Analysis Of Changing Trend Of Uremic Toxins And Their Association With Prognosis In Hospital-acquired Acute Kidney Injury Patients

Background. Uremic toxins are toxic substances which accumulated in the body with a continuous decline of renal function. Most of current researches focus on CKD population, and the uremic toxins have been shown to be associated with various complications and adverse outcomes in chronic kidney disease. Researches about uremic toxins in acute kidney injury are limited to small-molecule toxins such as creatinine and urea nitrogen. Researches about middle-molecule and protein-bound uremic toxins are scarce. We aimed to investigate the changing trend of uremic toxins and their association with prognosis in hospital-acquired acute kidney injury patients.Methods. We conducted a prospective single-center cohort study of 215 AKI patients, defined by the RIFLE staging criteria. Healthy subjects, critically ill patients with similar SOFA score without AKI and CKD patients with similar serum creatinine were served as control subjects matched in age and gender. Serum indoxyl sulfete (IS) concentration was measured in the four groups and the AKI patients were followed up for 90 days grouped by the tertile value of serum indoxyl sulfate. Serum P2-microglobin concentration was measured in 103 AKI patients and they were followed up for 90 days grouped by the median value of serum β2-microglobin.The concentrations of serum creatinine, urea nitrogen, β2-microglobin and indoxyl sulfate were measured before, at the time of and seven days after AKI diagnosis.Results. Higher serum IS was detected in patients with AKI compared with healthy subjects and critically ill patients without AKI. The serum IS level in patients with AKI was lower than that in CKD patients. There was a positive relationship between IS and β2-microglobin, serum creatinine as well as blood urea nitrogen.During the follow-up period, the mortality of the lowest IS tertile group(<2.54 ug/ml), the second highest group(2.54-9.24 ug/ml) and the highest IS tertile group(>9.24 ug/ml) was 27.9%,47.8%,60%, respectively(log rank test p= 0.001). Multivariate analysis (Cox regression) revealed that serum IS at diagnosis was independently associated with mortality of AKI after adjusted for age, gender, APACHE II, serum creatinine, sepsis, ventilation, MAP, ALT and albumin(p= 0.001). The hazard ratio was 1.00(reference), 2.029 and 3.268 for IS increasing according to tertiles. According to Kaplan-Meier plots, the 90-day survival curves of those patients with high concentration of serum β2-microglobin showed no significant difference with those with low concentration (log rank testp=0.884). The concentrations of serum creatinine and IS showed a trend of continuous elevation during the phase of AKI, while the urea nitrogen and β2-microglobin level did not increase and even decreased seven days after AKI diagnosis.Conclusions. The serum IS concentration in patients with AKI was higher than healthy subjects and critically ill patients without AKI but lower than CKD patients. Higher serum IS at diagnosis was independently associated with 90-day all-cause mortality of AKI patients. No association between serum β2-microglobin and 90-day all-cause mortality was found. During the phase of AKI, the changing trends of different uremic toxins were not the same.