Impact of renal-replacement therapy strategies on outcomes for patients with chronic kidney disease : a secondary analysis of the STARRT-AKI trial

Purpose To assess whether pre-existing chronic kidney disease (CKD) modified the relationship between the strategy for renal-replacement theraphy (RRT) initiation and clinical outcomes in the STARRT-AKI trial. Methods This was a secondary analysis of a multi-national randomized trial. We included patients who had documented pre-existing estimated glomerular filtration rate (eGFR) data prior to hospitalization, and we defined CKD as an eGFR <= 59 mL/min/1.73 m(2). The primary outcome was all-cause mortality at 90 days. Secondary outcomes included RRT dependence and RRT-free days at 90 days. We used logistic and linear regression and interaction testing to explore the effect of RRT initiation strategy on outcomes by CKD status. Results We studied 1121 patients who had pre-hospital measures of kidney function. Of these, 432 patients (38.5%) had CKD. The median (IQR) baseline serum creatinine was 130 (114-160) and 76 (64-90) mu mol/L for those with and without CKD, respectively. Patients with CKD were older and more likely to have cardiovascular comorbidities and diabetes mellitus. Patients with CKD had higher 90-day mortality (47% vs. 40%, p < 0.001) compared to those without CKD, though this was not significant after covariate adjustment (adjusted odds ratio [aOR], 1.05; 95% CI, 0.79-1.41). Patients with CKD were more likely to remain RRT dependent at 90 days (14% vs. 8%; aOR, 1.89; 95% CI, 1.05-3.43). CKD status did not modify the effect of RRT initiation strategy on 90-day mortality. Among patients with CKD, allocation to the accelerated strategy conferred more than threefold greater odds of RRT dependence at 90 days (aOR 3.18; 95% CI, 1.41-7.91) compared with the standard strategy, whereas RRT initiation strategy had no effect on this outcome among those without CKD (aOR 0.71; 95% CI, 0.34-1.47, p value for interaction, 0.009). Conclusion In this secondary analysis of the STARRT-AKI trial, an accelerated strategy of RRT initiation conferred a higher risk of 90-day RRT dependence among patients with pre-existing CKD; however, no effect was observed in the absence of CKD

Timing of initiation of renal-replacement therapy in acute kidney injury

BACKGROUND Acute kidney injury is common in critically ill patients, many of whom receive renal-replacement therapy. However, the most effective timing for the initiation of such therapy remains uncertain. METHODS We conducted a multinational, randomized, controlled trial involving critically ill patients with severe acute kidney injury. Patients were randomly assigned to receive an accelerated strategy of renal-replacement therapy (in which therapy was initiated within 12 hours after the patient had met eligibility criteria) or a standard strategy (in which renal-replacement therapy was discouraged unless conventional indications developed or acute kidney injury persisted for >72 hours). The primary outcome was death from any cause at 90 days. RESULTS Of the 3019 patients who had undergone randomization, 2927 (97.0%) were included in the modified intention-to-treat analysis (1465 in the accelerated-strategy group and 1462 in the standard-strategy group). Of these patients, renal-replacement therapy was performed in 1418 (96.8%) in the accelerated-strategy group and in 903 (61.8%) in the standard-strategy group. At 90 days, death had occurred in 643 patients (43.9%) in the accelerated-strategy group and in 639 (43.7%) in the standard-strategy group (relative risk, 1.00; 95% confidence interval [CI], 0.93 to 1.09; P = 0.92). Among survivors at 90 days, continued dependence on renal-replacement therapy was confirmed in 85 of 814 patients (10.4%) in the accelerated-strategy group and in 49 of 815 patients (6.0%) in the standard-strategy group (relative risk, 1.74; 95% CI, 1.24 to 2.43). Adverse events occurred in 346 of 1503 patients (23.0%) in the accelerated-strategy group and in 245 of 1489 patients (16.5%) in the standard-strategy group (P<0.001). CONCLUSIONS Among critically ill patients with acute kidney injury, an accelerated renal-replacement strategy was not associated with a lower risk of death at 90 days than a standard strategy. (Funded by the Canadian Institutes of Health Research and others; STARRT-AKI ClinicalTrials.gov number, NCT02568722.)