Objectives: Long-term outcome of acute kidney injury (AKI) in pediatric critical care unit (PICU) has not been well established. The aim of this study was to determine the 24 months outcome of AKI following admission to PICU. Methods: We followed 80 children admitted to PICU with a diagnosis of AKI,based on pediatric modified RIFLE criteria, for two years. The impact of AKI on the two-year mortality was estimated using the Cox proportionalhazards regression model. Factors affecting long-term progression to chronic kidney disease (CKD), including hypertension and proteinuria, were also evaluated. Results: The mortality at two years follow-up was 48% with the highest mortality occurred during the first four months post PICU admission (40%). By the end of two years; 22.2% had reduction in the GFR, 33.3% had proteinuria and 73.3% were hypertensive. Proteinuria of 30 mg/dl or more at baseline was associated with worse renal function during follow-up. Based on RIFLE criteria ; failure stage at the time of admission increased the two-year mortality rate by more than three times, as compared to risk stage. Renal injury, on the other hand, did not increase mortality rate. Conclusions: AKI was associated with high mortality particularly in the first four months following admission to PICU. Significant percentage of the survivors had evidence of CKD after two years of follow-up. FP-S01-2Prospective evaluation of urinary NGAL and IL-18 in first 48 hours after birth as early noninvasive predictive biomarkers of acute kidney injury during first week of life in NICU

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Histones are proteins that can be post‐translationally modified and these modifications will determine the expression of genes. Many studies have shown that it is very common for cancers to have mutations in their histone genes. The concept of synthetic lethality states that if a cell has a single mutation it will be able to survive. But if a second mutation is applied, the cell will become synthetically sick and/or die. In our study, we are seeking to determine synthetically lethal interactions between the histone H3 gene and RPD3 histone deacetylase enzyme. In order to discover potential genetic targets to develop therapies against cancers. To achieve this we used a genetically engineered yeast strain that has the histone H3 gene and RPD3 gene deleted. The H3 gene deletion is covered by a wild type H3 plasmid. These yeast were then transformed with plasmids from the SHIMA library. The yeast were then grown on plates lacking uracil and tryptophan. The individual colonies were then patched and replica plated onto tryptophan deficient media. Finally, they were replica plated onto agar plate media containing 5‐ FOA. The DNA from yeast deemed synthetically lethal or sick were then put through “Library Prep” which is a high throughput method used to isolate the H3 gene within the plasmid with low error rate. The lethals were then put into Next Generation sequencing, aligned, and transferred in the IGV. Finally, we were able to estimate with high accuracy the frequency of H3 mutants in our lethal pool. The top three frequencies discovered were F67A, F84A, and Q93A. They represented 35%, 12% and 10% of our lethal pool respectively. In total we discovered ten new potential synthetically lethal interactions between histone H3 and RPD3. We also used this information in combination with previous knowledge to generate a genetic interaction map for RPD3 from our findings. Although still in the preliminary stages when verified with duplication studies our new potential synthetically lethal interactions can be targets to develop cancer therapies. Also, the knowledge gained from our study can be used to understand genetic interaction between histones and histone modification enzymes.Support or Funding InformationSummer Medical Research Fellowship at Rowan University School of Osteopathic MedicineThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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