The causes of RM can be classified in a number of ways. According to the mechanisms of skeletal muscle damage, the causes have been categorized into four mechanisms: Hypoxic, physical, chemical and biological [4]. Other classification categories include surgical/medical, acquired/inherited and physical/non-physical [1, 15, 16]. In the present study, the most common cause of RM was trauma (a condition largely associated with RM [1, 2]), followed by sepsis and bee sting. Compared with other causes, patients with RM resulting from sepsis, bee sting and acute alcoholism were observed more frequently in the AKI group. In our study, the morbidity rate of AKI was 61.4%, which is almost in accord with previous reports [7–10], although this number varies between different studies.
Patients with RM-related AKI are associated with an increased risk of death and total health-related costs than those who do not develop AKI. Our analysis showed that the total mortality rate of these patients was 19.8%, whereas AKI patients experienced a significantly higher mortality rate than those without it (24.8% vs 11.8%, P < 0.01), which was within the wide range of reported mortality rates for his condition [9, 11, 12].
Different study populations (such as those with RM associated with drug use, trauma, wasp stings, infection and hospitalization) play an important role in the variations in AKI-associated morbidity, and the subsequent mortality rates of RM patients. In addition, different inclusion criteria (such as elevated CK, race and the definition of AKI itself) may also affect these results. A previous study reported that the incidence of AKI was highest according to the KDIGO definition, followed by the AKIN and RIFLE criteria [17].
Our results have identified several independent risk factors for secondary AKI, including age ≥ 60 years, chronic alcoholism, hypertension, MODS, elevated WBC count and increased serum phosphorus levels. The incidence of AKI was increased in patients aged > 60 years, according to the epidemiology of AKI in hospitalized Chinese adults [18]. Organ function decreases with age, and is accompanied by the onset of arteriosclerosis, diabetes and hypertension, which may increase susceptibility to AKI. We revealed that hypertension was one of the independent risk factors for AKI in RM patients; likewise, a previous study reported that diagnosed hypertension was an independent risk factor for AKI in patients with chronic kidney disease or after emergency department contrast-enhanced computerized tomography [19, 20]. In addition, a retrospective study of 43,611 patients demonstrated that the occurrence of AKI in hospitalized, previously normotensive adults was independently associated with increased blood pressure during the first 2 years after discharge [21]. However, there are also reports that patients with hypotension are at an increased risk of developing renal failure, decreased renal perfusion aggravate renal function [22, 23].
Consistent with a previous study of severe renal failure in patients with RM resulting from illicit drug use [24], the present study identified chronic alcoholism and leukocytosis as significant risk factors for the development of AKI. Moreover, animal research has confirmed that alcohol intoxication exacerbates RM-induced AKI through its oxidant and inflammatory effects [25].
Hyperphosphatemia is a common complication of RM with several proposed pathogenic factors, including the release of inorganic phosphorus into the plasma and reduced urinary phosphate excretion [26, 27]. In the present study, increased serum phosphate was determined to be an independent predictor for AKI-associated RM, which is in accordance with previously reported findings [28, 29]. Furthermore, phosphate has also been verified as a potential biomarker of disease severity and prognosis in AKI patients undergoing continuous renal replacement therapy [30]; this phenomenon was not observed in our study, which included patients with AKI of all stages.
Several studies have illustrated that MODS is one of the main drivers of mortality in a number of clinical conditions associated with secondary AKI, including severe acute pancreatitis and patients admitted to the intensive care unit [31, 32]. Our study was the first to identify a similar association in patients with RM, and that MODS is not only associated with the occurrence of secondary AKI, but also a worse patient prognosis.
The significant correlation between serum CK level and the risk of RM-induced AKI has also been demonstrated in previous studies [33–35]. In our study, according to univariate logistic regression analysis, a CK level ≥ 40000U/L was found to be a risk factor for the occurrence of RM-induced AKI, but this was not supported by the results of multivariate logistic regression. Differences in race, study population and inclusion criteria may also have influenced these results.