To our knowledge, the present retrospective cohort study is the first to compare the effectiveness of CVVHDF combined with SMT vs. SMT alone in preventing the occurrence of AKI in patients with RM and to analyze the related health costs. Our findings demonstrate that although a single session of CVVHDF could facilitate myoglobin elimination, its addition to SMT did not significantly improve the serum Mb level or the levels of other biochemical indices or the long-term renal prognosis. However, the addition of CVVHDF to SMT did greatly increase the hospitalization costs.
While the therapeutic effects of RRT on RM-induced AKI have been extensively studied, its usefulness as a preventive measure is yet to be determined. Currently available blood-purification techniques, such as high-flux hemodialysis, hemofiltration, hemodiafiltration, and plasmapheresis, can effectively eliminate myoglobin, which is a small protein molecule with a molecular weight of 17 kDa. Some studies have investigated the capacity of these blood-purification techniques to eliminate myoglobin. Sorrentino et al. measured the myoglobin clearance in 6 patients with RM-induced AKI, and found that high-flux hemodialysis effectively eliminated myoglobin, with a median myoglobin clearance of 90.5 mL/min (range, 52.4–126.3 mL/min) and a median myoglobin removal per treatment hour of 0.54 g (range, 0.15–2.21 g)[11]. Naka et al. reported the case of a 53-year-old woman with RM and AKI for whom hemofiltration resulted in a myoglobin clearance of 30.5–39.2 mL/min and removed 0.55–0.64 g myoglobin/treatment hour for 8 hours of treatment[12]. In a case series of 6 patients with RM-induced AKI, the mean myoglobin clearance was 81 mL/min (range, 42–131 mL/min) after hemodiafiltration with a postdilutional fluid substitution rate of 2–3 L/h[13]. A control study with a two-stage crossover design also verified that hemodiafiltration could effectively clear myoglobin[14]. Although we did not find any studies that confirmed that plasmapheresis eliminates myoglobin, we speculate that this is definitely the case because during plasmapheresis, plasma is non-selectively discarded and replaced with exogenous fresh plasma.
However, none of the above studies indicate whether these therapeutic measures can prevent the occurrence of RM-induced AKI because effective myoglobin clearance does not directly indicate a good prognosis[15]. Hence, cohort studies or randomized controlled trials with good control groups and renal survival data are required to directly investigate the ability of blood-purification techniques to prevent RM-induced AKI. We were unable to find any such studies via a literature search. We did find a systematic review that investigated the therapeutic effects of continuous renal replacement therapy (CRRT) for RM and RM-induced AKI[16]. This review included 4 studies from China, one of which contained patients without AKI and the other 3 studies contained patients with AKI. The review concluded that although CRRT may provide some benefits for RM patients, the poor methodological quality of the included studies and the lack of data on clinically important outcomes meant that there was insufficient evidence to discern any likely benefits of CRRT over conventional therapy for the prevention of RM-induced AKI[16]. A case report found that plasmapheresis did not prevent renal failure in a patient with RM-induced AKI[17]. We found no other study that explored the protective effects of plasmapheresis against RM-induced AKI. However, several studies have explored the therapeutic effects of plasmapheresis on RM-induced AKI and found that this treatment was effective[18, 19]. Nevertheless, as these studies were case reports or case analyses without a control group, Szpirt considered that the use of plasmapheresis was not justified for the treatment of RM and AKI[20].
CVVHDF is the most common CRRT technique, and combines hemofiltration and hemodialysis, so it could effectively clear both middle-molecular-weight urotoxins and micromolecular urotoxins, including myoglobin. Therefore, we conducted this retrospective cohort study to determine whether CVVHDF combined with the SMT vs. SMT only could prevent RM-induced AKI. Our study showed that although a single CVVHDF treatment facilitated myoglobin elimination, compared with SMT only, CVVHDF combined with SMT did not significantly improve the serum Mb levels or other biochemical indices or the long-term renal prognosis of patients with RM. Thus, we consider that the available clinical evidence does not show any benefit of hemodiafiltration to prevent RM-induced AKI.
Interestingly, an animal experiment was performed to explore the direct renal protective effect of continuous venovenous hemofiltration (CVVH) in the early stage of RM[21]. In this study, the 2 hind legs of mongrel dogs were intramuscularly injected with 50% hypertonic glycerol to establish RM, and 2 h after the injection, CVVH was performed for 8 h. The study confirmed that at the cellular and molecular levels, CVVH treatment mitigated myoglobin-induced mitochondrial damage by inhibiting the mitochondrial apoptotic pathway and cell apoptosis; the treatment also delayed the occurrence of oliguria and protected the renal function during the early stage of RM development[21]. However, we consider that this single animal experiment cannot accurately represent the actual clinical condition due to the following reasons: First, in clinical practice, patients generally receive blood-purification treatments 1–2 days or even longer after the occurrence of RM, rather than being treated 2 h after the pathogenic onset like in the animal experiment; by the time blood-purification treatment is initiated, myoglobin has already caused some renal damage at the molecular level. Second, the CRRT regimen in most dialysis centers is 6–12 h daily or every other day for several days, so the observation period should be longer; however, in the animal experiment, observations were performed before and after a single treatment. Third, even with extracorporeal circulation therapy, the kidneys are still the main organs responsible for removing myoglobin.
In our study, we also conducted a health economic analysis, and found that although the total duration of hospitalization did not differ between the treatment and control groups, both the total and daily hospitalization costs were significantly higher in the former than in the latter. Although few studies conduct health economic analyses, the cost of healthcare is a problem that cannot be ignored. CRRT, especially, is an expensive treatment requiring more medical insurance funds and patients’ financial resources, especially in less-developed areas.
The present study has certain limitations. First, this was a retrospective study with a small sample size. More large-scale prospective studies are required to explore this issue, including cohort studies and randomized controlled trials. Second, the ability of high-flux hemodialysis and plasmapheresis to prevent RM-induced AKI is also worth exploring.