showed that incremental hemodialysis compared to conventional hemodialysis (three times per week) improved mortality in those with a renal urea clearance >=3 ml/min/1.73 m2 or urine volume > 600 ml/day. The rationale behind the incremental schedule is that preserving residual kidney function would lead to better outcomes. However based on this incremental method, patients should be watched closely for the residual kidney function and switched at the right moment to three sessions per week otherwise there will be an overlap between the two phases and an information bias regarding the timing of residual renal function loss.

In developing countries and some developed countries, a twice-weekly schedule independent of residual kidney function is still accepted, sometimes because of lack of resources and some other times because of patients' resistance to undergo three sessions per week. Several studies have shown that patients on twice-weekly hemodialysis without residual kidney function have a shorter survival than those on three times per week. A recent prospective study from Korea showed that residual kidney function is not the only factor that would favor thrice over twice weekly HD. Another retrospective Indian study showed similar mortality between those on twice versus thrice-weekly HD while a Chinese observational study demonstrated longer survival in anuric patients on twice- than thrice-weekly dialysis. All these controversial studies make it unclear whether patients are still allowed to undergo twice-weekly hemodialysis.