Hello, OMED 2024. My name is Matthew Cerrone. I am a second year medical student at the New York Institute of Technology College of Osteopathic Medicine, and today I'll be discussing an important study focused on chronic kidney disease and its impact on cardiovascular health. Patients with CKD, whether in early or advanced stages, face an increased risk of cardiovascular events, including coronary artery disease, heart failure, arrhythmia, and even sudden cardiac death. A significant factor in this increased risk is dyslipidemia, which involves elevated triglycerides and low HTL cholesterol levels. Dyslipidemia is common among CKD patients and serves as a shared risk factor between CKD and cardiovascular disease, with persistent dyslipidemia exacerbating cardiovascular risks and contributing to mortality in CKD patients. In our lab, we've developed a reproducible mouse model of CKD induced by adenine to better understand the progression of cardiovascular disease within the context of CKD. Our previous research revealed a surprising finding. When mice with CKD induced by adenine were given a western diet, their plasma triglyceride levels and atherosclerosis paradoxically decreased compared to mice fed only the western diet. This was unexpected and prompted us to further investigate this phenomenon. Our study currently aims to explore whether this paradoxical reduction in lipid levels reverses when adenine is withdrawn and mice are switched back to a western diet. By evaluating changes in triglyceride and cholesterol levels and assessing urine output as an indicator of kidney function, we hope to clarify the role of adenine in lipid metabolism and determine if the effects are reversible. For this study, we used LDL receptor mutant mice from Jackson Laboratory, which carry a familiar hypercholesterolemia mutation. These mice were maintained under conditions with unrestricted food and water. The experimental setup involved 48 mice, which were divided equally by sex. We had two groups, a control group fed a western diet, an experimental group, an adenine group fed a western diet with supplemented with 0.2% adenine from 10 to 18 weeks of age. After this period, both groups were transitioned to a western diet only for an additional eight weeks. We measured urine output using metabolic cages at both the 18-week and 26-week marks to monitor kidney function and we assess blood chemistry by analyzing plasma triglyceride cholesterol levels using direct calorimetric assays. Statistical analysis was performed with Grefpet PRISM-9 software, utilizing a two-way ANOVA to evaluate the effects of adenine pretreatment with significance set at 0.05. And now to hear discuss the results in conclusion, my classmate Ben Caruso. Hi all. As Matt mentioned, my name is Ben Caruso. I'm a second year osteopathic medical student at NYIT.com. And for the beginning of our results, just to reiterate what Matt mentioned, at our first time point, we noted a significant paradoxical reduction in triglycerides as well as a significantly higher urine output in the adenine treatment group when in comparison to untreated control group. Meanwhile, at the V2 time point, eight weeks after adenine treatment was stopped, there was a rebound in triglyceride levels. However, polyuria remained significantly elevated and persisted in a group that previously was treated with adenine. Moreover, at both time points, there were no significant differences in cholesterol levels between the groups. Histologically, as you can see on our graphs, we determined that the adenine treated group displayed scattered chronic infiltration of inflammatory cells along with dilated renal tubules filled with pink casts. Ultimately, this study showed that after the cessation of adenine, triglycerides rebounded, but the urine output remained elevated, suggesting that adenine directly influenced triglyceride synthesis independent of kidney function. Also, the persistent polyuria indicates that the renal tubule damage caused by the adenine metabolite 2,8-dihydroxyadenine is irreversible. Although this polyuria is indicative of kidney dysfunction, future endeavors can focus more on primary biomarkers of chronic kidney disease, such as blood urea, nitrogen, cystatin C, and proteinuria in order to determine the CKD status in the mice after the cessation of adenine. Also, further investigation is warranted using this current model of inducible CKD on a background of familial hypercholesterolemia and its effects on atherosclerotic progression, CKD-induced vascular calcification, and cardiovascular disease in the hopes of reducing cardiovascular burden in patients with CKD. Thank you.

chronic kidney disease

cardiovascular health

dyslipidemia

adenine model

triglycerides