Early Diagnostic Value of Urinary NGAL in Acute Kidney Injury in Septic Patients.

Background: The aim of this study was to evaluate the predictive value of urinary neutrophil gelatinase-associated lipid (uNGAL) for the prediction of sepsis-associated acute kidney injury (SA-AKI). Methods: From September to December 2012, 110 patients were prospectively enrolled from the intensive care units (ICUs) of 3 general hospitals. After being admitted to the ICU, the patients were continuously observed for 72 hours. According to the Kidney Disease Improving Global Outcomes (KDIGO) criteria for the diagnosis of acute kidney injury (AKI), the patients were divided into the AKI group (33 patients) and non-AKI group (77 patients). Per the sepsis diagnostic criteria, the patients were classified as septic (79 patients) and non-septic (31 patients). Serum creatinine and uNGAL of the patients were analyzed daily. The difference in uNGAL in septic and non-septic patients, patients with and without AKI, and septic patients with with and without AKI were compared. In addition, the difference in serum creatinine and uNGAL in patients with and without AKI were recorded and compared, and the sensitivity and specificity of uNGAL and sCr for the diagnosis of AKI in the ICU patients were evaluated using the receiver operating characteristic (ROC) curve. Results: uNGAL levels were all significantly different in septic and non-septic patients (P = .001, P = .028, P = .010, respectively), patients with and without AKI (P = .001, P = .042, P = .001, respectively), septic patients with AKI and septic patients without AKI (P = .003, P = .012, P = .001, respectively) at 24, 48 and 72 hours after being admitted to the ICU, while the difference in sCr was not significant (P = .169) after 24 hours. The area under the ROC curve of uNGAL and sCr in patients admitted to the ICU at 24 hours were 0.828 (95% CI, 0.742 to 0.914) and 0.583 (95% CI, 0.471 to 0.695), respectively. The cutoff value of uNGAL was 170 ng/mL in patients admitted to the ICU at 24 hours, and the sensitivity and specificity were 0.778 and 0.784, respectively. The sensitivity of uNGAL was superior sCr. Conclusion: uNGAL has relatively high sensitivity and specificity in predicting the occurrence of AKI in septic patients, which is superior to sCr and has certain clinical early diagnostic value. uNGAL could be used as an indicator for early diagnosis of AKI in septic patients in the ICU.

Roflumilast, a Phosphodiesterases-4 (PDE4) Inhibitor, Alleviates Sepsis­induced Acute Kidney Injury.

BACKGROUND Sepsis causes acute kidney injury (AKI) in critically ill patients. Roflumilast, a phosphodiesterases-4 (PDE4) inhibitor, has been shown to be therapeutically effective in sepsis-induced organ injury. However, the function of roflumilast in sepsis-induced AKI is not clearly understood. The present study aimed to explore the protective effect of roflumilast on sepsis-induced AKI in mice. MATERIAL AND METHODS A sepsis model was established by cecal ligation and puncture surgery. Roflumilast (1 mg/kg and 3 mg/kg) was used once daily for 7 consecutive days for treatment. Kidney tissues were pathologically examined by hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining. The levels of kidney injury markers including blood urea nitrogen (BUN), creatinine (Cre), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL), and inflammatory cytokines including interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and IL-1ß were detected by their corresponding test kits. The protein expression was measured using western blot and cell apoptosis of kidney tissue was determined by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay. RESULTS Roflumilast was demonstrated to alleviate sepsis-induced AKI by reducing histopathological changes and decreasing the levels of kidney injury markers in a concentration-dependent way. The production of TNF-alpha, IL-6, and IL-1ß was significantly suppressed by roflumilast. Besides, roflumilast inhibited the activation of NLRP3 (nucleotide-binding domain (NOD)-like receptor protein 3) and NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells). Additionally, roflumilast inhibited cell apoptosis and changes in expression of apoptosis related proteins induced by sepsis. Finally, high concentration of roflumilast (3 mg/kg) did not have an adverse effect on liver, heart, lung, or spleen. CONCLUSIONS Our study indicated that roflumilast could ameliorate AKI induced by sepsis through restraining inflammatory response and apoptosis of the kidney, providing a molecular basis for a novel medical treatment of septic AKI.