The timing of when to initiate dialysis in a patient with acute or even chronic kidney disease (CKD) is one of the most common decisions that a nephrologist will make. Recently in AJKD, Jamale et al report findings from a prospective randomized trial performed in a single center in India comparing early start versus usual start dialysis in patients with community-acquired acute kidney injury (AKI). This is an intriguing and important topic associated with a high degree of potential risk with almost no prospective data to guide us. The dilemma is real. Are we putting a patient at risk by “waiting” for the development of uremic symptoms? Can we reduce this risk by simply starting dialysis earlier, before symptoms develop? The decision to start patients with CKD on dialysis was examined by the randomized prospective IDEAL (Initiating Dialysis Early and Late) trial published in the New England Journal of Medicine in 2010. This study demonstrated that patients with CKD who start HD early (eGFR 10-14 mL/min by the MDRD Study equation) achieved no benefit over patients who waited until eGFR fell below 5-7 mL/min. This was an important study that further vindicated waiting for mild uremic symptoms instead of picking an arbitrary creatinine or eGFR before initiating HD. Seventy-five percent of patients in the late group initiated HD after developing mild uremic symptoms or fluid overload.
In the current study by Jamale et al, 208 adults with community-acquired AKI were randomized into two groups. The early-start group initiated HD when serum urea nitrogen (SUN) reached 70 mg/dL or creatinine reached 7 mg/dL. The control usual-start group initiated HD when clinically indicated by uremic symptoms, fluid overload, or electrolyte abnormalities. There are several features of this study that are important to note. First, all of the patients in this study came from a single center in India. Second, the study population was younger (~42 yrs old) and were not as sick as what is typically seen in patients with AKI, with the average sequential organ failure assessment score (SOFA) score of ~7-8. Furthermore, sepsis only accounted for ~20% of AKI events, with the bulk of AKI events(~70%) attributed to tropical infections such as malaria, gastroenteritis, dengue, and leptospirosis. The primary end point was in-hospital mortality and dialysis dependence at the end of 3 months. Secondary end points were time to kidney recovery in days. There was no statistical difference in mortality between the two groups, however a trend was noted in more patients dying in the early-start compared to usual-start group (21/102 vs. 13/106, P=0.2). Average creatinine at initiation of HD was 7.4 mg/dL in the early-start vs. 10.6 mg/dL in the usual-start group. SUN was 71.7 mg/dL in the early-start vs. 100.9 mg/dL in the usual-start group. Five patients in each group were dialysis dependent at the conclusion of the study. Interestingly, time to recovery of kidney function in patients undergoing dialysis was significantly longer in the early-start (~7 days ) vs. usual-start groups (~5 days, P=0.02). As with the IDEAL trial, this prospective study by Jamale et al does not support the use of early-start dialysis in patients with AKI. Furthermore, these results suggest that early-start dialysis may be associated with a delayed recovery of kidney function after an AKI event. The authors postulate that this could be secondary to repeated hypotensive episodes during hemodialysis. As noted, this was a very unique study population so it is difficult to generalize these results to other patients with AKI from multi-organ system failure. However, I applaud the authors for undertaking this study as we have very little data to guide this important decision.
Dr. Matthew A. Sparks
eAJKD Advisory Board member