Three RCTs evaluated the dose of IHD in AKI (Suppl Tables 37 and 38). Schiffl et al.771 compared daily to alternate-day IHD in 146 ICU patients with AKI. RRT was started with rather high values of SCr (over 4.5 mg/dl [398 µmol/l]) and BUN (around 90 mg/dl [32.1 mmol/l urea]). The daily arm received a weekly Kt/V approximately two times higher than the alternate-day arm (5.8 ± 0.6 vs. 3 ± 0.6, respectively). Daily IHD resulted in lower mortality (28% vs. 46%, P = 0.01) and faster recovery of kidney function (9 ± 2 vs. 16 ± 6 days, P = 0.001). Major limitations of this study were inadequate randomization, a ‘‘very low dose’’ in the control group (actually less than that recommended for CKD). Also overall mortality in the study (34%) was lower than in other studies in this population, suggesting that the results may not generalize. Moreover, alternate-day IHD was associated with significant differences in fluid removal and dialysis-associated hypotension, suggesting that aspects other than solute control might modify patient outcomes.
The Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ARFTN) study563 was a RCT assessing the effects of intensive compared to less-intensive RRT in 1124 ICU patients with AKI in 27 Veterans Affairs– and university-affiliated North-American centers. Within each randomization arm patients were switched between IHD and CRRT or SLED, based on their hemodynamic status, reflecting average clinical practice in the USA. Intermittent treatments were prescribed at a Kt/V of 1.4, with a delivered Kt/V averaging 1.3, and were performed three (less-intensive arm) or six (more-intensive arm) times per week. Consequently, the weekly Kt/V was approximately 6.5 in the intensive and 3.9 in the less-intensive arm. Mortality at 60 days was similar in both groups (53.6% and 51.5%) as was the percentage of patients recovering kidney function (15.4% and 18.4%). Limitations of this study include the predominance of males, and the nonstandardized timing for initiating RRT. In addition, a significantly higher frequency of hypotension and electrolyte disturbances were seen in the more-intensive arm. Similar to what has been reported in chronic dialysis, acute IHD results in underdosing when Kt/V is not measured. In the ARFTN study, the first session of IHD had an average delivery of 1.1 Kt/V, while the prescribed dose was 1.4.
The Hannover Dialysis Outcome Study768 randomized 148 ICU patients with AKI to two different doses of SLED: a standard-dialysis arm dosed to maintain plasma urea levels between 120–150 mg/dl (20–25mmol/l), or an intensifieddialysis arm dosed to maintain plasma urea levels < 90 mg/dl ( < 15mmol/l). Patients were included with SCr around 3 mg/dl (265 µmol/l) and plasma urea around 60 mg/dl (10 mmol/l). The mean plasma urea was kept at 68 ± 24 mg/dl (11.3 ± 4 mmol/l) in the intensified and 114 ± 36 mg/dl (19 ± 6 mmol/l) in the standard group. Mortality at 28 days was not statistically different between groups (38.7% and 44.4%) and the frequency of survivors recovering kidney function at day 28 was very similar (63% and 60%).
In CKD, the analysis by Gotch and Sargent779 of the National Cooperative Dialysis Study showed that survival could be increased by increasing Kt/V to 1.0–1.2. Analysis of a large database of 2311 Medicare IHD patients also showed a strong association between the delivered IHD dose and mortality, with a decreased mortality risk of 7% for each 0.1 higher level of delivered Kt/V in CKD patients. However, above a Kt/V of 1.3, no further decrease in mortality was noted.780 The HEMO study, a large RCT comparing two different dialysis doses in CKD, also could not demonstrate a further reduction of mortality with equilibrated Kt/V of 1.43 compared to 1.16.781 If we assume that AKI patients should receive at least the same dose as CKD patients, it seems reasonable to recommend a thrice-weekly Kt/V of 1.3 or a weekly Kt/V of 3.9 (assuming at least thrice-weekly treatment), which also represents the lowest dose in the largest randomized trial in AKI (ARFTN study). Whether specific subgroups of AKI patients, such as those with hypercatabolism, may benefit from higher doses will require further investigation.
In conclusion, there are only two adequately designed and executed RCTs testing intermittent or extended RRT dose in AKI. Neither study showed improvement in mortality or renal recovery when the dialysis dose was increased, either by increasing Kt/V above 3.9 weekly or by achieving a plasma urea target below 90mg/dl (15 mmol/l) in AKI patients. However, consistent with the data on dose of IHD in CKD, and consistent with the lower-dose arm in the ARFTN study, we recommend thrice-weekly Kt/V of 1.3 or a weekly Kt/Vof 3.9 for IHD in AKI.
Seven RCTs have investigated the role of CRRT dose in AKI (Suppl Tables 37 and 38).531,562,563,768–770,772 While earlier single-center trials showed mixed results, two large multicenter trials have reached remarkably consistent conclusions concerning the dose of CRRT that should be provided to critically ill patients with AKI.
The ARFTN study563 compared standard-intensity predilution CVVHDF with a prescribed effluent flow of 20 ml/kg/h to high-intensity CVVHDF at 35 ml/kg/h. As discussed in Recommendation 5.8.3 rationale, there were no differences in outcomes between the two study arms. Importantly, more than 95% of the prescribed dose of CRRT was delivered in the less-intensive group. This represents a considerably greater intensity of delivered dose than is typically seen in clinical practice. As in chronic dialysis, studies in CRRT have shown that delivery usually falls substantially short of the prescribed dose.782 Thus, it will usually be necessary to prescribe a high dose of CRRT in order to achieve a specific target. For example, in order to achieve a delivered dose of 20–25 ml/kg/h, it is likely that the prescription will need to be in the range of 25–30 ml/kg/h. The Randomized Evaluation of Normal vs. Augmented Level of RRT study was conducted in 35 centers in Australia and New Zealand.562 It compared the effects of postdilution CVVHDF at doses of 25 and 40 ml/kg/h on 28- and 90-day mortality rates in 1464 AKI patients. The delivered dose was 88% and 84% of prescribed in the low- and high-dose groups, respectively. As in the ARFTN study, there was no difference in 28- or 90-day mortality between the two groups. Apart from a higher incidence of hypophosphatemia in the high-dose group, the complication rate was similar.562
In conclusion, there are now consistent data from two large multicenter trials showing no benefits of increasing CRRT doses in AKI patients above effluent flows of 20–25 ml/kg/h. In clinical practice, in order to achieve a delivered dose of 20–25 ml/kg/h, it is generally necessary to prescribe in the range of 25–30 ml/kg/h, and to minimize interruptions in CRRT.