Sustained acute kidney injury as an independent risk factor for neurodevelopmental and growth outcomes in a single NICU center.

PURPOSE: Acute kidney injury (AKI) is commonly seen in neonatal intensive care units (NICUs) and is potentially associated with adverse prognoses in later stages of life. Our study evaluated the impact of sustained AKI (SAKI) on both neurodevelopmental impairment (NDI) and early growth restriction (EGR) in neonates. METHODS: This case-control study retrospectively analyzed the medical records of neonates diagnosed with SAKI in the NICU of a tertiary medical center during the period from January 2007 to December 2020. Cases without subsequent follow-up and those resulting in death were excluded. We analyzed demographic, biochemical, and clinical outcome data. RESULTS: Of the 93 neonates with SAKI, 51 cases (54.8%) were included in this study, while 42 cases (45.2%) were excluded due to a lack of follow-up or death. An age-matched control group comprised 103 neonates, who had never experienced AKI or SAKI, were selected at random. In total, 59 (38.3%) cases were identified as NDI and 43 (27.9%) as EGR. Multivariate analysis revealed that patients with SAKI had significantly higher risks of developing NDI (odds ratio, [OR] = 4.013, p = 0.001) and EGR (OR = 4.894, p < 0.001). The AKI interval had an area under the receiver operating characteristic curve of 0.754 for NDI at 9.5 days and 0.772 for EGR at 12.5 days. CONCLUSIONS: SAKI is an independent risk factor for both NDI and EGR in neonates. Consequently, regular monitoring, neurological development assessments, and appropriate nutritional advice are crucial to these infants who have experienced renal injury.

Acrolein plays a culprit role in the pathogenesis of diabetic nephropathy in vitro and in vivo.

Objective: Diabetic nephropathy (DN), also known as diabetic kidney disease (DKD), is a major chronic complication of diabetes and is the most frequent cause of kidney failure globally. A better understanding of the pathophysiology of DN would lead to the development of novel therapeutic options. Acrolein, an α,ß-unsaturated aldehyde, is a common dietary and environmental pollutant. Design: The role of acrolein and the potential protective action of acrolein scavengers in DN were investigated using high-fat diet/ streptozotocin-induced DN mice and in vitro DN cellular models. Methods: Acrolein-protein conjugates (Acr-PCs) in kidney tissues were examined using immunohistochemistry. Renin-angiotensin system (RAS) and downstream signaling pathways were analyzed using quantitative RT-PCR and Western blot analyses. Acr-PCs in DN patients were analyzed using an established Acr-PC ELISA system. Results: We found an increase in Acr-PCs in kidney cells using in vivo and in vitro DN models. Hyperglycemia activated the RAS and downstream MAPK pathways, increasing inflammatory cytokines and cellular apoptosis in two human kidney cell lines (HK2 and HEK293). A similar effect was induced by acrolein. Furthermore, acrolein scavengers such as N-acetylcysteine, hydralazine, and carnosine could ameliorate diabetes-induced kidney injury. Clinically, we also found increased Acr-PCs in serum samples or kidney tissues of DKD patients compared to normal volunteers, and the Acr-PCs were negatively correlated with kidney function. Conclusions: These results together suggest that acrolein plays a role in the pathogenesis of DN and could be a diagnostic marker and effective therapeutic target to ameliorate the development of DN.